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Xinyu Yang,1,2 Qiaochu Li,1,2 Linbang Wang,3 Jiaxing Chen,1,2 Zhengxue Quan1,2 1Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Zhengxue Quan; Jiaxing Chen, Email quanzx18@126.com; cqykdxcjx@163.comPurpose: Ferroptosis is an underlying mechanism for various degenerative diseases, but its role in intervertebral disc degeneration remains elusive. This study aims to explore the key ferroptosis-related genes and its role in nucleus pulposus (NP) and annulus fibrosus (AF) degeneration.Methods: We analyzed the gene expression profiles of NP and AF from the Gene Expression Omnibus database. The ferroptosis-related differentially expressed genes (FRDEGs) in degenerated NP and AF were filtered, followed by GO and KEGG analysis. Feature FRDEGs were identified by the LASSO and SVM-RFE algorithms, and then Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were conducted. Immune infiltration analysis was conducted by CIBERSORT algorithm. We established drug networks via the Drug–Gene Interaction Database and competitive endogenous RNA (ceRNA) networks via miRanda, miRDB, and TargetScan database. The expression levels of the feature FRDEGs were assessed by the validation sets, single-cell RNA-seq, and experimental verification.Results: A total of 15 and 18 FRDEGs were obtained for NP and AF, respectively. GO and KEGG analysis revealed their implication in oxidative stress. Four (AKR1C1, AKR1C3, MUC1, ENPP2) and five (SCP2, ABCC1, KLF2, IDO1, CREB3) feature genes were identified for NP and AF, respectively. The GSEA and GSVA analysis showed that these feature genes were enriched in lots of biological functions, including immune response. CREB3 in degenerated AF was negatively correlated with Eosinophils via CIBERSORT algorithm. The drugs and ceRNAs targeting CREB3 and MUC1 were identified. Experimental verification and single-cell RNA-seq analysis revealed that MUC1 and CREB3 were downregulated in degenerated NP and AF, respectively.Conclusion: MUC1 and CREB3 were considered novel biomarkers for NP and AF ferroptosis, respectively. Drug and ceRNA networks were constructed for future drug development and investigation of new mechanisms of ferroptosis.Keywords: bioinformatics analysis, experimental verification, ferroptosis, nucleus pulposus, annulus fibrosus, single-cell RNA-seq

Zhipan Teng, Qi Li,* Xiao-fei Shen* Department of Otorhinolaryngology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-fei Shen; Qi Li, Department of Otorhinolaryngology, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, Jiangsu Province, 210008, People’s Republic of China, Email flyfly1205@126.com; liqi71520@hotmail.comObjective: Human microbiome is involved in the pathogenesis of allergic diseases, but the impact of nasal microbiota on allergic rhinitis (AR) symptoms severity has not been evaluated. This study aimed to characterize nasal microbiome in AR children and its correlations with AR symptoms.Methods: According to diagnostic guidelines for AR, 45 AR children and 40 healthy subjects were recruited from July to August in 2023. Based on the total score of nasal symptoms (TNSS), the 45 AR patients were divided into a mild AR group (MAR) (n = 16) and a moderate or severe AR group (MSAR) (n = 29). Nasal swabs were collected for microbiome analysis using 16S-rDNA sequencing.Results: The Simpson and Shannon indices were significantly higher in the AR group compared to the health control group, indicating an increase of nasal microbiota at the species evenness level in AR children. Moreover, the species evenness was significantly increased in the MSAR group compared to the MAR group. Staphylococcus (member of the Firmicutes phylum) was significantly dominant in the AR group, but Moraxella (member of the Proteobacteria phylum) was significantly dominant in the CG group. The LEfSe analysis showed that the mean relative abundances of Ralstonia in the MSAR group was higher than that in the MAR group. Meanwhile, the abundance divided by Ralstonia of Spearman correlation coefficients was positively correlated with the TNSS of AR symptoms (r = 0.4, P = 0.009).Conclusion: The elevation of species evenness in nasal microbiome was likely related to the aggravation of AR symptoms. The Ralstonia may play a pro-inflammatory role in AR.Plain Language Summary: In this study, 45 AR children and 40 healthy subjects were recruited and the AR patients were divided into a mild AR group (MAR) (n = 16) and a moderate or severe AR group (MSAR) (n = 29) based on the total score of nasal symptoms (TNSS). High throughput 16S rDNA analysis was employed to evaluate the nasal microbiome in AR children and its correlations with AR symptoms. We found that the Simpson and Shannon indices were significantly higher in the AR group than in the CG group, and in the MSAR group than in the MAR group, indicating that the rise of species evenness in nasal microbiome may be related to the occurrence and aggravation of AR symptoms. Staphylococcus (member of the Firmicutes phylum) was significantly dominant in the AR group, and the abundance of Ralstonia was positively correlated with the TNSS of AR symptoms.Keywords: nasal microbes, allergic rhinitis, symptoms severity, children

Yawen Zhang,* Qiao Li,* Lirong Li, Hao Guo, Fang He Laboratory 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*These authors contributed equally to this workCorrespondence: Fang He, Email hetrue@163.comPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a significant public health threat, particularly as a superbug responsible for nosocomial infections. In this study, we report a novel sequence type 6758 of K. pneumoniae harboring the blaNDM-1 gene.Material and Methods: Antimicrobial susceptibility testing was conducted according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). The complete genome sequence of the strain was determined using the Illumina NovaSeq 6000 platform and long-read MinION sequencer. Genomic features and resistance mechanisms of the strain were further comprehensively analysed using various bioinformatics approaches.Results: Antimicrobial susceptibility testing revealed that this strain exhibited resistance to multiple antimicrobials, including ceftazidime, ceftriaxone, cefazolin, cefepime, imipenem, meropenem, ampicillin/sulbactam, and sulfamethoxazole/trimethoprim. The genome analysis identified sixteen resistance genes. The blaNDM-1 carbapenemase gene is located on a 47,823 bp IncX3-type plasmid (pNDM-CRKP331). A total of 41 K. pneumoniae strains carrying similar IncX3-type plasmids were retrieved from the NCBI database, representing 20 sequence types (STs) across 11 countries. The most common resistance gene carried by these IncX3-type plasmids is blaNDM, and all these plasmids contain only the blaNDM gene. The blaNDM-carrying IncX3-type plasmids are widely prevalent in K. pneumoniae in China, spanning 15 STs.Conclusion: In summary, our study reports the first genome sequence of an ST 6758 K. pneumoniae strain containing the class B β-lactamase blaNDM-1 isolated from a clinical sample. Given the global emergence of blaNDM, measures should be taken to prevent the spread of these blaNDM-carrying IncX3-type plasmids. Our findings contribute to the understanding of the transmission mechanisms of blaNDM in K. pneumoniae.Keywords: carbapenem-resistant Klebsiella pneumoniae, blaNDM-1, whole-genome sequencing, IncX3 type plasmid, ST6758

Qiao-Qiao Liu,1,* Mao Mao,1,* Ning-Hua Lin,2,* Chen-Yang Xu,1,* Qian Li,1 Chang-Shuo Jiang,1 Shan-Wu Feng,1 Hong-Mei Yuan1 1Department of Anesthesiology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, 210004, People’s Republic of China; 2Department of Anesthesiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shan-Wu Feng; Hong-Mei Yuan, Department of Anesthesiology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, No. 123, Tianfei Lane, Mochou Road, Nanjing, Jiangsu, People’s Republic of China, Email Shanwufeng666@163.com; yuanhm667@126.comBackground: A single dose of epidural hydromorphone has been suggested as an alternative method for providing analgesia after caesarean section (CS). Nevertheless, the optimal dosage of epidural hydromorphone for postoperative pain relief following CS has yet to be determined.Methods: This trial included 30 singleton primiparous women undergoing scheduled caesarean delivery, who were recruited to determine doses of epidural hydromorphone using the modified Dixon sequential method. The initial hydromorphone dose was 0.75 mg, with adjustments based on the efficacy of the preceding participant’s dose over 12 hours. Various parameters such as blood pressure, heart rate, respiratory rate, visual analog scale (VAS) pain score, postoperative adverse reactions, and patient satisfaction with analgesic effect were recorded at each time point. The VAS scores were categorized as positive (score > 3) or negative (score ≤ 3). Participants received a single epidural injection of 0.2% ropivacaine 20 mg along with a study dose of hydromorphone. The median effective dose (ED50), 90% effective dose (ED90), and corresponding 95% confidence intervals (CIs) of hydromorphone with ropivacaine for analgesia after caesarean section were calculated using the probit method.Results: The ED90 and ED50 in our population were 1.105 mg (95% CI: 0.825– 2.324 mg) and 0.659 mg (95% CI: 0.434– 0.883 mg), respectively.Conclusion: Epidural hydromorphone can be safely used for postoperative analgesia in patients undergoing caesarean section, and the analgesic effect is satisfactory when the dosage is appropriate.Keywords: hydromorphone, ropivacaine, caesarean delivery, postoperative analgesia, ED50, ED90

Yihui Yu,1 Wei Li,1,2 Qian Li,1,2 Wenyan Liu,1,2 Sanquan Zhang,1,2 Xibao Zhang,1,2 Jingyao Liang1,2 1Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, People’s Republic of China; 2Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, 510095, People’s Republic of ChinaCorrespondence: Jingyao Liang; Xibao Zhang, Email ljy20221228@163.com; gzpfbfzs@163.comAbstract: Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. The treatment of vitiligo remains challenging, partly owing to the lack of efficient drug delivery system. Microneedles (MNs), an ideal transdermal drug delivery system, have emerged as promising drug delivery platform for vitiligo. Recently, the emergence of novel MNs with increased biocompatibility, including hydrogel and hollow MNs, further enhance the translational value of MNs in the treatment of vitiligo. However, up-to-date review of these advancements remains lacking. This review aims to summarize the most recent studies of MN-based drug delivery systems for vitiligo, highlighting the translational potential of MNs as a therapeutic platform for the treatment of vitiligo in the near future. Keywords: vitiligo treatment, microneedle design, advanced applications

Qiong Li,1 Cancan Zou,1 Linli Xie,1 Suzhen Ran,2 Yanlin Chen,1 Tianjing Yan1 1Department of Pathology, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China; 2Department of Ultrasound, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of ChinaCorrespondence: Tianjing Yan; Yanlin Chen, Email 64672420@qq.com; chenyl_doctor@163.comIntroduction: The coexistence of a complete hydatidiform mole with twin live fetuses in a triplet pregnancy is an extremely rare condition with an unknown incidence.Case Report: This report presents a case of a dichorionic diamniotic triplet pregnancy complicated by the coexistence of a complete hydatidiform mole and twin live fetuses. The pregnancy resulted in a preterm delivery at 30 weeks and 5 days of gestation, with both live fetuses surviving to date. During the pregnancy, the patient was diagnosed with pre-eclampsia and intrahepatic cholestasis. Post-delivery, she was found to have an invasive mole with lung metastases, which was ultimately successfully treated.Conclusion: This report highlights critical considerations for managing a multiple pregnancy complicated by a complete hydatidiform mole, alongside the associated potential complications. In light of the limited literature on the clinical management of this condition, our findings offer valuable insights into navigating the risks and optimizing patient outcomes.Keywords: hydatidiform mole, triplet pregnancy, live fetuses

Jiaxin Luo,1 Qingting Li,1,2 Robin Whittemore,3 Maritta Välimäki,4 Jia Guo1,2 1Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3School of Nursing, Yale University, New Haven, CT, USA; 4Department of Nursing Science, University of Turku, Turku, FinlandCorrespondence: Jia Guo, Email guojia621@163.comBackground: Positive parent-teen and peer relationships are crucial support resources for adolescents with type 1 diabetes mellitus (T1DM). There is quite a bit of research on parent-teen relationships in Western countries, less so with peer relationships. Additionally, information on these relationships and their influencing factors among adolescents from other regions with different family culture and peer cohesion is limited, which impedes the development of targeted interventions.Methods: This study analyzed baseline data from a randomized controlled trial in China involving 122 adolescents with T1DM aged 12– 18 years. Data were collected using established questionnaires on social-demographic and clinical characteristics, perceived stress, general self-efficacy, coping styles, diabetes self-management, and parent-teen and peer relationships. Multivariate linear regression analysis was conducted to determine the associating factors of parent-teen relationships and peer relationships respectively.Results: The total score of the parent-teen relationships subscale was 11.02 ± 2.77, within a theoretical range of 4– 16. The total score of the peer relationships subscale was 16.51 ± 2.42, within a theoretical range of 5– 20. Positive coping styles, less negative coping styles, and more collaboration with parents in diabetes self-management were associated with better parent-teen relationships. Younger age, positive coping styles, less negative coping styles, and higher goals for diabetes self-management were associated with better peer relationships.Conclusion: There is room to improve parent-teen relationships, maybe via encouraging more collaboration between parents and adolescents for diabetes management. The coping styles training is indicated to improve both relationships.Keywords: type 1 diabetes, adolescents, parent-teen relationships, peer relationships, associating factors

Qian Li, Leipeng Ren, Weitong Wu, Dangze Sun, Lin Wei, Chao Ding, Peijia Luo Department of Thoracic Surgery, Xi’an Chest Hospital, Xi’an, Shaanxi, 710100, People’s Republic of ChinaCorrespondence: Peijia Luo, Department of Thoracic Surgery, Xi’an Chest Hospital, Xi’an, Shaanxi, 710100, People’s Republic of China, Email 1171185306@qq.comBackground: To establish and validate a nomogram for predicting the culture results of Mycobacterium tuberculosis in superficial lymph nodes.Methods: The clinical data of patients with superficial lymph node tuberculosis admitted to Xi’an City Chest Hospital from November 23, 2018, to May 30, 2024, were selected and divided into a training set and a validation set according to a ratio of 7:3. Influencing factors were identified through multivariate logistic regression analyses. Using R version 4.3.2, we developed a predictive model and generated a nomogram based on this model. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curve analysis (CCA), and decision curve analysis (DCA).Results: The positive rate of superficial lymph node tuberculosis culture was 23.0% (103/446). Multivariate Logistic regression analysis showed that anti-tuberculosis treatment duration (OR=0.98, 95% CI: 0.97 ~ 0.99), initial treatment or retreatment (OR=0.12, 95% CI: 0.05 ~ 0.28), and adenosine deaminase (OR=1.12, 95% CI: 1.03 ~ 1.22) were independent factors affecting the culture results of Mycobacterium tuberculosis in superficial lymph nodes. The areas under the ROC curves were 0.86 (95% CI: 0.82– 0.91) for the training set and 0.89 (95% CI: 0.84– 0.95) for the validation set. The P values of calibration curves were 1.000 and 0.961, respectively, and the predicted values were in good agreement with the actual values. The threshold probabilities of clinical decision curves were 3%~64% and 1%~68%, respectively.Conclusion: The positive rate of Mycobacterium tuberculosis culture in superficial lymph nodes is low. The increase in retreatment patients and anti-tuberculosis treatment time are obstacle factors for Mycobacterium tuberculosis culture positivity, while an increase in adenosine deaminase is a promoting factor for Mycobacterium tuberculosis culture positivity. The nomogram model established based on these factors can be used to predict the results of Mycobacterium tuberculosis culture in superficial lymph nodes.Keywords: superficial lymph node tuberculosis, mycobacterium culture, predictive model, nomogram

Lanying Li,* Xinyuan Zhang,* Qian Li, Wen Zhong, Hua Zou Department of Laboratory Medicine, Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Zhong; Hua Zou, Department of Laboratory Medicine, Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University, 120 Longshan Road, Yubei District, Chongqing, 400016, People’s Republic of China, Tel +8615823827032 ; +8613512371464, Email 23119401@qq.com; 1316933969@qq.comPurpose: Candida vaginitis is widely prevalent worldwide and is one of the common gynecological disorders. The aim of this study is to analyze the sensitivity of recurrent vulvovaginal (RVVC) candidiasis to antifungal drugs and its relationship with vaginal microbiota.Patients and Methods: We Isolated and cultured Candida from RVVC patients, mass spectrometry and broth microdilution method were used to identify and determine MIC values of antifungal drugs. Clinical medical records and vaginal microbiota of RVVC patients were also collected.Results: The main pathogens causing RVVC are predominantly Candida albicans (70.26%), but in recent years, there has been an increasing proportion of Candida glabrata(24.46%). However, only 15.70% of Candida albicans were sensitive to Voriconazole, 35.84% to Fluconazole and 25.60% to Itraconazole. No fluconazole-resistant Candida glabrata was found. Most Candida krusei strains were sensitive to voriconazole (81.80%). More important MIC values of triazoles were increased in Candida species, when exposed to clotrimazole. In addition, we found that the vaginal microecology of candida vaginitis and bacterial vaginitis was significantly different.Conclusion: Triazoles resistant Candida species have emerged, leading to the failure of empirical anti-infective therapy. At the same time, the vaginal microecology of candida vaginitis and bacterial vaginitis was significantly different. In addition, a new breakpoint for Candida from RVVC needs to be established.Keywords: triazole, Candida, vulvovaginal candidiasis, vaginal microbiota

Qiangqiang Li,1 Na Li2 1School of Educational Science, Jiangsu Second Normal University, Nanjing, Jiangsu Province, People’s Republic of China; 2School of Humanities, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Qiangqiang Li, Email lqq11202316@jssnu.edu.cnBackground/Objective: Social media significantly influences adolescents’ prosocial behavior. With smartphones becoming ubiquitous, short videos have emerged as the predominant social media format for adolescents. However, the effects of adolescents’ engagement with short videos on their prosocial behavior remain uncertain. This study aims to address the problem of how short videos (content and consequences) affect prosocial behavior in adolescents, and simultaneously explores the differences of this effect among individuals with different social value orientations.Methods: The current study conducted two research laboratory experiments using the between-subject study design of two factors. Study 1 (N=148) reveals that viewing prosocial short videos significantly predicts adolescents’ prosocial behavior more so than neutral short videos. The interaction between short video content and social value orientation on prosocial behavior illustrates that the encouraging impact of prosocial content is primarily evident in prosocial individuals, rather than in pro-self individuals. In Study 2 (N=152), we introduce new dimensions by assessing adolescents’ response to varying consequences of the same prosocial behavior (ie, reward, punishment) within the short video context. Findings indicate that reward consequences significantly bolster adolescents’ prosocial behavior, whereas punitive measures tend to adversely affect it. Furthermore, the interaction between the consequences of prosocial short videos and social value orientation suggests that prosocial individuals exhibit no significant behavioral difference between rewards and punishments; instead, the reward/punishment consequences notably influence the prosocial behavior of pro-self individuals.Conclusion: Short videos (content and consequences) and social value orientations interactively influence adolescents’ prosocial behaviors. This study underscores the need to recognize individual differences in adolescents’ use of short videos and its impact on their prosocial behavior, particularly highlighting the crucial role of their social value orientations. Practically, the research offers valuable insights for parents and professionals seeking to foster adolescents’ prosocial behavior.Keywords: social media, prosocial behavior, short videos, social value orientation, adolescents

Ying Shao,1,&ast; Qianfei Li,2,&ast; Meirong Bian,3 Yue Wang,1 Xiaohong Zhang4 1Department of Ophthalmology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Nursing Department, Third hospital of Shanxi medical university, Shanxi Bethune hospital, Shanxi academy of medical sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Zhang, Nursing Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13453443366, Email zxhxb2013@126.comBackground: The “Key Points of the Core System of Medical Quality and Safety” (hereinafter referred to as the “Key Points”) was promulgated by the National Health Commission of China in 2018, requiring that nursing ward rounds should be carried out with reference to the three-level ward round system; In 2020 and 2022 editions of the “Evaluation Standards for Tertiary Hospitals”, which were implemented in China, required that nursing ward rounds should be carried out with reference to the “Key Points”. Additionally, the Action Plan for Comprehensively Improving Medical Quality (2023– 2025) also mentions the need to improve the quality of three-level ward rounds. However, there are no detailed guidelines regarding implementing “Nursing Three-level Ward Rounds”.Purpose: This study aimed to investigate the current situation of nursing three-level ward rounds in tertiary hospitals after the promulgation of the “Key Points of the Core System of Medical Quality and Safety” to provide insights and guidelines regarding relevant standards, so as to better implement of the requirements of “nursing ward rounds” in the “Evaluation Standards for Tertiary Hospitals” and “improving the quality of three-level ward rounds” in the “Action Plan”.Methods: A multi-center study was conducted in February 2024, including all tertiary public hospitals in the Shanxi Province, China. A questionnaire survey using the self-designed “Questionnaire on the Implementation of Nursing Three-level Ward Rounds” was carried out. The questionnaire included the basic information of the hospital and the implementation of the three-level (namely I, II, and III) rounds (including “five aspects”: ward round personnel, object, content, frequency, and record), which is expressed by quantity and composition ratio. Next is the text analysis method. First, the “five aspects” of the hospital that filled in the questionnaire survey with “nursing three-level ward rounds have been carried out” were assessed. Second, the five aspects of each hospital were assessed for consistency with the “Nursing Three-level Ward Rounds System” (hereinafter referred to as the “System”) of their respective hospitals.Third, the consistency of the “System” of the hospital with the “Key Points” was assessed. The results of the analysis of the former are expressed in terms of quantity and composition ratio; the results of the latter two were analyzed using Fisher’s exact test method to compare any differences.Results: Notably, 14 of the 67 tertiary public hospitals (20.9%) carried out nursing three-level ward rounds. There were 4– 10 situations in the five aspects of I, II, and III ward rounds filled in by the hospitals. The five aspects of the I, II, III ward rounds in 14 hospitals were significantly comparable with the “System”, which, in turn, was comparable with the “Key Points” (P < 0.05).Conclusion: Not all tertiary public hospitals in the Shanxi Province have not all carried out nursing three-level ward rounds. Furthermore, the five aspects of the hospitals that carried out nursing three-level ward rounds were not entirely consistent in terms of ward round personnel, object, content, frequency, and record. The filling in of the nursing three-level ward rounds carried out by the hospitals is inconsistent with the respective “System”; the “System” of the hospital is not in line with the “Key Points”.Impact on Nursing Work: Nursing administrators should be aware of the newly issued norms and requirements in their workplace, and revise the relevant systems in accordance with the norms and requirements in a timely manner. Additionally, the revision of the system should cover the core requirements of the norms and be practicable. The system should be supervised to ensure that 100% of the implementation is in accordance with the system.Keywords: nursing three-level ward rounds, tertiary hospitals, core system, current status of ward round, multi-center

Kai Huang,&ast; Jie Lu,&ast; Qin Li, Chuyi Wang, Sufan Ding, Xiangyang Xu, Lin Han Department of Cardiovascular Surgery, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Han, Email sh_hanlin@hotmail.comBackground: The accumulation of epicardial adipose tissue (EAT) is associated with cardiometabolic risks and adverse outcomes in heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). This study aims to identify genes secreted by EAT that contribute to the shared pathogenesis of HFpEF and AF, potentially serving as biomarkers for diagnosis.Methods: Data sets from the GEO database for HFpEF-EAT, HFpEF-heart tissue, AF-EAT, AF-PBMC, and AF-heart tissue were analyzed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) identified key genes in EAT linked to HFpEF and AF. Functional enrichment and connectivity map analyses explored common pathways and therapeutic targets. Machine learning techniques, including LASSO regression, random forest, and support vector machine, identified shared biomarkers. CIBERSORT was used to assess immune cell infiltration, while gene set enrichment analysis identified pathways related to hub genes. Receiver operating characteristic (ROC) curve analysis and experimental validation assessed the bioinformatics findings.Results: In the HFpEF dataset, 200 key genes were identified by intersecting HFpEF-EAT, HFpEF-heart tissue, WGCNA analyses, and secretory proteins. For AF, 232 related genes were identified through similar methods. Thirteen genes were common between HFpEF and AF, with two central genes, ITPKA and WNT9B, selected as potential biomarkers through machine learning and ROC analysis. Immune cell infiltration and gene set enrichment analysis revealed pathways related to ITPKA/WNT9B. These patterns were confirmed in human samples.Conclusion: This study identified EAT-derived secretory proteins as potential biomarkers for HFpEF and AF, with ITPKA and WNT9B as central hub genes. These findings offer insights into potential diagnostic and therapeutic strategies for HFpEF and AF.Keywords: heart failure with preserved ejection fraction, atrial fibrillation, epicardial adipose tissue, diagnostic value, secretory proteins

Xi Wu, Qin Li, Mingxing Wu, Haobo Huang, Zhe Liu, He Huang, Lei Wang Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of ChinaCorrespondence: Lei Wang, Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China, Email heartwl@126.comObjective: The research was carried out to determine and compare the efficiency of completely transradial access (cTRA) and transfemoral access (TFA) in retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI).Background: The cases of retrograde chronic total occlusion (CTO) percutaneous coronary intervention usually need the dual access. The transradial method is now used more frequently in CTO PCI, and improves the safety of CTO PCI.Methods: This retrospective, observational study was carried out in a single center. Participants were patients who underwent dual-access retrograde CTO PCI from January 2017 to October 2023, categorized into two groups: cTRA (biradial access) and TFA (bifemoral, or combined radial and femoral access). All patients in the cTRA group received conventional radial access. All punctures of the femoral artery were performed without fluoroscopic or ultrasound guidance. None of the patients in the TFA group accepted any arterial closure devices. Clinical, angiographic and procedural characteristics and the occurrence of in-hospital major adverse cardiovascular events (MACE) of the cTRA and TFA procedures were recorded.Results: This research involved 187 CTO PCI procedures with dual access, of which 88 were done using cTRA and the rest (99) were carried out through TFA. The J-CTO (Multicenter Chronic Total Occlusion Registry of Japan) score was lower in the cTRA group than TFA group (2.1± 0.6 vs 3.0± 0.8; P < 0.001). The technical success (84.1% vs 82.8%; P= 0.817), procedural success (80.7% vs 79.8%; P= 0.906) and in-hospital MACE rates (5.7% vs 4.0%; P= 0.510) were the same for both groups. For a J-CTO score of 3 or higher, technical success rate was significantly lower in the cTRA group than the TFA group (58.1% vs 74.2%; P < 0.001).Conclusion: In the retrograde CTO PCI, the percentages of success and in-hospital MACE were similar for both cTRA and TFA. Meanwhile, cTRA may be used for simpler lesions (J-CTO score < 3) as compared to TFA.Keywords: transradial approach, transfemoral approach, chronic total occlusion, retrograde, percutaneous coronary intervention

Zonglin Li,1,&ast; Xingming Shu,1,&ast; Xin Liu,1 Qiuyun Li,2 Yifu Hu,2 Bingbing Jia,2 Min Song3 1Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Grade 2023, Clinical Medicine College, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Song, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +8615883059785, Email songminlele2007@126.comAbstract: Gastric cancer (GC) is one of the most common malignant tumors in the digestive tract, and chemotherapy plays an irreplaceable role in the comprehensive treatment of GC. However, chemoresistance makes it difficult for patients with GC to benefit steadily from chemotherapy in the long term, which ultimately leads to tumor recurrence, metastasis, and patient death. Elucidating the detailed mechanism of chemoresistance in GC and identifying specific therapeutic targets will help to solve the difficult problem of chemoresistance and improve the prognosis of patients with GC. This review summarizes and clarifies the cellular and molecular mechanisms underlying chemoresistance for GC.Keywords: gastric cancer, chemoresistance, cellular mechanisms, molecular mechanisms

Yinying Li,1 Qiuming Li,2 Haihua Lei,3 Xiaorong Wei,4 Tao Feng,2 Huajiao Qin,2 Hongchun Huang,2 Minchao Duan1,2 1The Second Clinical Medical College, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 3Radiological department, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Clinical Laboratory, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of ChinaCorrespondence: Minchao Duan, Department of Respiratory and Critical Care Medicine, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China, Tel/Fax +86 15507711966, Email musicladyd@sina.comBackground: Pulmonary infection is a common clinical complication associated with glucocorticoid. There have been no reported cases of mixed infections involving Nocardia and Pneumocystis jirovecii combined with anti-synthetase syndrome (ASS) activity.Methods: This study conducted a retrospective analysis of the clinical data from a patient with active ASS, treated for a pulmonary coinfection.Results: The patient exhibited fever, asthma, and cough as initial symptoms. Chest CT scan revealed multiple infiltration shadows, consolidation shadows, nodules, mass shadows, and internal cavities in both lungs. BALF mNGS detected Nocardia terpene and Pneumocystis jiroveci. Treatment with sulfamethoxazole/trimethoprim and corticosteroids led to an improvement. However, the patient experienced recurrent fever and a new rash with the reduction of the glucocorticoid dosage. Further investigation identified positive anti-Jo-1 and anti-Ro-52 antibodies and myogenic lesions on electromyography, which confirmed the diagnosis of ASS. Following treatment with immunoglobulin, methylprednisolone, and cyclosporine, the patient’s condition significantly improved.Conclusion: Immunodeficiency patients are susceptible to opportunistic infections. mNGS is valuable for diagnosis and treatment. Although the image of Nocardia terpene and Pneumocystis jiroveci infections lack specificity, they exhibit distinctive features. Should fever and skin lesions reoccur post-effective anti-infective therapy, it is imperative to explore non-infectious causes and expedite autoantibody testing.Keywords: co-infection, Nocardia terpene, Pneumocystis jiroveci, anti-synthetase syndrome, anti-Ro-52 antibody, anti-Jo-1 antibody

Jiali Teng,1 Qian Li,1 Guihang Song,2 Youli Han1 1School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2Department of Medical Services Management, Gansu Healthcare Security Administration, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Youli Han, School of Public Health, Capital Medical University, 10 Xi Toutiao Road, Youanmenwai District, Beijing, People’s Republic of China, 100069, Email hanyouli@ccmu.edu.cn Guihang Song, Department of Medical Services Management, Gansu Healthcare Security Administration, 101 Guangchangnan Road, Chengguan District, Lanzhou, Gansu, People’s Republic of China, 730030, Email 285601604@qq.comPurpose: To control medical costs and regulate the behavior of providers, China has formed an original widely piloted case-based payment under the regional global budget, called the Diagnosis-Intervention Packet (DIP). This study aimed to evaluated the impact of the DIP payment reform on medical costs, quality of care, and medical service capacity in a less-developed pilot city in Northwest China.Patients and Methods: We used the de-identified case-level discharge data of hospitalized patients from January 2021 to June 2022 in pilot and control cities located in the same province. We performed difference-in-differences (DID) analysis to examine the differential impact of the DIP reform for the entire sample and between secondary and tertiary hospitals.Results: The DIP payment reform resulted in a significant decrease of total expenditure per case in the entire sample (5.5%, P < 0.01) and tertiary hospitals (9.3%, P < 0.01). In-hospital mortality rate decreased significantly in tertiary hospitals (negligible in size, P < 0.05), as did all-cause readmission rate within 30 days in the entire sample (1.1 percentage points, P < 0.01) and secondary hospitals (1.4 percentage points, P < 0.01). Proportion of severe patients increased significantly in the entire sample (1.2 percentage points, P < 0.05) and tertiary hospitals (2.5 percentage points, P < 0.01). We did not find the DIP reform was associated with a significant change in relative weight per case.Conclusion: The DIP payment reform in the less-developed pilot city achieved short-term success in controlling medical costs without sacrificing the quality of care for the entire sample. Compared with secondary hospitals, tertiary hospitals experienced a greater decline in medical costs and received more severe patients. These findings hold lessons for less developed countries or areas to implement case-based payments and remind them of the variations between different levels of hospitals.Keywords: DIP payment, medical costs, quality of care, medical service capacity, less developed city, case-based payment

Qiujing Li,1 Mingwu Li,2 Shuxian Wang,2 Alan F Geater,3 Jingyi Dai1 1Department of Public Laboratory, The Third People’s Hospital of Kunming City, Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 2Department of Tuberculosis, The Third People’s Hospital of Kunming City, Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 3Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, HatYai, Songkhla, ThailandCorrespondence: Jingyi Dai, Department of Public Laboratory, The Third People’s Hospital of Kunming City, Kunming, People’s Republic of China, Email daijingyidjy@163.comAbstract: This case reports a middle-aged male patient who was HIV-negative and initially misdiagnosed as pulmonary tuberculosis but was eventually diagnosed with disseminated Talaromyces marneffei (T. marneffei) infection by next-generation sequencing. The patient presented with respiratory symptoms, recurrent bone pain, and subcutaneous masses as the main symptoms. After one year of antifungal treatment, the symptoms improved obviously, but the symptoms recurred after two weeks of drug withdrawal, and the symptoms were relieved after re-administration of antifungal drugs again. This report highlights the need for the rapid evaluation of fungal infections with metagenomic next-generation sequencing (mNGS) in patients with an inadequate diagnostic basis for tuberculosis infection or a poor response to antituberculosis drugs. In addition, long-term follow-up is needed to observe disease recurrence in patients with disseminated T. marneffei infection.Keywords: Talaromyces marneffei, HIV-negative patient, tuberculosis, misdiagnose, Next-generation sequencing

Qinchuan Li,1 Wenju Guan,2 Jian Zhang,2 Min Chen,3 Ya Zou1 1Department of Clinical Pharmacology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China; 2Department of Oncology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China; 3Sichuan Academy of Medical Sciences. Department of Pharmacy, Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of ChinaCorrespondence: Ya Zou, Department of Clinical Pharmacology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China, Email zouya_1214@163.comBackground: Patients with nasopharyngeal carcinoma (NPC) combined with non-tuberculous Mycobacteria-pulmonary disease (NTM-PD) are very rare in the clinic, and our case is the first patient with NPC combined with NTM-PD. For oncologists, rapid control of the symptoms of infection is essential to the treatment of the primary disease.Case Presentation: A 58-year-old man who developed a NTM-PD after chemotherapy for nasopharyngeal carcinoma. Granulocytosis after chemotherapy is a major factor in the development of various infectious diseases. Nasopharyngeal tumor was found on MRI of the patient’s head, and nasopharyngeal malignant tumor was considered after pathological examination after endoscopic resection of intranasal lesion, and then nasopharyngeal non-keratonic carcinoma (T4N1M0, stage IV) was confirmed in the department of oncology. The patient developed bone marrow suppression after chemotherapy and was admitted to hospital due to septic shock. Chest CT examination indicated pulmonary infection, and empirical antibiotic treatment was not effective. The NGS results showed that the patient was infected with Mycobacterium abscess. We treated with cefoxitin followed by moxifloxacin to reduce the lung lesions significantly.Conclusion: NPC with NTM-PD is very rare, and the treatment of NTM-PD is very important for the prognosis of the patient’s primary disease. Our study provides experience for anti-infection treatment of patients with immunosuppression.Keywords: nasopharyngeal carcinoma, immunosuppressed, NTM, anti-infection, cefoxitin, moxifloxacin

Mengjie Xie,1,&ast; Fansu Meng,2,&ast; Panpan Wang,3,&ast; Alicia Marcelina Díaz-García,4 Marina Parkhats,5 Ralph Santos-Oliveira,6 Mulazim Hussain Asim,7 Nazish Bostan,8 Honghui Gu,9 Lina Yang,9 Qi Li,9 Zhenjiang Yang,9 Haibiao Lai,2 Yu Cai1 1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China / Guangdong Key Laboratory of Traditional Chinese Medicine Informatization / International Science and Technology Cooperation Base of Guangdong Province/School of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong, 528400, People’s Republic of China; 3The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 4Bioinorganic Laboratory, Faculty of Chemistry, University of Havana, Havana, 1400, Cuba; 5B. I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk, 220072, Belarus; 6Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Rio de Janeiro, RJ, 21941906, Brazil; 7College of Pharmacy, University of Sargodha, Punjab, 40100, Pakistan; 8Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan; 9Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, 518033, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Cai; Haibiao Lai, Email caiyu8@sohu.com; lhb8829@163.comAbstract: Data published in 2020 by the International Agency for Research on Cancer (IARC) of the World Health Organization show that breast cancer (BC) has become the most common cancer globally, affecting more than 2 million women each year. The complex tumor microenvironment, drug resistance, metastasis, and poor prognosis constitute the primary challenges in the current diagnosis and treatment of BC. Magnetic iron oxide nanoparticles (MIONPs) have emerged as a promising nanoplatform for diagnostic tumor imaging as well as therapeutic drug-targeted delivery due to their unique physicochemical properties. The extensive surface engineering has given rise to multifunctionalized MIONPs. In this review, the latest advancements in surface modification strategies of MIONPs over the past five years are summarized and categorized as constrast agents and drug delivery platforms. Additionally, the remaining challenges and future prospects of MIONPs-based targeted delivery are discussed. Keywords: Nanopreparations, Organic Nanomaterials, Inorganic Nanomaterials, Surface Engineering, Targeted Delivery

Qianqian Li,1,&ast; Yujie Liu,2,&ast; Zulun Zhang,1 Sheng Zhang,1 Xiao Ding,2 Faming Zhang1,3 1Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of China; 2Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3National Clinical Research Center for Digestive Diseases, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Faming Zhang, Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing, 210011, People’s Republic of China, Email fzhang@njmu.edu.cnPurpose: There is scarce evidence to support the effectiveness of faecal microbiota transplantation (FMT) in improving sleep among individuals with inflammatory bowel disease (IBD). Our study aimed to evaluate the effect of washed microbiota transplantation (WMT) (the new method of FMT) on the sleep of patients with IBD in short term.Patients and Methods: This prospective study was conducted as part of two interventional clinical trials (starting on February 2013 and expected to end on December 2025) and placed significant emphasis on evaluating sleep quality in patients with IBD. To measure subjective sleep, we used the Pittsburgh sleep quality index (PSQI). The primary endpoint was the PSQI score one month after WMT.Results: This stage study included 52 eligible patients evaluated by PSQI questionnaire who underwent WMT from January 2020 to March 2021 and 47 patients were enrolled for analysis. The age of the patients ranged from 13 to 60 years, with a mean of 33.4 years, and 57.4% (25/47) of the patients were male. The PSQI scores for all 47 patients one month after undergoing WMT were significantly lower (Cohen d = 0.59, p < 0.001) compared to the baseline. Moreover, baseline PSQI score was correlated with the difference value of the PSQI score before and after WMT (post-PSQI minus pre-PSQI) (r = 0.61, p < 0.05).Conclusion: The study suggests that WMT might be a helpful intervention for improving the sleep quality of patients with IBD, encouraging clinicians to consider its use in clinical practice for addressing poor sleep in IBD patients.Clinical Trial Registration: ClinicalTrials.gov; ID: NCT01793831, NCT01790061.Keywords: faecal microbiota transplantation, transendoscopic enteral tubing, sleep disorder, Crohn’s disease, ulcerative colitis, inflammatory bowel disease

Luohang Ni,&ast; Jianing Xu,&ast; Quanpeng Li, Xianxiu Ge, Fei Wang, Xueting Deng, Lin Miao Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueting Deng; Lin Miao, Email xtdeng@njmu.edu.cn; linmiao@njmu.edu.cnAbstract: Biliary tract cancer (BTC) represents a challenging malignancy characterized by aggressive behavior, high relapse rates, and poor prognosis. In recent years, immunotherapy has revolutionized the treatment landscape for various cancers, but its efficacy in BTC remains limited. This article provides a comprehensive overview of the advances in preclinical and clinical studies of immunotherapy for BTC. We explore the potential of immune checkpoint inhibitors in reshaping the management of BTC. Despite disappointing results thus far, ongoing clinical trials are investigating the combination of immunotherapy with other treatment modalities. Furthermore, research on the tumor microenvironment has unveiled novel targets for immunotherapeutic interventions. By understanding the current state of immunotherapy in BTC and highlighting future directions, this article aims to fuel further exploration and ultimately improve patient outcomes in this challenging disease.Keywords: biliary tract cancer, cancer immunotherapy, tumor microenvironment, immune checkpoint inhibitors, clinical trials

Xiao-Ling Shen,1,&ast; Zhuo-Yi Li,1,&ast; Qing Li,1 Kai Wang2 1Department of Women Health Care, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China; 2Department of Aristogenesis, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang; Qing Li, Email wangkai111909@163.com; lq5090@126.comPurpose: To verify whether there is lower incidence of adverse pregnancy outcomes after high-intensity focused ultrasound (HIFU) treatment than loop electrosurgical excision procedure (LEEP) in young women of childbearing age.Patients and Methods: This retrospective cohort study enrolled 46 patients treated with HIFU and 46 patients treated with LEEP. To compare the differences between the two groups, Fisher’s exact test or the Kruskal–Wallis (K-W/H) test was used in the univariate analysis, while the logistic regression method was applied for further verification.Results: Basic characteristics showed no differences between the two groups (P > 0.05) except for parity (P < 0.001). Preterm birth rates were 6.52% and 0.00% in patients with cervical high-grade squamous intraepithelial lesions (HSIL) treated with LEEP and HIFU, respectively. The incidence rates of premature rupture of membranes (PROM) were respectively 15.22% and 21.74% in the two groups. There was no significant difference in pregnancy outcomes between the two groups (P > 0.05).Conclusion: This study is the first to compare the pregnancy outcomes of patients with cervical HSIL who treated with LEEP and HIFU procedures. Both HIFU treatment and LEEP are available options for patients of reproductive age with cervical HSIL. Therefore, it is necessary to conduct prospective single-center or multicenter randomized controlled studies.Keywords: cervical high-grade squamous intraepithelial lesions, high-intensity focused ultrasound, loop electrosurgical excision procedure, pregnancy outcome

Jin-yu Shi,1,* Ting-ting Li,1,2,* Hui-ting Yang,1 Shi Zhang,2 Ran An,2 Liang Mao,2 Yang Li,2 Qian Li,2 Guang-yi Luan,2 Yan Shen,2 En-long Wang,2 Guang-hui Liu1,2 1First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-hui Liu, First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33, Beiling Street, Huanggu District, Shenyang, Liaoning, 110032, People’s Republic of China, Email guanghui04-09@163.comObjective: This study aimed to investigate the features and underlying principles of acupuncture points used in the treatment of headaches associated with blood stasis syndrome.Methods: Literature on the treatment of blood stasis headache with acupuncture and moxibustion was searched across three Chinese databases and one English database from January 1st, 2000, to January 1st, 2024. Relevant data including titles, journals, authors, keywords, interventions, main acupoints, and outcomes were extracted for further analysis.Results: A total of 112 papers with 102 complete prescriptions were analyzed. Of the 77 acupoints examined, 72 were meridian points, and 5 were extraordinary points, used 699 times in total. The top ten acupoints by frequency were Fengchi (GB20), Taiyang (EX-HN5), Baihui (GV20), Hegu (LI4), Shuaigu (GB8), Taichong (LR3), Xuehai (SP10), Touwei (ST8), Geshu (BL17), and Waiguan (TE5). Yang meridian points were used more frequently than Yin meridian points (82.8% vs 17.2%), with the Gallbladder Meridian of Foot Shaoyang being the most common. Nearly half of the acupoints (49.9%) were on the head and neck, and 23.1% on the lower limbs. Specific acupoints accounted for 53.5% of the total frequency. Fengchi (GB20) and Taiyang (EX-HN5) showed the highest correlation. Association rule mining highlighted combinations like Fengchi (GB20) with Taiyang (EX-HN5) and Baihui (GV20). Cluster analysis yielded five clusters.Conclusion: The study provides insights into selecting effective acupoints and combinations for clinical acupuncture practice and experimental studies in treating blood stasis headaches. Acupoints like Fengchi (GB20), Taiyang (EX-HN5), and Baihui (GV20) may be effective for clinical treatment, but further studies are needed to validate their efficacy.Keywords: headache, blood stasis syndrome, acupuncture, treatment rule, data mining

Lei Tan,1,2,&ast; Han She,1,2,&ast; Yi Wang,1,2,&ast; Yuanlin Du,1 Jun Zhang,1 Yunxia Du,1 Yinyu Wu,1 Wei Chen,1 Bingqiang Huang,1 Duanyang Long,1 Xiaoyong Peng,2 Qinghui Li,2 Qingxiang Mao,1 Tao Li,2 Yi Hu1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Li; Yi Hu, Email lt200132@163.com; huyi921@sina.comBackground: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer’s (AR) and Lactate Ringer’s solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear.Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury.Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats’ survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity.Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.Keywords: myocardial injury, hemorrhagic shock, mitochondria, ferroptosis

Longyin Zhu,&ast; Juan Cai,&ast; Jia Fang, Lingyu Ran, Huan Chang, Huhai Zhang, Jiamin Zeng, Qin Yang, Chunxiao Fu, Qingping Li, Qianguang Pan, Hongwen Zhao Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comObjective: Analyze risk factors for cardiac surgery-associated acute kidney injury (CSA-AKI) in adults and establish a nomogram model for CSA-AKI based on plasma soluble urokinase-type plasminogen activator receptor (suPAR) and clinical characteristics.Methods: In a study of 170 patients undergoing cardiac surgery with cardiopulmonary bypass, enzyme-linked immunosorbent assay (ELISA) measured plasma suPAR levels. Multivariable logistic regression analysis identified risk factors associated with CSA-AKI. Subsequently, the CSA-AKI nomogram model was developed using R software. Predictive performance was evaluated using a receiver operating characteristic (ROC) curve and the area under the curve (AUC). Internal validation was performed through the Bootstrap method with 1000 repeated samples. Additionally, decision curve analysis (DCA) assessed the clinical applicability of the model.Results: Multivariable logistic regression analysis revealed that being male, age ≥ 50 years, operation time ≥ 290 minutes, postoperative plasma suPAR at 2 hours, and preoperative left ventricular ejection fraction (LVEF) were independent risk factors for CSA-AKI. Employing these variables as predictive factors, a nomogram model was constructed, an ROC curve was generated, and the AUC was computed as 0.817 (95% CI 0.726– 0.907). The calibration curve indicated the accuracy of the model, and the results of DCA demonstrated that the model could benefit the majority of patients.Conclusion: Being male, age ≥ 50 years, operation time ≥ 290 minutes, low preoperative LVEF, and elevated plasma suPAR at 2 hours are independent risk factors for CSA-AKI. The nomogram model established based on these risk factors has high accuracy and clinical value, serving as a predictive tool for assessing the risk of CSA-AKI.Keywords: nomogram, acute kidney injury, prediction model, risk factors, cardiac surgery

Kaixin Wang,1 Lingfei Yang,2 Qingsheng Li,2 Xuan Yang,1 Ziyi Chen,2 Yongyan Zhou,3 Yanjie Jia,1 Zhe Gong1 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Academy of Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Electrocardiogram, Zhoukou Center Hospital, Zhoukou, People’s Republic of ChinaCorrespondence: Yanjie Jia; Zhe Gong, The First Affiliated Hospital of Zhengzhou University, Department of Neurology, Postal FfCode 450052, No. 1 Jianshe East Road, Zhengzhou, People’s Republic of China, Email jiayanjie1971@aliyun.com; gongzhe1415@163.comBackground: Ischemic stroke (IS) is one of the leading causes of death and disability in the world, and alcohol consumption has been gaining attention as an independent risk factor for IS. Blood-brain barrier (BBB) dysfunction and neuroinflammation are the core of cerebral ischemia/reperfusion (I/R) injury, and pericytes play a crucial role in the structure and function. This study is to explore the effects of long-term alcohol consumption on IS and the potential mechanisms of pericytes.Methods: Rat models of long-term alcohol intake followed by transient middle cerebral artery occlusion stroke (EtOH+tMCAO) and cell models of oxygen-glucose deprivation/reoxygenation (OGD/R) with alcohol pre-treatment were constructed.Results: Worsened infarct volume, neurological scores, and BBB disruption were observed in the EtOH+tMCAO group compared with the tMCAO group, and immunofluorescence staining showed increased pericytes NLPR3 inflammasome activation at the ischemic penumbra. In vitro, pericyte mortality and LDH release elevated pre-treated by alcohol after OGD/R, and amplified expression of NLRP3 inflammasome was detected by Western blotting and qPCR. Alcohol pre-treatment activated the TLR4/NF-κB pathway, and transfecting pericytes with TLR4-small interfering RNA (siRNA) to block TLR4 signaling markedly restrained NLRP3 inflammasome over-activation. Injecting TAK-242 in rats alleviated neurological impairment caused by alcohol.Conclusion: Long-term alcohol pre-treatment aggravated ischemic stroke-induced brain damage by activating NLRP3 inflammasome via TLR4/NF-κB signaling pathway in the pericytes.Keywords: cerebral ischemia, chronic ethanol exposure, pericytes, TLR4, NLRP3 inflammasome

Wenwu Zhang,1,2,&ast; Yuhan Xiao,3,&ast; Xin Zhu,1 Yanxia Zhang,1 Qin Xiang,1 Shunhong Wu,1 Xiaoyu Song,1 Junxiu Zhao,3 Ruanfei Yuan,1 Qiguang Li,1 Bin Xiao,1 Linhai Li1 1Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People’s Republic of China; 2Department of Laboratory Medicine, Suzhou Municipal Hospital, Affiliated to Nanjing Medical University, Suzhou, 21500, People’s Republic of China; 3School of Public Health, Dali University, Dali, 671000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linhai Li; Bin Xiao, Email mature303@126.com; xiaobin2518@163.comPurpose: Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored.Patients and Methods: The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays.Results: MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3.Conclusion: MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy.Keywords: meiosis-specific protein, pan-cancer, prognosis biomarker, immune infiltration, cell cycle

Xuanwen Luo, Suqin Chen,&ast; Weiliang Luo,&ast; Qingyun Li, Yening Zhu, Jiming Li Department of Neurology, Huizhou Central People’s Hospital, Huizhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiliang Luo; Suqin Chen, Department of Neurology, Huizhou Central People’s Hospital, No. 41, Eling North Road, Huizhou, Guangdong Province, 516001, People’s Republic of China, Tel +8613631986803, Fax +867522288160, Email lwl306@126.com; csq621@139.comPurpose: To investigate the benefit (90-day mRS score) and rate of major complications (early symptomatic intracranial hemorrhage-SICH) after reperfusion therapy (RT) (including intravenous thrombolysis -IVT and mechanical thrombectomy -MT) in patients over 80 years with acute ischemic stroke (AIS).Patients and Methods: AIS patients aged over 80 admitted to Huizhou Central People’s Hospital from September 2018 to 2023 were included in this study. Data on SICH, NIHSS, and mRS were analyzed. A good prognosis was defined as a mRS ≤ 2 or recovery to pre-stroke status at 90 days.Results: Of 209 patients, 80 received non-RT, 100 received IVT and 29 underwent MT. The non-RT group had the lowest baseline NIHSS while the MT group had the highest (non-RT 6.0 vs IVT 12.0 vs MT 18.0, P < 0.001). Higher NIHSS was associated with increased SICH risk (OR 1.083, P=0.032), while RT was not (OR 5.194, P=0.129). The overall SICH rate in the RT group was higher but not significantly different after stratification by stroke severity. Poor prognosis was associated with higher admission NIHSS, stroke due to large artery atherosclerosis (LAA) combined with cardioembolism (CE), and stroke-associated pneumonia (SAP) (OR 0.902, P< 0.001; OR 0.297, P=0.029; OR 0.103, P< 0.001, respectively). The RT group showed a greater reduction in NIHSS (delta NIHSS) than the non-RT group (non-RT 2.0 vs IVT 4.0 vs MT 6.0, P< 0.005). For severe AIS, the IVT group had a better prognosis at 90 days (non-RT 0% vs IVT 38.2%, P=0.039). No 90-day mortality difference was found between groups after stratification.Conclusion: Stroke severity, rather than RT, is an independent risk factor for SICH in AIS patients over 80. RT in severe stroke patients improves NIHSS at 90 days, suggesting RT is safe and effective in this demographic. Further studies with larger samples are required to confirm these findings.Keywords: acute ischemic stroke, elderly, intravenous thrombolysis, mechanical thrombectomy, symptomatic intracranial hemorrhage, therapeutic efficacy

Yan Li, Qi Li, Guangchao Zhao, Haopeng Zhang, Haixing Zhong, Yi Zeng Department of Anesthesia and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, Xi’an, 710000, People’s Republic of ChinaCorrespondence: Yi Zeng; Haixing Zhong, Department of Anesthesia and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, Xi’an, 710000, People’s Republic of China, Tel +8613991267646 ; +8613991946615, Email zengyi1014@163.com; haixing.zhong@139.comBackground: To investigate the effects of nalbuphine on emergency agitation (EA), which affects up to 80% of the children following otolaryngology procedures, in children undergoing cochlear implantation.Methods: A prospective double-blinded randomized controlled clinical trial was conducted between November 2020 and October 2022. Eligible children, aged 6 months to 3 years old, were randomly assigned to either 0.1 mg/kg, 0.15 mg/kg, 0.2 mg/kg nalbuphine or 0.9% saline groups. EA was defined by the Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10. Extubation time, post-anesthesia care unit (PACU) length of stay, severe EA (PAED ≥ 15), peak PAED score, the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale, Ramsay sedation score, and adverse events were also recorded.Results: A total of 104 children were enrolled, with 26 children in each group. Nalbuphine significantly reduced the EA occurrence from 73.1% in the saline group to 38.5%, 30.8%, and 26.9% in the 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg nalbuphine groups, respectively (P < 0.001), without affecting the extubation time and PACU length of stay. More children (34.6%) in the 0.9% saline group experienced severe EA. Higher dose nalbuphine (0.15 mg/kg, 0.2 mg/kg) showed lower peak PAED score, better analgesia and sedation effect compared with 0.1 mg/kg nalbuphine and saline groups. However, 0.2mg/kg nalbuphine caused undesired over-sedation in two (7.7%) children. No other adverse events were reported.Conclusion: Young children undergoing cochlear implantation surgery were at a high risk of EA and postoperative pain, while 0.2 mg/kg nalbuphine might be an ideal candidate for EA and pain prevention when used under close monitoring.Trial Registration: ChiCTR2000040407.Keywords: emergence agitation, nalbuphine, cochlear implantation, postoperative pain

Di Wang,1,2 Qiqi Li,1,2 Chunsheng Xiao,2 Hao Wang,2 Shujun Dong1 1The First Outpatient Department, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Hao Wang, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Chaoyang District, Changchun, 130022, People’s Republic of China, Tel +86-431-85262110, Email wangh@ciac.ac.cn Shujun Dong, The First Outpatient Department, Hospital of Stomatology, Jilin University, Room 101, Building G5, Phase 3, China Resources Ziyun Mansion, the Intersection of Jinhu Road and Nanhu Middle Street, Nanguan District, Changchun, 130021, People’s Republic of China, Tel +86-431-80621155, Email dsj@jlu.edu.cnAbstract: Periodontitis is a disease of inflammation that affects the tissues supporting the periodontium. It is triggered by an immunological reaction of the gums to plaque, which leads to the destruction of periodontal attachment structures. Periodontitis is one of the most commonly recognized dental disorders in the world and a major factor in the loss of adult teeth. Scaling and root planing remain crucial for managing patients with persistent periodontitis. Nevertheless, exclusive reliance on mechanical interventions like periodontal surgery, extractions, and root planning is insufficient to halt the progression of periodontitis. In response to the problem of bacterial resistance, some researchers are committed to finding alternative therapies to antibiotics. In addition, some scholars focus on finding new materials to provide a powerful microenvironment for periodontal tissue regeneration and promote osteogenic repair. Nanoparticles possess distinct therapeutic qualities, including exceptional antibacterial, anti-inflammatory, and antioxidant properties, immunomodulatory capacities, and the promotion of bone regeneration ability, which made them can be used for the treatment of periodontitis. However, there are many problems that limit the clinical translation of nanoparticles, such as toxic accumulation in cells, poor correlation between in vitro and in vivo, and poor animal-to-human transmissibility. In this paper, we review the present researches on nanoparticles in periodontitis treatment from the perspective of three main categories: inorganic nanoparticles, organic nanoparticles, and nanocomposites (including nanofibers, hydrogels, and membranes). The aim of this review is to provide a comprehensive and recent update on nanoparticles-based therapies for periodontitis. The conclusion section summarizes the opportunities and challenges in the design and clinical translation of nanoparticles for the treatment of periodontitis. Keywords: anti-inflammatory, antibacterial, guided tissue regeneration, nanofibers, hydrogel, films

Yanzhao Zhou,1,&ast; Jingzhong Ouyang,2– 4,&ast; Hongcai Yang,5,&ast; Zhengzheng Wang,2,&ast; Yi Yang,3,4,&ast; Qingjun Li,2 Haitao Zhao,6 Jinxue Zhou,2 Qiang Li1 1Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Li, Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China, Email liqiang@tjmuch.com Jinxue Zhou, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, People’s Republic of China, Email zhoujx888@126.comPurpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions.Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models.Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI.Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.Keywords: hepatocellular carcinoma, immunotherapy, body mass index, body composition, obesity paradox

Wenhao Zhang,1,2 Qingli Li,1,2,&ast; Rutie Yin1,2,&ast; 1Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rutie Yin, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email yrtt2013@163.com Qingli Li, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of China, Email liqingli73@163.comAbstract: WEE1 kinase is involved in the G2/M cell cycle checkpoint control and DNA damage repair. A functional G2/M checkpoint is crucial for DNA repair in cancer cells with p53 mutations since they lack a functional G1/S checkpoint. Targeted inhibition of WEE1 kinase may cause tumor cell apoptosis, primarily, in the p53-deficient tumor, via bypassing the G2/M checkpoint without properly repairing DNA damage, resulting in genome instability and chromosomal deletion. This review aims to provide a comprehensive overview of the biological role of WEE1 kinase and the potential of WEE1 inhibitor (WEE1i) for treating gynecological malignancies. We conducted a thorough literature search from 2001 to September 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of WEE1i and gynecologic oncology. WEE1i has been shown to inhibit tumor activity and enhance the sensitivity of chemotherapy or radiotherapy in preclinical models, particularly in p53-mutated gynecologic cancer models, although not exclusively. Recently, WEE1i alone or combined with genotoxic agents has confirmed its efficacy and safety in Phase I/II gynecological malignancies clinical trials. Furthermore, it has become increasingly clear that other inhibitors of DNA damage pathways show synthetic lethality with WEE1i, and WEE1 modulates therapeutic immune responses, providing a rationale for the combination of WEE1i and immune checkpoint blockade. In this review, we summarize the biological function of WEE1 kinase, development of WEE1i, and outline the preclinical and clinical data available on the investigation of WEE1i for treating gynecologic malignancies.Keywords: WEE1 inhibitor, cell cycle, gynecological malignancies, adavosertib, clinical trials

Yufeng Liu,1,&ast; Yan Chen,2,&ast; Zhongwen Zhi,1,&ast; Ping Wang,1 Mengchao Wang,1 Qian Li,1 Yuqian Wang,1 Liandong Zhao,1 Chun Chen1 1Department of Neurology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, Jiangsu, 223002, People’s Republic of China; 2Department of Neurological Medicine, Siyang Hospital of Traditional Chinese Medicine, Siyang, Jiangsu, 223700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Chen; Liandong Zhao, Department of Neurology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, No. 62, South Huaihai Road, Huai’an, Jiangsu, 223002, People’s Republic of China, Email hongzecc@163.com; zld202109@163.comPurpose: Stroke-associated pneumonia (SAP) usually complicates stroke and is linked to adverse prognoses. Triglycerides, total cholesterol, and body weight index (TCBI) is a new and simple calculated nutrition index. This study seeks to investigate the association between TCBI and SAP incidence, along with its predictive value.Patients and Methods: Nine hundred and sixty-two patients with acute ischemic stroke were divided into SAP group and Non-SAP group. The TCBI was divided into three layers: T1, TCBI < 948.33; T2, TCBI 948.33– 1647.15; T3, TCBI > 1647.15. Binary Logistic regression analysis was used to determine the relationship between TCBI levels and the incidence of SAP. Furthermore, restricted cubic splines (RCS) analysis was utilized to evaluate the influence of TCBI on the risk of SAP.Results: TCBI in the SAP group was markedly lower compared to that in the Non-SAP group (P < 0.001). The Logistic regression model revealed that, using T3 layer as the reference, T1 layer had the highest risk for SAP prevalence (OR = 2.962, 95% CI: 1.600– 5.485, P = 0.001), with confounding factors being controlled. The RCS model found that TCBI had a linear relationship with SAP (P for nonlinear = 0.490, P for overall = 0.004). Moreover, incorporating TCBI into the A2DS2 (Age, atrial fibrillation, dysphagia, sex, and severity) model substantially enhanced the initial model’s predictive accuracy.Conclusion: Low TCBI was associated with a higher risk of SAP. In clinical practice, TCBI has shown predictive value for SAP, contributing to early intervention and treatment of SAP.Keywords: acute ischemic stroke, stroke-associated pneumonia, nutritional status, TCBI

Qianfeng Li,1,&ast; Bo Wang,2,&ast; Jun Yang,3 Yuan Wang,1 Faliang Duan,1 Ming Luo,1 Chungang Zhao,4 Wei Wei,2 Lei Wang,3 Sha Liu2,5 1Department of Neurosurgery, Wuhan No.1 Hospital, Wuhan, People’s Republic of China; 2Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 4Jilin Jianda Modern Agricultural Research Institute, Changchun, People’s Republic of China; 5Department of General Practice, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Wang; Sha Liu, Email wanglei@hgyy.org.cn; sha.liu@whu.edu.cnBackground: Aging is recognized as the key risk for intracerebral hemorrhage (ICH). The detailed mechanisms of aging in ICH warrant exploration. This study aimed to identify potential aging-related genes associated with ICH.Methods: ICH-specific aging-related genes were determined by the intersection of differentially expressed genes (DEGs) between perihematomal tissues and corresponding contralateral parts of four patients with ICH (GSE24265) and 349 aging-related genes obtained from the Aging Atlas database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses were performed to identify the potential biological functions and pathways in which these ICH-specific aging-related genes may be involved. Then, PPI network was established to identify the hub genes of ICH-specific aging-related genes. Meanwhile, miRNA-mRNA and transcription factor (TF)-mRNA regulatory networks were constructed to further explore the ICH-specific aging-related genes regulation. The relationship between these hub genes and immune infiltration was also further explored. Additional single-cell RNA-seq analysis (scRNA-seq, GSE167593) was used to locate the hub genes in different cell types. Besides, expression levels of the hub genes were validated using clinical samples from our institute and another GEO dataset (GSE206971).Results: This study identified 24 ICH-specific aging-related genes, including 22 up-regulated and 2 down-regulated genes. The results of GO and KEGG suggested that the ICH-specific aging-related genes mainly enriched in immunity and inflammation-related pathways, suggesting that aging may affect the ich pathogenesis by regulating inflammatory and immune-related pathways.Conclusion: Our study revealed 24 ICH-specific aging-related genes and their functions highly pertinent to ICH pathogenesis, providing new insights into the impact of aging on ICH.Keywords: intracerebral hemorrhage, aging, immune infiltration, single-cell RNA sequencing, molecular docking

Xin Tang,1,&ast; Qifu Li,1,&ast; Gaoyangzi Huang,1 Ziwen Chen,2 Ya Huang,1 Xianmei Pei,1 Siwen Zhao,1 Zili Liu,1 Taipin Guo,1 Fanrong Liang2 1School of Second Clinical Medicine/The Second Affiliated Hospital, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 2College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taipin Guo, School of Second Clinical Medicine/The Second Affiliated Hospital, Kunming, People’s Republic of China, Email gtphncs@126.com Fanrong Liang, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email acuresearch@126.comPurpose: Acute lumbar sprain (ALS) is a common clinical disease characterized by persistent intolerable low back pain and limitation of movement, and quick pain relief and restoration of mobility in a short time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of contralateral acupuncture (CAT) on SI3 combined with active exercise in treating ALS.Methods and Analysis: This study is a randomized controlled trial which will recruit 118 eligible participants aged 18 to 55 years with ALS at the Second Affiliated Hospital of Yunnan University of Chinese Medicine between March 2024 and December 2026. Participants will be randomly assigned to the acupuncture group or the sham-acupuncture group in a 1:1 ratio. The acupuncture group will receive a 10-minute acupuncture treatment combined with active exercise, while the sham-acupuncture group will receive a 10-minute sham acupuncture treatment combined with active exercise. Randomization will use a computer-generated sequence with allocation concealed in opaque envelopes. The primary outcome will be the pain visual analogue scale (VAS) scores after 10 minutes of treatment. Secondary outcomes will include the pain VAS scores at other time points (2, 4, 6, and 8 minutes post-treatment), the lumbar range of motion (ROM) scores at various time points, blinded assessment, the treatment effect expectancy scale, and the rescue analgesia rate. The analysis will follow the intention-to-treat principle. The primary outcome will be analyzed using ANCOVA, and secondary outcomes with repeated measures ANOVA. The rescue analgesia rate will be assessed using either the χ2 test or Fisher’s exact test.Discussion: This study is the first randomized controlled trial to assess the immediate efficacy of CAT in combination with active exercise for ALS. This study will provide a simple, rapid, and effective treatment for the clinical management of ALS.Keywords: acute lumbar sprain, immediate efficacy, contralateral acupuncture, active exercise, randomized controlled trial

Hang Wang,1,&ast; Bobin Hu,1,&ast; Hengkai Liang,1 Rongming Wang,1 Lu Wei,1 Tumei Su,1 Qingmei Li,1 Qianbing Yin,1 Yanfei Feng,1 Minghua Su,1 Jianning Jiang1,2 1Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianning Jiang; Minghua Su, Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Tel +86-0771-5356531, Email gxjjianning@163.com; smh9292@163.comPurpose: Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved.Patients and Methods: We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels.Results: After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC.Conclusion: HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.Keywords: hepatitis B virus, long-term antiviral therapy, hepatocellular carcinoma, integration, gene rearrangement

Qian Li,1,2 Caifeng Luo,1 Jianqin Ye,3 Zekun Bian,1 Weiyi Sun,1 Man Zhou,4 Mingzhu Rong4 1School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Department of Neurosurgery, Xiangcheng People’s Hospital, Suzhou, Jiangsu, People’s Republic of China; 3Department of Nursing, Xiangcheng People’s Hospital, Suzhou, Jiangsu, People’s Republic of China; 4Department of Neurology, Suzhou Municipal Hospital, Suzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Caifeng Luo, School of Medicine, Jiangsu University, No. 301 Xuefu Road, Jingkou District, Zhenjiang, 212013, People’s Republic of China, Email lcf0105@163.comPurpose: Stroke is a major disease endangering the health of Chinese people, and patients need to rely on the care of family members, which brings heavy caregiving burdens and pressures to caregivers and families, thus disrupting the stable family structure. In view of this, this study was to analyse the current status of family resilience among caregivers of stroke patients in Chinese nuclear families, and to explore the correlation and mechanism of action among perceived stress, illness uncertainty and family resilience.Patients and Methods: This study used a cross-sectional research design. A total of 350 carers of stroke patients in nuclear families from four tertiary hospitals in Suzhou City, Jiangsu Province, China were selected by convenience sampling method and assessed by using demographic questionnaires, the Chinese Perceived Stress Scale (CPSS), the Parental Perceptions of Uncertainty Scale-Family (PPUS-FM), and a short Chinese version of the Family Resilience Assessment Scale (FRAS-C). Based on the above data, structural equation model was used to test the mediating role of perceived stress between illness uncertainty and family resilience.Results: Family resilience among caregivers of stroke patients in nuclear families was at the medium lower level, illness uncertainty was at the medium level, and perceived stress was at the relatively high level. Illness uncertainty was positively correlated with perceived stress (P< 0.01) and negatively correlated with family resilience (P< 0.01). Illness uncertainty directly predicted family resilience (β = − 0.516, p < 0.05). And the pathway between illness uncertainty and family resilience was partially mediated by perceived stress (Effect= − 0.091, 95% CI [− 0.141, − 0.055]).Conclusion: Healthcare professionals should pay adequate attention to the level of illness uncertainty and perceived stress among carers of stroke patients, with the need to take measures to reduce carers’ illness uncertainty and perceived stress in order to improve family resilience.Keywords: nuclear family, stroke, caregivers, perceived stress, illness uncertainty, family resilience

Min Jiang,1,&ast; Hui Zhang,2,&ast; Wenjun Lu,3 Xuedan Qiu,1 Chenyao Lin,1 Rongqing Zhao,1 Qingcao Li,1 Qiaoping Wu1 1Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China; 2Clinical Laboratory, Ninghai County Chengguan Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 3Intensive Care Units, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingcao Li; Qiaoping Wu, The Affiliated LiHuiLi Hospital of Ningbo University, 1111 Jiangnan Road, Ningbo, Zhejiang Province, 315040, People’s Republic of China, Tel +86-574-55835786, Fax +86-574-55835781, Email lqc_lab@163.com; lhlyywqp@163.comBackground: Klebsiella pneumoniae (KP) is a common nosocomial pathogen. Capsules are an important component of KP’s virulence, among which the K1, K2, K5, K20, K54, and K57 serotypes are predominant and exhibit varying degrees of virulence.Methods: The capsule and virulence genes of 150 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 213 carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolates were examined by polymerase chain reaction (PCR). The isolates were tested for hypermucoviscosity by string tests. Phylogenetic relationships between KP isolates were analyzed using multilocus sequence typing (MLST) and a Galleria mellonella infection model confirmed the differences in virulence.Results: A total of 111 of 363 isolates of KP were detected, the highest detected serotypes were K1, K5, and K2, and CSKP was detected more frequently than CRKP. There was a greater prevalence of K1 and K2 serotypes in CSKP, while in CRKP, K5 serotypes were more prevalent. K1 isolates had the highest detection rates for hypermucoviscosity Klebsiella pneumoniae (hmKP) and hypervirulent Klebsiella pneumoniae (hvKP), and carried the most virulence genes. K54 isolates had the lowest detection rate of hmKP while K5 isolates had the lowest detection rate of hvKP and carried the fewest virulence genes. MLST results for serotypes K1, K20, and K57 showed significant homogeneity, while those for serotypes K2, K5, and K54 showed diversity. The Galleria mellonella infection model showed that the K1 serotype was the most virulent and the K54 serotype was the weakest.Conclusion: CSKP isolates were detected more frequently than CRKP isolates for capsular serotype detection. K1 isolates had the most virulence gene and strongest virulence, K5 isolates carried the fewest virulence genes, and K54 isolates had the weakest virulence. Furthermore, significant homogeneity was observed among K1, K20, and K57 isolates.Keywords: Klebsiella pneumoniae, capsular serotypes, virulence, MLST

Qingchen Li,1– 3 Xinyi Liu,1,2 Jiasong Yang,1,2,4 Yumeng Dai,1,2 Wensheng Li1,2,4 1Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, Shanghai, 201103, People’s Republic of China; 2Shanghai Aier Eye Institute, Shanghai, 201103, People’s Republic of China; 3Department of Ophthalmology, the Second Xiangya Hospital of Central South University, Changsha, Hunan Province, 410011, People’s Republic of China; 4Aier School of Ophthalmology, Central South University, Changsha, Hunan Province, 410015, People’s Republic of ChinaCorrespondence: Wensheng Li, Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, No. 83 Wuzhong Road, Xuhui District, Shanghai, 201103, People’s Republic of China, Email drlws@qq.comPurpose: To compare Barrett TK Universal II and Barrett Universal II TCRP calculations in the power calculations for 3 presbyopia-correcting intraocular lenses (PC-IOL).Methods: This observational study involved 64 eyes from 64 patients who prepared to undergo extraction of crystalline lenses combined with PC-IOL (Symfony ZXR00, PanOptix TFNT00, or AT LISA tri 839MP) implantation. All eyes underwent ocular biometric measurements with IOLMaster 700 and Pentacam HR, and the interdevice agreement of measurements including total keratometry (TK, IOLMaster 700) and total corneal refractive power (TCRP, Pentacam HR) was evaluated. IOL power calculations were performed using TK-based Barrett TK Universal II and TCRP-based Barrett Universal II calculations, respectively.Results: Paired t-tests showed that the differences in white-to-white diameter, central corneal thickness, anterior chamber depth, and mean TK between IOLMaster 700 and Pentacam HR were slight but significant (all P< 0.05), and the differences in recommended IOL power for emmetropia between two Barrett calculations were also significant in 3 PC-IOLs (all P< 0.05). The ROC curve showed that the AUC was 0.917 (95% CI, 0.820– 0.971) for the absolute value of the difference between TK and TCRP in discriminating the difference of ≥ ± 0.5 D in predicted IOL power with best cutoff values of 0.4 D.Conclusion: The novel Barrett TK Universal II formula built in IOLMaster 700 is comparable to TCRP-based Barrett Universal II calculation for IOL power calculation of PC-IOLs, and the convenience of using the Barrett TK Universal II formula should be founded on measurement consistency between devices.Keywords: presbyopic corrections, intraocular lens power calculation, refractive prediction accuracy, swept-source optical biometer, scheimpflug tomography

Hanfang Zhou,1 Qingyin Li,1 Zhijun Liu,2 Keman Li,1 Xiaomin Geng,3 Xiaoyi Fang1 1Institute of Developmental Psychology, Beijing Normal University, Beijing, People’s Republic of China; 2School of Education, Hunan University of Science and Technology, Xiangtan, People’s Republic of China; 3State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, People’s Republic of ChinaCorrespondence: Xiaoyi Fang, Institute of Developmental Psychology, Beijing Normal University, No. 19 Xin Jie Kou Wai Street, Hai Dian District, Beijing, 100875, People’s Republic of China, Email fangxy@bnu.edu.cnBackground: The significant influence of family emotional expressiveness (FEE) on adolescents’ face-to-face social interactions is well-established. However, there has been limited investigation into potential links between FEE and adolescents’ online social behaviors, especially cyberbullying bystander behaviors, which are pivotal in cyberbullying incidents. This study aimed to assess the relative importance of different aspects of FEE (positive FEE vs. negative FEE vs. the Positive-to-Negative ratio) in predicting adolescents’ cyberbullying bystander behaviors, and the mediating roles of affective and cognitive empathy in these relationships.Methods: A sample of 1,952 adolescents (Mage = 14.18, SD = 1.33) completed questionnaires, including the Family Emotional Expressiveness Questionnaire, Basic Empathy Scale, and Cyberbullying Bystander Behavior Scale. SPSS 26.0 and Mplus 8.3 were used for analysis.Results: (1) Positive FEE exhibited a positive association with protective behavior and a negative association with indifferent behavior. Conversely, negative FEE showed positive associations with reinforcing and indifferent behaviors. However, the Positive-to-Negative ratio did not exhibit significant associations with any of the three bystander behaviors. (2) Negative FEE emerged as relatively more significant than both positive FEE and the Positive-to-Negative ratio in predicting reinforcing and indifferent behaviors. (3) Affective empathy mediated the relationship between positive FEE and reinforcing behavior, while cognitive empathy mediated the relationship between positive FEE and protective and indifferent behaviors. Moreover, cognitive empathy exerted a more influential role than affective empathy in this mediation process.Conclusion: Various aspects of FEE demonstrated distinct relationships with three cyberbullying bystander behaviors, with affective and cognitive empathy playing an important mediating role in the association. This finding holds substantial implications for the development of cyberbullying prevention strategies. Such strategies could target the reduction of negative emotional expression within adolescent families and the cultivation of both cognitive and affective empathy.Keywords: family emotional expressiveness, positive-to-negative ratio, empathy, cyberbullying bystander behaviors, adolescent

Qianqian Li,&ast; Ran Wang,&ast; Xingshun Qi Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingshun Qi, Department of Gastroenterology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang, Liaoning Province, 110840, People’s Republic of China, Tel +86-24-28897603, Fax +86-24-28851113, Email xingshunqi@126.comAbstract: Isolated splenic vein thrombosis (ISVT) is a very rare venous thromboembolism in the absence of pancreatic diseases, which can cause acute abdominal pain and chronic left-side portal hypertension. Herein, we reported a 40-year-old female patient who developed ISVT after taking oral contraceptives. Anticoagulation with oral rivaroxaban was the first-line choice of therapy in this case. Since then, abdominal pain alleviated, but she did not achieve vessel recanalization. Thus, a 7-day systemic thrombolysis with urokinase was given. Abdominal pain disappeared, but ISVT was not significantly improved. During follow-up period, long-term anticoagulation with oral rivaroxaban was given. Collectively, this case indicates the possibility of oral contraceptives as a risk factor of ISVT as well as anticoagulation combined with systemic thrombolysis as a choice of treatment for ISVT. Certainly, long-term follow-up is necessary in this case.Keywords: splenic vein thrombosis, oral contraceptives, anticoagulation, rivaroxaban, thrombolysis

Yuanyuan Su,1,* Ning Lu,2,* Pei Wang,3,* Qian Li,2 Hua Wen,2 Jie Zhang,2 Ling Fan,2 Jie Li,2 Zhaoxiang Yu,4 Manli Cui,2 Mingxin Zhang2 1Department of General Medicine, the People’s Hospital of Yubei District of Chongqing, Chongqing, People’s Republic of China; 2Department of Gastroenterology, the First Affiliated Hospital of Xi’an Medical College, Xi’an, Shaanxi, People’s Republic of China; 3Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 4Department of General Surgery, the First Affiliated Hospital of Xi’an Medical College, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Manli Cui, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, Email cuiml1587@163.com; Mingxin Zhang, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, Email zmx3115@xiyi.edu.cn.Objective: This study aims to explore the nexus between students’ psychological well-being and the manifestation of gastrointestinal symptoms (GISs) amid the health lockdown enforced in Xi’an, focusing on the student populace of Xi’an Medical College and Shaanxi University of Traditional Chinese Medicine.Materials and methods: A survey encompassing psychological parameters and GISs was administered to a randomized cohort of 1327 college students drawn from Xi’an Medical College and Shaanxi University of Traditional Chinese Medicine. The survey instrument was developed utilizing the Questionnaire Star platform. Subsequent to data collection, analysis was performed using GraphPad Prism 9 and SPSS 22.0.Results: Comparative analysis revealed statistically significant disparities (P < 0.05) in various GISs between the periods during and preceding the health lockdown, encompassing symptoms such as nausea/vomiting, acid reflux, postprandial fullness/early satiety, anorexia, decreased appetite, bloating, abdominal discomfort, abdominal pain, diarrhea, and constipation. Notably, the mean score for Generalized Anxiety Disorder 7 (GAD-7) was 3.31± 3.92, indicating mild anxiety, while the mean score for Patient Health Questionnaire-2 (PHQ-2) was 1.15± 1.28, suggesting mild depression. Detailed evaluation of anxiety revealed prevalence rates of 34% among respondents, with 34.2% of these individuals reporting concurrent GISs, while among those evaluated for depression (38.8% of the sample), 44.2% reported concurrent GISs. Furthermore, multiple linear regression analysis unveiled a negative correlation between GISs during the health lockdown and lifestyle scores, while positive correlations were observed with GISs preceding the lockdown, anxiety, and depression. The formulated multiple linear regression equation for GISs during the health lockdown is delineated as follows: 14.693– 0.342 life style + 0.725GISs before health lockdown + 0.218anxiety + 0.564 depression.Conclusion: This investigation underscores the substantial impact of anxiety and depression on the student body, accentuating their role in precipitating GISs during health lockdown situations. The psychological well-being of medical students during exigent circumstances such as natural disasters warrants heightened attention, necessitating proactive measures aimed at emotional regulation to mitigate the onset of GISs.Keywords: COVID-19, health lockdown, gastrointestinal symptoms, anxiety, depression

Lu Zhu,1,&ast; Jing Li,1,&ast; Zhao-Qin Wang,1,2,&ast; Yun-Jia Gu,1 Guo-Na Li,3 Wen-Jia Wang,1 Guang-Bin Pen,1 Qi Li,1 Meng-Die Wu,1 Hui-Rong Liu,1,2 Yan Huang,1,2 Lu-Yi Wu1 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3School of Acupuncture, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Yi Wu, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai City, 200437, People’s Republic of China, Email luyitcm@163.com Yan Huang, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, No. 650 Wanping South Road, Xuhui District, Shanghai City, 200030, People’s Republic of China, Email huangyan@shutcm.edu.cnObjective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC.Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores.Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P< 0.01), there were also statistical differences between the groups at the above time points (average P< 0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P< 0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group.Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.Keywords: hepatocellular carcinoma pain, transcutaneous electrical acupoint stimulation, cancer pain, randomized controlled trial

Haonan Guan,&ast; Guoyou Zhang,&ast; Qiqi Li, Jie Lian, Zhaoyang Dong, Lian Zhu, Kaiyan Xiao Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaiyan Xiao, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, People’s Republic of China, Tel +86 021 23271699, Fax +86 021 63136856, Email xky7026@163.comAbstract: Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.Keywords: soft-tissue tumors, lipoprotein, atorvastatin, foam cells, lipid-lowering therapy

Xiaoguang Xiao,1 Jianhai Sun,2 Dongsheng Zhang,3 Linjun Li,4 Haibo Zhou,5 Yongjun Li,6 Quan Li,7 Zhongshi He,8 Yang Fu,9 Qiwen Duan,10 Guping Zheng,11 Ze Tang,12 Qian Chu,1,&ast; Yuan Chen1,&ast; 1Department of Oncology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Oncology, Hubei Zhongshan Hospital, Wuhan, Hubei, People’s Republic of China; 3Department of Oncology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, People’s Republic of China; 4Department of Oncology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, People’s Republic of China; 5Department of Oncology, Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of China; 6Department of Oncology, Yichang Second People’s Hospital, Yichang, Hubei, People’s Republic of China; 7Department of Oncology, Xiangyang Central Hospital, Xiangyang, Hubei, People’s Republic of China; 8Department of Oncology, Xiangyang No 1 People’s Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei, People’s Republic of China; 9Department of Oncology, Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, Hubei, People’s Republic of China; 10Department of Oncology, Taihe Hospital, Shiyan, Hubei, People’s Republic of China; 11Department of Oncology, Xiaogan Central Hospital, Xiaogan, Hubei, People’s Republic of China; 12Department of Oncology, Huangshi Central Hospital, Huangshi, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Chu; Yuan Chen, Email qianchu@tjh.tjmu.edu.cn; chenyuantj2023@126.comBackground: Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain.Patients and Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST).Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5– 11.5] hours vs.16.0 [95% CI:11.5– 22.5] hours; p< 0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0– 3.5) than in the oxycontin group.(3.0; 2.5– 4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5– 3.0) vs 4.5;3.0– 6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32).Conclusion: Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p< 0.001), without significantly increasing adverse events (p=0.32).Keywords: cancer pain, opioid titration, oxycontin tablets, hydromorphone, patient-controlled subcutaneous analgesia

Xiuying Li,1 Xin Wang,1 Xiuwu Qu,1 Ningning Shi,1 Qinqing Li,1 Zhifang Yan,1 Yandong Li,2 Yingli Wang3 1Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of China; 2Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 3Shanxi Modern Traditional Chinese Medicine Engineering Laboratory, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of ChinaCorrespondence: Yandong Li; Yingli Wang, Email liyandongzhongnan@163.com; wyl@sxtcm.edu.cnPurpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients.Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed.Results: The developed micelles had a particle size of (89.62 ± 1.33) nm and a zeta potential of (− 4.9 ± 0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ± 6.98) μmol/L was significantly lower than that of free Que (141.10 ± 6.39) μmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats.Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.Keywords: matrix metalloproteinases, quercetin, macrophages, methotrexate, anti-inflammatory

Yufei Wang,1,&ast; Xiaoteng Ma,1,&ast; Zhiqiang Yang,1,2 Qiuxuan Li,1 Yujie Zhou,1,3 Fei Gao,1,3 Zhijian Wang1,3 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Ministry of Education, Beijing, People’s Republic of China; 2Cardio-Metabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3The Key Laboratory of Remodeling-Related Cardiovascular Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Wang; Fei Gao, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-related Cardiovascular Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Anzhen Avenue &num;2, Chaoyang District, Beijing, 100029, People’s Republic of China, Email zjwang1975@hotmail.com; fgaomd@163.comBackground and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability.Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318– 40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157– 2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646– 0.756] to 0.728 [95% CI: 0.677– 0.780]; DeLong’s test, P = 0.020).Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.Keywords: absolute eosinophil count, SYNTAX I score, SYNTAX II score, cardiovascular and cerebrovascular events, acute coronary syndrome, percutaneous coronary intervention

Qi Li,1,&ast; Cong Gao,1 Xinrui Zhao,1 Jiahui Li,1 Qinghong Shen,1 Li Chen2,&ast; 1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Li, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email 1589898345@qq.com Li Chen, Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Email cswtth@163.comObjective: The study was aimed to investigate the influence factor between preoperative inflammatory indicators and drainage tube retention time in patients with breast cancer.Methods: This retrospective study enrolled 121 patients with breast cancer who were undergoing surgery between October 2020 and June 2021. The enumeration data were used the Chi-square test, and the measurement data were used the t-test analysis. The univariate and multivariate logistic regression models were performed to access the risk factors for affecting drainage tube retention time in patients with breast cancer. The receiver operating characteristic curve (ROC) was performed to test the prediction effect of the model.Results: Through the median extraction time of postoperative drainage tube retention time, all patients were divided into two groups: drainage tube retention time (DTRT) < 13 (d) and drainage tube retention time (DTRT) ≥ 13 (d). The results showed that type of surgery, total lymph nodes (TLN), pathological T stage, NLR were related to the drainage tube retention time (P< 0.05). Moreover, the univariate and multivariate logistic regression analysis performed that Hb, type of surgery, pathological T stage, chest wall drainage tube, NRI were the independent risk predictors of affecting drainage tube retention time. Furthermore, a significant correlation existed between NRI and drainage tube retention at different times (P < 0.05).Conclusion: NRI is an independent risk factor for postoperative drainage tube extraction time and can effectively predict the probability of drainage tube retention time. Thus, it can also provide personalized nursing intervention for patients with breast cancer after drainage tube retention time and the rehabilitation process.Keywords: breast cancer, inflammatory indicator, drainage tube, operation, nutritional indicator

Yue Zhang,1,&ast; Qi Li,1,&ast; Jiang-Lin Xiang,2 Xing-Hua Li,1 Jing Li3 1Department of Radiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Infectious Disease, Chongqing University Three Gorges Hospital, Chongqing, 404000, People’s Republic of China; 3Medical Department, Liangjiang New Area Renhe Community Health Service Center, Chongqing, 401147, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Li, Medical Department, Liangjiang New Area Renhe Community Health Service center, Chongqing, 401147, People’s Republic of China, Tel +86 18716469389, Email lijing_345678@163.com Xing-Hua Li, Tel +86 18584603726, Email 595904844@qq.comPurpose: To investigate potential differences in clinical and computed tomography (CT) features between patients with the SARS‐CoV‐2 Omicron variant and the original strain.Patients and Methods: This retrospective study included 69 hospitalized patients infected with Omicron variant from November to December 2022, and 96 hospitalized patients infected with the original strain from February to March 2020 in Chongqing, China. The clinical features, CT manifestations, degrees of lung involvement in different stages on CT, and imaging changes after the reverse-transcription polymerase chain reaction (RT-PCR) results turned negative were compared between the two groups.Results: For clinical features, patients with Omicron were predominantly old people and females, without manifestation of any clinical symptoms, who had low serum levels of C-reactive protein and procalcitonin. Shorter interval from symptoms onset to initial CT scan was observed in Omicron patients compared to patients with the original strain (all P < 0.05). For CT features, patients with Omicron were more likely to present with round-like opacities and tree-in-bud pattern (all P < 0.05), but less likely to exhibit a diffuse distribution, patchy and linear opacities, as well as vascular enlargement pattern (all P < 0.05). The Omicron group was more susceptible to exhibiting lower CT involvement scores in each stage (all P < 0.05) and imaging progression after the RT-PCR results turned negative (P < 0.001).Conclusion: Patients infected with the Omicron variant exhibited less severe changes on chest CT compared to those infected with the original strain. Furthermore, imaging progression under low viral load conditions was more common in patients with Omicron than in those with the original strain.Keywords: severe acute respiratory syndrome coronavirus-2, pneumonia, computed tomography

Qingchen Li,1– 3,&ast; Xiaolin Xie,1,2,&ast; Jiasong Yang,1,2,4 Peng Gao,5 Wensheng Li1,2,4 1Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, Shanghai, 201103, People’s Republic of China; 2Shanghai Aier Eye Institute, Aier Eye Hospital Group Co. Ltd, Shanghai, 201103, People’s Republic of China; 3Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, 410011, People’s Republic of China; 4Aier School of Ophthalmology, Central South University, Changsha, Hunan Province, 410015, People’s Republic of China; 5Department of Ophthalmology, Shanghai Tenth People’s Hospital of Tongji University, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Li, Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, No. 83 Wuzhong Road, Xuhui District, Shanghai, 201103, People’s Republic of China, Email drlws@qq.comPurpose: To observe the outcome of bilateral femtosecond laser-assisted clear lens extraction with trifocal intraocular lens (IOL) implantation for presbyopia correction and evaluate its feasibility in early presbyopic adults.Methods: Prospective case series of eyes with clear crystalline lenses that underwent femtosecond laser-assisted lens extraction and trifocal IOL (Acrysof IQ PanOptix, Model TFNT00, Alcon) implantation between 2021 and 2023 were followed up for at least 3 months after surgery. Outcome measures included monocular uncorrected visual acuity at near (UNVA, 40 cm), intermediate (UIVA, 60 cm), and distance (UDVA, 5 m), monocular manifest refraction, corrected distance visual acuity (CDVA), defocus curve assessment, and spectacle independence at both near and distance.Results: A total of 60 eyes from 30 consecutive patients were included, and their mean age was 50.4± 6.5 years. After surgery, the mean UNVA (LogMAR) increased from 0.28± 0.16 to 0.08± 0.07, UIVA increased from 0.25± 0.12 to 0.09± 0.06, and UDVA increased from 0.27± 0.21 to 0.01± 0.08. The enhancements of UNVA, UIVA and UDVA were all significant (P < 0.05). The optometric results showed that the mean postoperative spherical equivalent (SE) was − 0.21± 0.24 D, and the mean postoperative CDVA (LogMAR) was − 0.00± 0.06. The preoperative spectacle independences at near and distance were 46.7% (14/30) and 56.7% (17/30), respectively, and both increased to 100% at 3 months after surgery.Conclusion: Satisfactory visual outcomes and safe surgical procedures were observed in this study, which demonstrate that bilateral femtosecond laser-assisted clear lens extraction with PanOptix IOL implantation could be a feasible approach for presbyopia correction in working-age Chinese patients.Keywords: presbyopia-correcting, clear lens extraction, refractive lens exchange, trifocal intraocular lens, refractive surgery