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Wen Wu,1,2,* Yu-Pei Zhang,1,2,* Yu-Meng Pan,2 Zhen-Jie He,1,2 Yan-Ping Tan,1 Ding-Deng Wang,1,2 Xing-Guang Qu,1,2 Zhao-Hui Zhang1,2 1Department of Critical Care Medicine, Yichang Central People’s Hospital, Yichang, Hubei, 443003, People’s Republic of China; 2The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhao-Hui Zhang, Department of Critical Care Medicine, Yichang Central People’s Hospital, Yichang, 443003, Hubei, People’s Republic of China, Tel/Fax +86-0717-6481546, Email zhaohuizhang0630@163.comPurpose: This study aims to evaluate the predictive efficacy of the C-reactive protein/albumin ratio (CAR), a cost-effective, easily accessible, and reproducible biomarker obtained from standard blood tests, in forecasting acute kidney injury (AKI) among patients undergoing acute pancreatitis (AP). Considering that changes in the CAR are associated with AKI incidence in AP cases, this work aims to explore whether CAR can be used as the innovative, inflammation-based diagnostic marker for AKI in AP patients.Methods: The current retrospective cohort study consecutively enrolled AP patients admitted to First College of Clinical Medical Science of China Three Gorges University during the period from January 2019 to October 2023. Data were extracted systematically in electronic medical records from these hospitalized individuals, including baseline demographic and clinical characteristics. To ascertain the association of the CAR level with the development of AKI, we carried out multivariate logistic regression, adjusting for potential confounders. These confounders were initially identified through univariate regression. Furthermore, the potential effect modifiers in the relationship between CAR and AKI occurrence were explored by stratified logistic regression.Results: Totally, 1514 AP were recruited, including 257 (16.9%) with AKI. CAR was positively correlated with AKI. When adjusting for potential confounders, the AKI risk in patients in the upper CAR tertile (2.628– 22.994) increased by 83% relative to those in lower tertile (0.05– 0.289) (OR 1.83, 95% CI 1.13– 2.96, P = 0.013). The AKI risk tended to increase according to the increasing CAR tertile (P for trend = 0.013). No significant interactions were observed among subgroups based on age, sex, BMI, admission to ICU, hypertension, DM, chronic obstructive pulmonary disease, severity of AP, etiology of AP, demand for CRRT, mechanical ventilation, and blood transfusion (all P > 0.05).Conclusion: A higher CAR is significantly related to the higher AKI incidence in AP patients in the Chinese population.Keywords: acute pancreatitis, acute kidney injury, CRP/albumin ratio, cohort study

Liying Zhan,1,&ast; Zhihua Lv,2,&ast; Yunjing Zhang,3,&ast; Jingdi Chen,4 Lu Wang,1 Raojuan Huang,5 Yaqi Sun,5 Wei Wu1 1Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Clinical Laboratory, Institute of Translational medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 4Department of Orthopedics, the Airborne Military Hospital, Wuhan, Hubei, People’s Republic of China; 5First Clinical College of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu, Email weiwu2012@whu.edu.cnPurpose: Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied.Methods: We conducted a retrospective analysis of microbiological results through both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with nosocomial CNS infections. The aim of this study was to assess the clinical diagnostic effect of nosocomial mNGS in this population.Results: The study included 26 cases of nosocomial CNS infections in total. A total of 69.2% (18/26) of the samples tested positive for mNGS, which is substantially greater than the 7.7% (2/26; p< 0.05) detected through conventional techniques. Administration of antibiotics before culture is most likely the cause of the low CSF culture rate. Twenty-five pathogenic strains that were missed by standard testing. Three pathogens that were consistent with the mNGS results were positive by routine tests. Eight cases were negative by mNGS due to low pathogen CSF titres. Compared to traditional testing, mNGS demonstrated 100% sensitivity and 33.3% specificity in diagnosing CNS infections. The thirty-day mortality rate was 26.9% (7/26).Conclusion: Routine microbiologic testing frequently falls short of detecting all neuroinvasive pathogens. Our research suggests that mNGS offers an alternative means of detecting nosocomial CNS infections. By applying mNGS to CSF samples from patients with meningitis or encephalitis, we were able to improve the ability to diagnose nosocomial neurologic infections.Keywords: metagenomic next-generation sequencing, cerebrospinal fluid, central nervous system infections, diagnosis

Lin Song,&ast; Xiaosu Yuan,&ast; Zhonghao Zhao, Peiyan Wang, Weiwei Wu, Jianxun Wang School of Basic Medicine, Qingdao University, Qingdao, 266071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxun Wang, School of Basic Medicine, Qingdao University, Qingdao, People’s Republic of China, Tel +86 532 82991791, Email wangjx@qdu.edu.cnBackground: Myocardial infarction (MI) is characterized by irreversible cardiomyocyte death resulting from an inadequate supply of oxygenated blood to the myocardium. Recent studies have indicated that ferroptosis, a form of regulated cell death, exacerbates myocardial injury during MI. Concurrently, the upregulation of CD47 on the surface of damaged myocardium following MI impairs the clearance of dead cells by macrophages, thereby hindering efferocytosis. In this context, simultaneously inhibiting ferroptosis and enhancing efferocytosis may represent a promising strategy to mitigate myocardial damage post-MI.Methods: In this study, we engineered platelet membrane-coated hollow mesoporous silicon nanoparticles (HMSN) to serve as a drug delivery system, encapsulating ferroptosis inhibitor, Ferrostatin-1, along with an anti-CD47 antibody. We aimed to assess the potential of these nanoparticles (designated as Fer-aCD47@PHMSN) to specifically target the site of MI and evaluate their efficacy in reducing cardiomyocyte death and inflammation.Results: The platelet membrane coating on the nanoparticles significantly enhanced their ability to successfully target the site of myocardial infarction (MI). Our findings demonstrate that treatment with Fer-aCD47@PHMSN resulted in a 38.5% reduction in cardiomyocyte ferroptosis under hypoxia, indicated by decreased lipid peroxidation and increased in vitro. Additionally, Fer-aCD47@PHMSN improved cardiomyocyte efferocytosis by approximately 15% in vitro. In MI mice treated with Fer-aCD47@PHMSN, we observed a substantial reduction in cardiomyocyte death (nearly 30%), decreased inflammation, and significant improvement in cardiac function.Conclusion: Our results demonstrated that the cooperation between the two agents induced anti-ferroptosis effects and enhanced dead cardiomyocyte clearance by macrophage as well as anti-inflammation effects. Thus, our nanoparticle Fer-aCD47@PHMSN provides a new therapeutic strategy for targeted therapy of MI. Keywords: myocardial infarction, ferroptosis, efferocytosis, HMSN

Yu Qiu,1,2,&ast; Yan Chen,1,2,&ast; Haoyang Shen,1,2 Shuixin Yan,1,2 Jiadi Li,1,2 Weizhu Wu1 1The Affiliated Lihuili Hospital, Ningbo University, Ningbo, 315000, People’s Republic of China; 2Health Science Center, Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhu Wu, The Affiliated Lihuili Hospital, 1111 Jiangnan Road, Ningbo, Zhejiang, 315000, People’s Republic of China, Tel +86 574 13957402451, Email wuweizhu1128@163.comPurpose: This study investigated the correlation between the Naples prognostic score (NPS), clinicopathological traits, and the postoperative prognoses of patients with triple-negative breast cancer (TNBC). Based on NPS, a predictive nomogram was developed to estimate the long-term survival probabilities of patients with TNBC post-surgery.Patients and Methods: We retrospectively examined the clinical records of 223 women with TNBC treated at Ningbo Medical Center, Lihuili Hospital between January 1, 2016 and December 31, 2020. Blood tests and biochemical analyses were conducted before surgery. The prognostic nutritional index (PNI), controlling nutritional status (CONUT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and NPS were determined based on blood-related markers. A Kaplan-Meier survival analysis assessed the association between NPS, PNI, CONUT score, overall survival (OS), and breast cancer-specific survival (BCSS). Predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) and C index. The patients were randomly divided into the training and the validation group (6:4 ratio). A nomogram prediction model was developed and evaluated using the R Software for Statistical Computing (RMS) package.Results: NPS outperformed other scores in predicting inflammation outcomes. Patients with an elevated NPS had a poorer prognosis (P< 0.001). Lymph node ratio (LNR), surgical method, postoperative chemotherapy, and NPS independently predicted OS, whereas M stage, LNR, and NPS independently predicted BCSS outcome. The OS and BCSS predicted by the nomogram model aligned well with the actual OS and BCSS. The decision curve analysis showed significant clinical utility for the nomogram model.Conclusion: In this study, NPS was an important prognostic indicator for patients with TNBC. The nomogram prognostic model based on NPS outperformed other prognostic scores for predicting patient prognosis. The model demonstrated a clear stratification ability for patient prognosis, which emphasized the potential benefits of early intervention for high-risk patients.Plain Language Summary: In this study, we aimed to understand how the Naples prognostic score (NPS) scoring system could predict the prognosis for patients with triple-negative breast cancer (TNBC). TNBC is a type of breast cancer that can be difficult to treat. Medical records of 223 women with TNBC were retrospectively analyzed. These women had their blood tested before surgery to check for certain markers related to nutrition and inflammation. NPS was used along with other scores to determine their accuracy in predicting survival. NPS was better at predicting outcomes than the other scores. The patients with higher NPS scores tended to have poorer outcomes. We also created a visual tool called a nomogram to help doctors predict patient outcomes based on the NPS scores. NPS can be a valuable tool for doctors treating patients with TNBC because it can help them predict how well a patient might do after surgery. This information could be used to tailor treatment plans for these patients. The nomogram provides a user-friendly way for doctors to use NPS in their practice. Overall, this study showed that NPS is a powerful tool for predicting outcomes for patients with TNBC, which could lead to better treatment decisions and improved outcomes for these patients.Keywords: triple-negative breast cancer, Naples prognostic score, prognostic factor, nomogram predictive model

Jiaoquan Chen, Shanshan Ou, Weihong Wu, Hui Zou, Huaping Li, Huilan Zhu Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, 510095, People’s Republic of ChinaCorrespondence: Huilan Zhu, Department of Dermatology, Guangzhou Dermatology Hospital, 56 Hengfu Road, Guangzhou, Guangdong, 510095, People’s Republic of China, Email zhlhuilan@126.comBackground: Although omalizumab has shown success in treating chronic spontaneous urticaria (CSU) patients unresponsive to antihistamines, the exact mechanism of action and predictive markers of response remain unclear.Purpose: The aim of this study was to examine the correlation between baseline levels of biomarkers and clinical parameters with omalizumab response and response rate in patients with CSU.Methods: This retrospective study included 82 adult CSU patients who received omalizumab 300mg every 4 weeks for 16 weeks between January 2022 and December 2023. Treatment response was assessed using UAS7 and DLQI scores at baseline and weeks 4, 8, 12, and 16. Responders were defined as patients achieving UAS7 < 7, with early and late responders categorized based on response within or after 4 weeks, respectively. Baseline clinical features and laboratory biomarkers were compared between responders and non-responders.Results: The overall response rate was 71.95% (59/82), with 23 early responders and 36 late responders. Responders had significantly lower baseline UAS7 (median: 28 vs 35, P < 0.01), DLQI (median: 8 vs 15, P < 0.001), and IL-17 levels (median: 0.53 vs 1.26 pg/mL, P < 0.001) compared to non-responders. Baseline UAS7 > 31, DLQI > 9.5, and IL-17 > 0.775 pg/mL predicted non-response with sensitivities of 78.26%, 100%, and 78.26%, and specificities of 67.8%, 59.32%, and 72.88%, respectively. ASST positivity and comorbid allergic diseases were associated with early response (P < 0.05). Adverse events were reported in 6.09% of patients, including mild injection site reactions and transient urticaria exacerbation, not requiring treatment discontinuation.Conclusion: This study suggests that omalizumab is an effective and safe treatment option for antihistamine-refractory CSU. Baseline UAS7, DLQI, ASST status, serum total IgE levels, and IL-17 may serve as potential predictors of omalizumab response. Notably, ASST positivity and comorbid allergic diseases were associated with an early response to treatment. These findings highlight the importance of considering individual patient characteristics when predicting the likelihood and timing of response to omalizumab in CSU.Keywords: Chronic spontaneous urticaria, omalizumab, response, early responder, late responder

Zijuan Ma,1,&ast; Yunge Fan,1,&ast; Zhijun Yu,1 Wenxuan Wu,1 Xiangting Zhang,1 Huolian Li,1 Shaochen Zhao,2 Yang Li,3 Yuanyuan Li,4 Dongfang Wang,1 Fang Fan1 1Center for Studies of Psychological Application, School of Psychology, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of China; 2Research Center for Guangdong-Hong Kong-Macao Policing Model Innovation, China People’s Police University, Guangzhou, People’s Republic of China; 3Department of Educational Psychology, Faculty of Education, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongfang Wang; Fang Fan, School of Psychology, South China Normal University, Shipai Road, Guangzhou, 510631, People’s Republic of China, Email wdfpsyc@126.com; fangfan@scnu.edu.cnPurpose: Although experimental psychopathology using PET, EEG, and fMRI is at the forefront of understanding the underlying mechanisms of sleep inertia, many questions concerning causality remain unanswerable due to ethical constraints and the use of small and heterogeneous samples in experimental methods. There is a pressing need for a novel perspective in a large and relatively homogeneous population to fully capture and elucidate longitudinal processes and dynamic causality that culminate in episodes of sleep inertia over time. Therefore, this study aimed to reveal the causal relationships between symptoms of sleep inertia across its distinct patterns.Patients and Methods: A total of 1636 intern nurses participated in the first survey (94.1% validity rate), then 1277 intern nurses were followed up (82.9% tracing rate). Symptoms of sleep inertia were self-reported using the Sleep Inertia Questionnaire. The cross-lagged panel network models were used to examine unique longitudinal relationships between symptoms of sleep inertia across distinct trajectories.Results: Four distinct trajectories of sleep inertia were established. Additionally, we found differences in those symptoms with the highest influence on other symptoms at the subsequent point across the networks of four trajectories, particularly, “Difficulty in concentrating” in the persistent-high group and “Feeling tense” in the deteriorating groups.Conclusion: The current study highlights changes in sleep inertia based on the long-term course over time. Notably, symptoms of “Difficulty in concentrating” and “Feeling tense” are imperative to address these specific symptoms within subpopulations.Keywords: sleep inertia, change patterns, network structures, intern nurse, shift work

Xinling Zhao,1,2,&ast; Huijin Jie,3,&ast; Jun Wang,1 Yu Liu,4 Yilin Liu,2 Fuyi Qin,2 Qing Long,2 Xi Hou,5 Xin-Wen Zhang,6 Wenzhi Wu,7 Xiaoqin Wu,2 Jing Li,8 Yong Zeng2 1Department of Clinical Psychology, People’s Hospital of Chongqing Liang Jiang New Area, Chongqing, People’s Republic of China; 2Department of Psychiatry, the Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Haining Fourth People’s Hospital, Haining, People’s Republic of China; 4Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 5Department of Clinical Psychology, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China; 6Department of Psychiatry, Hong He Second People’s Hospital, Jian Shui, People’s Republic of China; 7Faculty of psychology, Beijing Normal University, Beijing, People’s Republic of China; 8Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Li; Yong Zeng, Email lijingjingjing222@163.com; zengyong@kmmu.edu.cnBackground: Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma.Methods: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children’s Depression Inventory (CDI) and Children’s Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control.Results: The serum levels of BDNF were significantly lower (p< 0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p< 0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028). BDNF was negatively correlated with CDRS-R (r=− 0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value.Conclusion: Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.Keywords: brain-derived neurotrophic factor, p-mTOR, major depressive disorder, suicide, adolescent, childhood trauma

Min Lei,1,2,&ast; Zheng Jiang,1,2,&ast; Peng Xu,1,2 Zhenglin Chang,1– 3 Yuyan Zhang,4 Shike Zhang,1,2 Lingyue An,1,2,5 Shujue Li,2,3 Tao Zeng,2,3 Hans-Göran Tiselius,6 Yuhao Zhou,1,2 Guohua Zeng,2,3 Wenqi Wu1,2 1Department of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 2Guangdong Key Laboratory of Urology, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 4Guangzhou Institute of Dermatology, Guangzhou, Guangdong, 510095, People’s Republic of China; 5Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 6Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, 14186, Sweden&ast;These authors contributed equally to this workCorrespondence: Wenqi Wu; Guohua Zeng, Email 2009681012@gzhmu.edu.cn; gzgyzgh@vip.sina.comBackground: The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS).Methods: Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed.Results: Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients.Conclusion: The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.Keywords: kidney stones, bacterial spectrum, antibiotic resistance, stone culture, urine culture

Dongrui Xu,1,&ast; Xiaoyi Yang,1,&ast; Wenjuan Wu,2 Jiankang Yang1 1School of Basic Medical Sciences, Dali University, Dali, Yunnan, People’s Republic of China; 2Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiankang Yang, School of Basic Medical Sciences, Dali University, Dali, Yunnan, People’s Republic of China, Email jkyang1984@126.com Wenjuan Wu, Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email wuwj1021@126.comBackground: Despite the availability of numerous therapies, the treatment of acne vulgaris remains challenging. Novel drug targets for acne vulgaris are still needed.Methods: We conducted a Mendelian randomization analysis to explore possible drug targets for acne vulgaris. We utilized summary statistics obtained from the dataset of acne vulgaris, including 399,413 individuals of European ancestry. We gathered genetic instruments for 566 plasma proteins from genome-wide association studies. In order to strengthen the findings from Mendelian randomization, various methods were employed, including bidirectional Mendelian randomization analysis, Bayesian co-localization, phenotype scanning, and single-cell analysis. These methods facilitated the identification of reverse causality, the search for reported variant-trait associations, and the determination of the cell types that is the primary source of protein. Furthermore, using the plasma proteins in the deCODE cohort, we conducted a replication of the Mendelian randomization analysis as an external validation.Results: At the significance level of Bonferroni (P < 8.83× 10− 5), a protein-acne pair was discovered through Mendelian randomization analysis. In plasma, increasing TIMP4 (OR = 1.15; 95% CI, 1.09– 1.21; P = 1.01× 10− 7) increased the risk of acne vulgaris. The absence of reverse causality was observed in the TIMP4 protein. According to Bayesian co-localization analysis, TIMP4 shared the same variant with acne vulgaris (PPH4 = 0.93). TIMP4 was replicated in deCODE cohort (OR = 1.17; 95% CI, 1.10– 1.24; P = 1.48× 10− 7). Single-cell analysis revealed that TIMP4 was predominantly detected in myeloid cells in blood, and was detected in almost all cell types in skin tissue.Conclusion: The integrative analysis revealed that the level of plasma TIMP4 has a direct influence on the risk of developing acne vulgaris. This implies that TIMP4 protein could serve as a potential target for the development of drugs aimed at treating acne vulgaris.Keywords: plasma proteome, acne vulgaris, drug target, biomarker, Mendelian randomization, TIMP4

Peijun Li,1,&ast; Yingqi Wang,1,&ast; Yuanyuan Cao,2 Jiacheng Shi,1 Meiling Jiang,2 Xiaoyu Han,2 Linhong Jiang,1 Yidie Bao,1 Weibing Wu,2 Xiaodan Liu1,3,4 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai, 200438, People’s Republic of China; 3Institute of Rehabilitation Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Liu; Weibing Wu, Email hzhp403@126.com; wwb75@126.comBackground: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear.Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1β, TNF-α, and RhoA/ROCK were determined by Western blotting.Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably.Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.Keywords: chronic obstructive pulmonary disease, diaphragmatic atrophy, exercise training, inflammation, RhoA/ROCK signaling

Lu Zhang,1– 3,&ast; Fei Teng,1,2,&ast; Huajie Xin,1,2 Wei Xu,1,2 Wei Wu,4 Chenguo Yao,3 Zhiqiang Wang1,2 1Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 2Center of Thoracic Cancer, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3The State Key Laboratory of Power Transmission Equipment and System Security and New Technology, College of Electrical Engineering, Chongqing University, Chongqing, 400044, People’s Republic of China; 4College of Biological Engineering, Chongqing University, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Zhang; Zhiqiang Wang, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Email luzhang_524@aliyun.com; zhiqiangwang@21cn.comAbstract: Patients diagnosed with glioma typically face a limited life expectancy (around 15 months on average), a bleak prognosis, and a high likelihood of recurrence. As such, glioma is recognized as a significant form of malignancy. Presently, the treatment options for glioma include traditional approaches such as surgery, chemotherapy, and radiotherapy. Regrettably, the efficacy of these treatments has been less than optimal. Nevertheless, a promising development in glioma treatment lies in the use of hydrogel nano-systems as sophisticated delivery systems. These nano-systems have demonstrated exceptional therapeutic effects in the treatment of glioma by various responsive ways, including temperature-response, pH-response, liposome-response, ROS-response, light-response, and enzyme-response. This study seeks to provide a comprehensive summary of both the therapeutic application of hydrogel nano-systems in managing glioma and the underlying immune action mechanisms. Keywords: glioma, hydrogel nano-system, immunotherapy, tumor immune microenvironment

Wenxia Wu,1,2,&ast; Jingwei Tian,1,&ast; Lisha Xiao,1 Haochen Mai,1 Phei Er Saw,3– 5 Meng Zhang1,2 1Department of General Practice, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of General Practice, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Shanwei, Guangdong, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 4Guangzhou Key Laboratory of Medical Nanomaterials, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 5Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Phei Er Saw; Meng Zhang, Email zhangm7@mail.sysu.edu.cn; caipeie@mail.sysu.edu.cnBackground: The incidence of cancer is increasing, and cancer survivors are also growing exponentially. Cancer is defined as a new chronic disease. Nevertheless, the management of cancer in the form of chronic diseases in China is still in its infancy, without a standardized care model.Objective: This study aimed to explore the current status of management of cancer care from the patient’s perspective.Methods: This cross-sectional study was a questionnaire survey of patients diagnosed with cancer, including information of the current situation of daily medical consultation, status of comorbidity, and expectations of seeking cancer care in future. Chi-square test and logistic regression analysis were used to explore the factors influencing patients’ choice of cancer management mode.Results: A total of 200 cancer patients were included in the study. The majority (n = 150) of cancer patients chose an oncologist in a tertiary hospital for cancer care. Difficulty in registration (45%), time-consuming (34.5%), repeated examinations (34.5%) and different treatment opinions (12.0%) were the main difficulties they encountered currently during tertiary hospital visits. In community hospital, lack of trust in general practitioners (n = 33) and the necessary drugs or testing items in community hospitals (n = 47) were the main difficulties during their visits. Logistic regression analysis showed that male (OR = 2.737, 95% CI, 1.332– 5.627, p = 0.006) and elderly patients (OR = 3.186, 95% CI, 1.172– 8.661, p = 0.023) were more likely to choose general practitioners (GPs) in community hospitals. Twenty-nine (14.5%) patients hope to have an integrated multidisciplinary management in tertiary and community hospitals with the active participation of GPs for cancer care.Conclusion: Improving drug availability, equipment and quality of cancer care services can help to increase cancer patients’ recognition of community hospital. In addition, the multidisciplinary management integrated tertiary hospitals and communities with the participation of GPs is a worth exploring mode that improves the management of cancer care.Keywords: cancer care, chronic disease management, general practitioners, GPs, multidisciplinary

Chenxi Li,1,&ast; Xiaolei Chen,2,&ast; Xiaowen Zhu,1 Mengjiao Cao,3 Qunfeng Tang,3 Wenjun Wu1,4 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Neurology, Jiangnan University Medical Center, Wuxi No. 2 People’s Hospital, Wuxi, People’s Republic of China; 3Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Fax +86-510-85737592, Email wuwenjung@163.comPurpose: Arterial stiffness is often increased in overweight or obese individuals before the development of hypertension (HT). This study aimed to determine the connection between pancreatic fat and atherosclerosis in overweight and obese people without HT.Patients and methods: We included 128 patients who were non-hypertensive and overweight or obese in a study between December 2019 and November 2022. Medical history was collected, and all participants underwent a physical examination and blood tests. Pancreatic fat content was measured by magnetic resonance imaging (MRI) and was grouped into quartiles based on pancreatic fat fraction (PFF). The upper three quartiles (PFF≥ 10.33%) were defined as non-alcoholic fatty pancreas disease (NAFPD) and the first quartile (PFF< 10.33%) as non-NAFPD. High baPWV (H-baPWV) and low baPWV (L-baPWV) were classified according to the median baPWV (1159 cm/s). The effect of NAFPD on baPWV was examined using binary logistic regression. The study population consisted of 96 NAFPD and 32 non-NAFPD cases.Results: Participants with NAFPD had significantly higher levels of baPWV than people without. The rates of NAFPD and the PFF values varied significantly in the L-baPWV and H-baPWV groups. Logistic regression analysis suggested that the presence of NAFPD was independently correlated with increased baPWV after adjusting for age, smoking, body mass index, blood pressure, lipid profiles, and glycemic index.Conclusion: NAFPD is an independent risk factor for increased baPWV in individuals with overweight and obesity but no HT, suggesting that the presence of NAFPD may be a warning signal of early atherosclerosis.Keywords: obesity, non-alcoholic fatty pancreas disease, overweight, arterial stiffness, brachial-ankle pulse wave velocity

Shuxiu Xiao,1,&ast; Lili Lu,1,&ast; Zhiyuan Lin,2,&ast; Xinming Ye,3 Sheng Su,3 Chenlu Zhang,4 Yang You,4 Wei Li,4 Xiaowu Huang,3 Weizhong Wu,5 Yuhong Zhou1,4 1Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 5Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhong Zhou; Weizhong Wu, Email zhou.yuhong@zs-hospital.sh.cn; wu.weizhong@zs-hospital.sh.cnBackground: Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8+ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8+ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC.Methods: TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN+CD8+ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI.Results: The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8+ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8+ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN+CD8+ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8+ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8+ T cells.Conclusion: LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy. Keywords: hepatocellular carcinoma, layilin, CD8+ T cell exhaustion, prognosis

Jingliang Wu,1,&ast; Qiao Lu,1,2,&ast; Jialin Zhao,3,&ast; Wendi Wu,3 Zhihua Wang,1 Guohua Yu,4 Guixiang Tian,2 Zhiqin Gao,2 Qing Wang5 1School of Medicine, Weifang University of Science and Technology, Weifang, 262700, People’s Republic of China; 2School of Life Science and Technology, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 4Department of Oncology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China; 5Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wang, Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China, Tel +86 158 6362 6389, Email wfwq8899@163.comPurpose: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells.Methods: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro “condition medium of fibroblasts + MCF-7” cell model and in vivo “ 4T1/NIH-3T3” co-implantation mice model were established to evaluate the anti-tumor effect of drugs.Results: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect.Conclusion: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.Keywords: drug delivery, cancer-associated fibroblasts, glucocorticoids, combination therapy

Jingnan Zhao,1 Chengyu Qian,2 Youqiao Jiang,1,3 Wangrui He,1 Wenhua Wu1 1Tuberculosis Control Department, Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, 330029, People’s Republic of China; 2Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 3Young Scientific Research and Innovation Team, Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, Jiangxi, 330029, People’s Republic of ChinaCorrespondence: Wangrui He, Tuberculosis Control Department, Jiangxi Provincial Center for Disease Control and Prevention, No. 555, Beijing East Road, Nanchang, Jiangxi, 330029, People’s Republic of China, Email jxcdccbs@126.comPurpose: In this study, we aimed to determine the transmission pattern of multidrug-resistant tuberculosis (MDR-TB) isolates circulating in Jiangxi Province with whole-genome sequencing (WGS). In addition, we also sought to describe mutational resistome of MDR-TB isolates.Patients and Methods: A total of 115 MDR-TB isolates determined by the phenotypic proportion method of drug susceptibility testing between January 2018 and December 2022 from provincial drug surveillance (DRS) in Jiangxi were included in our analysis. The demographic data and treatment history were extracted from the National TB Registry System. WGS was used to analyze the genotypic characteristics of drug resistance and transmissions.Results: About 62.6% of MDR-TB strains were isolated from cases that received previous anti-tuberculosis treatment. According to the WGS results, 96.5% were genotypic MDR-TB, and more than half of MDR-TB isolates tested were also resistant to streptomycin (59.1%), ethambutol (56.5%), and fluroquinolones (53.0%), while resistance to cycloserine and linezolid was lowest, only in two (1.7%) and one (0.9%) isolate, respectively. Ser450Leu in rpoB (57.9%), Ser315Thr in katG (74.1%), Met306Val in embB (40.0%), Lys43Arg in rpsL (75.0%), Ala90Val in gyrA (32.8%) were predominant mutant types among the rifampin-, isoniazid-, ethambutol-, streptomycin-, fluoroquinolones-resistant isolates, respectively. Lineage 2 (East Asian genotype) occurred at the highest frequency with 97 cases (84.3%), followed by lineage 4 (Euro-American genotype) with 18 cases (15.7%). Additionally, 5 clusters consisting of 10 isolates were identified in the present study, demonstrating a clustering rate of 8.7%.Conclusion: MDR/Rifampicin-Resistant (RR)-TB epidemic in this region is driven by lineage 2 clade that also show higher resistance to other anti-tuberculosis drugs. Lower cluster rates compared with a relatively higher proportion of new MDR-TB cases indicate that a considerable number of MDR-TB cases remain undiagnosed.Keywords: Mycobacterium tuberculosis, drug resistant, whole-genome sequencing, genetic diversity, transmission dynamics

Yingxuan Hu,1,&ast; Junqin Ma,1,&ast; Bingmei Chen,2 Jiahui Pang,1 Wen Liang,2 Wen Wu1 1Department of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Radiology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Wu; Wen Liang, Email wuwen66@163.com; liangwendoc@163.comPurpose: This study was conducted to explore the differences in functional changes in the pain matrix in patients with chronic back pain (CBP) at different stages and identify whether these brain changes were related to the pain duration.Patients and Methods: In this study, 29 healthy individuals and 54 patients with CBP were recruited. According to the pain duration, 25 patients (3 to 12 months) were divided into the CBP-S group and 29 patients (≥ 24 months) were divided into the CBP-L group. All subjects completed clinical pain-related measurement and functional magnetic resonance imaging (fMRI) scans. Moreover, the amplitude of low-frequency fluctuation (ALFF), functional connectivity (FC), and correlation analysis were conducted in this study.Results: Compared with healthy controls, patients in the CBP-L group showed significantly decreased ALFF in the left precuneus. In the FC analysis, patients in the CBP-S and CBP-L groups showed significantly decreased FC in several regions in the bilateral orbitofrontal cortices (OFC) and the left ventral posterior insula. Moreover, there were significant differences in the FC between the left hyper granular insula and the probabilistic area in OFC in pairwise group comparisons. The correlation analysis results demonstrated that pain duration was correlated with these functional brain changes, and the ANCOVA results revealed that pain intensity and pain interference scores did not affect the FC analysis results.Conclusion: There are different changes in the pain neural matrix in patients with chronic pain at different stages. Furthermore, the pain duration is related to brain functional changes.Keywords: chronic back pain, pain duration, fMRI, resting-state, pain matrix

Wanying Wu,1,2,&ast; Congzhuo Jia,1,2,&ast; Xiayan Xu,1– 3 Yibo He,1,2 Yun Xie,1,2,4 Yang Zhou,1,2 Hongyu Lu,1,2 Jin Liu,1,2 Jiyan Chen,1,2 Yong Liu1,2 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 4School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiyan Chen; Yong Liu, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email chenjiyandr@126.com; liuyong@gdph.org.cnBackground: Inflammation contributes to the initiation and advancement of both coronary atherosclerosis and type 2 diabetes mellitus (T2DM). Recent evidence has underscored the platelet-to-HDL-cholesterol ratio (PHR) as a promising inflammatory biomarker closely linked to the severity of coronary artery disease (CAD). Nevertheless, the risk of adverse clinical outcomes remains unclear among CAD patients with varying PHR levels and glycemic status.Methods: A total of 56,316 CAD patients were enrolled, primarily focusing on mortality outcomes. Patients were categorized into four subgroups based on median baseline PHR values and glycemic status: lower PHR (PHR-L) and higher PHR (PHR-H) with or without T2DM. Cox proportional hazard model and subgroup analysis were employed to investigate the association between PHR and glycemic status with mortality.Results: Over a median 5.32-year follow-up, 8909 (15.8%) patients experienced all-cause mortality, with 3873 (6.9%) deaths attributed to cardiovascular causes. Compared to individuals in PHR-L/non-DM, those in PHR-H/non-DM, PHR-L/DM and PHR-H/DM groups exhibited a higher risk of all-cause death [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06– 1.18; HR 1.21, 95% CI 1.14– 1.29; HR 1.43, 95% CI 1.34– 1.52, respectively], as well as cardiac mortality [HR 1.19, 95% CI 1.08– 1.30; HR 1.58, 95% CI 1.44– 1.74; HR 1.89, 95% CI 1.72– 2.07, respectively]. Cox proportional hazard model also revealed the highest mortality risk among patients in PHR-H/DM compared to other groups (P < 0.05). Restricted cubic spline regression analysis revealed a positive linear association between PHR and all-cause as well as cardiac mortality (P for non-linearity > 0.05) after adjustment. Additionally, subgroup analysis indicated consistent effects on cardiac mortality within diverse subsets.Conclusion: In this real-world observational cohort analysis, elevated PHR levels joint with T2DM were related to adverse long-term clinical outcomes in CAD patients. PHR levels may serve as a valuable tool for identifying high-risk individuals within this specific group.Trial Registration: The Cardiorenal ImprovemeNt II registry NCT05050877.Keywords: platelet-to-HDL-cholesterol ratio, coronary artery disease, diabetes, all-cause mortality, cardiovascular mortality

Jiayang Li,1,2,&ast; Wenqi Wu,3,&ast; Meilin Wu,4 Zhitao Zhou,4 Jiajie Wang,1 Mingjie Qiu,4 Li Xu,4 Jianan Ren,1,2 Xiuwen Wu1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3School of Medicine, Nanjing University, Nanjing, People’s Republic of China; 4Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuwen Wu; Jianan Ren, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Email wuxiuwen@nju.edu.cn; jiananr@nju.edu.cnPurpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains.Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently.Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%).Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next “superbug” highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.Keywords: KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae, Bloodstream infections, risk factors, molecular characteristics, mortality

Chen Lin,1 Jing Wang,2 Kexin Cai,2 Yuqing Luo,2 Wensi Wu,1 Siming Lin,2 Zhihong Lin,2 Shaodan Feng2 1Department of Emergency, The Third Affiliated People’s Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Zhihong Lin; Shaodan Feng, Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Tel +86 59187981975, Email fzlinzh@163.com; sdfeng@fjmu.edu.cnPurpose: To address the critical mortality rates among sepsis-associated acute kidney injury (SA-AKI) patients, early prognosis is vital. This study investigates the relationship between coagulation indices and the 28-day mortality rate in patients with SA-AKI.Patients and Methods: This study was a retrospective cohort analysis including patients with SA-AKI admitted to the First Hospital of Fujian Medical University as a training cohort (n = 119) and patients admitted to the Third People’s Hospital of Fujian University of Traditional Chinese Medicine as a validation cohort (n = 51). We examined the relationship between coagulation indices and 28-day mortality in SA-AKI, the cumulative mortality at different activated partial thromboplastin time (APTT) levels, and the nonlinear relationship between APTT and 28-day mortality. Receiver operating characteristic curves were plotted, and the area under the curve was calculated to assess the predictive power of APTT. Finally, subgroup analyses were performed to assess the robustness of the association.Results: Overall, 119 participants with a mean±standard deviation age of 70.47± 15.20 years were included in the training cohort: 54 died, 65 survived. According to univariate and multivariate COX regression analyses, APACHE II score, CRP level, Lac level, and APTT level were independent risk factors for 28-day adverse prognosis. After controlling for some variables, an elevated baseline APTT (≥ 37.7 s) was associated with an elevated risk of 28-day mortality (HR, 1.017; 95% CI, 1.001– 1.032), and Kaplan–Meier analyses further confirmed the increased mortality in the group with a higher APTT. The same results were shown when the validation cohort was analyzed (HR, 1.024; 95% CI, 0.958– 1.096). Subgroup analyses showed the stability of the association between APTT and poor prognosis in SA-AKI.Conclusion: In essence, APTT elevation is synonymous with increased 28-day mortality rates, indicating a poor prognosis in SA-AKI scenarios.Keywords: APTT, prognosis, retrospective studies, critical illness

Wei Wu,1– 4,&ast; Wenbin Lu,5,&ast; Dongmei Hong,1– 4 Xiya Yu,1– 4 Lize Xiong1– 4 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 3Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 4Clinical Research Centre for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 5Faculty of Anesthesiology, Changhai Hospital, Naval Medical University/Second Military Medical University, PLA, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiya Yu; Lize Xiong, Tel +86-21-55603999 ; +86-21-55603002, Fax +86-21-56660851, Email yuxiyash@163.com; mzkxlz@126.com; lizexiong@tongji.edu.cnBackground: The hemoglobin-albumin-lymphocyte-platelet (HALP) index is a novel biomarker reflecting systemic inflammation and nutritional status which are important for coronavirus disease 2019 (COVID-19) mortality. However, the association between HALP and mortality in patients with COVID-19 has yet to be investigated.Methods: A cohort of COVID-19 Omicron BA.2 infected patients admitted to the Shanghai Fourth People’s Hospital, School of Medicine, Tongji University from April 12, 2022 to June 17, 2022 was retrospectively analyzed. Laboratory examinations on hospital admission, including hemoglobin, albumin, and lymphocyte and platelet, were collected. The association between baseline HALP and in-hospital poor overall survival (OS) was assessed using Kaplan–Meier curves, Cox regression models, interaction, and stratified analyses.Results: A total of 2147 patients with COVID-19 Omicron BA.2 infection were included in the final analyses, and mortality in the hospital was 2.65%. Multivariate analysis indicated that low HALP index was independently associated with in-hospital mortality of COVID-19 patients [hazard ratio (HR) = 2.08; 95% confidence interval (CI) = 1.17– 3.73]. Subgroup analysis demonstrated that low HALP index was an independent risk factor for in-hospital mortality in COVID-19 patients with age ≥ 70 (HR = 2.22, CI = 1.18– 4.15) and severe cases (HR = 2.09, CI = 1.13– 3.86).Conclusion: HALP index is independently related to in-hospital poor OS for COVID-19 Omicron BA.2 infected patients, especially for age ≥ 70 and severe cases. HALP index on hospital admission is a useful candidate biomarker for identifying high risk of mortality in COVID-19 Omicron BA.2 infected patients.Keywords: biomarkers, COVID-19, hemoglobin-albumin-lymphocyte-platelet index, mortality, Omicron BA.2

Traidit Thianthanyakij,1,2,&ast; Yinghui Zhou,1,&ast; Mengyi Wu,3,&ast; Yuting Zhang,4 Jui-Ming Lin,1 Yan Huang,4 Yuou Sha,1 Jiayi Wang,1 Sirapath Peter Kong,2 Jinran Lin,1 Qingmei Liu,1 Wenyu Wu1,5,6 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China; 2Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Dermatology, Jing’an District Central Hospital, Shanghai, 200040, People’s Republic of China; 6Academy for Engineering and Technology, Fudan University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Liu; Wenyu Wu, Email liuqing.mei@163.com; wenyu_wu@fudan.edu.cnBackground: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties.Objective: To assess the efficacy of SAB in modulating hair growth.Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis.Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38.Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.Keywords: salvianolic acid B, hair growth, hair cycle, hair follicle, dermal papilla cells

Xiaoying Meng,1,2 Fei Li,2 Wenpei Wu,3 Juncang Wu1,2 1Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 2The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical College, Hefei, Anhui, 230011, People’s Republic of ChinaCorrespondence: Juncang Wu, Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China, Email wujuncang126@126.comPurpose: To investigate the quantitative assessment of carotid plaque by each parameter of dual-layer detector spectral CT and its diagnostic value in patients with acute cerebral infarction.Patients and Methods: Eighty-three patients with carotid atherosclerotic plaques who underwent spectral CT scanning were retrospectively included. Forty-two patients with acute ischaemic stroke (AIS) were included in the study group, and 41 patients without AIS were included in the control group. We compared the detection of carotid plaques in the two groups and the differences in the spectral quantitative parameters of the plaques in the two groups, and their diagnostic efficacy was obtained.Results: The detection rate of carotid plaques in the AIS group was higher than that in the non-AIS group (p< 0.05); the carotid plaques in the AIS group mainly consisted of non-calcified plaques, while those in the non-AIS group mainly consisted of calcified plaques. The effective atomic number (Zeff), slope of the energy spectrum curve (λH), electron density (ED), and iodine-no-water value of the carotid plaques in the AIS group were lower than those in the non-AIS (p< 0.05). For the differentiation of the carotid plaques in the AIS group from those in the non-AIS group, the area under the curve (AUC) of Zeff amounted to 0.637 (cut-off value: 11.865; sensitivity: 72.5%; specificity: 56.2%), the AUC of λH amounted to 0.628 (cut-off value: 19.56; sensitivity: 76.3%; specificity: 51.6%), and that for ED amounted to 0.624 (cut-off value: 110.45; sensitivity: 60.0%; specificity: 64.1%), AUC of iodine-no-water value amounted to 0.645 (cut-off value: 9.125; sensitivity: 61.3%; specificity: 65.6%).Conclusion: In summary, the quantitative parameters of dual-layer detector spectral CT can be used to assess plaque stability and have certain value in the diagnosis of AIS. The quantitative parameters can effectively differentiate carotid plaques in AIS and non-AIS patients.Keywords: ischemic stroke, carotid plaque, spectral CT, effective atomic number, iodine density values, anhydrous iodine values, electron density

Yufeng Ling,1 Menglu Duan,1 Wen Lyu,1 Jie Yang,1,2 Yu Liu,1,3 Shuangshuang Ren,1,4 Wenlei Wu1,3 1Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 2Department of Periodontology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 3Department of Senior Specialist, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 4Department of Cariology and Endodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Wenlei Wu; Shuangshuang Ren, Tel +025-83620252 ; +025-83620215, Email wlwu@nju.edu.cn; zjndrenss@163.comIntroduction: Periodontitis, a chronic inflammatory disease prevalent worldwide, is primarily treated through GTR for tissue regeneration. The efficacy of GTR, however, remains uncertain due to potential infections and the intricate microenvironment of periodontal tissue. Herein, We developed a novel core-shell structure multifunctional membrane using a dual-drug-loaded coaxial electrospinning technique (Lys/ACP-CNF), contains L-lysine in the outer layer to aid in controlling biofilms after GTR regenerative surgery, and ACP in the inner layer to enhance osteogenic performance for accelerating alveolar bone repair.Methods: The biocompatibility and cell adhesion were evaluated through CCK-8 and fluorescence imaging, respectively. The antibacterial activity was assessed using a plate counting assay. ALP, ARS, and RT-qPCR were used to examine osteogenic differentiation. Additionally, an in vivo experiment was conducted on a rat model with acute periodontal defect and infection. Micro-CT and histological analysis were utilized to analyze the in vivo alveolar bone regeneration.Results: Structural and physicochemical characterization confirmed the successful construction of the core-shell fibrous structure. Additionally, the Lys/ACP-CNF showed strong antibacterial coaggregation effects and induced osteogenic differentiation of PDLSCs in vitro. The in vivo experiment confirmed that Lys/ACP-CNF promotes new bone formation.Conclusion: Lys/ACP-CNF rapidly exhibited excellent antibacterial activity, protected PDLSCs from infection, and was conducive to osteogenesis, demonstrating its potential application for clinical periodontal GTR surgery. Keywords: anti-microbial therapy, L-lysine, electrospun membrane, osteogenic, periodontal tissue regeneration

Jianmei Lu,1,2,&ast; Yongzhu Zeng,1,&ast; Huashuai Zhong,1 Wei Guo,1 Yuyan Zhang,1 Wanting Mai,3 Yucui Qin,4 Xiaodan Su,3 Bo Zhang,5 Weisen Wu,1 Yu Zhu,1 Qiujie Huang,6 Yong Ye1,7– 9 1Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China; 2The Second Nanning People’s Hospital, Nanning, People’s Republic of China; 3The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 4Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Scientific Research Center, Guilin Medical University, Guilin, People’s Republic of China; 6Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China; 7Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning, People’s Republic of China; 8Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Nanning, People’s Republic of China; 9Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Huang, Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China, Email hqj8@163.com Yong Ye, Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China, Email yong-ye@163.comBackground and Purpose: Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease.Methods: The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing.Results: The nanoparticles prepared in this study have an average particle size of (255.9± 5.10) nm, with an encapsulation rate of (72.83± 2.13) % and a drug loading of (4.65± 0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice.Conclusion: This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.Keywords: nanoparticles, colonic targeting, metabolic disorders, gut microbiota

Anping Lu,1,2,&ast; Fangyi Yu,2,&ast; Xiaohan Tan,2 Xiaohong Jin,1 Xiaohua Wang,3 Wenya Wu1 1Nursing Department, The First People’s Hospital of Changshu, Changshu, 215500, People’s Republic of China; 2School of Nursing, Medical College, Soochow University, Suzhou, 215006, People’s Republic of China; 3Division of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenya Wu, Nursing Department, The First People’s Hospital of Changshu, Changshu, 215500, People’s Republic of China, Tel +86-1386236425, Fax +86-512-52223921, Email 106313851@qq.comPurpose: Previous research has consistently shown that self-perception of aging (SPA) is an important predictor of health and longevity, while Chinese rural elderly patients with hypertension had poorer SPA. Whether it was associated with their mortality kept unknown. The objective of this study was to investigate the long-term mortality and analyze the association between SPA and this mortality in the specific context of rural elderly patients with hypertension.Patients and Methods: This study is a longitudinal investigation of the mortality in elderly patients with hypertension in rural Suzhou, China. Sociodemographic and clinical data, SPA, and six-year mortality were investigated. We used binary logistic regression and subgroup analyses to assess the effect of SPA at baseline on six-year mortality.Results: A total of 280 hypertensive patients aged 60 years and older participated in the study, of whom 21 died, with a six-year mortality rate of 7.5%. After controlling for covariates, the “Emotional representation” dimension (OR=2.824, 95% CI:1.034– 7.712) in SPA remained a risk factor for death. In subgroup analyses of the group aged 75 years and older, high scores on the “Timeline cyclical” (OR=14.125, 95% CI: 1.258– 158.593) and “Emotional representations” (OR=2.567, 95% CI:1.066– 6.182) dimensions were associated with a higher risk of death, while weekly nut intake may have mitigated the negative SPA effect on mortality.Conclusion: Poorer self-perception of aging was associated with a high risk of mortality in rural elderly patients with hypertension, while the habit of weekly nut intake might help reduce this risk in the group aged 75 years or older.Keywords: China, hypertension, mortality, rural population, self-perception

Zongwei Xue,1,&ast; Xiaoyan Zhu,2– 4,&ast; Wenqi Wu,1 Yan Zhu,5 Yuhao Xu,1 Ming Yu1 1Department of Neurology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 2Department of Neurology, People’s Hospital of Yangzhong City, Yangzhong, Jiangsu, 212299, People’s Republic of China; 3School of Clinical Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China; 4Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu, 225000, People’s Republic of China; 5Department of Radiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhao Xu; Ming Yu, Department of Neurology, The Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, 212001, People’s Republic of China, Tel +86 187 9601 7221, Email xuyuh0217@163.com; yuming7251@163.comBackground: Cognitive impairment is one of the common concomitant symptoms of depression. The aims of the present study were to predict the occurrence of mild cognitive impairment (MCI) in patients with depression.Methods: In this study, 217 patients with depression were recruited. Demographic data, serum indices and ERP indices from all participants were collected in the baseline period. The participants were followed for one year, and data from 200 patients were included in final analysis. Patients with depression were divided into those with MCI group (DWM group; n=145) and those without MCI (DWOM group; n=55). Data from the DWM group and the DWOM group were used to construct a logistic regression model, and a receiver operating characteristic (ROC) curve was drawn. Another 72 patients were used to validate the accuracy of our model.Results: Compared with DWOM individuals, DWM individuals were more likely to live alone (P< 0.05), had lower baseline serum levels of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and fibroblast growth factor 22 (FGF22) (P< 0.05), and exhibited higher baseline latencies of P300, mismatch negativity (MMN), and N200 (P< 0.05). Baseline serum BDNF and FGF22 levels, along with the P300 latency, were selected to construct the regression model using logistic regression. The regression equation was , and the combination of the 3 indices yielded an area under the ROC curve (AUC) of 0.790 and a predictive accuracy of 0.806.Conclusion: The logistic regression model and ROC curves based on serum BDNF and FGF22 levels and the P300 latency could provide a more effective means to predict the occurrence of MCI in patients with depression.Keywords: depression, mild cognitive impairment, brain-derived neurotrophic factor, fibroblast growth factor 22, P300, prediction

Wenpei Wu,1,2,&ast; Zhi Geng,3– 5,&ast; Aimei Wu,2,&ast; Xinyi Chen,6,7 Xiaoying Meng,2 Qianyun Zhang,2 Zheng Tan,2 Hong Yue,2 Juncang Wu1,2 1Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Department of Neurology, Hefei Second People’s Hospital, Hefei, Anhui, 230011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 5Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, 230000, People’s Republic of China; 6Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 7The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncang Wu; Hong Yue, Intersection of Guangde Road and Leshui Road, Hefei, Anhui, 230011, People’s Republic of China, Tel/Fax +86 551 13956076148 ; +86 551 18949855780, Email wujuncang126@126.com; yuehong01@foxmail.comBackground and Purpose: The role of serum uric acid (UA) level in patients suffering from stroke remains controversial. Our aim was to investigate the effect of UA level on clinical outcomes in patients with intracerebral hemorrhage (ICH).Methods: In the retrospective cohort study, we analyzed data from 250 patients with intracerebral hemorrhage (85 women and 165 men) to investigate the difference in UA levels between patients with a good prognosis and those with a poor prognosis. Additionally, we analyzed the impact of UA levels on the risk of short-time prognosis of ICH patients.Results: Patients with a good prognosis presented with significantly lower levels of UA (348.71 ± 84.97 μmol/L) than those with poor prognosis (393.06 ± 148.46 μmol/L). Furthermore, multivariate logistic regression model demonstrated that a high UA level was a likely risk factor for worse prognosis among patients suffering in ICH (odds ratio [95% confidence interval], 1.006 [1.0012, 1.0108]; P = 0.015). Additionally, UA has a threshold effect value of 363.9 μmol/L and was presented in levels that were in a nonlinear relationship with incidence rate of short-time prognosis outcome of ICH patients.Conclusion: Our findings indicate that higher UA levels can increase the risk of poor clinical prognosis in patients with ICH and high UA levels are not conductive to the clinical prognosis of patients with ICH. These findings provide a new perspective on the treatment and prevention of ICH.Keywords: intracerebral hemorrhage, uric acid, oxidative stress, follow-up, nonlinear relationship, prognosis

Sheng Tian,1,2 Heqing Zheng,1,2 Wei Wu,1,2,&ast; Lanxiang Wu1,2,&ast; 1Department of Neurology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Institute of Neuroscience, Nanchang University, Nanchang, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu; Lanxiang Wu, Email 13807038803@163.com; 1127370500@qq.comPurpose: Previous studies have shown that pyroptosis plays a vital role in the progress of neuropathic pain (NP), but the molecular mechanisms have not been fully elucidated. The aim of this study was to identify crucial pyroptosis-related genes (PRGs) in NP.Methods: We identified pyroptosis-related differentially expressed genes (PRDEGs) in NP by machine learning analysis of the GSE24982 and GSE60670 datasets. Furthermore, these PRDEGs were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and Friends analysis, respectively. Meanwhile, receiver operator characteristic (ROC) analysis was performed to assess the diagnostic value of PRDEGs in NP. Finally, we performed immune infiltration analysis of key PRDEGs using CIBERSORTR R package.Results: We found that 5 PRDEGs by least absolute shrinkage and selection operator (LASSO) regression and random forest and verified by RT-qPCR. GO, KEGG and GSEA revealed that these PRDEGs were mainly enriched in regulation of neuron death, IL-4 signaling, IL-23 pathway, and NF-κB pathway. ROC analysis revealed that most of the PRDEGs performed well in diagnosing NP. We also revealed transcription factors, miRNA regulatory networks and drug interaction networks of PRDEGs. For immune infiltration analysis, PRDEGs were mainly correlated with dendritic cells, monocytes and follicular T helper cells, suggested that it might be involved in the regulation of neuroimmune-related signaling.Conclusion: A total of five PRDEGs were can be employed as NP biomarkers, particularly Tlr4, Il1b and Casp8, and provide additional evidence for a vital role of pyroptosis in NP.Keywords: pyroptosis, machine learning, neuropathic pain, neuroinflammation, bioinformatic analysis

Ye Ren,1,&ast; Xiaochuan Cui,2,&ast; Xiaowen Zhu,1 Hua Guo,2 Qunyan Zhou,3 Peng Yuan,4 Haiyan Cheng,1 Wenjun Wu1 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Sleep Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Nutrition Department, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Department of Rehabilitation, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, Wuxi People’s Hospital, No. 299, Qingyang Road, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Email wuwenjung@163.comPurpose: The present study aimed to evaluate the efficiency of traditional anthropometric and body composition parameters in predicting apnea hypopnea index (AHI) change after weight loss.Patients and Methods: Chinese adults with overweight and obesity were included into this study containing two parts. A cross-sectional study was conducted in 137 individuals using the baseline data from two weight loss intervention trials. The second part was the weight-loss intervention study conducted in 60 overweight and obese patients with obstructive sleep apnea (OSA). All participants underwent physical examination, bioelectrical impedance analysis and overnight polysomnography. Multivariate linear regression models were used to identify the most accurate parameters to predict AHI and the mediation analysis to evaluate the mediators between weight loss and AHI reduction.Results: Waist circumference (WC), body mass index and fat mass were positively associated with AHI after adjusting multiple collinearities in the cross-sectional study. After weight-loss intervention, body weight decreased from 94.6 ± 15.3 to 88.0 ± 13.9 kg, and AHI decreased from 41.9 (13.0,66.9) to 20.7 (8.7,51.2) events/h. Among these parameters, only percentage changes in WC and AHI across the intervention were positively intercorrelated after controlling for covariates (adjusted r = 0.271, P = 0.041). The mediation analysis supported WC as a mediator between weight loss and AHI reduction (standardized indirect effect [95% CI] = 4.272[0.936,7.999]).Conclusion: Both general and abdominal obesity are of high prognostic value for OSA. WC as an easily accessible parameter mediates the effects of weight loss in decreasing OSA severity.Plain Language Summary: Current Knowledge: Obesity is a well-recognized risk factor for the development of obstructive sleep apnea (OSA), whereas weight loss has been written into the treatment guidelines for overweight and obese patients with OSA. However, the anthropometric parameters more related to OSA have not been fully clarified, and an easily acquired index is needed to predict the effect of weight loss on apnea hypopnea index (AHI) improvement.Study Impact: This study found that both general obesity and abdominal obesity were positively associated with AHI, and waist circumference mediated the effect of weight loss in improving AHI. These results provide an easily acquired index to monitor the effect of weight loss on OSA.Keywords: obesity, obstructive sleep apnea, weight loss, waist circumference, body composition

Yuan Li,1,2 Xianxu Yang,3 Jiejie Lu,1 Kai Chen,3 Weiwei Wu,3 Ming Zhang,3 Wanni Li1 1Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of ChinaCorrespondence: Wanni Li, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, 570100, Hainan, People’s Republic of China, Email liwanni1204@outlook.comAbstract: Eosinophilic pustular folliculitis (EPF) is a rare skin disease. The typical skin lesions of classic EPF are localized on the upper limbs’ face, trunk, and extensor surfaces. However, when the skin lesions initially appear on the palms and soles, it is not easy to diagnose as EPF. Here, we report a case of a male patient who presented with erythematous plaques, pustules, and crusted erosions on the hands and feet, which were misdiagnosed as eczema ten years ago. Over ten years, the patient experienced recurrent erythematous patches with bumps and itching on the face, trunk, and extremities after improving the hand and foot lesions. A histopathological biopsy was performed to establish a definitive diagnosis, revealing pustules formed by eosinophilic infiltrates within the hair follicles. The diagnosis was confirmed as eosinophilic pustular folliculitis. The patient was treated with oral indomethacin at a dosage of 75mg/day, resulting in the disappearance of the skin lesions. After a 3-month follow-up, no recurrence was observed.Keywords: eosinophilic pustular folliculitis, indomethacin

Yuming Shao,1 Wenxiang Wu,2 Fangzhou Fan,2 Haifeng Liu,3 Yongliang Ming,2 Wangwei Liao,2 Chunyu Bai,2 Yuhua Gao2 1Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Forensic Science Center of Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 2Precision Medicine Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272067, People’s Republic of ChinaCorrespondence: Chunyu Bai; Yuhua Gao, No. 133 Hehua Road, Jining, Shandong, 272067, People’s Republic of China, Tel +86-573-3616565, Email chunyu_bai@hotmail.com; anngyh@126.comAim: Acute pancreatitis is an inflammatory disorder of the pancreas, which causes abnormal activation of immune cells. The macrophages were accumulated in pancreas and infiltrated into islets during the AP process to induce abnormal glucose metabolism. However, the role of macrophages in abnormal glucose metabolism remains understood. Extracellular vesicles act in the regulation of intercellular function, but whether EVs secreted by macrophages contribute to β cell failure and apoptosis in AP is unclear. Based on this, the aim of this study was to reveal the role of macrophages-EVs in AP and develop a treatment for symptoms of hyperglycemia in AP.Methods: The AP model was established and treated by various doses of melatonin to analyze the therapeutic effect. The accumulation and polarization of macrophages in the AP pancreas were observed, and the β cells were incubated with pancreatic derived EVs to analyze the role in β cell failure and apoptosis.Results: The results showed that macrophages were recruited and polarized to M1 phenotype macrophages in the pancreas of AP mice, which obtained inflammatory EVs that contained specific miRNAs to induce β cell failure and apoptosis. Then, the EVs derived from M1 macrophages triggered β cell failure and apoptosis. Melatonin prevented polarization of macrophages to the M1 phenotype in vivo, which reduced the secretion of inflammatory EVs, changed the abundance of miRNAs in EVs, and therefore decreased inflammatory EV-mediated β cell failure and apoptosis.Conclusion: Our results demonstrate that similar to 20S proteasome inhibitor MG132, analyses indicated that melatonin prevented degradation of IκBα through the ubiquitylation pathway to restrict p50 subunits to the cytoplasm of macrophages, inhibited activation of the NF-κB pathway to downregulate the transcription of specific miRNAs, and reduced miRNA transport into EVs.Keywords: acute pancreatitis, diabetes mellitus, macrophages, EVs, melatonin

Wenbo Wu,1,&ast; Xiaoli Yu,2,&ast; Jiaxiang Sun,3 Yuanyuan Han,3 Yuanye Ma,1 Guoqing Zhang,1 Qingming Ma,4 Qiang Li,3 Hongfei Xiang1 1Department of Orthopedics, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Qingdao, 266100, People’s Republic of China; 3College of Physics, Center for Marine Observation and Communications, Qingdao University, Qingdao, 266021, People’s Republic of China; 4Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, 266021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfei Xiang; Qingming Ma, Tel +86-532-61807860, Email xianghf@qdu.edu.cn; qma@qdu.edu.cnBackground: As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity.Methods: In this study, a Fe3O4@ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- Fe3O4@ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of Fe3O4@ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance.Results: DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p< 0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p< 0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance.Conclusion: In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- Fe3O4@ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential.Keywords: osteosarcoma chemotherapy, zeolite imidazolate framework, PH-responsive, nanocarriers, tumor targeting

Chenglin Miao,1,&ast; Yali Cui,1– 3,&ast; Yingying Li,1 Qianqian Qi,1 Wenling Shang,1 Huilian Chen,2,3 Yujie Gao,2,3 Ruomei Yuan,2,3 Qichen Long,4 Wenjing Wu,1 Xia Wang,1 Ziyi Yan,1 Yongmei Jiang1,5 1Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Laboratory Medicine, Meishan Women and Children’s Hospital, Alliance Hospital of West China Second University Hospital, Sichuan University, Meishan, Sichuan Province, People’s Republic of China; 3Department of Laboratory Medicine, West China Second University Hospital (Tianfu), Sichuan University/Sichuan Provincial Children’s Hospital, Meishan, Sichuan Province, People’s Republic of China; 4Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 5Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ziyi Yan; Yongmei Jiang, Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China, Tel +86 28 8857050 ; +86 28 85501543, Email yan_z_y2@qq.com; jiangyongmeiwst@163.comPurpose: This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments.Methods: In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored.Results: PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81± 2.32) × 105. The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process.Conclusion: The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae.Keywords: Streptococcus pneumoniae, fusion protein vaccine, PiuA-PlyD4, immunoinformatics prediction, protective efficacy

Lingyan Sun,1– 3,&ast; Yan Chen,4– 6,&ast; Tingting Qu,7,8 Keren Shi,4– 6 Xinhong Han,4– 6 Wenhao Wu,7,8 Yan Jiang,4– 6 Yunsong Yu4– 6 1Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Key Laboratory of Clinical in Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China; 3Institute of Laboratory Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, People’s Republic of China; 6Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 7State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 8Infection Control Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunsong Yu, Tel +86 138 0579 0432, Email yvys119@zju.edu.cnPurpose: We aimed to characterize a novel blaNDM-5 and blaKPC-2 co-carrying hybrid plasmid from a clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) strain.Methods: Antimicrobial susceptibility was determined by the broth microdilution method. Plasmid size and localization were estimated using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Plasmid transfer ability was evaluated by conjugation experiments. Whole genome sequencing (WGS) was performed using Illumina NovaSeq6000 and Oxford Nanopore MinION platforms. Genomic characteristics were analyzed using bioinformatics methods.Results: Strain ZY27320 was a multidrug-resistant (MDR) clinical ST11 K. pneumoniae strain that confers high-level resistance to carbapenems (meropenem, MIC 128 mg/L; imipenem, MIC 64 mg/L) and ceftazidime/avibactam (MIC > 128/4 mg/L). Both S1-PFGE–Southern blotting and whole genome sequencing revealed that the carbapenemase genes blaKPC-2 and blaNDM-5 were carried by the same IncFIIpHN7A8:IncR:IncN hybrid plasmid (pKPC2_NDM5). Conjugation experiments indicated that pKPC2_NDM5 was a non-conjugative plasmid.Conclusion: This is the first report of a hybrid plasmid carrying both carbapenemase genes blaNDM-5 and blaKPC-2 in a clinical K. pneumoniae ST11 isolate that confers resistance to both ceftazidime/avibactam and carbapenems, thereby presenting a serious threat to treatment in clinical practice.Keywords: blaNDM-5, blaKPC-2, Klebsiella pneumoniae, hybrid plasmid, IS 26

Kailin Xing,1,&ast; Xinyu Bian,2,&ast; Dongmin Shi,3,&ast; Shuangshuang Dong,1 Hongxin Zhou,1 Shuxiu Xiao,4 Jinjin Bai,4 Weizhong Wu1,4 1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai, 200032, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210000, People’s Republic of China; 3Department of Medical Oncology, Shanghai Changzheng Hospital, Shanghai, 200072, People’s Republic of China; 4Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhong Wu, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China, Tel +86-21-60268628, Fax +86-21-64037181, Email wu.weizhong@zs-hospital.sh.cnBackground: MicroRNA-612 (miR-612) has been proven to suppress the formation of invadopodia and inhibit hepatocellular carcinoma (HCC) metastasis by hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA)-mediated lipid reprogramming. However, its biological roles in HCC cell ferroptosis remain unclear.Methods and Results: In this study, we found that HCC cells with high metastatic potential were more resistant to ferroptosis, indicating that ferroptosis is related to HCC metastasis. The levels of lipid reactive oxygen species (ROS) were found to be much lower in HCC cells with high metastatic potential by flow cytometry (FCM). We used HCC cells with miR-612 overexpression/knockout and HADHA overexpression/knockdown to test cell viability after stimulation with RSL3. HCC cells overexpressing miR-612 were more sensitive to ferroptosis, and miR-612 could increase lipid ROS levels. Furthermore, colony formation assays and Transwell assays showed that miR-612 could inhibit the proliferation and metastasis of HCC cells by promoting ferroptosis. We next confirmed that miR-612 influenced HCC cell ferroptosis by regulating HADHA. HADHA could upregulate the expression of key enzymes in the mevalonate (MVA) pathway. HADHA overexpression upregulated the expression of CoQ10 and decreased polyunsaturated fatty acid (PUFA) levels and lipid peroxide abundance. miR-612 also suppressed HCC cell proliferation and metastasis by enhancing RSL3- and lovastatin-induced ferroptosis in vivo.Conclusion: Overall, miR-612 promotes ferroptosis in HCC cells and affects HCC proliferation and metastasis by downregulating CoQ10 and increasing cellular PUFA levels and lipid peroxides via the HADHA-mediated MVA pathway.Keywords: HCC, Ferroptosis, miR-612, HADHA, MVA pathway

Huiying Lv, Yawen Zhuang, Weijing Wu Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, People’s Republic of ChinaCorrespondence: Weijing Wu, Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, No. 34, Zhongshan Bei Road, Lichen District, Quanzhou, Fujian Province, People’s Republic of China, Tel +8615159883230, Fax +86 595 22770258, Email wuweijing2010@163.comBackground: Tannerella forsythia is a gram-negative anaerobic bacterium commonly found in the oral cavity. It is among the common pathogenic bacteria associated with gingivitis, chronic periodontitis, and aggressive periodontitis. However, there is currently no literature discussing lung abscesses primarily caused by T. forsythia infection.Presentation: This article presents the case of a 55-year-old male with a massive lung abscess. The patient underwent ultrasound-guided percutaneous drainage, and the sample was sent for pathogen metagenomic next-generation sequencing (mNGS) testing. The test indicated that the lung abscess was primarily caused by T. forsythia infection. A literature review was conducted to understand the characteristics of this pathogen as well as its clinical features and suitable treatment approaches.Conclusion: Currently, there is no literature specifically mentioning T. forsythia as a primary pathogen causing lung abscesses. This anaerobic bacterium is commonly found in the oral cavity and is difficult to cultivate using routine culture methods. mNGS emerges as a value diagnostic method for identifying this pathogen. Treatment recommendations include drainage and antibiotic selection encompassing common periodontal pathogens such as red complex bacteria and Actinomyces.Keywords: Tannerella forsythia, lung abscess, metagenomic next-generation sequencing, drainage

Teng Long,1,2,&ast; Zhoutian Yang,1,2,&ast; Huilan Zeng,1,2,&ast; Weijie Wu,1,2 Zhiwen Hu,1,2 Zhenyun Yang,1,2 Dandan Hu,1,2 Zhongguo Zhou,1,2 Minshan Chen,1,2 Yaojun Zhang1,2 1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minshan Chen; Yaojun Zhang, Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Dongfeng East Road 651, Guangzhou, Guangdong, 510000, People’s Republic of China, Tel +86-20-87343828, Fax +86-20-87343585, Email chenmsh@sysucc.org.cn; zhangyuj@sysucc.org.cnPurpose: To compare the treatment efficacy and safety of transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors for patients with unresectable hepatocellular carcinoma (HCC).Patients and Methods: 81 unresectable HCC patients were retrospectively analyzed, including 30 or 51 patients treated with either TKIs and PD-1 inhibitors combined with TACE (TTP) or HAIC (HTP), respectively. Tumor response and survival outcomes were compared.Results: The median overall survival (mOS) was 21.0 months in the TTP group and 15.0 months in the HTP group (P = 0.525; HR = 1.23; 95% CI 0.66– 2.29). The median progression-free survival (mPFS) was 6.7 months in the TTP group and 9.9 months in the HTP group (P = 0.160; HR = 0.70; 95% CI 0.42– 1.16). After Propensity Score Matching (PSM), the mOS was 21.0 months in the TTP group and 18.0 months in the HTP group (P = 0.644; HR = 1.20; 95% CI 0.56– 2.58). The mPFS was 6.4 months in the TTP group and 15.0 months in the HTP group (P = 0.028; HR = 0.49; 95% CI 0.26– 0.93). The disease control rate in overall response (90.2% vs 76.7%, P = 0.116, before PSM; 91.7% vs 75.0%, P = 0.121, after PSM) and intrahepatic response (94.1% vs 80.0%, P = 0.070, before PSM; 91.7% vs 79.2%, P = 0.220, after PSM) were higher in the HTP group than in the TTP group.Conclusion: Though including more advanced tumors, the clinical outcomes of HAIC combined with TKIs and PD-1 inhibitors are comparable to TACE-based combination therapy for unresectable HCC. Nevertheless, HTP significantly improved the PFS benefits in HCC patients with with large tumor burden or vascular invasion.Keywords: transarterial chemoembolization, hepatic arterial infusion chemotherapy, tyrosine kinase inhibitors, programmed cell death protein − 1, hepatocellular carcinoma

Wenjing Wu,1,2 Yongmei Jiang,1,2 Wei Zhou,1,2 Linghan Kuang1,2 1Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Linghan Kuang, Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-8550-1201, Email hanhan840106@163.comObjective: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is spreading worldwide, becoming a serious threat to public health. The present study aimed to analyze the molecular epidemiology and drug resistance mechanism of CRKP isolated from neonatal patients in Sichuan, Southwest China.Methods: CRKP isolates were collected from neonatal patients of West China Second University Hospital from June 2017 to June 2021. Antimicrobial susceptibility testing was performed using broth microdilution. Whole-genome sequencing of all isolates were performed to determine the antimicrobial resistance genes, sequence typing, phylogenetic relationships.Results: In total, 41 nonduplicate CRKP isolates were collected. All isolates were highly resistant to the cephalosporins and carbapenems, however, they were all susceptible to amikacin, tigecycline, ciprofloxacin, and colistin. Various resistance genes were detected, blaNDM-5 (n = 35, 85.4%) was the predominant carbapenemase genes. The most common replicon type was IncX3, which was harbored by 36 (87.8%) isolates, followed by IncFIB (n = 34, 82.9%), and IncFII (n = 32, 78.0%). The 41 CRKP isolates belonged to 8 sequence types (STs) and ST789 (n = 29, all had blaNDM-5) was the dominant sequence type.Conclusion: The study revealed that blaNDM was the most dominant carbapenemase resistance gene. ST789 CRKP strains carrying blaNDM-5 were a tremendous menace to neonates in this hospital. Therefore, effectively implement prevention and control measures need to be taken for the prevention and treatment of CRKP infection in the neonatal ward.Keywords: Klebsiella pneumoniae, carbapenemase, NDM-5, ST789, neonates

Wan Y, Lv M, Zhou K, et al. Nat Sci Sleep. 2023;15:511-522. The authors wish to advise that an unauthorized version of the Chinese MMSE was used by the study team without permission. The MMSE is a copyrighted instrument and may not be used or reproduced in whole or in part, in any form or language, or by any means without written permission of PAR (www.parinc.com). The issue was resolved between the authors and PAR. The authors confirm that no test items from the unauthorized version of the Chinese MMSE are included in the article.

Zhichao Xing,1,&ast; Anping Su,1,&ast; Li Mi,1 Yujie Zhang,1 Ting He,1 Yuxuan Qiu,2 Tao Wei,1 Zhihui Li,1 Jingqiang Zhu,1 Wenshuang Wu1 1Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingqiang Zhu; Wenshuang Wu, Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email zhujingqiang@scu.edu.cn; wenshuang_wu@163.comAbstract: Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA’s significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA’s action represents a crucial research direction to pursue in the future.Graphical Abstract: Keywords: Withaferin A, Withania somnifera, dietary supplement, anti-cancer activity, pharmacological mechanism, direct target

Baifen Song,1 Yanmei Huang,2 Jinzhu Ma,2 Liquan Yu,2 Yongzhong Yu,2 Chen Peng,1 Wenxue Wu1 1Key Laboratory of Animal Epidemiology and Zoonosis, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2The College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of ChinaCorrespondence: Wenxue Wu, Key Laboratory of Animal Epidemiology and Zoonosis, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of China, Tel/Fax +86-010-62733048, Email wuwenxue@cau.edu.cnBackground: Virus infection can cause the changes of lncRNA expression levels to regulate the interaction between virus and host, but the relationship between BHV-1 infection and lncRNA has not been reported.Methods: In this study, in order to reveal the molecular mechanism of RNA in BoHV-1 infection, the Madin-Darby bovine kidney (MDBK) cells were infected with BoHV-1, transcriptome sequencing were performed by next-generation sequencing at 18 h or 24 h or 33 h of viral infection and then based on the competitive endogenous RNA (ceRNA) theory, lncRNA-miRNA-mRNA networks were constructed using these high-throughput sequencing data. The network analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation and exploration of ncRNA ceRNAs in BoHV-1 infection.Results: The results showed that 48 lncRNAs, 123 mRNAs and 20 miRNAs as differentially expressed genes, and the mitogen activated protein kinase (MAPK) pathway and calcium signaling pathway were significantly enriched in the ceRNA network. Some differentially expressed lncRNA genes were randomly selected for verification by RT-qPCR, and the results showed that their expression trend was consistent with the results of transcriptome sequencing data.Conclusion: This study revealed that BoHV-1 infection can affect the expression of RNAs in MDBK cells and the regulation of ceRNA network to carry out corresponding biological functions in the host, but further experimental studies are still necessary to prove the hub genes function in ceRNA network and the molecular mechanism in BoHV-1 infection.Keywords: BoHV-1, bioinformatics analysis, ceRNA network, next-generation sequencing

Jiaoquan Chen,&ast; Nanji Yu,&ast; Weihong Wu, Shanshan Ou, Quan Chen, Huilan Zhu Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huilan Zhu, Department of Dermatology Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, People’s Republic of China, Email zhlhuilan@126.comBackground: Although dupilumab is an effective treatment approach for chronic actinic dermatitis (CAD) in some cases, its effectiveness and safety in CAD have not been sufficiently assessed.Purpose: Evaluation of the effectiveness and safety of dupilumab in patients with recalcitrant CAD was performed.Methods: We retrospectively reviewed the medical records of CAD patients treated with dupilumab. Data regarding demographics were collected, and disease severity scores were assessed using the following: Clinical Severity Score of CAD (CSS-CAD), Atopic Dermatitis Control Tool (ADCT), Dermatology Life Quality Index (DLQI), and Numeric Rating Scale (NRS)-itch scores.Results: After 12 weeks of treatment, there was a significant decrease in disease severity scores of 16 CAD patients. Only one patient achieved a good response and most of the patients (62.5%, 10/16) had no significant symptom improvement after 4 weeks of treatment. However, after 12 weeks of treatment, 43.75% (7/16) of the patients reached excellent response (> 75% improvement of CSS-CAD), 31.25% (5/16) good response (50%– 75% improvement of CSS-CAD), 6.25% (1/16) partial response (25%– 50% improvement of CSS-CAD), and only 18.75% (3/16) no response (< 25% improvement of CSS-CAD). One patient complained of injection site reaction at the first injection.Conclusion: This study supports dupilumab as an effective and safe treatment option for patients with recalcitrant CAD. Patients may require at least 4 weeks of treatment before the partial response is noted.Keywords: chronic actinic dermatitis, dupilumab, photodermatitis, atopic dermatitis

Xin Zhao,1,&ast; Pingyuan Ge,1,&ast; Shaohua Lei,1 Siqi Guo,1 Peng Zhou,1 Li Zhao,1 Yiyu Qi,1 Xiaotong Wei,2 Weizhen Wu,2 Ningjing Wang,2 Rui Guo,3 Nianyun Yang,1 Qingqing Xiao,1 Qichun Zhang,1,2 Huaxu Zhu1 1Department of Traditional Chinese Medicine Processing and Preparation, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qichun Zhang; Huaxu Zhu, Email zhangqichun@njucm.edu.cn; zhuhx@njucm.edu.cnIntroduction: Neuroinflammation is one of the major pathogeneses in Alzheimer’s disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inefficient ability of therapeutic drugs to permeate through the blood‒brain barrier (BBB). Accordingly, drug combination treatment and drug carrier delivery have become important therapeutic tools for the treatment of multifactorial diseases, especially AD.Methods: Inflammatory cytokine levels in microglia, including NO, TNF-α, IL-1β, IL-4, and IL-10, were detected. The Morris water maze and object location task were used to investigate the learning and memory functions of APP/PS1 mice in different treatment groups. The number of neurons and plasticity of synapses were evaluated by immunofluorescence double labelling. Additionally, the ratio of β-amyloid plaques and the number of activated microglia were evaluated by immunofluorescence staining. The concentrations of β-amyloid plaques and inflammatory factors in the hippocampus were determined by ELISA. Microglia-derived exosomes (Exos) were extracted and purified by size exclusion chromatography. The distribution of exosomes and drugs was investigated in vitro and in vivo.Results: Compared to single drug interventions, the combination of Ber and Pal (Ber/Pal) modulated microglial inflammatory cytokine levels. Ber/Pal promoted the recovery of learning and memory impairment in APP/PS1 mice. Immunofluorescence staining indicated that Ber/Pal restored neurons, inhibited Aβ plaque formation and microglial activation, and regulated the secretion of inflammatory factors. Exos promoted the accumulation of drugs in cells and tissues and improved the targeting of drugs across the BBB.Conclusion: Ber/Pal could offer a synergistic and more comprehensive therapeutic effect in AD. Additionally, the microglia-derived Exos-Ber/Pal delivery system promoted the targeting and permeation of drugs into the brain, suggesting a creative strategy for targeting AD therapy by regulating neuroinflammation in microglial cells.Keywords: Alzheimer’s disease, neuroinflammation, phytoconstituents, drug combination, BBB permeability, exosomes

Wenjia Fan,1,2,&ast; Jie Li,1,2,&ast; Lingxia Chen,2 Wenhao Wu,2 Xi Li,3 Weihong Zhong,1 Hongying Pan2 1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China; 2Department of Infectious Disease, Zhejiang Provincial People’s Hospital, Hangzhou, 310014, People’s Republic of China; 3Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongying Pan; Weihong Zhong, Tel/Fax +86-571-8589-3602 ; +86-571-88813378, Email hypanzjsrmyy@126.com; whzhong@zjut.edu.cnPurpose: Time-consuming culture methods and wet-mount microscopy (WMM) with low sensitivity have difficulties in diagnosing Vulvovaginal candidiasis (VVC). Rapid and highly sensitive polymerase chain reaction coupled with quantum dot fluorescence analysis (PCR-QDFA) for the diagnosis of VVC has not been reported to date. This study was the first to evaluate the performance of PCR-QDFA for diagnosis of Candida strains in the leukorrhea samples from patients with suspected VVC.Patients and Methods: Leukorrhea samples from all visited patients were taken from the vagina using vaginal swabs by clinicians. We evaluated patients admitted with suspected VVC who completed WMM for diagnosis and reported the diagnostic effectiveness of PCR-QDFA and Candida culture (gold standard) when testing leucorrhea samples.Results: A total of 720 leukorrhea samples from 387 VVC-positive patients and 333 VVC-negative patients were included in this study. Of the 387 leukorrhea samples from the VVC-positive patients, 391 Candida strains were identified by culture. 99.23% (388/391) Candida strains were included in the PCR-QDFA list. The 388 Candida strains belonged to four different species of Candida, including C. albicans (n = 273, 70.36%), C. glabrata (n = 85, 21.91%), C. tropicalis (n = 16, 4.12%), and C. krusei (n = 14, 3.61%). PCR-QDFA diagnosed Candida strains in 340/384 (88.54%) of the leucorrhea samples with Candida strains infection. The sensitivity of PCR-QDFA for C. albicans, C. glabrata, C. tropicalis, and C. krusei was 89.01%, 85.88%, 81.25% and 92.86%, respectively. The specificity of PCR-QDFA for C. albicans, C. glabrata, C. tropicalis and C. krusei was 93.69%, 99.37%, 99.71%, and 99.57%, respectively.Conclusion: The highly sensitive and specific PCR-QDFA technique can be exploited as a rapid (approximately 4 h) diagnostic tool for common Candida strains of leucorrhea samples from patients with suspected VVC.Keywords: PCR-QDFA, VVC, NAC, diagnostic performance, Candida culture

Bo Li,1 Weiqing Wu,1 Aijun Liu,1 Lifeng Feng,1 Bin Li,1 Yong Mei,1 Li Tan,1 Chaoyang Zhang,2 Yangtao Tian1 1Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China; 2Department of Ultrasound Medicine, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of ChinaCorrespondence: Yangtao Tian, Department of Pancreatic Surgery, Shangluo Center Hospital, 37 Shangyang, Shangzhou, Shangluo, Shaanxi, 726000, People’s Republic of China, Email 928763821@qq.comBackground: Severe acute pancreatitis (SAP) can progress to lung and kidney dysfunction, and blood clotting within 48 hours of its onset, and is associated with a high mortality rate. The aim of this study was to establish a reliable diagnostic prediction model for the early stage of severe pancreatitis.Methods: The clinical data of patients diagnosed with acute pancreatitis from October 2017 to June 2022 at the Shangluo Central Hospital were collected. The risk factors were screened by least absolute shrinkage and selection operator (LASSO) regression analysis. A novel nomogram model was then established by multivariable logistic regression analysis.Results: The data of 436 patients with acute pancreatitis, 45 (10.3%) patients had progressed to SAP. Through univariate and LASSO regression analyses, the neutrophils (P < 0.001), albumin (P < 0.001), blood glucose (P < 0.001), serum calcium (P < 0.001), serum creatinine (P < 0.001), blood urea nitrogen (P < 0.001) and procalcitonin (P = 0.005) were identified as independent predictive factors for SAP. The nomogram built on the basis of these factors predicted SAP with sensitivity of 0.733, specificity of 0.9, positive predictive value of 0.458 and negative predictive value of 0.967. Furthermore, the concordance index of the nomogram reached 0.889 (95% CI, 0.837– 0.941), and the area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis was significantly higher than that of the APACHEII and ABISAP scoring systems. The established model was validated by plotting the clinical decision curve analysis (DCA) and clinical impact curve (CIC).Conclusion: We established a nomogram to predict the progression of early acute pancreatitis to SAP with high discrimination and accuracy.Keywords: acute pancreatitis, prediction model, risk factor, nomogram, decision curve analysis

Yahui Wan,1 Mengdi Lv,2 Kaili Zhou,1 Zheng Li,3 Xueyun Du,1 Wei Wu,4 Rong Xue4 1Departments of Neurology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, 300308, People’s Republic of China; 2Departments of Neurology, Tianjin First Central Hospital, Tianjin, 300190, People’s Republic of China; 3Departments of Neurology, Binhai Hospital, Peking University, Tianjin, 300450, People’s Republic of China; 4Departments of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of ChinaCorrespondence: Rong Xue, Departments of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Email xuerong1403@126.comPurpose: To evaluate the correlation between sleep microstructure, autonomic nervous system activity, and neuropsychological characteristics in chronic insomnia (CI) patients with obstructive sleep apnea (OSA).Patients and Methods: Forty-five CI-OSA patients, forty-six CI patients and twenty-two matched healthy control subjects (HCs) were enrolled. CI-OSA patients were then divided into two groups: mild OSA and moderate-to-severe OSA. All participants completed neuropsychological tests, which included the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Mini-mental State Examination (MMSE). The autonomic nervous system activity and sleep microstructure were examined by the PSM-100A.Results: The CI-OSA patients exhibited higher scores on the PSQI, ESS, ISI, HAMA, and HAMD than HCs and CI patients (all p < 0.01). The CI-OSA patients had a lower proportion of stable sleep, REM sleep and a higher proportion of unstable sleep ratio (all p < 0.01) than HCs and CI patients (all p < 0.01). The CI-OSA patients had higher ratios of LF and LF/HF, and lower ratios of HF and Pnn50% (all p < 0.01) than HCs and CI patients (all p < 0.01). Compared to CI-mild OSA patients, the CI-moderate-to-severe OSA patients presented with a higher ESS scores, higher ratios of LF and LF/HF, and lower ratios of HF (all p < 0.05). In CI-OSA patients, higher HAMD scores were correlated with decreased MMSE scores (r=− 0.678, p < 0.01). A higher LF ratio was correlated with higher HAMD and HAMA scores (r=0.321, p=0.031, r =0.449, p =0.002), and a higher HF ratio was correlated with lower HAMD and HAMA scores (r=− 0.321, P =0.031, r =− 0.449, p =0.002).Conclusion: OSA exacerbates the abnormalities of sleep microstructure and the autonomic nervous dysfunction in CI patients. Dysfunction of the autonomic nervous system could contribute to mood deterioration in CI with OSA patients.Keywords: chronic insomnia, obstructive sleep apnea, OSA, depression, sleep microstructure, autonomic function

Xin Tan, Wenjie Liu, Ying Chang, Wanmin Wu, Lichun Yang, Jiewei Liu Cataract Department, Shanxi Eye Hospital, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Jiewei Liu, Cataract Department, Shanxi Eye Hospital, Taiyuan, Shanxi Province, People’s Republic of China, Tel +86-13834648535, Email Jieweiliu1967@sina.comPurpose: The safety and stability of implantable collamer lens (ICL) implantation are closely related to the vault. We aimed to assess clinical data from patients with similar anterior segment anatomy who received ICL of the same model placed in the same position and analyze common range and factors affecting the vault inter-eye difference.Patients and Methods: A prospective study was performed, including 162 eyes of 81 patients with a bilateral ICL (V4c) implantation. Subjects were evaluated before the surgery and 1 day, 1 week, and 1 month postoperatively, and they were divided into 4 groups based on the ICL size. Bivariate correlation and multiple linear regression (stepwise) analyzed associations between vault inter-eye differences and horizontal sulcus-to-sulcus diameter, anterior chamber depth, lens thickness, ICL size, spherical equivalent, and vault.Results: One month after surgery, mean vault inter-eye differences were 74.59 ± 55.59 μm. Nearly 70% of patients presented with vault inter-eye differences lower than 100 μm. The second eye vault variance of 69% was attributed to the first eye vault. Vault inter-eye differences were positively correlated with ICL spherical equivalent (regression equation: vault inter-eye differences (μm) = 139.415 + 6.295 × ICL spherical equivalent). Vaults after ICL implantation were similar in fellow eyes, with some considerable differences. The 95% confidence interval of the vault inter-eye difference was − 34.4 ~ 183.6 μm.Conclusion: In eyes with similar anterior segment anatomy, there is a 95% probability that the vault will vary from − 34.4 μm to − 183.6 μm when a similar ICL is implanted. These results can help surgeons to select an appropriate ICL size to achieve an ideal vault. The smaller the spherical equivalent, the larger the difference between the two vaults, which provides a reference for size in moderate myopia. ICL spherical equivalent affects and predicts vault inter-eye differences after ICL implantation.Keywords: implantable collamer lens, vault, inter-eye differences

Zhen Shi,1 Pengfei Li,1 Wentao Wu,1 Yunduo Jiang,1 Yansong Wang1– 3 1Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2NHC Key Laboratory of Cell Transplantation, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 3Heilongjiang Provincial Key Laboratory of Hard Tissue Development and Regeneration, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Yansong Wang, Email wyshmu1975@163.comBackground: Percutaneous endoscopic interlaminar discectomy (PEID), one of the main techniques of spinal endoscopy, has achieved excellent results in treating lumbar disc herniation (LDH). However, its efficacy has not been systematically described in patients with LDH accompanied by Modic changes (MC).Purpose: The purpose of this study was to observe the clinical efficacy of PEID treatment of LDH accompanied by MC.Patients and Methods: A total of 207 patients who underwent PEID surgery for LDH were selected. According to the existence and type of MC on preoperative lumbar magnetic resonance images (MRI), they were divided into normal group (no MC, n=117), M1 group (MC I, n=23), and M2 group (MC II, n=67). According to the severity of MC, they were divided into MA group (grade A, n=45) and MBC group (grade B and C, n=45). The visual analog scale (VAS) score, Oswestry disability index (ODI) score, Disc height index (DHI), Lumbar lordosis angle (LL) and modified Macnab criteria were used to assess clinical outcomes.Results: Postoperative back pain and leg pain VAS scores and ODI scores were significantly improved in all groups compared with preoperative scores. Patients with MC showed a deterioration in postoperative back pain VAS scores and ODI scores as time went by, and postoperative DHI decreased significantly compared with preoperative. Postoperative LL did not change significantly in each group. There was no significant difference in complications, recurrence rate and excellent rate between the groups.Conclusion: Whether accompanied by MC or not, the efficacy of PEID for LDH was significant. However, postoperative back pain and functional status of patients with MC tend to deteriorate as time went by, especially those with type I or severe MC.Keywords: Modic changes, MC type, MC grade, percutaneous endoscopic interlaminar discectomy, lumbar disc herniation, low back pain

Qin Zhang,1,&ast; Wenyi Wu,1,&ast; Lulu Sheng,1 Xuan Xi,1 Yuanke Zhou,1 Yi Wen,2 Qin Liu1 1School of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Liu, School of Public Health, Chongqing Medical University, No. 1 YixueyuanRoad, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-18623598789, Email liuqin@cqmu.edu.cnPurpose: To help firstborn children in families expecting a second child navigate the role transition more smoothly, we investigated the emotional and behavioral changes of firstborn children during the transition to siblinghood (TTS) and the factors that contribute to these changes.Patients and Methods: From March to December 2019, a total of 97 firstborn children (Mage=3.00± 0.97, and female = 51) were included in the study through a questionnaire survey of their mothers, and two follow-up visits were conducted in Chongqing, China. Individual in-depth interviews were conducted with 14 mothers.Results: Both quantitative and qualitative results suggest that emotional and behavioral problems of firstborn children tend to increase during TTS, particularly in issues such as anxiety/depression, somatic complaints, withdrawal, sleep problems, attention problems, and aggressive behavior, as well as internalization problems, externalization problems and total problems in the quantitative study (P< 0.05). A poor father-child relationship may increase emotional and behavioral problems in firstborn children (P=0.05). Further qualitative analysis found that younger age and outgoing personality of the firstborn child may improve the emotional and behavioral problems.Conclusion: The firstborn children did have more emotional and behavioral problems during TTS. But these problems can be regulated by family factors and their own characteristics.Keywords: emotion and behavior, transition to siblinghood, firstborn children, preschool, mixed method