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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

Jian Zhou,1,2,&ast; Housheng Zheng,1,&ast; Huiru Zhang,1 Wenqiang Yu,1 Baoer Li,1 Liang Ye,1 Lu Wang1 1Hyperbaric Oxygen Department, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Wang, Hyperbaric oxygen department, Shenzhen University General Hospital, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-21839715, Email luwangszu@163.com Liang Ye, International Cancer Center, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-26631420, Fax +86-0755-86671943, Email liangyeszu@163.comObjective: MCM5 is a DNA licensing factor involved in cell proliferation and has been previously established as an excellent biomarker in a number of malignancies. Nevertheless, the role of MCM5 in GBM has not been fully clarified. The present study aimed to investigate the potential roles of MCM5 in the treatment of GBM and to elucidate its underlying mechanism, which is beneficial for developing new therapeutic strategies and predicting prognosis.Methods: Firstly, we obtained transcriptomic and proteomic data from the TCGA and CPTAC databases on glioma patients. Employing the DeSeq2 R package, we then identified genes with joint differential expression in GBM tissues subjected to chemotherapy. To develop a prognostic risk score model, we performed univariate and multivariate Cox regression analyses. In vitro knockdown and overexpression of MCM5 were used to further investigate the biological functions of GBM cells. Additionally, we also delved into the upstream regulation of MCM5, revealing associations with several transcription factors. Finally, we investigated differences in immune cell infiltration and drug sensitivity across diverse risk groups identified in the prognostic risk model.Results: In this study, the chemotherapy-treated GBM samples exhibited consistent alterations in 46 upregulated and 94 downregulated genes at both the mRNA and protein levels. Notably, MCM5 emerged as a gene with prognostic significance as well as potential therapeutic relevance. In vitro experiments subsequently validated the role of increased MCM5 expression in promoting GBM cell proliferation and resistance to TMZ. Correlations with transcription factors such as CREB1, CTCF, NFYB, NRF1, PBX1, TEAD1, and USF1 were discovered during upstream regulatory analysis, enriching our understanding of MCM5 regulatory mechanisms. The study additionally delves into immune cell infiltration and drug sensitivity, providing valuable insights for personalized treatment approaches.Conclusion: This study identifies MCM5 as a key player in GBM, demonstrating its prognostic significance and potential therapeutic relevance by elucidating its role in promoting cell proliferation and resistance to chemotherapy.Keywords: glioblastoma, minichromosome maintenance protein 5, chemotherapeutic drug resistance

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

The aim of this study is to scientifically substantiate the possibilities of complex use of cycle- and power-ergometry in determining aerobic and anaerobic-aerobic performance of power nature. Materials and methods. Young athletes (boys) aged 15–16 (n = 91) of the Brovary Higher School of Physical Education (Kyiv region) (experimental group), who participated in the study, were divided into two groups. Group А (n = 47) – speed-power sports (boxing, freestyle wrestling); group B (n = 44) – endurance sports (track and field athletics: 800, 1500, 3000 and 5000-meters race, bicycle racing 50 and 75 km). Sports experience was 3–5 years and more. The control group (group К) consisted of students aged 15–16, who did not play sports (n = 25). Physical working capacity was determined using two methods: submaximal cycle ergometric test PWC170 and submaximal power ergometric test PWC170. Method of power ergometry (patent of Ukraine No 49417) has no analogues in countries of near and far abroad. Results. The fact of the specific influence of different kinds of dosed physical exercises (strength and power exercises) on PWC170 indicators was established. Thus, no probable differences in aerobic performance indicators were found in wrestlers and boxers during the cycle ergometric test. And conversely, under the conditions of power ergometric testing, we find a significant increase in their PWC170 indicators in relation to athletes of endurance sports. The opposite character of changes was observed when testing the track and field athletes and bike riders. According to the results of the conducted cycle ergometry, these athletes had a significant increase in aerobic performance indicators in comparison with the athletes of speed-power sports. However, the changes of anaerobic-aerobic performance were not significant. It was observed that the adolescents, who did not play sports, had statistically insignificant changes in PWC170 indicators both in the conditions of cycle ergometric and power ergometric testing. Conclusions. The fact of specific influence of different types of training exercises on the body functions of adolescents was confirmed. The possibility of introducing the methods of complex use of aerobic (cycle ergometry) and anaerobic-aerobic loads (power-ergometry) into the practice of medico-biological control of young athletes is shown. Diagnostics of various types of physical working capacity (PWC170) will provide the coach with operational information about the functional state of the athletes’ body, which will allow to effectively manage a training process.

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

Background: Non-Hodgkin lymphoma (NHL) represents a heterogenous group of malignant lymphoproliferative neoplasms originating from lymphoid tissue cells and having distinct clinical, cytomorphological, immunological and molecular and genetic features. Primary orbital lymphomas are rare and account for approximately 1% of all NHL. Lymphomas are, however, the most common primary orbital tumor in adults 60 years of age and older. Purpose: To present a rare case of primary B-cell MALT lymphoma of marginal zone of the upper eyelid, to highlight its clinical features, and to demonstrate the importance of a multidisciplinary approach to its treatment. Results: A male patient presented to the eye clinic complaining of bilateral pterygium and periodic nasal congestion. Within the course of examination and prolonged observation, the ophthalmologist suspected the symptoms of massive orbital disease, and the patient was referred for magnetic resonance imaging (MRI) of the brain. On the basis of imaging assessment and the oncologist’s opinion, the patient was hospitalized at the Podillia Regional Oncology Center with a preliminary diagnosis of orbital lymphoma. Thereat, a final diagnosis of “extranodal, non-Hodgkin’s B-cell lymphoma of the marginal zone (MALT lymphoma) of Stage 3a, with metastases in the lungs, pleura and lymph nodes of the mediastinum” was established. At the moment, he is under observation by an oncologist and on the way to stabilization of his major disease. Conclusion: Management of orbital non-Hodgkin’s lymphomas remains a challenge requiring a multidisciplinary approach involving ophthalmologists and oncologists.

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

A mathematical model is developed that makes it possible, within the framework of a single phenomenological approach, to investigate the stability of a planar phase boundary during directional solidification of binary alloy, taking into account the effect of a density change and heat transfer in the solid phase. The study reveals a complex picture of alternating areas of stability and instability, which is sensitive to changes in parameters of growth and temperature gradient at the interface. Areas of instability are formed by the development of a set of disturbances of different frequencies and rates of propagations. As shown, the irreducible liquid-phase flow caused by density change plays a major role in the loss of stability of the solidification front and is realized for perturbations with any wave number k > 0.

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

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

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

BACKGROUND: While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing-associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimers disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age-associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. OBJECTIVE: We performed a pilot study to determine whether improving epidermal function reduces circulating pro-inflammatory cytokine levels in aged humans. METHODS: Thirty-three aged humans were topically treated twice-daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age-related, plasma cytokines (IL-1β, IL-6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. RESULTS: We also found significantly higher baseline levels of IL-1β, IL-6 and TNFα in aged vs. young humans (P

BACKGROUND:While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing-associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age-associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. OBJECTIVE:We performed a pilot study to determine whether improving epidermal function reduces circulating pro-inflammatory cytokine levels in aged humans. METHODS:Thirty-three aged humans were topically treated twice-daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age-related, plasma cytokines (IL-1β, IL-6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. RESULTS:We also found significantly higher baseline levels of IL-1β, IL-6 and TNFα in aged vs. young humans (P

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