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Cheng Chen, Yong Zou, Xiangbing Zheng, Taotao Hu, Jie Ni, Daohong Kan, Zongyin Yin, Lingxiao Ye, Bing Liu Department of Burn and Plastic Surgery, The Second People’s Hospital of Yibin (West China Yibin Hospital, Sichuan University), Yibin, Sichuan, People’s Republic of ChinaCorrespondence: Bing Liu, Email 4444093330@qq.comObjective: To investigate the role of the TopBP1 interacting checkpoint and replication regulator (TICRR) in cutaneous melanoma (CM) as a prognostic biomarker and therapeutic target.Methods: TICRR expression in tumour samples was explored using the TCGA and the GTEx database. The Kaplan-Meier survival curve, nomogram model and risk score curve were established to evaluate the prognostic role of TICRR in CM. Tissue samples of CM patients were obtained to validate the TICRR expression further. Several experiments in vitro were conducted to investigate the effect of TICRR upon CM aggressiveness and to explore underlying mechanisms.Results: TICRR was overexpressed in CM tissue and was correlated with poor prognosis of CM patients. The knockdown of TICRR decreased the proliferation, migration, and invasion of CM cells, whereas overexpression produced the opposite effect. Furthermore, TICRR suppression substantially attenuated the activation of PI3K/AKT/mTOR signalling, while the PI3K/AKT inhibitor LY294002 could partially reverse the aggressiveness-enhancing effect induced by TICRR overexpression. It was further confirmed that TICRR was closely related to immune cell infiltration activities by using immune infiltration and immunofluorescence analysis.Conclusion: TICRR overexpression may enhance CM aggressiveness by activating the PI3K/Akt/mTOR pathway and promoting immune infiltration. TICRR was verified as a potential prognostic biomarker and therapeutic target for CM.Keywords: cutaneous melanoma, TICRR, immune infiltration, invasion, prognosis

Li Ye,1 Xiwei Sun,2 Yiping Li,1 Yali Zeng,1 Lacuo Zhuoma,1 Dinglun Zhou,2 Qinying He,3 Ju Wang,4 Wei Yang,1 Hang Yu,1 Yihui Yang,1 Shu Liang,1 Dan Yuan1 1Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan, People’s Republic of China; 2West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Center for AIDS/STD Control and Prevention, Chengdu Center for Disease Control and Prevention, Chengdu, Sichuan, People’s Republic of China; 4Center for AIDS/STD Control and Prevention, Liangshan Center for Disease Control and Prevention, Xichang, Sichuan, People’s Republic of ChinaCorrespondence: Dan Yuan; Shu Liang, Email ydtv1130@163.com; liangshu523@163.comBackground: Sichuan Province was severely affected by the HIV, and there was a scarcity of data regarding the survival time and influencing factors for People Living with HIV/AIDS (PLWH) in Sichuan Province who have received Antiretroviral Therapy (ART). Therefore, it is necessary to conduct a survival analysis for PLWH receiving ART.Methods: A retrospective cohort study was conducted on PLWH who had received ART≥ 6 months in Sichuan Province from January 1, 2003, to December 31, 2022. The Kaplan-Meier method was used to calculate median survival time and plot survival curves, while a Cox proportional hazards regression model was applied to analyze factors affecting survival time. Bilateral tests were performed, with P≤ 0.05 considered statistically significant.Results: The cumulative survival rates at 1, 3, 5, and 10 years for the 223,386 subjects were 94.54%, 89.07%, 84.82%, and 76.44%, respectively. Multivariate analysis using the Cox regression model indicated lower mortality risks for females (HR=0.59, 95% CI: 0.54– 0.65), homosexual transmission (HR=0.43, 95% CI: 0.33– 0.55), and baseline BMI≥ 24 (HR=0.81, 95% CI: 0.72– 0.90). Higher mortality risks were associated with age≥ 50 years at diagnosis (HR=3.21, 95% CI: 2.94– 3.50), being unmarried or divorced (HR=1.23, 95% CI: 1.11– 1.37), living separately (HR=1.32, 95% CI: 1.22– 1.43), baseline BMI < 18.5 (HR=1.27, 95% CI: 1.13– 1.41), presence of single-drug resistance (HR=1.25, 95% CI: 1.15– 1.36), baseline WHO stage IV (HR=1.27, 95% CI: 1.09– 1.47), and a diagnosis-to-treatment interval > 12 months (HR=1.27, 95% CI: 1.15– 1.41). Compared to those with CD4(+) T cell count of 200– 350cells/μL, 350– 500cells/μL, and > 500cells/μL at baseline, individuals with < 200cells/μL had higher mortality risks (HR=0.73, 95% CI: 0.67– 0.79; HR=0.57, 95% CI: 0.51– 0.64; and HR=0.58, 95% CI: 0.51– 0.66, respectively).Conclusion: The survival rate for PLWH receiving ART in Sichuan Province was relatively high. Male gender, age over 50 at diagnosis, being unmarried, divorced, or living separately, presence of single-drug resistance, low baseline BMI, baseline CD4+ T cell < 200cells/μL, baseline WHO stage IV, and a diagnosis-to-treatment interval > 12 months were risk factors for the survival of PLWH.Keywords: PLWH, antiretroviral therapy, survival analysis

Peng Zhou,1 Lingling Ye,2 Shixiao Li3 1Department of Pharmacy, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Science and Education, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China; 3Department of Clinical Microbiology Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Shixiao Li, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, No. 150, Ximen Street, Taizhou, Zhejiang Province, 317000, People’s Republic of China, Email lsx0992@126.comObjective: Klebsiella pneumoniae liver abscess (KPLA) is an invasive infectious disease with a considerable prevalence and complications. This study aimed to determine the predicted value of aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) for positive blood cultures and sepsis in patients with KPLA.Methods: We evaluated 248 consecutive participants diagnosed with KPLA. Demographic characteristics, clinical features, and laboratory test results of the participants were recorded. Multivariate logistic regression analysis was performed to identify the risk factors. Receiver operating characteristic (ROC) analyses were conducted to evaluate the discriminatory ability of APRI and FIB-4.Results: 30.2% (75 of 248) KPLA patients presented with positive blood cultures, and 70 (28.2%) developed sepsis. Among the positive blood culture and sepsis groups, the APRI and FIB-4 showed statistically significant increases. Multivariate analysis showed that APRI (odds ratio [OR] = 1.190, 95% confidence interval [CI] 1.051– 1.347, p = 0.006) and FIB-4 (OR = 1.110, 95% CI 1.046– 1.179, p = 0.001) were independent prognostic factors for positive blood cultures. Both APRI (OR = 1.505, 95% CI 1.149-1.988, p = 0.004) and FIB-4 (OR = 1.187, 95% CI 1.054-1.336, p = 0.005) were independent risk factors for sepsis. The area under the ROC curve (AUC) of APRI and FIB-4 for predicting positive blood cultures of KPLA was 0.783 and 0.766, respectively. APRI had an AUC of 0.801, with a sensitivity and specificity of 71.4% and 81.5%, respectively, for predicting sepsis in patients with KPLA, and the prediction performance of APRI was better than that of FIB-4 (AUC = 0.798).Conclusion: In our study, APRI and FIB-4 are effective methods for predicting KPLA patients with positive blood cultures and sepsis.Keywords: klebsiella pneumoniae liver abscess, positive blood culture, sepsis, aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index

Hong Yang,1 Maogang Chen,2 Ying Hu,1 Mengjiao Xu,1 Yiping Li,1 Lunhao Liu,1 Dan Yuan,1 Fengshun Yuan,1 Ling Li,1 Li Ye,1 Chang Zhou,1 Yan Zhang,1 Shu Liang,1 Ling Su1 1Department of AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of China; 2Department of Microbiology, Liangshan Yi Autonomous Prefecture Center for Disease Control and Prevention, Xichang, People’s Republic of ChinaCorrespondence: Shu Liang; Ling Su, Email liangshu523@163.com; sl7512@163.comBackground: Men who have sex with men (MSM) is one main type of high-risk activities facilitating HIV-1 transmission in Sichuan province. Previous works on HIV-1 incidence and prevalence among MSM only concentrated before 2018, the situation after that is unknown. In addition, the distribution of hot-spots related to current HIV-1 epidemic is also rarely known among MSM in Sichuan.Objective: To update trends of HIV-1 prevalence and incidence and to visualize hot-spots of ongoing transmission in Sichuan province during surveillance period among MSM between 2018 and 2022.Methods: Limiting Antigen Avidity assay was performed to detect recent infection within new HIV-1 diagnoses founded during surveillance period among MSM. The HIV-1 prevalence and incidence were calculated according to an extrapolation method proposed by publications and guidelines. Trend tests were performed using χ2 tests with linear-by-linear association. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spots of HIV-1 recent infections among MSM.Results: Between 2018 and 2022, 16,697 individuals participated in HIV-1 MSM sentinel surveillance program, of which 449 samples (98.25%) were tested with LAg-Avidity EIA, and 230 samples were classified as recent infection. Respectively, the overall prevalence and incidence were 2.74% and 3.69% (95% CI: 3.21, 4.16) and both had significant declining trends (p < 0.001). Luzhou city had a highest HIV-1 incidence (10.74%, 95% CI: 8.39, 13.10) over the study period and was recognized as a hot-spot for recent HIV-1 infection among MSM.Conclusion: During the surveillance period, both HIV-1 prevalence and incidence were declining. However, Luzhou city had an unusually high HIV-1 incidence and became an emerging hot-spot of recent HIV-1 infection among MSM. This finding suggested focused attention, cross-regional intervention strategies, and prevention programs are urgently required to curb the spread of ongoing transmission.Keywords: human immunodeficiency virus type 1, HIV-1 recent infection, incidence, hot-spots, men who have sex with men

Xi-Xin Fan,1,2,&ast; Lichao Ye,3,&ast; Ya-Hui Yang,1,2 Wen-Jian Huang,2,4 Chih-Yuan Ko2 1The School of Public Health, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Clinical Nutrition, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China; 3Department of Neurology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China; 4Huidong Center for Chronic Disease Control, Huizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chih-Yuan Ko, Department of Clinical Nutrition, The Second Affiliated Hospital of Fujian Medical University, No. 34, Zhongshanbei Road, Licheng District, Quanzhou, Fujian Province, 362000, People’s Republic of China, Tel +86 0595-26655200, Email yuanmomoko@gmail.comPurpose: Migraine is a complex neurovascular disorder with obesity as a notable risk factor. This study aimed to investigate an under-researched area of the association between migraine duration and body composition.Patients and Methods: Patients with migraine from a neurology outpatient department were enrolled and were categorized into four groups based on illness duration: 1 year, 1– 5 years, 5– 10 years, and > 10 years. Patient demographics, blood biochemistry, and body composition data were collected and analyzed statistically.Results: Patients with migraine were predominantly female, with lower education levels, significant work stress, poor sleep, and limited exercise. Longer migraine duration corresponded to increased obesity metrics. Notably, those patients with under 1 year of illness showed elevated blood lipid and liver function levels, whereas those with > 10 years showed increased weight, waist circumference, body mass index, and fat content, despite higher physical activity. Significant positive correlation between obesity metrics and migraine duration was seen in patients who had migraine for > 1 year.Conclusion: Our findings indicate that protracted episodes of migraine could amplify obesity tendencies, underscoring the imperative of weight regulation in migraine intervention to diminish ensuing adiposity-associated hazards.Keywords: migraine, illness duration, obesity, body composition

Xiaolu Li,1,&ast; Yizhong Wang,1,2,&ast; Rong Cao,1 Fangfei Xiao,1 Xufei Wang,1 Lin Ye,1 Yongmei Xiao,1 Dan Li,1 Ting Zhang1,2 1Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yizhong Wang; Ting Zhang, Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, 355 Luding Road, Shanghai, 200062, People’s Republic of China, Tel/Fax +86 2152976335, Email wangyz@shchildren.com.cn; zhangt@shchildren.com.cnBackground: Our previous study reported a high rate of recurrence in children with Clostridioides difficile (C. difficile) infection (CDI) after conventional antibiotic therapy. Here, we aimed to explore whether metronidazole and vancomycin resistant C. difficile isolates are circulating in pediatric CDI.Methods: Antimicrobial susceptibility testing (AST) using the agar dilution method according to the Clinical and Laboratory Standard Institute (CLSI) were performed on C. difficile isolates collected from children with CDI between 2019 and 2022 at the Shanghai Children’s Hospital. Whole-genome sequencing (WGS) was performed on all C. difficile isolates, and the presence of antibiotic resistance genes (ARGs) were identified using Resfinder and the Comprehensive Antibiotic Resistance Database (CARD). The presence of plasmid pCD-METRO was detected using SRST2 (v0.2.0) against 8 pCD-METRO coding sequences.Results: A total of 50 C. difficile isolates were collected from stools of CDI children. The overall resistance rate on all isolates was 30.00% for metronidazole, 6.00% for vancomycin, 0% for rifaximin, 2.00% for rifampin, 24.00% for meropenem, 100.00% for ceftriaxone and clindamycin, 86.00% for erythromycin, 30.0% for levofloxacin, and 50.0% for tetracycline. Multidrug-resistant (MDR) was presented in 44 isolates (88.00%). Sixteen reported potential ARGs relating with resistance to antibiotic classes of aminoglycoside (AAC(6’)-Ie-APH(2”)-Ia, aad(6), ANT(6)-Ib, APH(2”)-If, APH(3’)-IIIa), lincosamide-clindamycin-erythromycin (ErmB, ErmQ), fluoroquinolones (CdeA), glycopeptides (vanRG), nucleoside (SAT-4), tetracycline (tetM, tetA(P), tetB(P), tetO), and trimethoprim (dfrF) were identified. However, the pCD-METRO plasmid and vanA/B were not detected in any isolates.Conclusion: C. difficile isolates from children with reduced susceptibility to metronidazole and vancomycin are emerging in pediatric CDI in China. The lack of pCD-METRO plasmid and vanA/B associated with reduced antibiotic susceptibility suggests there are additional mechanisms of resistance.Keywords: Clostridioides difficile, antibiotic resistance, metronidazole, vancomycin, children

Yilan Hu,1,2 Jiaqi Bao,1,2 Zhicheng Gao,1,2 Lifang Ye,2 Lihong Wang1,2 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of ChinaCorrespondence: Lihong Wang, Heart Center, Department of Cardiovascular Medicine, Zhejiang, Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of China, Email wanglhnew@126.comAbstract: Obesity is becoming increasingly prevalent in China and worldwide and is closely related to the development of hypertension. The pathophysiology of obesity-associated hypertension is complex, including an overactive sympathetic nervous system (SNS), activation of the renin–angiotensin–aldosterone system (RAAS), insulin resistance, hyperleptinemia, renal dysfunction, inflammatory responses, and endothelial function, which complicates treatment. Sodium–glucose cotransporter protein 2 (SGLT-2) inhibitors, novel hypoglycemic agents, have been shown to reduce body weight and blood pressure and may serve as potential novel agents for the treatment of obesity-associated hypertension. This review discusses the beneficial mechanisms of SGLT-2 inhibitors for the treatment of obesity-associated hypertension. SGLT-2 inhibitors can inhibit SNS activity, reduce RAAS activation, ameliorate insulin resistance, reduce leptin secretion, improve renal function, and inhibit inflammatory responses. SGLT-2 inhibitors can, therefore, simultaneously target multiple mechanisms of obesity-associated hypertension and may serve as an effective treatment for obesity-associated hypertension.Keywords: sodium-glucose cotransporter protein 2 inhibitors, obesity-associated hypertension, metabolism, neuro-humoral regulation, inflammation

Zhicheng Gao,1,2,&ast; Jiaqi Bao,1,2,&ast; Liuyang Wu,2 Kaiyu Shen,1 Qiqi Yan,2 Lifang Ye,2 Lihong Wang2 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihong Wang, Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 85894275, Email wanglhnew@126.comPurpose: Lymphocyte to C-reactive protein ratio (LCR) is a recognized systemic inflammatory marker and novel prognostic indicator for several cancers. This study investigated the relationship between preoperative LCR and new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).Patients and Methods: Patients with AMI (n=662) with no history of atrial fibrillation (AF) were enrolled and classified into NOAF and non-NOAF groups based on the occurrence of postoperative NOAF during hospitalization. Logistic regression models were used to analyze NOAF risk factors and to assess the association between preoperative LCR and NOAF incidence. We constructed a new nomogram from the selected NOAF risk factors, and tested its predictive performance, degree of calibration, and clinical utility using receiver operating characteristic and calibration curves, decision curve analysis, and clinical impact curves.Results: Overall, 84 (12.7%) patients developed NOAF during hospitalization. The LCR was significantly lower in the NOAF group. Preoperative LCR accurately predicted NOAF after AMI and was correlated with increased NOAF risk. Age, body mass index, diabetes, serum albumin levels, uric acid levels, left atrium (LA) diameter, left ventricular ejection fraction, left circumflex artery stenosis > 50%, and Killip class II status were independent predictors of NOAF after AMI. In addition, a new nomogram combined with LCR was constructed to stratify the risk of NOAF in patients with AMI. The performance of the new nomogram was satisfactory, as shown by the receiver operating characteristic curve, calibration curve, decision curve analysis and clinical impact curve.Conclusion: Preoperative LCR was an independent predictor of NOAF in patients with AMI after PCI. The novel nomogram combined with LCR could rapidly and individually identify and treat patients at a high risk of NOAF.Keywords: C-reactive protein, acute myocardial infarction, atrial fibrillation, nomogram, left ventricular ejection fraction

Jinbao Huang,1,* Heng Weng,1,* Ling Ye,1 Meiqin Jiang,1 Yangyu Li,2 Hongyan Li3 1Department of Respiratory Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China; 2Department of Clinical Laboratory Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China; 3Department of Critical Care Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongyan Li, Department of Critical Care Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, No. 602 Middle 817 Road, Taijiang District, Fuzhou, 350004, People’s Republic of China, Email fjsrmyylhy@163.comBackground: To evaluate the clinical value of metagenomic next-generation sequencing (mNGS) in screening of lower respiratory tract infections (LRTIs) and human tumors.Methods: Human samples included bronchoalveolar lavage fluid (BALF), sputum, lung biopsy tissue, and peripheral blood from 188 patients who were admitted to our hospital between January 2020 and September 2022 were analyzed using mNGS for simultaneous pathogen and chromosome copy number variation (CNV) detection. Traditional microbial culture and comprehensive microbial test (CMT) were also conducted. The diagnostic efficiencies of the three methods (mNGS, traditional culture, and CMT groups) were compared.Results: Among the 188 patients, 149 (79.3%) were in the LRTIs group and 39 (20.7%) were in the non-LRTIs group. The diagnostic sensitivity and accuracy of the mNGS group were higher than those of the traditional culture and CMT groups (P < 0.001; P < 0.001; P < 0.001; P < 0.001), and the specificity was higher than that of the CMT group (P = 0.039) but lower than that of the traditional culture group (P = 0.006). The positive predictive values of the mNGS and traditional culture groups were higher than that of the CMT group (P = 0.004; P = 0.011). The negative predictive value of the mNGS group was higher than that of the CMT group (P = 0.003). In addition, all samples were subjected to simultaneous chromosome CNV detection, and 8% (15/188) were positive for CNV. Of the 15 patients, 10 were initially misdiagnosed as non-neoplastic diseases, with a misdiagnosis rate of 66.7% (10/15). The BALF CNV test was performed on 13 patients diagnosed with primary or metastatic lung cancer, with a positivity rate of 38.5%.Conclusion: The sensitivity and accuracy of pathogen diagnosis using mNGS were better than those of traditional culture and CMT. CNV detection is an important auxiliary diagnostic tool for cancer, particularly for screening occult tumors. Keywords: metagenomics, next-generation sequencing, respiratory infectious diseases, pathogen diagnosis, genomic instability

Xingchen Shang,1,2,&ast; Linfei Ye,1,&ast; Xiaohua Gu,3 Aihua Zhou,4 Yunmei Xu,5 Yiran Zhang,1 Yuexia Liao,1 Lin Li6 1School of Nursing, Yangzhou University, Yangzhou, People’s Republic of China; 2School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 3Delivery Room, Yangzhou Maternal and Child Care Service Centre, Yangzhou, People’s Republic of China; 4Delivery Room, Taizhou Second People’s Hospital, Taizhou, People’s Republic of China; 5Obstetrics and Gynecology Department, Baoying People’s Hospital, Yangzhou, People’s Republic of China; 6Department of Nursing, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Li, Department of Nursing, The Affiliated Hospital of Yangzhou University, No. 368, Hanjiang Middle Road, Yangzhou, 225000, People’s Republic of China, Tel +86 13585233313, Email 361350908@qq.comBackground: Most pregnant women do not reach the recommendation for physical activity (PA). As a subcategory of PA, exercise is also essential. Evidence on pregnant women’s attitudes and barriers to PA and exercise self-efficacy in China is scarce.Aim: To explore the levels and influencing factors of attitudes and barriers to PA and exercise self-efficacy among pregnant women.Methods: A cross-sectional study of 311 pregnant women was conducted from August to December 2022. Individual characteristics, pregnant women’s attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy were measured using the self-designed demographic questionnaire, pregnant women’s attitudes toward exercise questionnaire, barriers to prenatal PA and exercise questionnaire, and the pregnancy exercise self-efficacy scale, respectively.Results: More than 90% of pregnant women believed exercise benefits themselves and their babies, and 40.8% of pregnant women did not know how to exercise. Women encounter different types of barriers to PA and exercise. Intrapersonal barriers included the proportion of feelings of tiredness (56.6%), low energy (54.7%), lack of interest or motivation (49.2%), feelings of illness and morning sickness (46.6%), and large body weight (43.7%). Interpersonal barriers included pregnant women being advised to avoid PA and exercise (49.2%), lack of clear advice about the intensity and dose of exercise (41.8%), no one to exercise with (38.9%), and lack of advice from healthcare professionals (38.6%). Weather conditions were the most significant environmental barriers (41.2%). The total score of pregnancy exercise self-efficacy was (38.50± 7.33). Education level, parity, and attitudes toward exercise independently predict pregnant women’s attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy, respectively.Conclusion: Pregnant women have a favorable attitude toward exercise and relatively good exercise self-efficacy but lack knowledge of exercise. They face numerous barriers. Medical professionals should encourage pregnant women with lower levels of education to exercise and assist multipara in overcoming obstacles.Keywords: attitudes, barriers, exercise self-efficacy, physical activity, pregnancy

Wei Su,1,2 Dong Liu,2 Pingliang Yang,3 Ling Ye1 1Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Department of Pain Management, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610011, People’s Republic of China; 3Department of Anesthesiology, the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of ChinaCorrespondence: Ling Ye, Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423593, Email zerodq_hx@163.comPurpose: The aim of this study was to analysis of the opioid use of opioid native zoster-related pain (ZRP) patients to evaluate the impact of opioid use on pain control and quality of life improvement based on the clinical database.Patients and Methods: We conducted a retrospective cohort study to identify opioid native patients who were hospitalized in the pain department between May 1, 2020, and May 1, 2021. The primary outcomes were persistent opioid use after discharge, visual analogue scale (VAS) at the admission, VAS remission rate during hospitalization, VAS score and quality of life at follow-up. Then, we assessed patient-level risk factors for persistent opioid use after the discharge.Results: A total of 350 patients met the inclusion criteria. Of those patients, 255 (72.9%) were administered with opioid during hospitalization, and 95 (27.1%) patients were not. Opioid prescription during hospitalization was independently associated with increased odds of persistent use after the discharge (adjusted odds ratio, 20.74; 95% CI, 4.504– 95.474; P < 0.01). In the two groups, the VAS score at admission and the VAS score at follow-up were different. In the group with opioids during hospitalization, the persistent opioid use after discharge was more common (38% vs 2.1%) compared to patients without opioids, and VAS remission rate during hospitalization was less, restrictions on daily life, work or housework, and social activities were more common, and mood, diet and sleep were worse, respectively.Conclusion: Opioids prescription during hospitalization might increase the risk of chronic opioid use in opioid native ZRP patients, and it has limited benefits in pain control and quality of life improvement. Even though PHN was painful and intractable, the use of opioids should also be more cautious, and strict follow-up, management in this population.Keywords: opioids, persistent opioid use after discharge, real-life, zoster-related pain, postherpetic neuralgia

Bin Yang,1,&ast; Qingsong Lai,2,&ast; Aiqi Chen,2 Li Ye,1 Xiaohua Wang,1 Yulin Lai,2 Dan Liu,3 Mao-Qiang Man3 1Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou City, Guangdong, 510091, People’s Republic of China; 2Department of Dermatology, Medical Center for Public Health of Puning, Puning City, Guangdong, 515300, People’s Republic of China; 3Department of Product Development, Dermatology Hospital, Southern Medical University, Guangzhou City, Guangdong, 510091, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao-Qiang Man, Department of Dermatology, Dermatology Hospital, Southern Medical University, 2 Lujing Road, Guangzhou City, 510091, Guangdong, People’s Republic of China, Tel +86 20 8725 7353, Email mqman@hotmail.comBackground/Objective: Epidermal function is altered in a number of cutaneous and extracutaneous disorders. To determine whether epidermal function is also altered in children with obesity, we assessed the correlation between the body mass index (BMI) z score and epidermal function in children.Participants and Methods: Participants were enrolled from outpatient clinic, schools and kindergartens. Epidermal biophysical properties, including transepidermal water loss rate, stratum corneum hydration and skin surface pH, were measured on the flexor forearm and shin. Correlations between epidermal biophysical properties and BMI were analyzed. In addition, the association of epidermal biophysical properties with BMI z score was also determined.Results: Overall, BMI did not differ significantly between boys and girls among the age groups. BMI z scores correlated negatively with stratum corneum hydration levels and positively with skin surface pH in boys, but not in girls. The negative correlation between TEWL and BMI z score was not significant. Moreover, stratum corneum hydration levels were lower in boys with a BMI z score of ≥ 2 than in those with a BMI z score of − 2 to 0.99.Conclusion: Both stratum corneum hydration levels and skin surface pH are significantly correlated with BMI z scores in boys, but not in girls. Whether epidermal function influences BMI or vice versa remains to be determined.Keywords: transepidermal water loss, stratum corneum hydration, skin surface pH, body mass index, BMI z score

Dandan Wu,1,&ast; Junxiao Cong,1,&ast; Jiali Wei,1 Jing Hu,1 Wenhao Sun,1 Wei Ran,2 Chenghui Liao,1 Housheng Zheng,1 Liang Ye1 1Department of Immunology, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Ye, Department of Immunology, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-26631420, Fax +86-0755-86671943, Email liangyeszu@163.comBackground: The emergence of the coronavirus disease 2019 (COVID-19) pandemic and the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) requires the continuous development of safe, effective, and affordable prevention and therapeutics. Nanobodies have demonstrated antiviral activity against a variety of viruses, providing a new candidate for the prevention and treatment of SARS-CoV-2 and its variants.Methods: SARS-CoV-2 glycoprotein spike 1 subunit (S1) was selected as the target antigen for nanobody screening of a naïve phage display library. We obtained a nanobody, named Nb-H6, and then determined its affinity, inhibition, and stability by ELISA, Competitive ELISA, and Biolayer Interferometry (BLI). Infection assays of authentic and pseudotyped SARS-CoV-2 were performed to evaluate the neutralization of Nb-H6. The structure and mechanism of action were investigated by AlphaFold, docking, and residue mutation assays.Results: We isolated and characterized a nanobody, Nb-H6, which exhibits a broad affinity for S1 and the receptor binding domain (RBD) of SARS-CoV-2, or Alpha (B.1.1.7), Delta (B.1.617.2), Lambda (C.37), and Omicron (BA.2 and BA.5), and blocks receptor angiotensin-converting enzyme 2 (ACE2) binding. Moreover, Nb-H6 can retain its binding capability after pH or thermal treatment and effectively neutralize both pseudotyped and authentic SARS-CoV-2, as well as VOC Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.2 and BA.5) pseudoviruses. We also confirmed that Nb-H6 binds two distinct amino acid residues of the RBD, preventing SARS-CoV-2 from interacting with the host receptor.Conclusion: Our study highlights a novel nanobody, Nb-H6, that may be useful therapeutically in SARS-CoV-2 and VOC outbreaks and pandemics. These findings also provide a molecular foundation for further studies into how nanobodies neutralize SARS-CoV-2 and variants and imply potential therapeutic targets for the treatment of COVID-19.Keywords: COVID-19, antiviral medication, single-domain antibody, neutralizing antibody, bio-screening

Hong Yang, Yiping Li, Mengjiao Xu, Ying Hu, Fengshun Yuan, Lunhao Liu, Ling Li, Dan Yuan, Li Ye, Chang Zhou, Yan Zhang, Ling Su, Shu Liang Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of ChinaCorrespondence: Shu Liang; Ling Su, Email liangshu523@163.com; sl7512@163.comBackground: Sichuan Province has gradually become a hot-spot for HIV/AIDS. Little is known about the HIV-1 incidence and prevalence among four sub-groups since 2015. Meanwhile, the distributions of hot-spot areas related to recent infection cases that indicate current transmission among the four subgroups are also rare.Objective: The main purpose of this study was to assess the HIV-1 prevalence and incidence and to visualize the distributions of hot-spot areas of current transmission among four subgroups (people who inject drugs, male STD clinic attendees, female sex workers and men who had sex with men) during the surveillance period in Sichuan province between 2016 and 2022.Results: Of the 267,617 individuals, 2158 HIV-positive samples were tested with Lag-Avidity EIA, among which 493 samples were identified as recent infections. Among people who inject drugs (PWID), both HIV-1 prevalence (from 1.41% to 0.34%) and incidence (from 0.03% to 0.140%) showed a significant decreasing trend. Among men who had sex with men (MSM), female sex workers (FSWs), and male STD clinic attendees, HIV-1 prevalence indicated significant decreasing trends, whereas HIV-1 incidence showed no significant changes. Spatial analysis demonstrated the formation of hot-spots and clusters of current transmissions sharing regional differences, mainly concentrated in the southeast, and most of these were consecutive hot-spots.Conclusion: The prevention and control were efficacious and persistent. However, among the other three subgroups, there is a need for a regional cooperative in prevention and control approaches and collaborative research in many aspects.Keywords: human immunodeficiency virus, recent infection, hot spots, people who inject drugs, PWID, male STD clinic attendees, mSTD, female sex workers, FSWs

Yong Ling,1,&ast; Xuejiao Hu,1,&ast; Guansheng Zheng,1 Weitao Ye,2 Kaixuan Yuan,1 Long Ye,1 Weiye Huang,3 Benshun Tian,1 Bing Gu1 1Department of Clinical Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China; 2Department of Radiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Benshun Tian; Bing Gu, Department of Laboratory Medicine, Guangdong Provincial People’s Hospital, 106 Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong, 510000, People’s Republic of China, Email tbs20161017@163.com; gb20031129@163.comAbstract: Scrub typhus is a vector-borne infectious disease caused by Orientia tsutsugamushi. Accurate and timely diagnosis at the early infection stage could save the patients’ lives. Traditional technologies were limited to rapidly and successfully detecting Orientia tsutsugamushi due to poor specificity, especially in the condition of atypical symptoms. The technology of Metagenomic next-generation sequencing (mNGS) is amenable to finding the real pathogen because it holds potential as a diagnostic platform for unbiased pathogen identification and precision medicine. Herein, we reported two clinical case reports relative to the Orientia tsutsugamushi infection diagnosed by mNGS. We hope these two cases will improve clinical diagnosis.Keywords: scrub typhus, metagenomic next-generation sequencing, Orientia tsutsugamushi

Lu Gao, Lei Ye, Yiquan Zhang, Ke Zhang, Xianxiang Wang, Bao Chun Cheng, Hongwei Cheng Department of Neurosurgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Hongwei Cheng; Bao Chun Cheng, Department of Neurosurgery, First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui Province, 230022, People’s Republic of China, Email hongwei.cheng@ahmu.edu.cn; ayfycheng@qq.comObjective: This study aimed to explore the related risk factors in patients who underwent hemilaminectomy for lumbar spinal schwannoma resection and who experienced deterioration of postoperative lower back pain in comparison to preoperative pain levels.Methods: This retrospective study recruited 61 patients from the First Affiliated Hospital of An Hui Medical University between January 2018 and June 2019. All data were collected from clinical records and analyzed at 1-month and at 1-year follow-up. The visual analog scale (VAS) was used to evaluate pain, and neurologic function was assessed using the Modified McCormick Scale. Intraoperative neurophysiological monitoring was used to assess neuronal integrity and mitigate injury. Statistical analysis of the data was performed using the SPSS version 19 software.Results: Preoperative pain improved dramatically in the 1-year follow-up (VAS: preoperative, 3.84± 2.19; 1-year follow-up, 2.13± 2.26; P< 0.001). The pain-improved group and worsened group showed a significant difference at 1-month (VAS: 1.76± 1.56; 5.54± 1.26; P< 0.05) and at 1-year (VAS: 0.83± 1.09; 4.80± 1.58; P< 0.05) follow-up. The pain-improved and worsened groups had a significant difference in tumor size and hemilaminectomy removal segments at 1-month and 1-year follow-up, but A-train occurrence on electromyography could only be seen as a statistical difference in the 1-month follow-up. Logistic regression analysis revealed that tumor size was an independent risk factor for postoperative lower back pain deterioration.Conclusion: The hemilaminectomy approach is a safe and effective method that can dramatically relieve pain in spinal lumbar schwannoma resection. Tumor size is an independent risk factor for postoperative lower back pain. A-train on spontaneous electromyography has been shown to be a reliable predictive factor for the evaluation of postoperative lower back pain. However, further detailed analysis of A-train characteristics can provide a more accurate warning during surgery.Keywords: lumbar spinal schwannoma, lower back pain, hemilaminectomy, electromyography, intraoperative monitoring

Chengyu Yang,1,2,&ast; Li Yang,3,4,&ast; Lei Yang,5 Shuiming Li,5 Ling Ye,1,6 Jinfeng Ye,5 Chengshui Chen,3,4,7 Yiming Zeng,8 Mengchan Zhu,1 Xiaoping Lin,8 Qing Peng,9 Yun Wang,5,10 Meiling Jin1,6 1Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, People’s Republic of China; 4Key Laboratory of Interventional Pulmonology of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, People’s Republic of China; 5Longhua Innovation Institute for Biotechnology, Shenzhen University, Shenzhen, Guangdong, 518055, People’s Republic of China; 6Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Zhejiang, 324000, People’s Republic of China; 8Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian, 362000, People’s Republic of China; 9Department of Pulmonary and Critical Care Medicine, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China; 10Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meiling Jin, Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China, Email jin.meiling@zs-hospital.sh.cn Yun Wang, Longhua Innovation Institute for Biotechnology, Shenzhen University, Shenzhen, Guangdong, 518055, People’s Republic of China, Email yunw@szu.edu.cnBackground: Frequent exacerbation (FE) and infrequent exacerbation (IE) are two phenotypes of chronic obstructive pulmonary disease (COPD), of which FE is associated with a higher incidence of exacerbation and a serious threat to human health. Because the pathogenesis mechanisms of FE are unclear, this study aims to identify FE-related proteins in the plasma via proteomics for use as predictive, diagnostic, and therapeutic biomarkers of COPD.Methods: A cross-sectional study was conducted in which plasma protein profiles were analyzed in COPD patients at stable stage, and differentially expressed proteins (DEPs) were screened out between the FE and IE patients. FE-related DEPs were identified using data-independent acquisition-based proteomics and bioinformatics analyses. In addition, FE-related candidates were verified by enzyme-linked immunosorbent assay.Results: In this study, 47 DEPs were screened out between the FE and IE groups, including 20 upregulated and 27 downregulated proteins. Key biological functions (eg, neutrophil degranulation, extracellular exosome, protein homodimerization activity) and signaling pathways (eg, arginine and proline metabolism) were enriched in association with the FE phenotype. Receiver operating characteristic (ROC) analysis of the 11 combined DEPs revealed an area under the curve of 0.985 (p < 0.05) for discriminating FE from IE. Moreover, correlation and ROC curve analyses indicated that creatine kinase, M-type (CKM) and fat storage-inducing transmembrane protein 1 (FITM1) might be clinically significant in patients with the FE phenotype. In addition, plasma expression levels of CKM and FITM1 were validated to be significantly decreased in the FE group compared with the IE group (CKM: p < 0.01; FITM1: p < 0.05).Conclusion: In this study, novel insights into COPD pathogenesis were provided by investigating and comparing plasma protein profiles between the FE and IE patients. CKM, FITM1, and a combinative biomarker panel may serve as useful tools for assisting in the precision diagnosis and effective treatment of the FE phenotype of COPD.Keywords: chronic obstructive pulmonary disease, frequent exacerbation, data-independent acquisition, proteomics, bioinformatics analysis

Juan Li,1 Yuanyuan Zhai,1 Bowen Xiao,2 Xiaoying Xia,3 Jingyao Wang,1 Yanan Zhao,1 Li Ye,1 Yan Li1 1Shanghai Institute of Early Childhood Education, Shanghai Normal University, Shanghai, People’s Republic of China; 2Psychology Department, Carleton University, Ottawa, Ontario, Canada; 3School of Early Childhood Education, Shanghai Normal University Tianhua College, Shanghai, People’s Republic of ChinaCorrespondence: Yan Li, Shanghai Institute of Early Childhood Education, Shanghai Normal University, 100 Guilin Road, Xuhui District, Shanghai, People’s Republic of China, Email liyan@shnu.edu.cnIntroduction: Maternal distress increased during the COVID-19 pandemic, significantly impacting children’s media use. The purpose of this study was to explore the influence mechanism of maternal COVID-19 distress on preschoolers’ problematic media us through a moderated mediation model; specifically, we examined the possible mediating roles of parenting stress and negative instrumental use of media in parenting and the moderating role of supportive co-parenting.Methods: An online survey was conducted in a sample of 1357 children (Mage = 4.01, SD = 1.06; 47.4% boys) and their parents from six public kindergartens in Shanghai, China. The mothers provided information by completing measures on their levels of distress related to COVID-19, parenting stress levels, digital parenting practices, and perception of supportive co-parenting from their partners. Additionally, both parents rated their children’s problematic media use.Results: (1) maternal COVID-19 distress was significantly and positively related to children’s problematic media use; (2) this relationship was sequentially mediated by parenting stress and parents’ negative instrumental use of media in parenting; and (3) supportive co-parenting moderated the serial mediation path by reducing the effect of maternal COVID-19 distress on parenting stress.Conclusion: The findings provide some support and guidance for preventing children’s problematic media use and enhancing parental adaptation during the COVID-19 pandemic or in potentially adverse situations.Keywords: maternal COVID-19 distress, children’s problematic media use, parenting stress, negative instrumental use of media in parenting, supportive co-parenting

Ruoyang Lin,1 Renpin Chen,1 Lechi Ye,2 Zhiming Huang,1 Xianfan Lin,1 Tanzhou Chen1 1Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, People’s Republic of China; 2Department of Colorectal and Anal Surgery, the First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Tanzhou Chen, Tel +8613706661269, Email cctzz@163.comBackground: Researches showed RNA methylation genes can affect the prognosis of tumors. Thus, the study aimed to comprehensively analyze the effects of RNA methylation regulatory genes in prognosis and treatment of colorectal cancer (CRC).Methods: Prognostic signature associated with CRCs were constructed by differential expression analysis, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Receiver operating characteristic (ROC) and Kaplan–Meier survival analyses were used to validate the reliability of the developed model. Gene Ontology (GO), Gene set variation analysis (GSVA), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation. Finally, normal and cancerous tissue were collected to validate gene by quantitative real-time PCR (qRT-PCR).Results: A prognostic risk model based on leucine rich pentatricopeptide repeat containing (LRPPRC) and ubiquitin-like with PHD and ring finger domains 2 (UHRF2) was constructed and relevant to the overall survival (OS) of CRC. Functional enrichment analysis revealed that collagen fibrous tissue, ion channel complex and other pathways were significantly enriched, which might help explain the underlying molecular mechanisms. There were significant differences in ImmuneScore, StromalScore, ESTIMATEScore between high- and low-risk groups (p < 0.05). Ultimately, qRT-PCR validation showed that a significant upregulation in the expression of LRPPRC and UHRF2 in cancerous tissue, which verified the effectiveness of our signature.Conclusion: In conclusion, 2 prognostic genes (LRPPRC and UHRF2) related to RNA methylation were identified by bioinformatics analysis, which might supply a new insight into the treatment and evaluation of CRC.Keywords: colorectal cancer, prognosis, RNA methylation regulatory genes, tumor microenvironment, immunotherapy

Wusheng Deng,1,&ast; Yun Jiang,2,&ast; Jiaoxia Qin,1,&ast; Gang Chen,3,&ast; Yongjie Lv,1 Yanmei Lei,1 Jing Luo,1 Kangkang Hong,1 Bing Huang,1 Luhai Qin,4 Xiujia Tang,1 Liumei Ye,1 Yuhai Dang,1 Chao Wang,1 Feiyang Long,1 Ke Wang,1 Jinliang Kong1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Pulmonology, Hechi Traditional Chinese Medicine Hospital, Hechi, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinliang Kong; Ke Wang, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Email kjl071@163.com; keewang@hotmail.comBackground: Aspergillus fumigatus is an opportunistic fungal pathogen, which is commonly found in lungs and rarely causes infections in mediastinum. Mediastinal Aspergillus abscess is a serious infectious condition, and is characterized by difficult diagnosis due to its clinical manifestations being nonspecific.Case Presentation: Here, we report a case of a mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. The patient was a 45-year-old woman who presented with a 20-day history of sore throat without any underlying diseases. Chest computed tomography (CT) showed a mass in the anterior superior mediastinum. Metagenomic next-generation sequencing (mNGS) identified Aspergillus fumigatus sequences in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) tissue, indicating the mediastinal Aspergillus fumigatus infection of this patient. The following mediastinal biopsy histological analysis and tissue fungi culture also suggested Aspergillus fumigatus infection, confirming the mNGS detection. The patient was diagnosed with mediastinal aspergillosis caused by Aspergillus fumigatus. After timely voriconazole treatment, the patient was discharged with good condition.Conclusion: Our study presented a rare case with mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. As a new clinical diagnostic method, mNGS could assist timely diagnosis and precise treatment of Aspergillus infection.Keywords: mediastinal abscess, Aspergillus fumigatus, metagenomic next-generation sequencing, diagnosis, case report

Xingchen Shang,1,2 Linfei Ye,1 Lin Li3 1School of Nursing, Yangzhou University, Yangzhou, People’s Republic of China; 2School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 3Department of Nursing, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of ChinaCorrespondence: Xingchen Shang, Email 007210@yzu.edu.cn

Hong Yang, Yiping Li, Fang He, Fengshun Yuan, Lunhao Liu, Ling Li, Dan Yuan, Li Ye, Chang Zhou, Yan Zhang, Ling Su, Shu Liang Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of ChinaCorrespondence: Shu Liang; Ling Su, Email liangshu523@163.com; sl7512@163.comBackground: Sichuan Province is severely affected by the HIV epidemic in China. Little is known about the characteristics of recent infections among new HIV diagnoses, which is critical to prevention strategies, evaluation of the HIV epidemic and health resource allocation. Meanwhile, individuals at primary stages of infection are related to the hot-spot areas of ongoing transmission in new HIV diagnoses, which is also rarely known.Objective: This article aimed to report the proportion of recent infections among new HIV diagnoses, and to reveal demographic characteristics associated with HIV recent infections, and finally, to indicate the hot-spot areas of ongoing transmission in Sichuan province between 2018 and 2020.Methods: Limiting Antigen (LAg)-Avidity assay was performed to detect recent infection within new HIV diagnoses reported in odd months between 2018 and 2020. Results were reclassified according to the data on CD4 cell count, antiretroviral treatment and the existence of an AIDS-defining illness. Logistic regression was used to determine characteristics associated with HIV recent infections. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spot areas of HIV recent infections.Results: 42,089 newly diagnosed HIV-1 cases were tested using the LAg-Avidity EIA. In total, 5848 (13.89%) of those were classified as HIV recent infections. Female, age between 18– 25 years and men who had sex with men were related to higher proportion of HIV recent infections. Logistic regression revealed that MSM aged between 18– 25 years were more likely to be classified as recent infection. Spatial analysis demonstrated significant clustering in Chengdu, Yibin, Luzhou city between 2018 and 2020. Hot spots were mainly clustered in the center of Sichuan in 2018, but gradually spread to southwest and northwest between 2019 and 2020.Conclusion: Enhanced preventive measures among relevant risk groups and areas where the potential HIV-1 transmission is ongoing is urgently needed to curb further spread.Keywords: human immunodeficiency virus, HIV, HIV recent infection, Sichuan, hot spots

Liuyang Wu,1,2 Wei Wang,2 Yang Gui,2 Qiqi Yan,1,2 Guangxin Peng,2 Xin Zhang,2 Lifang Ye,2 Lihong Wang2 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of ChinaCorrespondence: Lihong Wang, Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, Zhejiang Province, 310014, People’s Republic of China, Tel +86 136-6669-0589, Email wanglhnew@126.com; wlhhz2013@126.comPurpose: Our study aimed to identify new-onset atrial fibrillation (NOAF) risk factors in acute myocardial infarction (AMI) patients after treatment with percutaneous coronary intervention (PCI) and investigate whether their nutritional status can be a predicting factor of NOAF.Patients and Methods: We analyzed 662 AMI patients after PCI for NOAF occurrence during follow-up hospitalization and divided them into an NOAF and non-NOAF group. The patients’ nutritional status was assessed using the controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI). The Kaplan‒Meier analysis was used to assess NOAF-free survival in varying degrees of malnutrition. Cox proportional hazards models were used to identify the risk factors for NOAF.Results: Eighty-four (12.7%) patients developed NOAF during hospitalization. There was a statistically significant difference in the occurrence of NOAF among different categories of nutritional status. The CONUT score and GNRI classifications were independent predictors of NOAF. NOAF occurrence was associated with older age, higher uric acid levels, higher N-terminal pro-B-type natriuretic peptide levels, greater left atrial size, and worse Killip class upon admission.Conclusion: The nutritional status can affect NOAF occurrence in AMI patients after PCI. The CONUT score and GNRI are ideal tools for evaluating the nutritional status of AMI patients, with an excellent predictive effect on NOAF.Keywords: atrial fibrillation, acute myocardial infarction, malnutrition, controlling nutritional status, geriatric nutritional risk index

Haibo Li,1,2,&ast; Yuan Fang,1,2,&ast; Xu Li,2,&ast; Jingting Chen,1 Yao Xiong,1 Yongzhou Shi,3 Shengli Li,1 Lincai Ye,4 Shoubao Wang,1,&ast; Jianda Zhou2,&ast; 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Neurosurgery, Neihuang Chinese Medicine Hospital, Anyang, People’s Republic of China; 4Department of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shoubao Wang; Jianda Zhou, Email wxldragon198418@163.com; zhoujianda@csu.edu.comAim: The development of microsurgery has greatly advanced vascularized composite allotransplantation (VCA). However, like organ transplantation, VCA is also limited by acute rejection, and concerns regarding long-term survival and function of the transplanted graft. Therefore, it is necessary to elucidate the molecular mechanisms underlying acute rejection caused by VCA, in order to improve patient survival.Methods: Firstly, we used Brown Norway rats and Lewis rats to construct animal model of VCA. Regularly record the appearance changes of all subjects. Specimens were collected for histological examination, microRNAs (miRNAs) sequencing and RT-qPCR verification when acute immune rejection occurred. Then, bioinformatics analysis was employed to predict miRNA related molecules and pathway information. Finally, differentially expressed miRNAs were tested and verified.Results: MiRNAs are small non coding RNA transcripts that regulate gene expression at the post-transcriptional level. Studies have shown that miRNAs are involved in immune regulation and several miRNAs have been identified that are potential diagnostic and prognostic biomarkers of acute rejection. In this study, we found that the expression levels of rno-miR-21-5p, rno-miR-340-5p, rno-miR-1-3p and rno-miR-195-5p are significantly associated with acute rejection following VCA.Conclusion: This miRNA signature can potentially an auxiliary diagnostic indicator of rejection, which can help clinicians adjust the immunosuppressive program in time during acute rejection.Keywords: vascularized composite tissue allograft1, VCA2, miRNAs4, acute rejection5

Paula Sagmeister,1,&ast; Jimmy Daza,2,&ast; Andrea Ofner,1 Andreas Ziesch,1 Liangtao Ye,1,3,4 Najib Ben Khaled,1,3 Matthias Ebert,2,5 Julia Mayerle,1 Andreas Teufel,2,5 Enrico N De Toni,1,3 Stefan Munker1,3 1Department of Medicine II, LMU Munich, Munich, Bavaria, Germany; 2Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden Wurttenberg, Germany; 3Liver Center Munich, LMU Munich, Munich, Bavaria, Germany; 4Center of Digestive Disease, Sun Yat-Sen University, Shenzhen, Guangdong, People’s Republic of China; 5Center for Preventive Medicine and Digital Health Baden-Württenberg (CPDBW), Heidelberg University, Mannheim, Baden Wurttenberg, Germany&ast;These authors contributed equally to this workCorrespondence: Paula Sagmeister, Email sagmeister.paula@hotmail.comIntroduction: Although the treatment paradigm for hepatocellular carcinoma (HCC) has recently shifted in favour of checkpoint inhibitor (CPI)-based treatment options, the tyrosine kinase inhibitors (TKI) currently approved for the treatment of HCC are expected to remain the cornerstone of HCC treatment alone or in combination with CPIs. Despite considerable research efforts, no biomarker capable of predicting the response to specific TKIs has been validated. Thus, personalized approaches to HCC may aid in determining optimal treatment lines for 2nd and 3rd lines. To identify new biomarkers, we examined differential sensitivity and investigated potential transcriptomic predictors.Methods: To this aim, the sensitivity of nine HCC cell lines to sorafenib, lenvatinib, regorafenib, and cabozantinib was evaluated by a prolonged treatment scheme to determine their respective growth rate inhibition concentrations (GR50). Subgroups discriminated by GR50 values underwent differential expression and gene set enrichment analysis (GSEA).Results: The nine cell lines showed broadly different sensitivities to different TKIs. GR50 values of sorafenib and regorafenib clustered closer in all cell lines, whereas treatments with lenvatinib and cabozantinib showed diversified GR50 values. GSEA showed the activation of specific pathways in sensitive vs non-sensitive cell lines. A signature consisting of 14 biomarkers (GAGE12H, GJB6, PTCHD3, PRH1-PRR4, C6orf222, HBB, C17orf99, GOLGA6A, CRYAA, CCL23, RP11-347C12.3, RP11-514O12.4, FAM180B, and TMPRSS4) discriminates the cell lines’ response into three distinct treatment profiles: 1) equally sensible to sorafenib, regorafenib and cabozantinib, 2) sensible to lenvatinib, and 3) more sensible to regorafenib than sorafenib.Conclusion: We observed diverse responses to either of the four TKIs. Subgroup analysis of TKI effectiveness showed distinct transcriptomic profiles and signaling pathways associated with responsiveness. This prompts more extensive studies to explore and validate pharmacogenomic and transcriptomic strategies for a personalized treatment approach, particularly after the failure of CPI treatment.Keywords: biomarkers, sorafenib, lenvatinib, regorafenib, cabozantinib

Fengjin Shao,1– 3 Rui Liu,1 Xun Tan,1– 4 Qiaoyan Zhang,1– 3 Lujie Ye,1– 3 Bingxuan Yan,1– 3 Ying Zhuang,1,2,4 Jiaxue Xu1,2,4 1Department of Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Veterinary Medical Center, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 3Institute of Preventive Veterinary Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 4Hainan Institute of Zhejiang University, Sanya, Hainan Province, People’s Republic of ChinaCorrespondence: Xun Tan, Department of Veterinary Medicine, Zhejiang University, Yuhangtang Road 866, Hangzhou, 310058, People’s Republic of China, Tel +86 571 8898 2393, Fax +86 571 8898 2310, Email tanxun@zju.edu.cnPurpose: Pulmonary arterial hypertension (PAH) is a progressive and fatal pulmonary vascular disease initiated by endothelial dysfunction. Mesenchymal stromal cells (MSCs) have been shown to ameliorate PAH in various rodent models; however, these models do not recapitulate all the histopathological alterations observed in human PAH. Broiler chickens (Gallus gallus) can develop PAH spontaneously with neointimal and plexogenic arteriopathy strikingly similar to that in human patients. Herein, we examined the protective effects of MSC transplantation on the development of PAH in this avian model.Methods: Mixed-sex broilers at 15 d of age were received 2× 106 MSCs or PBS intravenously. One day later, birds were exposed to cool temperature with excessive salt in their drinking water to induce PAH. Cumulative morbidity from PAH and right-to-left ventricle ratio were recorded. Lung histologic features were evaluated for the presence of endothelial damage, endothelial proliferation and plexiform lesions. Expression of proinflammatory mediators and angiogenic factors in the lung was detected. Matrigel tube formation assay was performed to determine the angiogenic potential of endogenous MSCs.Results: MSC administration reduced cumulative PAH morbidity and attenuated endothelial damage, plexiform lesions and production of inflammatory mediators in the lungs. No significant difference in the expression of paracrine angiogenic factors including VEGF-A and TGF-β was determined between groups, suggesting that they are not essential for the beneficial effect of MSC transplantation. Interestingly, the endogenous MSCs from birds receiving MSC transplantation demonstrated endothelial differentiatial capacity in vitro whereas those from the mock birds did not.Conclusion: Our results support the therapeutic use of MSC transplantation for PAH treatment and suggest that exogenous MSCs produce beneficial effects through modulating inflammation and endogenous MSC-mediated vascular repair.Graphical Abstract: Keywords: plexiform lesion, right ventricular hypertrophy, VEGF-A, TGF-β, angiogenesis, bone marrow

Wu X, Xu Q, Chen P, et al. Cancer Manag Res. 2019;11:8125–8133. We, the Editor and Publisher of Cancer Management and Therapy are retracting the published article. Concerns were raised following the authors request to correct images in Figure 5. It was found some of the images had been duplicated. Specifically, Images from Figure 5A, shRNA-SMYD3-3, and 5B, Control, shRNA-NC and shRNA-SMYD3-3 have regions of overlap and duplication. When approached for an explanation, the authors were cooperative but were unable to adequately address the concerns raised and could not provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors listed in this publication have been informed and agree with this decision. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Gangqiang Guo,1,&ast; Huijing Wang,2,&ast; Xinya Tong,1,&ast; Lele Ye,1 Xinyu Shi,1 Su Fang,1 Ya Hu,3 Fei Han,2 Chaosheng Chen,3 Ning Ding,1 Bofeng Su,3 Xiangyang Xue,1 Huidi Zhang3 1Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research & Precision Medicine, Wenzhou Key Laboratory of Cancer-Related Pathogens & Immunity, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 2Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 3Department of Nephrology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bofeng Su; Huidi ZhangDepartment of Nephrology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Email 24449681@qq.com; hd_zhang@163.comObjective: Enhancer RNAs (eRNAs), a class of non-coding RNAs, play indispensable roles in regulating target gene transcription and maintaining cell identity in cooperation with promoters. In this study, we investigated the transcriptional landscape and potential functions of eRNAs in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).Methods: PBMCs from five patients with stable SLE, five patients with active SLE, and ten healthy individuals (HCs) were subjected to RNA-sequencing. Putative regulators, differential expression, and pathways were analyzed. eRNAs that were significantly upregulated were first validated by RT-qPCR in 12 samples. Then, candidate eRNAs were confirmed in a validation cohort of 45 samples. We conducted comprehensive pathway analyses to explore the correlations between the candidate eRNAs and SLE pathology.Results: By analyzing eRNA transcript data from PBMCs from SLE patients and HCs, we identified various eRNAs and functional super-enhancers potentially related with SLE. The SLE-specificity of eRNAs seemed to be largely driven by SLE-specific transcription factors (TFs). A Venn diagram of eRNAs differentially expressed in stable, active, and total SLE vs HCs revealed that 13 and 23 eRNAs were commonly upregulated and downregulated, respectively, in patients with stable SLE and those with active SLE. The commonly upregulated eRNAs participate in regulating SLE-related pathways. Only eRNA TCONS_00034326 was significantly (P < 0.05) upregulated in PBMCs of patients with SLE when compared with those of HCs as indicated by RT-qPCR. The area under the receiver-operating curve of TCONS_00034326 for distinguishing SLE patients from HCs was 0.691. Through its putative SLE-related master TF, TCONS_00034326 is involved in multiple SLE-relevant signaling pathways, especially tumor necrosis factor signaling.Conclusion: This study unraveled the transcriptional landscape of eRNAs, eRNA-related TFs, and super-enhancers in PBMCs from SLE patients and HCs. We identified a panel of SLE-relevant eRNAs, providing potential targets in SLE pathogenesis.Keywords: enhancer RNA, eRNA, systemic lupus erythematosus, SLE, PBMCs, transcription factors, TFs, super-enhancer

Zeying Feng,1,2,&ast; Yaxin Liu,1,2,&ast; Yun Kuang,2 Shuang Yang,2 Jinlei Li,2 Ling Ye,2 Jie Huang,2 Qi Pei,3 Yuanyuan Huang,1,4 Guoping Yang1– 3 1XiangYa School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 3Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Clinical Research and Develpment Division II, Jiangsu Hengrui Medicine Co., Ltd., Shanghai, 201200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan HuangClinical Research and Develpment Division II, Jiangsu Hengrui Medicine Co., Ltd., 1288 Haike Road, Pudong District, Shanghai, 201200, People’s Republic of ChinaEmail yuanyuan.huang@hengrui.comGuoping YangThe Third Xiangya Hospital, Central South University, Yinpenling Street, Yuelu District, Changsha, Hunan, 410013, People’s Republic of ChinaTel +86 731-89918665Fax +86 731-88618326Email ygp9880@126.comPurpose: Abiraterone acetate tablets (I)(N-AbA) is a novel tablet co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). This study aimed to compare the pharmacokinetics, bioequivalence, safety, and food effects of N-AbA with the reference ZYTIGA® (R-AbA) in healthy Chinese male subjects.Patients and Methods: This study was conducted in three parts. Part I was an open, dose-escalation trial conducted in 16 Chinese healthy males; Part II was a randomized, open-label, 2 × 4 crossover, single-dose bioequivalence trial conducted in 36 subjects; Part III was a randomized, 3 × 3 crossover trial conducted on 24 volunteers to investigate the effect of food on the pharmacokinetics of N-AbA.Results: The exposure (AUC0-∞) and maximum concentration (Cmax) of abiraterone and excipient SNAC were linear in the range of 75– 450 mg dose. The bioavailability of N-AbA 300 mg was equivalent to that of R-AbA 1000 mg. The drug exposure of prednisone and prednisolone was not affected by SNAC co-administration. The Cmax of orally administered abiraterone as R-AbA in a modified fed state was 5.9 times and AUC0-∞ was 4.3 times, respectively, higher than those in of orally administered abiraterone as N-AbA in a high-fat diet. The Cmax and AUC0-∞ of orally administered abiraterone as N-AbA on a high-fat diet were 2.2 times and 2 times, respectively, higher than those on a fasting state. All adverse events reported in the three parts of the study were grade 1 or 2, and no serious adverse events were reported.Conclusion: These three Phase I trials showed that N-AbA and excipient SNAC had excellent linear pharmacokinetic characteristics. A single dose of N-AbA 300 mg was bioequivalent to R-AbA 1000 mg in healthy subjects under fasting conditions. Meanwhile, SNAC had no effect on the pharmacokinetics of prednisone and prednisolone. The effect of food on N-AbA was significantly lower than that on R-AbA.Keywords: food effect, pharmacokinetics, abiraterone acetate, bioequivalence

Yingying Zeng,1,2 Xiaomin Xue,1,2 Hui Cai,1,2 Guiping Zhu,1,2 Mengchan Zhu,1,2 Jian Wang,1,2 Xixi Song,1,2 Yuqing Mo,1,2 Xin Gao,1,2 Jiaye Zhou,3 Ling Ye,1,2 Meiling Jin1,2 1Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Meiling Jin; Ling YeDepartment of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of ChinaTel +86 21-64041990Email mljin118@163.com; ye.ling@zs-hospital.sh.cnBackground: The clinical features, treatment, and prognosis of allergic bronchopulmonary aspergillosis (ABPA) are not well-defined.Objective: We aimed to investigate the clinical characteristics, therapy, and prognosis of ABPA to aid its clinical recognition.Methods: A total of 232 patients with ABPA were analyzed retrospectively. The characteristics of ABPA in terms of its misdiagnosis, computed tomography classification, therapy, and its relationship with asthma were analyzed, and risk factors for acute exacerbation of ABPA were analyzed based on follow-up data.Results: Of the 232 ABPA patients, 132 had a history of misdiagnosis. Compared with the misdiagnosed patients, ABPA patients with central bronchiectasis, a high total eosinophil count, and mucus plugs were less likely to be misdiagnosed. Compared with serological ABPA, ABPA with central bronchiectasis was more likely to occur in older people and in patients with mucus plugs, and decreased forced vital capacity and diffusing capacity for carbon monoxide. ABPA patients with asthma were more likely to have bronchiectasis, decreased lung function in 1 s FEV1 and FEV1/FVC, and shorter time to first acute exacerbation compared with ABPA patients without asthma. Patients receiving glucocorticoids plus antifungal therapy had a longer time to first exacerbation than those receiving glucocorticoid therapy alone. Univariate and multivariate analyses revealed that duration of asthma history, duration of misdiagnosis, mucus plugs, and poor pulmonary function were risk factors for acute exacerbation of ABPA.Conclusion: To our knowledge, this is the largest sample size study of ABPA in China. ABPA patients with a history of asthma and/or central bronchiectasis on high-resolution computed tomography are prone to frequent acute exacerbations. The use of glucocorticoids combined with antifungal drugs can prolong the time to the first acute exacerbation in ABPA patients. Longer durations of asthma history and misdiagnosis, mucus plugs, and poor pulmonary function are risk factors for acute exacerbation of ABPA.Keywords: allergic bronchopulmonary aspergillosis, central bronchiectasis, diagnosis, follow-up, treatment

Xiaohua Wang,1,2 Si Wen,2 Li Ye,2 Dan Liu,2 Mao-Qiang Man,2 Bin Yang1,2 1Department of Dermatology, Jinan University, Guangzhou City, Guangdong Province, People’s Republic of China; 2The Dermatology Hospital, Southern Medical University, Guangdong, 510091, People’s Republic of ChinaCorrespondence: Bin YangThe Dermatology Hospital, Southern Medical University, 2 Lujing Road, Guangzhou, 510091, People’s Republic of ChinaEmail yangbin1@smu.edu.cnIntroduction: Although it is well known that epidermal function changes with aging, the transcriptomic basis and possible signaling pathways for aging-associated functional changes remain largely unknown.Methods: Here, we employed RNA sequencing techniques to assess epidermal gene expression profiles in the epidermis of mice aged 1, 2, 6, 12 and 20 months.Results: A total of 132 genes displayed reductions in expression levels with aging, while expression levels of 406 genes increased with aging. Epidermal gene expression was prominently upregulated in 2-month-old vs 1-month-old mice, while more genes were downregulated in 12-month-old mice. Upregulation of genes associated with immune/inflammatory responses was observed in the epidermis of aged mice in comparison to that of young mice, whereas downregulated signaling pathways in the epidermis of aged mice were primarily involved in metabolism, such as fatty acid elongation, glutathione metabolism and biosynthesis of antibiotics. Some signaling pathways, such as chemokine signaling, cytokine/cytokine receptor interaction signaling and IL-17 signaling pathways, were remarkably upregulated in 12-month-old mice. Steroid synthesis, metabolic pathway, thermogenesis and proteasome pathways were steadily downregulated, starting at 2 months old.Conclusion: These results indicate that the epidermis of aged mice displays an upregulation of genes associated with inflammatory signaling pathways, and downregulation of genes related to metabolic signaling pathways.Keywords: aging, epidermis, gene expression

Wei Wang,1,2,&ast; Zaoxiu Hu,3,&ast; Mingsheng Ma,4 Haoyuan Yin,4 Yunchao Huang,1 Guangqiang Zhao,1 Xin Cui,1 Qinling Sun,1 Yantao Yang,1 Yichen Yang,1 Biying Wang,1 Lianhua Ye1 1Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Thoracic Surgery, Taihe Hospital (Hubei University of Medicine), Shiyan, People’s Republic of China; 3Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Thoracic Surgery, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua YeDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province, People’s Republic of ChinaEmail lhye1204@aliyun.comPurpose: Currently, there is no uniform standard to guide postoperative adjuvant chemotherapy for patients with multifocal non-small cell lung cancers (NSCLCs) ≤ 3 cm. Therefore, there is an urgent need to explore prognostic molecular markers to identify high-risk patients with multifocal NSCLCs ≤ 3 cm. We aimed to explore the potential value of metastasis-associated protein 1(MTA1) expression in risk stratification of patients with multifocal NSCLCs ≤ 3 cm.Methods: We retrospectively analyzed the clinical data and postoperative survival data of patients with multifocal NSCLCs ≤ 3 cm. Paraffin-embedded tissue sections were used for immunohistochemistry. Semiquantitative immunoreactivity scoring (IRS) system was used to evaluate the nuclear expression of MTA1. SPSS software (version 23.0) was used to analyze the data.Results: The IRS of MTA1 nuclear expression in 259 lesions of 119 patients ranged from 2.2 to 11.7 (median: 5.6). Our results showed that MTA1 expression was highest in high-risk pathological subtypes of lung adenocarcinoma. MTA1 expression in multiple primary lung cancers (MPLCs) was lower than that in intrapulmonary metastases (IPMs). The median follow-up duration was 25.97 months. The disease-free survival (DFS) of patients with MPLCs was significantly better than that of patients with IPMs, and the DFS of patients with high MTA1 expression was significantly worse than that of patients with low MTA1 expression. Multivariate Cox analysis showed that high MTA1 expression (hazard ratio: 7.937, 95% confidence interval: 2.433– 25.64, p =0.001) was a statistically significant predictor of worse DFS in patients with multifocal NSCLCs ≤ 3 cm.Conclusion: MTA1 expression can stratify the risk in patients with multifocal NSCLCs ≤ 3 cm. Patients with MTA1 immunohistochemical score > 5.6 are at a high risk of postoperative recurrence, and these patients may benefit from postoperative adjuvant chemotherapy.Keywords: multifocal, non-small cell lung cancer, MTA1, multiple primary lung cancers, intrapulmonary metastases, risk of postoperative recurrence

Chang Zhou,1,&ast; Rui Kang,2,&ast; Shu Liang,1 Teng Fei,2 Yiping Li,1 Ling Su,1 Ling Li,1 Li Ye,1 Yan Zhang,1 Dan Yuan1 1Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of China; 2School of Resource and Environmental Sciences, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Yuan Email ydtv1130@163.comBackground: Sichuan Province, in the interior of Southwest China, is the most severe HIV-affected area in China. Few data are currently available for people living with HIV/AIDS (PLWH) with virological failure of antiretroviral therapy (ART). Estimating the HIV-1 drug-resistant spread influencing factors and transmission patterns of the HIV-1 epidemic of PLWH with ART virological failure are critical in Sichuan.Methods: We evaluated the drug-resistant transmission patterns on 5790 PLWH in 2018 with identified pol sequences of the five main HIV-1 subtypes (ie, subtype B, CRF08_BC, CRF85_BC, CRF07_BC, and CRF01_AE) in Sichuan Province, China. The multivariate logistic regression model was used to explore potential influencing factors of the spread of drug resistance (DR) clustering in the genetic transmission network. Spatial analyses were applied to demonstrate drug-resistant spatial clustering patterns of spatial connections of HIV-1 intercity transmission. Genetic transmission networks were performed by comparing sequences, calculating the pairwise distance, and visualizing the network.Results: There were identified 452 transmission clusters containing 2159 of 5790 patients (37.29%) in the HIV-1 genetic transmission networks. Some clinical and demographic factors (eg, route of transmission, subtype) determined the DR clustering in the genetic transmission networks. The high drug-resistant clustering rates were mainly distributed in the Southern and Northeast of Sichuan Province (eg, Deyang, Neijiang), especially for CRF85_BC, which showed the highest clustering rate. Some cities had with strong intracity links (eg, Yibin, Neijiang), some cities had with strong transmission links with another city (eg, Ziyang and Guangyuan), 12 of 37 drug resistance mutation sites had a significant difference in the five subtypes (P < 0.001).Conclusion: Our findings revealed the HIV-1 drug-resistant spread influencing factors and transmission patterns of PLWH with ART virological failure, which showed regions with high drug-resistant transmission of PLWH may not be a match for regions with severe epidemics in Sichuan, and it provided evidence-based to drug-resistant transmission targeting interventions.Keywords: HIV-1, antiretroviral resistance, transmitted drug resistance, spatial analyses

Yue Shao,1 Jun Luo,1 Liu Ye,2 Hao-Yu Ran,1 Hao-Ming Shi,1 Cheng Zhang,1 Qing-Chen Wu1 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2The First Branch, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Cheng Zhang; Qing-Chen WuDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaEmail zhangchengcqmu@126.com; wuqingchencqmu@126.comBackground: Long non-coding RNAs (lncRNAs) can act as a competitive endogenous RNA (ceRNA) to regulate gene expression by sequestering the microRNA (miRNA). However, the lncRNA-miRNA-mRNA ceRNA network in thoracic aortic dissection (TAD) has been rarely documented.Methods: Three Gene Expression Omnibus (GEO) datasets were used to detect differentially expressed mRNAs, miRNAs, and lncRNAs in TAD. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for the differentially expressed mRNAs. A protein–protein interaction network for differentially expressed mRNAs was also constructed, and hub genes were identified. We established a ceRNA network of TAD based on the differentially expressed miRNAs, mRNAs and lncRNAs, and verified our results using an independent dataset and quantitative real-time PCR (qRT-PCR).Results: In TAD, 267 lncRNAs, 81 miRNAs, and 346 mRNAs were identified as differentially expressed. The established ceRNA network consisted of seven lncRNA nodes, three mRNA nodes, and three miRNA nodes, and the expression of miRNAs in TAD was opposite to that of lncRNAs and mRNAs. Subsequently, an independent GEO dataset and qRT-PCR were used to validate the expression of three mRNAs. In addition, the expression differences in SLC7A5, associated miRNA and lncRNA were verified. According to gene set enrichment analysis of SLC7A5, the most significant KEGG pathway was considerably enriched in spliceosome and pentose phosphate pathway.Conclusion: We established a novel ceRNA regulatory network in TAD, which provides valuable information for further research in the molecular mechanisms of TAD.Keywords: bioinformatics analysis, ceRNA, expression profile, thoracic aortic dissection

Yida Li,1,2,&ast; Liqing Zou,1,2,&ast; Li Chu,1,2 Luxi Ye,1,2 Jianjiao Ni,1,2 Xiao Chu,1,2 Tiantian Guo,1,2 Xi Yang,1,2 Zhengfei Zhu1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengfei Zhu; Xi YangDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, People’s Republic of ChinaTel +86-18017312901; +8617321296901Fax +86-2164175242Email fuscczzf@163.com; ntgeorge@qq.comBackground: Radiation-induced lung injury (RILI) is a main threat to patients who received thoracic radiotherapy. Thus, understanding the molecular mechanism of RILI is of great importance. Circular RNAs (circRNAs) have been found to act as a regulator of multiple biological processes, and the circRNA-microRNA (miRNA)-mRNA axis could play an important role in the signaling pathway of many human diseases including radiation injury.Methods: First, the circRNA and miRNA of RILI in a mouse model were investigated. The mice received 12 Gy of thoracic irradiation, and the irradiated lung tissues at 48 hours after irradiation were analyzed by RNA sequencing (RNA-seq) compared with normal lung tissues. Then, Gene Ontology analysis of the target mRNAs of the significantly differently expressed circRNAs was performed.Results: In the irradiated group, inflammatory changes in lungs were observed; 21 significantly up-regulated and 33 down-regulated significantly miRNAs were identified (p < 0.05). Among 27 differentially expressed circRNAs, 10 were down-regulated and 17 were up-regulated in the irradiated group [log2 (fold change) > 1 or < − 1, p< 0.05]. These differentially expressed miRNAs took part in a series of cellular processes, such as positive regulation of alpha-beta T-cell proliferation, interstitial matrix, collagen fibril organization, chemokine receptor activity, cellular defense response, and B-cell receptor signaling pathway. The differentially expressed circRNAs were related to Th1 and Th2 differentiation pathways, and the predicted mRNAs were verified.Conclusion: This study revealed immune-related molecular pathways play an important role in the early response after radiotherapy. In the future, research on the target mechanism and early intervention of circRNAs with associated miRNAs such as circRNA5229, circRNA544, and circRNA3340, could benefit the treatment of RILI.Keywords: circRNA, miRNA, radiation-induced lung injury, T cell proliferation

Tianxing Dai,1,&ast; Jing Li,2,&ast; Xu Lu,3,&ast; Linsen Ye,1 Haoyuan Yu,1 Lele Zhang,1 Mingbin Deng,1 Shuguang Zhu,1 Wei Liu,3 Guoying Wang,4 Yang Yang1 1Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoying WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, People’s Republic of ChinaTel +86-020-83062703Fax +86-020-83395651Email wanggy3@126.comYang YangDepartment of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of ChinaTel +86-020-85252177Fax +86-020-85252276Email yysysu@163.comPurpose: Ferroptosis, as a novel regulated cell death form, has a close interaction with metabolism, which is largely unknown in cancer. In the present study, we conducted a comprehensive analysis of ferroptosis-related metabolic genes to delineate the metabolic signatures induced by ferroptosis and evaluate its prognostic significance in hepatocellular carcinoma (HCC).Methods: The ferroptosis-related metabolic genes (Fer-MRGs) were identified by correlation analyses with transcriptome data from The Cancer Genome Atlas and Gene Expression Omnibus. Then, univariate and the least absolute shrinkage and selection operator Cox regression analysis was used to establish a novel risk score model. Univariate and multivariate COX analyses were used to identify independent prognostic factors for overall survival (OS) of HCC, and a nomogram was developed. The Fer-MRGs’ expression was further evaluated by quantitative real-time polymerase chain reaction in HCC.Results: A total of 77 metabolic genes were identified as Fer-MRGs, and 26 were found with prognostic values for OS of HCC. Then, a novel nine-gene (AKR1C3, ATIC, G6PD, GMPS, GNPDA1, IMPDH1, PRIM1, RRM2, and TXNRD1) risk score model was constructed. Survival analyses showed worse OS in high-risk patients both in the training and validation groups. The model was also identified as an independent prognostic factor for HCC, and a prognostic nomogram for OS was further established with superior discriminative capacity and prediction accuracy. Notably, close correlations were also identified between the risk score and the expression of immune checkpoint genes, immune subtypes of tumor, and susceptibility of HCC to chemotherapeutic agents. Finally, elevated expression of eight Fer-MRGs (except for IMPDH1) was further verified in 16 pairs of HCC tumor and adjacent tissues.Conclusion: These results indicated the intense interaction between ferroptosis and metabolism, the significant role of ferroptosis-related MRGs, and the great potential of the novel risk score model for prognosis prediction in HCC.Keywords: hepatocellular carcinoma, ferroptosis, metabolism, gene signature, prognosis

Tianxing Dai,1,2 Linsen Ye,1,2 Haoyuan Yu,1,2 Kun Li,1,2 Jing Li,3 Rongqiang Liu,4 Xu Lu,1,2 Mingbin Deng,1,2 Rong Li,1,2 Wei Liu,2 Yang Yang,1 Guoying Wang4 1Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 2Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 3Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 4Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of ChinaCorrespondence: Yang YangDepartment of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of ChinaTel +86-020-85252177Fax +86-020-85252276Email yysysu@163.comGuoying WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of ChinaTel +86-020-83062703Fax +86-020-83395651Email wanggy3@126.comPurpose: The aldo-keto reductase (AKR) superfamily members have been proposed with multiple roles in various tumors. Here, a comprehensive analysis on the integral role of AKR genes was conducted to evaluate the expression profile, regulation network, and prognostic significance in hepatocellular carcinoma (HCC).Materials and Methods: Transcriptome datasets of HCC were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus. Univariate and multivariate Cox regression analyses were used to build a novel risk score model, and then were further used to identify independent prognostic factors for overall survival (OS) of HCC. A prognostic nomogram was developed and validated. The expression of these critical AKR members was also evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry in HCC specimens.Results: Eight differentially expressed AKR genes were identified in HCC. The dysregulation of most AKR genes was negatively correlated with DNA methylation, and a regulation network with transcription factors (TFs) was also established. Then, three critical AKR genes (AKR1B10, AKR1D1, and AKR7A3) were screened out to build a novel risk score model. Worse OS was observed in high-risk patients. Besides, a prognostic nomogram based on the model was further established and validated in both the TCGA and GSE14520 cohorts, which showed superior performance in predicting the OS of HCC patients. Notably, close correlations were identified between the risk score and tumor immune microenvironment, somatic mutation profiles, and drug susceptibilities of HCC. Finally, the upregulated AKR1B10 and downregulated AKR1D1 and AKR7A3 were further verified in HCC tumor and adjacent tissues from our institution.Conclusion: The dysregulated AKR genes could be mediated by DNA methylation and TFs in HCC. The risk model established with superior prognostic performance further suggested the significant role of AKR genes involved in the progression of HCC.Keywords: hepatocellular carcinoma, aldo-keto reductase, AKR, risk score model, nomogram, prognosis

Cuihong Wang,1 Guanying Yu,2 Ying Xu,1 Chengfei Liu,1 Qian Sun,1 Wenqing Li,1 Junhua Sun,1 Yuhua Jiang,1 Lan Ye1 1Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China; 2Department of Gastrointestinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, 250013, People’s Republic of ChinaCorrespondence: Lan YeCancer Center, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of ChinaEmail sdeyyelan@email.sdu.edu.cnIntroduction: Glioma is the most common malignant brain tumor in adults. Radiation is a key therapy in glioma. However, the radioresistance of glioma was a big challenge. HLA complex P5 (HCP5) has been reported dysregulated in several types of malignant tumor, including glioma. The role of HCP5 in the radiosensitivity of glioma is so far unknown. The present study aimed to investigate the effect of HCP5 on radiosensitivity in gliomas.Methods: The levels of HCP5 and microRNA (miR)-128 were detected using qRT-PCR. The cell growth curve was used to show the cell proliferation and evaluate the radiosensitivity of glioma cells following exposure to X-ray. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to test the cellular senescence. Luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to determine the correlation between HCP5 and miR-128.Results: HCP5 level of glioma cells was significantly higher than human astrocytes, whereas miR-128 level was lower in glioma cells. Besides, the HCP5 expression was increased in glioma tissues compared to normal brain tissues (NBTs). Knockdown of HCP5 inhibited cell proliferation and increased radiosensitivity in glioma cells. MiR-128 was predicted to be a target of HCP5. It was demonstrated that HCP5 directly bound to miR-128 and regulated its expression in glioma cells. Furthermore, the effects of HCP5 knockdown on radiosensitivity of glioma cells were attenuated by the inhibitor of miR-128.Conclusion: These findings suggested that interaction between lncRNA HCP5 and microRNA-128 could regulate the radiosensitivity of glioma cells by intervening in cellular senescence. This might be used as the potential radio-sensitization targets for glioma therapy.Keywords: glioma, radiosensitivity, HLA complex P5, microRNA-128, cellular senescence

Jianchang Qian,1,* Sihui Yin,1,* Lin Ye,1 Zhe Wang,2 Sheng Shu,1,3 Zhenxin Mou,1,3 Mingjiang Xu,1 Nipon Chattipakorn,4 Zhiguo Liu,1 Guang Liang1,3,5 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 4Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 5Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang Liang; Zhiguo LiuChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of ChinaTel/Fax +86-577-86699396Email wzmcliangguang@163.com; lzgcnu@163.comAim: Elevated inflammatory signaling has been shown to play an important role in diabetic kidney disease (DKD). We previously developed a new anti-inflammatory compound LG4. In the present study, we have tested the hypothesis that LG4 could prevent DKD by suppressing inflammation and identified the underlying mechanism.Methods: Streptozotocin-induced type 1 diabetic mice were used to develop DKD and evaluate the effects of LG4 against DKD. To identify the potential targets of LG4, biotin-linked LG4 was synthesized and subjected to proteome microarray screening. The cellular mechanism of LG4 was investigated in HG-challenged SV40MES13 cells.Results: Although LG4 treatment had no effect on the body weight and blood glucose levels, it remarkably reversed the hyperglycemia-induced pathological changes and fibrosis in the kidneys of T1DM mice. Importantly, hyperglycemia-induced renal inflammation evidenced by NF-κB activation and TNFα and IL-6 overexpression was greatly ameliorated with LG4 treatment. Proteosome microarray screening revealed that JNK and ERK were the direct binding proteins of LG4. LG4 significantly reduced HG-induced JNK and ERK phosphorylation and subsequent NF-κB activation in vivo and in vitro. In addition, LG4 did not show further anti-inflammatory effect in HG-challenged mesangial cells with the presence of JNK or ERK inhibitor.Conclusion: LG4 showed renoprotective activity through inhibiting ERK/JNK-mediated inflammation in diabetic mice, indicating that LG4 may be a therapeutic agent for DKD.Keywords: indole-2-carboxamide derivative, diabetic kidney disease, inflammation, MAPK, NF-κB

Xiaohua Wang,1,* Qingsong Lai,2,* Baoqing Zheng,1 Li Ye,1 Si Wen,1 Yunling Yan,1 Bin Yang,1 Mao-Qiang Man1 1Dermatology Hospital, Southern Medical University, Guangdong, 510091, People’s Republic of China; 2Center for Chronic Disease Prevention and Control of Puning City, Puning, Guangdong, 515300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Qiang Man; Bin YangDermatology Hospital, Southern Medical University, 2 Lujing Road, Yuexiu District, Guangzhou, Guangdong, 510091, People’s Republic of ChinaEmail mqman@hotmail.com; yangbin101@hotmail.comBackground: Although the characteristics of pruritus in some skin diseases are documented, characteristics of pruritus related to gender-, age-, and skin disorder have not yet been well defined.Objective: To characterize dermatosis-associated pruritus in Chinese patients.Methods: A cross-sectional study was carried out in a single center. The intensity of pruritus was evaluated using a 0– 10 visual analog scale (VAS). Skin disorders were diagnosed by dermatologists. The prevalence and intensity of pruritus were compared among skin disorders, and between males and females.Results: Valid questionnaires were obtained from 1,246 female and 864 male patients. Patients with acne, eczematous dermatitis, and urticaria accounted for 18%, 17%, and 14%, respectively. Both the prevalence and severity of pruritus varied greatly with skin disorders (p< 0.0001). Patients with either urticaria or eczematous dermatitis displayed a higher prevalence of pruritus (92% and 82%, respectively), while subjects with urticaria exhibited the highest VAS in comparison to those with other skin disorders (p< 0.05 to p< 0.001 vs the others). Moreover, both the prevalence and severity of pruritus were positively associated with age in both males and females (p< 0.0001). Furthermore, 60 out of 77 patients (78%) with topical glucocorticoid-induced dermatitis experienced pruritus, with a VAS of 2.03± 0.21. Finally, a lower VAS was found in subjects with oily skin than those with either dry or normal skin.Conclusion: The prevalence and severity of pruritus vary with skin disorders, skin type, age, and gender in Chinese patients.Keywords: skin disorder, pruritus, prevalence, severity, gender, age

Daqing Yang,1 Rizeng Li,1 Jianfu Xia,1 Wencai Li,1 Lili Ma,2 Lechi Ye,3 Haibo Xue4 1Department of Colorectal Surgery, Wenzhou Central Hospital, Wenzhou 325000, People’s Republic of China; 2Department of Rheumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 3Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 4The First Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of ChinaCorrespondence: Haibo XueThe First Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of ChinaEmail xuehaibo0409@163.comBackground: Long noncoding RNAs (lncRNAs) play essential functions in the development of several cancers, including colorectal cancer (CRC). Nevertheless, how PCAT18 regulates CRC tumorigenesis remains unclear. In this research, we aimed to investigate the roles of PCAT18 in CRC.Materials and Methods: qRT-PCR and Western blot were used to analyze RNA and protein levels. CCK8, colony formation, transwell and wound healing assays were utilized to analyze proliferation, migration and invasion. Luciferase reporter assay was used to analyze RNA interactions.Results: PCAT18 was found to be highly expressed in CRC tissues and cells. PCAT18 level was positively correlated with lymph node metastasis and TNM stage. Functionally, PCAT18 silencing induced impairment of CRC proliferation, migration and invasion. Besides, PCAT18 was identified to inhibit miR-759. PCAT18 promotes SPRR3 expression through binding to miR-759. Furthermore, miR-759 inhibitors or SPRR3 ectopic expression partially rescued the abilities of proliferation, migration and invasion in CRC cells transfected with sh-PCAT18.Conclusion: Therefore, our study demonstrated that PCAT18 contributes to CRC progression through regulating miR-759/SPRR3 axis, which provides a new theoretical basis of explaining CRC tumorigenesis.Keywords: long noncoding RNA, PCAT18, miR-759, SPRR3, colorectal cancer

Yuanfeng Xue,1,* Junhong Ding,1,* Yulong Liu,2 Yuchun Pan,1 Penglai Zhao,3 Zhiwen Ren,1 Jian Xu,1 Liangliang Ye,1 Ying Xu2 1Department of Neurosurgery, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch Southeast University, Nanjing 211200, People’s Republic of China; 2College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 3Department of Neurosurgery, Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanfeng Xue; Ying Xu Tel +8613951706820; +8651185038451Email 672455219@qq.com; ingyx@sina.com.cnObjective: Traumatic brain injury (TBI) is a serious health problem with few available treatment options. Rh-erythropoietin (rh-EPO) is a potential therapeutic drug for TBI, but it cannot cross the blood–brain barrier (BBB) directly. In this regard, a novel strategy to deliver rh-EPO for enhanced TBI treatment is via the development of Tween 80 modified albumin nanoparticles using electrostatic spray technology.Methods: The rh-EPO loaded Tween 80 modified albumin nanoparticles (rh-EPO-Tw-ABNPs) were prepared by electrostatic spray technology, while the process parameters were optimized via a single factor design. Investigation of physicochemical properties, bioactivity and stability of rh-EPO-Tw-ABNPs was carried out. The in vitro release and biocompatibility with nerve cells were also analyzed. The in vivo brain targeting efficiency, brain edema relieving effect and the expression of aquaporin 4 (AQP4) and glial fibrillary acidic protein (GFAP) in the brain were evaluated in TBI model rats.Results: The particle size of optimal rh-EPO-Tw-ABNPs was about 438 ± 45 nm, with a zeta potential of − 25.42 ± 0.8 mv. The average drug loading ratio of rh-EPO-Tw-ABNPs was 21.3± 3.7 IU/mg with a relative bioactivity of 91.6 ± 4.1%. The in vitro release of rh-EPO from the nanoparticles was rather slow, while neither the blank Tw-ABNPs nor rh-EPO-Tw-ABNPs exhibited toxicity on the microglia cells. Furthermore, in vivo experiments indicated that the rh-EPO-Tw-ABNPs could enhance the distribution of EPO in the brain and relieve brain edema more effectively. Moreover, compared with an rh-EPO injection, the rh-EPO-Tw-ABNPs could increase the AQP4 level but reduced GFAP expression in the brain with more efficiency.Conclusion: The rh-EPO-Tw-ABNPs could enhance the transport of rh-EPO into the brain with superior therapeutic effect for TBI.Keywords: traumatic brain injury, rh-erythropoietin, Tween 80 modified albumin nanoparticle, electrostatic spray technology

Mengchan Zhu,* Maosong Ye,* Jian Wang, Ling Ye, Meiling Jin Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meiling Jin; Ling Ye Email jin.meiling@zs-hospital.sh.cn; ye.ling@zs-hospital.sh.cnBackground: Chronic obstructive pulmonary disease (COPD) has become a major cause of morbidity and mortality worldwide. Increasing evidence indicates that aberrantly expressed microRNAs (miRNAs) are involved in the pathogenesis of COPD. However, an integrative exploration of miRNA–mRNA regulatory network in COPD plasma remains lacking.Methods: The microarray datasets GSE24709, GSE61741, and GSE31568 were downloaded from the GEO database and analyzed using GEO2R tool to identify differentially expressed miRNAs (DEMs) between COPD and normal plasma. The consistently changing miRNAs in the three datasets were screened out as candidate DEMs. Potential upstream transcription factors and downstream target genes of candidate DEMs were predicted by FunRich and miRNet, respectively. Next, GO annotation and KEGG pathway enrichment analysis for target genes were performed using DAVID. Then, PPI and DEM-hub gene network were constructed using the STRING database and Cytoscape software. Finally, GSE56768 was used to evaluate the hub gene expressions.Results: A total of nine (six upregulated and three downregulated) DEMs were screened out in the above three datasets. SP1 was predicted to potentially regulate most of the downregulated DEMs, while YY1 and E2F1 could regulate both upregulated and downregulated DEMs. 1139 target genes were then predicted, including 596 upregulated DEM target genes and 543 downregulated DEM target genes. Target genes of DEMs were mainly enriched in PI3K/Akt signaling pathway, mTOR signaling pathway, and autophagy. Through the DEM-hub gene network construction, most of the hub genes were found to be potentially modulated by miR-497-5p, miR-130b-5p, and miR-126-5p. Among the top 12 hub genes, MYC and FOXO1 expressions were consistent with that in the GSE56768 dataset.Conclusion: In the study, potential miRNA–mRNA regulatory network was firstly constructed in COPD plasma, which may provide a new insight into the pathogenesis and treatment of COPD.Keywords: microRNAs (miRNAs), chronic obstructive pulmonary disease (COPD), bioinformatics analysis, miRNA–mRNA regulatory network

Le Ye,1,* Mingli Li,2,* Zhankui Wang,3,* Zhongwei Yang,4,* Jinyuan Zhang,5,* Hongwei Fang,5,* Zhenzhou He,1 Xiangrui Wang5 1Department of Pain Management, The South Campus of Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 20025, People’s Republic of China; 2Department of Anesthesiology, The Shanghai First Rehabilitation Hospital, Shanghai 200090, People’s Republic of China; 3Department of Orthopedics, The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, People’s Republic of China; 4Department of Anesthesiology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200127, People’s Republic of China; 5Department of Anesthesiology and Intensive Care Unit, Dongfang Hospital, Tongji University, Shanghai 200123, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangrui WangDepartment of Anesthesiology and Intensive Care Unit, Dongfang Hospital, Tongji University, Shanghai 200123, People’s Republic of ChinaEmail xiangruiwang@vip.sina.comPurpose: The causative mechanisms triggering myofascial pain syndrome (MPS) are still in debate. It is becoming evident that mitochondrial dysfunction may regulate pathways controlling MPS. The aim of this study was to investigate whether AMPK-PGC-1α-SIRT3 axis is associated with depression of mitochondrial function in the rat MPS model.Methods: A total of 32 Sprague–Dawley rats were randomly divided into control group and experimental group. The expression level of mRNA and protein of gastrocnemius medialis (GM) was analyzed by Western blot and RT-PCR. The histopathological findings were investigated through electron microscopes in GM of all groups.Results: Our results showed that MPS induces continuous depression of mitochondrial biogenesis and function via down-regulation of PGC-1α-SIRT3 axis accompanying with ATP fuel crisis as compared to control group. However, the expression level of SIRT3 mRNA did not change. Additionally, a correlated reduction of the mRNA and protein expression level of NRF-1 and TFAM, known as the downstream target of PGC-1α, suggesting further transcription of nuclear genes encoding mitochondria functional proteins for promoting mitochondria proliferation, oxidative phosphorylation and energy production is continuously depressed. Furthermore, phosphorylation extent of AMPK is also declined following MPS, and it is negatively correlated with reduction of ATP generation, suggesting that the complex network involves different inhibition in transcription, post-translational modification and a plethora of other effectors that mediate the inhibition roles.Conclusion: We here suggested that the down-regulation in AMPK-PGC-1α-SIRT3 axis network may be the basis for the association between mitochondrial dysfunction and MPS, where a vicious circle further aggravates the disease symptoms with ongoing ATP energy crisis.Keywords: myofascial pain syndrome, mitochondrial biogenesis, myofascial trigger points, PGC-1α, ATP crisis, gastrocnemius medialis muscle

Xiaohua Wang,1,* Qingsong Lai,2,* Baoqing Zheng,1 Li Ye,1 Si Wen,1 Yunling Yan,1 Bin Yang,1 Mao-Qiang Man1 1Dermatology Hospital, Southern Medical University, Guangdong 510095, People’s Republic of China; 2Puning City Chronic Disease Prevention and Control Center, Guangdong 515300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Qiang Man; Bin Yang Email mqman@hotmail.com; yangbin101@hotmail.comBackground/Aim: Although the characteristics of cutaneous sensory symptoms in the general population have been documented, dermatological condition-associated skin pain has not been characterized yet. In the present study, we aimed to characterize dermatological condition-associated skin pain in the Chinese.Subjects and Methods: A questionnaire was given to outpatients to identify self-proclaimed skin pain at our dermatology clinic. The severity of skin pain was assessed using pain scale 0– 10. Prevalence and pain severity were compared between males and females.Results: A total of 2144 patients, including 1254 females and 890 males aged 13– 94 years, were included in this study. The overall prevalence of skin pain was 9.93% in this cohort. The prevalence of skin pain varied greatly with dermatological conditions (p< 0.0001). Moreover, a higher prevalence of skin pain was observed in males than in females (p< 0.05). Among the dermatological conditions reported, higher skin pain scales were found in subjects with either glucocorticoid-induced dermatitis (4.20 ± 0.73) or herpes zoster (4.00 ± 0.29). While the overall pain scales were comparable between males and females (2.38 ± 0.13 versus 2.68 ± 0.13), pain scales in patients with eczematous dermatitis were higher in females than in males (p< 0.05). Furthermore, pain scales correlated positively with age. However, pain scales did not differ between subjects with versus without a family history of cutaneous sensory symptoms. These results demonstrate that the prevalence and severity of dermatological condition-associated skin pain vary with dermatological conditions and gender in the Chinese.Conclusion: Patients with some dermatological conditions may experience skin pain. Although the pain is moderate, it can negatively impact the quality of patients’ lives. Alleviation of skin pain should be considered when treating patients with certain dermatological conditions.Keywords: skin disorders, skin pain, gender, prevalence

Zihuang Li,1 Ling Ye,2 Jingwen Liu,1 Daizheng Lian,1 Xianming Li1 1Department of Radiation Oncology, The Second Clinical Medical College of Jinan University, Shenzhen Municipal People’s Hospital, Shenzhen 518020, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, People’s Republic of ChinaCorrespondence: Zihuang Li; Xianming LiDepartment of Radiation Oncology, The Second Clinical Medical College of Jinan University, Shenzhen Municipal People’s Hospital, Shenzhen 518020, People’s Republic of ChinaTel +86 755 22942428Email li.zihuang@szhospital.com; li.xianming@szhospital.comPurpose: In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC.Methods: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS).Results: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects.Conclusion: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.Keywords: dendritic block copolymer, sorafenib, enhanced therapy, TPGS, hepatocellular carcinoma

Hai-Lin Liu,1,* Rui-Hao Zhou,2,* Li-Li Luo,1 Xue Yuan,1 Ling Ye,2 He-Guo Luo1 1Department of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, People’s Republic of China; 2Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: He-Guo LuoDepartment of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, People’s Republic of ChinaEmail 542534631@qq.comBackground: Although ultrasound-guided transversus abdominis plane block (TAPB) is widely used in multimodal analgesia after cesarean delivery (CD), the complications of TAPB during analgesia after CD have rarely been reported.Methods: A total of 84 cases of CD were randomly assigned to either a ropivacaine group (R group) or ropivacaine + dexamethasone group (RD group) in this double-blind trial. The pain site and pain degree at rest and during activity at 2 h, 6 h, 10 h, 12 h, 14 h, 16 h, 20 h, and 24 h after maternal surgery were recorded. The consumption of opioids at 24h, postoperative nausea, vomiting, exhaustion, and other adverse reactions were recorded.Results: A total of 80 patients were included in the analysis of results. A total of 19 patients developed ISP, 14 in the R group and 5 in the RD group. The incidence of ISP in the R and RD groups was 35% and 12.5%, respectively. The results described above showed that combining dexamethasone with ropivacaine reduced the incidence of ISP, and the difference was statistically significant (P< 0.05). Two groups of women with positive ISP had higher values of opioid consumption than women with negative ISP, but the difference was not significant.Conclusion: Dexamethasone as an adjuvant for ropivacaine can effectively relieve the ISP of ultrasound-guided TAPB after CD, and can enhance the analgesic effect of ropivacaine.Keywords: dexamethasone, ropivacaine, cesarean delivery, transversus abdominis plane block, postoperative analgesia, injection site pain

Qian Liu,1,* Qing Zhong,2,* Guoqiang Tang,1,* Ling Ye3 1Department of Anesthesiology, First People’s Hospital, Zigong, Sichuan, People’s Republic of China; 2Department of Anesthesiology, People’s Hospital, Jianyang, Sichuan, People’s Republic of China; 3Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling YeDepartment of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaEmail zerodq_hx@163.comBackground: Central post-stroke pain (CPSP) is refractory to pharmacotherapy (eg, NSAIDs, opioids, antidepressants, and anticonvulsants), and may require transcranial or deep brain stimulation.Case Presentation: A 67-year-old woman presented with severe paroxysmal cramp-like pain on the right side, including the head and both upper and lower extremities. The pain started 5 years earlier, was initially mild and occasional, but gradually intensified to an unbearable degree with an average of 10– 15 daily episodes, each lasting for 5– 10 mins. The patient disclosed “hemorrhagic stroke” 10 years ago that resulted in hemiplegia on the right side. CT examination verified the lesion. The patient received daily injection of 2-mL 2% lidocaine under ultrasound guidance to block the stellate ganglion. Pain subsided rapidly in both intensity and frequency. On the seventh day, the patient no longer had pain episodes. At the last follow-up, 9 months later, the patient was free from pain.Conclusion: Ultrasound-guided stellate ganglion block is a viable alternative for CPSP that is refractory to pharmacotherapy.Keywords: central post-stroke pain, cramp-like pain, ultrasound, stroke, stellate ganglion block

Jun Li, 1, 2 Yan Yin, 2 Ling Ye, 2 Yunxia Zuo 3 1National Clinical Research Center for Geriatrics and Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, People’s Republic of China; 2Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, People’s Republic of China; 3Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, People’s Republic of ChinaCorrespondence: Ling YeDepartment of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, People’s Republic of ChinaTel +86-28-85423593Email zerodq_hx@163.comBackground: Chronic headache is common but difficult to treat. Most patients respond poorly to drugs. Nerve block is an effective treatment but has no continuous effect. The pulsed radiofrequency (PRF) technique has been shown to be effective in relieving head pain and extending the effect of nerve block.Objective: The purpose of this study is to evaluate the long-term efficacy of C2 dorsal root ganglion after pulsed radiofrequency (PRF) guided by ultrasound for chronic headache.Setting: The Department of Pain Management, West China Hospital.Methods: Twenty patients who did not respond to medications and peripheral nerve blocks underwent ultrasound-guided PRF of the C2 dorsal root ganglion. The patients were followed up for 6 months. Visual analog scale (VAS) score was evaluated at 1 week, 1 month, 3 months, and 6 months. The quality of life (QOL) was assessed by Brief Pain Inventory (BPI) scores which were rated at pre-procedure and 1 month, 3 months, and 6 months after the procedure. The occurrence of complications was evaluated and reported.Results: Mean VAS scores were significantly decreased at 1 week, 1 month, 3 months and 6 months compared to the pre-procedure mean VAS score. Mean BPI scores decreased significantly at each postoperative time point compared to the preoperative baseline and low scores remained throughout the follow-up period: 45.05± 3.44 at pre-procedure, 10.60 ± 2.37 at 1 weeks, 12.50 ± 2.46 at 1 month, 12.90 ± 2.62 at 3 months, and 11.63 ± 2.98 at 6 months. Mild complications occurred, including 1 case (4.7%) of transient cervicalgia (lasting for 24 hrs) and 3 cases (14.2%) of transient dizziness (lasting for 30 mins).Limitations: Firstly, it included a small sample of patients. Another is the short duration of the follow-up.Conclusion: C2 PRF may be considered as an alternative treatment for chronic headache.Keywords: ultrasound guidance, pulsed radiofrequency, dorsal root ganglion, chronic intractable headache, translateral approach