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Ziyuan Yang,1,2 Jiaan Xu,3 Ting Kang,1,2 Xuepeng Chen,1,2 Chengcong Zhou4 1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 2Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, People’s Republic of China; 3College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Chengcong Zhou, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email 1092141931@qq.com Xuepeng Chen, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, 166 North Qiutao Road, Hangzhou, 310006, People’s Republic of China, Email cxp1979@zju.edu.cnAbstract: Osteoblasts (OBs), which are a crucial type of bone cells, derive from bone marrow mesenchymal stem cells (MSCs). Accumulating evidence suggests inflammatory cytokines can inhibit the differentiation and proliferation of OBs, as well as interfere with their ability to synthesize bone matrix, under inflammatory conditions. NLRP3 inflammasome is closely associated with cellular pyroptosis, which can lead to excessive release of pro-inflammatory cytokines, causing tissue damage and inflammatory responses, however, the comprehensive roles of NLRP3 inflammasome in OBs and their differentiation have not been fully elucidated, making targeting NLRP3 inflammasome approaches to treat diseases related to OBs uncertain. In this review, we provide a summary of NLRP3 inflammasome activation and its impact on OBs. We highlight the significant roles of NLRP3 inflammasome in regulating OBs differentiation and function. Furthermore, current available strategies to affect OBs function and osteogenic differentiation targeting NLRP3 inflammasome are listed and analyzed. Finally, through the prospective discussion, we seek to provide novel insights into the crucial role of NLRP3 inflammasome in diseases related to OBs and offer valuable information for devising treatment strategies.Keywords: osteoblast, pyroptosis, NLRP3 inflammasome, osteogenic differentiation

Yutao Peng,1 Chanjuan Zhou2 1Department of Function, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, People’s Republic of China; 2Department of Clinical Psychology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, People’s Republic of ChinaCorrespondence: Chanjuan Zhou, Department of Clinical psychology, The First Affiliated Hospital, Hengyang Medical School, University of South China, 69 Chuan Shan Road, Hengyang, Hunan, 421001, People’s Republic of China, Tel +86 13212694904, Email zhouchanjuan_86@163.comAim: Scutellaria baicalensis, a traditional Chinese medicinal herb renowned for its anti-inflammatory, antioxidant, and anti-tumor properties, has shown promise in alleviating cognitive impairment associated with Alzheimer’s disease. Nonetheless, the exact neuroprotective mechanism of Scutellaria baicalensis against Alzheimer’s disease remains unclear. In this study, network pharmacology was employed to explore the possible mechanisms by which Scutellaria baicalensis protects against Alzheimer’s disease.Methods: The active compounds of Scutellaria baicalensis were retrieved from the TCMSP database, and their corresponding targets were identified. Alzheimer’s disease-related targets were obtained through searches in the GeneCards and OMIM databases. Cytoscape 3.6.0 software was utilized to construct a regulatory network illustrating the “active ingredient-target” relationships. Subsequently, the target genes affected by Scutellaria baicalensis in the context of Alzheimer’s disease were input into the String database to establish a PPI network. GO analysis and KEGG analysis were conducted using the DAVID database to predict the potential pathways associated with these key targets. Following this, the capacity of these active ingredients to bind to core targets was confirmed through molecular docking. In vitro experiments were then carried out for further validation.Results: A total of 36 active ingredients from Scutellaria baicalensis were screened out, which corresponded to 365 targets. Molecular docking results demonstrated the robust binding abilities of Baicalein, Wogonin, and 5,2’-Dihydroxy-6,7,8-trimethoxyflavone to key target proteins (SRC, PIK3R1, and STAT3). In vitro experiments showed that the active components of Scutellaria baicalensis can inhibit STAT3 expression by downregulating the PIK3R1/SRC pathway in Neuro 2A cells.Conclusion: In summary, these findings collectively suggest that Scutellaria baicalensis holds promise as a viable treatment option for Alzheimer’s disease.Keywords: Scutellaria baicalensis, Alzheimer’s disease, network pharmacology, molecular docking

Houxi Xu,1,2,* Hongqun Zhang,1,3,* Songxian Sun,2 Jingyuan Zhang,2 Jiege Huo,1,3 Chunxiang Zhou2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing People’s Republic of China; 3The Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxiang Zhou, School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email chunxiangzhou@njucm.edu.cn Jiege Huo, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Email huojiege@jsatcm.comBackground: An increasing corpus of evidence has identified the involvement of N-acetyltransferase 1 (NAT1), a member of the NAT family, in the progression of various cancers. However, the specific function of NAT1 in colon cancer (COAD) remains elusive. This study aims to decip her the role of NAT1 in COAD and its associated mechanisms.Methods: The Tumor Immunity Evaluation Resource (TIMER), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases were employed to assess the NAT1 expression level in COAD. The differential expression between COAD and normal colon tissue was further validated using quantitative real-time reverse-transcription PCR (RT-qPCR) and Western blot (WB) analyses. Additionally, survival analysis of NAT1 in COAD was carried out using the PrognoScan database and TCGA dataset. The functions of NAT1 were explored through gene set enrichment analysis (GSEA) and immuno-infiltration analysis.Results: There was a significant reduction in NAT1 expression in COAD samples compared to normal tissue. Notably, low NAT1 expression in COAD correlated significantly with various clinical parameters such as tumor stage (T stage, N stage, M stage, pathologic stage), primary therapy outcome, carcinoembryonic antigen (CEA) level, and lymphatic invasion. The downregulation of NAT1 was also strongly linked with poor outcomes in overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). Cox regression analysis highlighted NAT1 as an independent prognostic indicator for overall survival in COAD patients. GSEA results revealed NAT1’s involvement in multiple pathways, including the neuroactive ligand-receptor interaction, olfactory transduction, olfactory signaling, extracellular matrix receptor interaction, calcium signaling, and focal adhesion pathways. Furthermore, NAT1 expression was found to significantly correlate with infiltration levels of various immune cells.Conclusion: The findings reveal NAT1’s potential as a valuable prognostic biomarker for COAD. Moreover, its associated mechanisms offer insights that might pave the way for therapeutic interventions for COAD patients.Keywords: NAT1, COAD, prognosis, immune infiltration, RT-qPCR, western blot

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

Simin Liu,1,2 Xiu Zhou,1,2 Huiying Jie,1,2 Zetong Zheng,1,2 Bing Cai,1,2 Qingyun Mai,1– 3 Canquan Zhou1– 3 1Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, People’s Republic of China; 3Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, People’s Republic of ChinaCorrespondence: Canquan Zhou, Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 1 Zhongshan Second Road, Guangzhou, 510080, People’s Republic of China, Fax +86 87330736, Email zhoucanquan@mail.sysu.edu.cnPurpose: To determine the impact of polycystic ovary syndrome on in vitro fertilization/intracytoplasmic sperm injection and embryo transfer outcomes while analyzing the influencing factors.Patients and Methods: A retrospective cohort study comprised 4839 patients who underwent their first cycle of IVF/ICSI treatment from January 2016 to December 2021. Cumulative pregnancy rates, cumulative live birth rates, and late miscarriage rates compared between the PCOS group and control group. Subgroup analysis and binary regression were used to analyze the influence of BMI on clinical outcomes among individuals diagnosed with PCOS.Results: Non-obese PCOS patients exhibited higher cumulative pregnancy rates, cumulative live birth rates, and late miscarriage rates compared to the control group with the normal BMI population (84.7% vs71.2%, P < 0.001; 74.1% vs 61.6%, P < 0.001; 4.1% vs 2.0%, P = 0.002), but there was no significant difference in early miscarriage rates between the two groups.Conclusion: Non-obese PCOS patients demonstrated a notably higher cumulative live birth rate but also a higher risk of late miscarriage compared to non-PCOS females with a normal BMI.Keywords: body mass index, cumulative live birth rate, in vitro fertilization, intracytoplasmic sperm injection, late miscarriage, polycystic ovary syndrome

Antao Lin,&ast; Yan Wang,&ast; Hao Zhang, Kai Zhu, Dan Zhou, Jianwei Guo, Wenhao Zhao, Chuanli Zhou, Xuexiao Ma Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuexiao Ma; Chuanli Zhou, Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266000, People’s Republic of China, Tel +8618661807895 ; +8618661809796, Email maxuexiaospinal@163.com; justin_5257@hotmail.comObjective: We explore the endoscopic revision and surgical techniques for L4/5 recurrent disc herniation (rLDH) after percutaneous endoscopic transforaminal discectomy (PETD).Methods: A retrospective study was conducted. From January 2016 to September 2022, 96 patients who underwent percutaneous endoscopic lumbar discectomy for L4/5 rLDH after PETD were enrolled in the study. Based on the revision approach, the patients were divided into PETD group (57 cases) and percutaneous endoscopic interlaminar discectomy (PEID) group (39 cases). Visual Analogue Scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and modified MacNab standard were recorded to evaluate the clinical outcomes.Results: No significant differences were found in the demographic data and intraoperative blood loss between the two groups (P> 0.05), but the time of operation and intraoperative X-ray fluoroscopy exposures in the PEID group were significantly less than that in the PETD group (P< 0.05). The patients’ postoperative clinical indexes gradually improved, and the VAS score, ODI index, and JOA score of the patients in both groups showed significant improvement compared with the preoperative period at the 1-week, 1-month, and 6-month postoperative follow-ups (P < 0.05). There was no serious complication observed during the follow-up.Conclusion: For recurrent LDH after PETD of L4/5 segments, percutaneous endoscopic revision can achieve satisfactory results. Among them, PEID has a shorter operative and fluoroscopy time and allows avoidance of the scar that forms after the initial surgery, so it can be considered preferred when both procedures can remove the disk well. However, for some specific types of herniation, a detailed surgical strategy is required.Keywords: endoscopic revision, recurrent lumbar disc herniation, percutaneous endoscopic lumbar discectomy

Li-Jen Cheng,1 Benfa Gong,2 Christopher H Young,3 Prabhuram Krishnan,1 Ying Wang,2 Hui Wei,2 Chunlin Zhou,2 Shuning Wei,2 Yan Li,2 Qiuyun Fang,2 Jia Zhong,4 Eric Q Wu,5 Yingchang Mi,2 Jianxiang Wang2 1Medical Affairs, Astellas Pharma Singapore Pte. Ltd., Singapore; 2Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People’s Republic of China; 3Advanced Informatics & Analytics, Astellas Pharma US Inc., Northbrook, IL, USA; 4Analysis Group, Inc., Beijing, People’s Republic of China; 5Analysis Group, Inc., Boston, MA, USACorrespondence: Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China, Tel +86 13821389157, Email wangjx@ihcams.ac.cnIntroduction: For acute myeloid leukemia (AML), prognosis is particularly poor in patients harboring FMS-like tyrosine kinase 3 (FLT3) gene mutations, though routine screening for these mutations at diagnosis has been shown to be insufficient. The understanding of the impact of FLT3 mutations on treatment decisions is limited.Methods: In this retrospective, observational study, we investigated the key epidemiological characteristics, treatment patterns and responses among adult patients with newly diagnosed (ND) AML in China, who initiated treatment from January 1, 2015, to December 31, 2019, or progressed to relapsed/refractory (R/R) AML by December 31, 2020.Results: Of the 853 ND AML patients included, 63.4% were screened for FLT3 status, and 20.1% tested positive (FLT3MUT) at initial diagnosis. Of 289 patients who progressed to R/R AML during the study period, 24.9% were screened at the diagnosis of R/R AML, and 19.4% tested positive; 20.5% of screened patients changed FLT3 status at first diagnosis of R/R AML. Initial treatment regimens or treatment responses did not seem to differ in patients with ND AML by FLT3 mutation status. In patients with R/R AML, there was an apparent difference in second-line treatment choices by FLT3 mutation status; however, the number of FLT3-mutated patients were limited to demonstrate any meaningful distinction. FLT3-mutated R/R AML was associated with shorter relapse time.Conclusion: Study findings showed that there was a lack of routine testing for FLT3 mutations at first diagnosis of R/R AML, and initial treatment decisions did not differ by FLT3 mutation status. Given the clinical burden of FLT3MUT, likelihood of FLT3 status changes, and emerging FLT3 inhibitors, further routine FLT3 screening is needed to optimize treatment of R/R AML. Keywords: acute myeloid leukemia, epidemiology, real-world, retrospective study

Yuye Chen,1 Yue Liu,2 Hong Lv,1 Qian Li,1 Jingjia Shen,1 Weiyun Chen,2 Jia Shi,1 Chenghui Zhou3 1Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, 100037, People’s Republic of China; 2Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of ChinaCorrespondence: Chenghui Zhou, Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-137-1889-4919, Email chenghuizhou@vip.163.com Jia Shi, Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases, No. 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email shijia@fuwai.comBackground: The potential myocardial protective effect of nicorandil (NICD) in patients undergoing percutaneous coronary intervention has been established. However, its efficacy in the context of cardiac surgery remains controversial. The present study aimed to evaluate the myocardial protective effect of perioperative NICD use in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).Methods: We retrospectively gathered data from patients undergoing cardiac bypass surgery between 12/2018 and 04/2021 in Fuwai Hospital. Subsequently, the patients were divided into two groups, NICD group and non-nicorandil (non-NICD) group. A 1, 3 propensity score matching (PSM) was conducted. The primary outcome was the incidence of myocardial injury. The secondary outcomes included the mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of chest drainage, the drainage volume, the total cost, the incidence of acute kidney injury (AKI), and the incidence of acute liver injury (ALI). Subsequently, we divided the entire population into two distinct subgroups based on their administration of NICD, and performed a comprehensive subgroup analysis.Results: A total of 2406 patients were ultimately included in the study. After PSM, 250 patients in NICD group and 750 patients in non-NICD group were included in the analysis. Perioperative NICD reduced the incidence of myocardial injury (47.2% versus 38.8%, P=0.025). Our subgroup analysis revealed that preoperative NICD administration not only provided myocardial protection benefits (45.7% vs 35.8%, OR 0.66, 95% CI [0.45– 0.97], P=0.041), but also demonstrated statistically significant reduction in ALI, the ICU and hospital LOS, and the duration of chest drainage (all P< 0.05).Conclusion: The perioperative NICD administration may confer myocardial protection in patients undergoing cardiac surgery with CPB. Furthermore, the preoperative utilization of NICD has the potential to mitigate the incidence of postoperative ALI, a reduction in the ICU and hospital LOS, and the duration of chest drainage.Keywords: nicorandil, cardiopulmonary bypass, perioperative myocardial injury, acute kidney injury, acute liver injury

Jiaxin Zeng,1,&ast; Chen Zhou,2,&ast; Qun Yi,1,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Huiguo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Jiarui Zhang,1 Lige Peng,1 Jiaqi Pu,1 Haixia Zhou1 On behalf of the MAGNET AECOPD Registry Investigators1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Center of Infectious Diseases, Division of Infectious Diseases in State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiu jiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cnBackground: The Rome severity classification is an objective assessment tool for the severity of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on readily measurable variables but has not been widely validated. The aim of this study is to evaluate the validity of the Rome classification in distinguishing the severity of AECOPD based on short-term mortality and other adverse outcomes.Methods: The Rome severity classification was applied to a large multicenter cohort of inpatients with AECOPD. Differences in clinical features, in-hospital and 60-day mortality, intensive care unit (ICU) admission, mechanical ventilation (MV) and invasive mechanical ventilation (IMV) usage were compared among the mild, moderate and severe AECOPD according to the Rome proposal. Moreover, univariate logistic analysis and Kaplan Meier survival analysis were also performed to find the association between the Rome severity classification and those adverse outcomes.Results: A total of 7712 patients hospitalized for AECOPD were included and classified into mild (41.88%), moderate (40.33%), or severe (17.79%) group according to the Rome proposal. The rate of ICU admission (6.4% vs 12.0% vs 14.9%, P < 0.001), MV (11.7% vs 33.7% vs 45.3%, P < 0.001) and IMV (1.4% vs 6.8% vs 8.9%, P < 0.001) increased significantly with the increase of severity classification from mild to moderate to severe AECOPD. The 60-day mortality was higher in the moderate or severe group than in the mild group (3.5% vs 1.9%, 4.3% vs 1.9%, respectively, P < 0.05) but showed no difference between the moderate and severe groups (2.6% vs 2.5%, P > 0.05), results for in-hospital mortality showed the same trends. Similar findings were observed by univariate logistic analysis and survival analysis.Conclusion: Rome severity classification demonstrated excellent performance in predicting ICU admission and the need for MV or IMV, but how it performs in differentiating short-term mortality still needs to be confirmed.Keywords: AECOPD, the Rome severity classification, short-term mortality, intensive care unit admission, mechanical ventilation, multicenter cohort

Chaoe Zhou,1,&ast; Jun Li,2,&ast; Fude Zhou,3 Lei Huang,4 Xinmin Liu,1 Haichao Li5 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 3Renal Division, Department of Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinmin Liu, Department of Geriatrics, Peking University First Hospital, Tel +86-10-8357-2128, Beijing, 100034, People’s Republic of China, Email lxm2128@163.com Haichao Li, Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Tel +86-10-8357-2128, Beijing, 100034, People’s Republic of China, Email lhch91767@sina.comAbstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported secondary Pneumocystis jirovecii pneumonia (PJP) infection during the treatment of DRESS syndrome. A 53-year-old man was admitted to the hospital due to a persistent fever lasting for 5 days. He had a medical history of hypertension, psoriasis, urticaria, and had recently been treated with carbamazepine for nerve spasm two weeks ago. After admission, the patient presented with a high fever accompanied by chills, abdominal pain, bilateral upper limb muscle pain, and generalized lymph nodes enlargement. Laboratory tests revealed elevated eosinophils and atypical lymphocytes. Subsequently, the patient developed multiple internal organ complications, including oliguria, elevated serum creatinine, liver enzymes, and cardiac troponin I. Based on diagnostic criteria, the patient was diagnosed with DRESS syndrome. To manage the DRESS syndrome, the patient was successively or simultaneously prescribed methylprednisolone, cyclosporin and intravenous immunoglobulin, resulting in an improvement of the condition. However, during the treatment, the patient was infected with Pneumocystis jirovecii. Despite targeted therapy with trimethoprim/sulfamethoxazole, primaquine and clindamycin successively, no remission was observed. Chest CT scans exhibited multiple exudations in both lungs, indicative of interstitial pneumonia. Unfortunately, the patient’s oxygenation progressively declined, leading to his untimely demise. This rare case further highlights the need for clinicians to be aware of the risk of Pneumocystis jirovecii infection in DRESS syndrome patients treated with long-term and high-dose glucocorticoid therapy.Keywords: DRESS syndrome, Pneumocystis jirovecii pneumonia, carbamazepine, glucocorticoid therapy, case report

Tao Sun,1,2 Shilin Xiao,1 Miaomiao Wang,1 Qian Xie,1 Liang Zhang,1 Mingfu Gong,1 Dong Zhang,1 Chunyu Zhou1 1Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, People’s Republic of ChinaCorrespondence: Dong Zhang; Chunyu Zhou, Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao Street, Shapingba District, Chongqing, People’s Republic of China, Tel +86 23 68763842, Email hszhangd@tmmu.edu.cn; zhouchy@tmmu.edu.cnAbstract: Acute liver injury (AIL), a fatal clinical disease featured with a swift deterioration of hepatocyte functions in the short term, has emerged as a serious public health issues that warrants attention. However, the effectiveness of existing small molecular antioxidants and anti-inflammatory medications in alleviating AIL remains uncertain. The unique inherent structural characteristics of liver confer it a natural propensity for nanoparticle capture, which present an opportunity to exploit in the formulation of nanoscale therapeutic agents, enabling their selective accumulation in the liver and thereby facilitating targeted therapeutic interventions. Significantly increased reactive oxygen species (ROS) accumulation and inflammation response have been evidenced to play crucial roles in occurrence and development of AIL. Nanozymes with ROS-scavenging capacities have demonstrated considerable promise in ROS elimination and inflammation regulation, thereby offering an appealing therapeutic instrument for the management of acute liver injury. In this review, the mechanisms of different type of ALI were summarized. In addition, we provide a comprehensive summary and review of the available ROS-scavenging nanozymes, including transition metal-based nanozymes, noble metal nanozymes, carbon-based nanozymes, and some other nanozymes. Furthermore, the challenges still need to be solved in the field of ROS-scavenging nanozymes for ALI alleviation are also discussed.Keywords: acute liver injury, nanozyme, ROS-scavenging, antioxidant, anti-inflammation

Yan Zhang,1 Haolin Jiang,2 Wenkai Xiang,3 Jun Zhu,3 Xueqin Hou,3 Shu Liang,1 Dan Yuan,1 Chang Zhou,1 Ling Su1 1Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People’s Republic of China; 2Department of Epidemiology and Statistics, Chengdu Medical College, Chengdu, People’s Republic of China; 3Center for AIDS/STD Control and Prevention, Guangyuan Center for Disease Control and Prevention, Guangyuan, People’s Republic of ChinaCorrespondence: Ling Su, Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, No. 6, Middle School Road, Wuhou District, Chengdu, Sichuan Province, 610000, People’s Republic of China, Tel +8618982092195, Email sl7512@163.comPurpose: Guangyuan was selected as the first pilot city of molecular transmission network in Sichuan Province to implement dynamic monitoring. This study aim to insight the characteristics of HIV-1 molecular epidemiology and explore the influencing factors of transmission dynamics. Furthermore, it predict the driving factors of network expansion by established a transmission risk prediction model.Patients and Methods: A longitudinal cohort study was conducted to obtain a total of 1434 plasma samples from newly diagnosed HIV-infected patients from 2010 to June 2022. Phylogenetic relationship and cluster analysis were performed using HIV-1 polymerase (pol) gene sequences to study the risk factors of clustering. We applied Logistic ML algorithms to establish a transmission risk prediction model, and model performance was checked using 10-fold cross-validation in the training set and receiver operating characteristic (ROC) curve analysis.Results: A total of 1360 pol sequences linked demographics obtained in this study cover approximately 94.8% of newly notified infections from 2010 to June 2022. The major epidemic genotypes were CRF07_BC, CRF01_AE, CRF08_BC and B subtypes, accounting for 93.82% of all. The differences of some clinical and demographic factors (eg, age, marital status) were statistically significant (P< 0.05). We identified 136 clusters containing 654 HIV-1 pol sequences and observed that some characteristics (eg, over 50 years, married) were more likely to associated to the clusters (P< 0.05). The predictive model showed excellent predictive ability to forecast cluster growth.Conclusion: The epidemic genotypes were relatively complex and diverse in Guangyuan. There was a potential transmission association caused widely spread in local area after the new strains entering. The transmission risk prediction model showed excellent predictive ability to forecast cluster growth which can predict the risk factors causing clusters expansion and provide a guidance for precise intervention strategies.Keywords: HIV-1, genotype, cluster analysis, transmission risk prediction model

Ze Liu,1,2 Chenhan Zhou,1,2 Hongbin Guo,1,2 Min Wang,2,3 Jieyu Liang,1,2 Yi Zhang1,2 1Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yi Zhang; Jieyu Liang, Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China, Email zhangyi0205@csu.edu.cn; jamesliang8@aliyun.comObjective: Thromboangiitis obliterans (TAO) is a segmental nonatherosclerotic inflammatory vascular disease characterized by recurrent progressive inflammatory reactions and thrombosis in the small and medium-sized arteries and veins of the extremities. However, there are few bibliometric studies on TAO. Therefore, this study was employed to generalize the research status, hotspots and development trends of TAO-related research.Methods: The data from 1999 to 2022 were collected from the Web of Science core collection database, and analyzed through bibliometrics software. VOSviewer was utilized to carry out academic collaboration between different countries/regions, institutions, and authors, visualization map of co-cited authors, journals, reference, and co-occurring keywords. CiteSpace was used to analyze the dual-map of journals, keyword bursts, and timeline of keywords. Bar and pie charts in this study were statistically analyzed and graphed through Microsoft Excel 2021. Scimago Graphica was applied to map the academic collaboration between different countries/regions.Results: A total of 553 literatures were involved in this study. Japan at the leading global position not only in the number of publications, but also total citations, average citations and H-index. Institution with the major contribution to TAO research is Mashhad University of Medical Sciences, and Nagoya University. Annals of Vascular Surgery, Angiology, Journal of Vascular Surgery are the main publication channel for articles related to TAO. Fazeli, B., Iwai, T., and Kihara, Y. are major contributors in this field. The studies on TAO keywords could be grouped into four clusters: Etiology, Mechanism, Cell therapy and Clinical therapy.Conclusion: Although the number of TAO publications has fluctuated over the past 20 years, it has generally shown a steady upward trend. Etiology and treatment research on TAO and some keywords such as trail, therapy, outcome, management, stem cells, angioplasty, and activation will become a hot spot in the future.Keywords: thromboangiitis obliterans, Buerger’s disease, bibliometrics analysis, visual analysis, web of science, CiteSpace, VOSviewer, scimago graphica

Jinpeng Shi,1,&ast; Jiayu Li,1,&ast; Haowei Wang,1,&ast; Xuefei Li,2 Qi Wang,1 Chao Zhao,2 Lei Cheng,2 Ruoshuang Han,1 Peixin Chen,1 Haoyue Guo,1 Zhuoran Tang,1 Caicun Zhou,1 Zhemin Zhang,1 Fengying Wu1 1Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengying Wu; Zhemin Zhang, Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, No. 507, Zheng Min Road, Shanghai, 200433, People’s Republic of China, Tel +86 21 6511 5006, Email fywu@163.com; zhemindoc@163.comPurpose: Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.Materials and Methods: We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.Results: Seven distinct TAN subtypes were defined, of which, the N3 cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N3 might be a pro-tumorigenic TAN subtype. N1 and N5 clusters were considered to be well differentiated and mature neutrophils based on CXCR2 expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.Conclusion: Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy. Keywords: tumor-associated neutrophil, single-cell RNA-sequencing, non-small cell lung cancer, tumor microenvironment, heterogeneity

Cong Zhou,1 Hui Zhang,1 Maosuo Xu,1 Yajuan Liu,1 Baoyu Yuan,2 Yong Lin,1 Fang Shen1 1Department of Clinical Laboratory, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Fang Shen; Yong Lin, Department of Clinical Laboratory, Shanghai Fifth People’s Hospital, Fudan University, No. 128, Ruili Road, Minhang District, Shanghai, 200240, People’s Republic of China, Tel +86 18021073261 ; +86 18718168695, Email shenfang5th@aliyun.com; linyong7007@163.comBackground: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has recently aroused an extremely severe health challenge and public concern. However, the underlying mechanisms of fitness costs that accompany antibiotic resistance acquisition remain largely unexplored. Here, we report a hv-CRKP-associated fatal infection and reveal a reduction in virulence due to the acquisition of aminoglycoside resistance.Methods: The bacterial identification, antimicrobial susceptibility, hypermucoviscosity, virulence factors, MLST and serotypes were profiled.The clonal homology and plasmid acquisition among hv-CRKP strains were detected by XbaI and S1-PFGE. The virulence potential of the strains was evaluated using Galleria mellonella larvae infection model, serum resistance assay, capsular polysaccharide quantification, and biofilm formation assay. Genomic variations were identified using whole-genome sequencing (WGS).Results: Four K. pneumoniae carbapenemase (KPC)-producing CRKP strains were consecutively isolated from an 86-year-old patient with severe pneumonia. Whole-genome sequencing (WGS) showed that all four hv-CRKP strains belonged to the ST11-KL64 clone. PFGE analysis revealed that the four ST11-KL64 hv-CRKP strains could be grouped into the same PFGE type. Under the pressure of antibiotics, the antimicrobial resistance of the strains increased and the virulence potential decreased. Further sequencing, using the Nanopore platform, was performed on three representative isolates (WYKP586, WYKP589, and WYKP594). Genomic analysis showed that the plasmids of these three strains underwent a large number of breaks and recombination events under antibiotic pressure. We found that as aminoglycoside resistance emerged via acquisition of the rmtB gene, the hypermucoviscosity and virulence of the strains decreased because of internal mutations in the rmpA and rmpA2 genes.Conclusion: This study shows that ST11-KL64 hv-CRKP can further evolve to acquire aminoglycoside resistance accompanied by decreased virulence to adapt to antibiotic pressure in the host.Keywords: hypervirulent carbapenem-resistant Klebsiella pneumoniae, within-host evolution, plasmids, whole-genome sequencing

Chongchong Zhou,1,2,&ast; Jingxuan Wei,1,&ast; Kai Xu,1 Yingtao Lin,3,4 Lingli Zhang,1 Xin Li1,4,5 1Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Research Management, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Department of Drug Clinical Trial Institution, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 4Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Health Policy, School of Health Policy and Management, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Li; Lingli Zhang, School of Pharmacy, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, People’s Republic of China, Email xinli@njmu.edu.cn; zhanglingli@njmu.edu.cnBackground: Tislelizumab plus chemotherapy improved overall survival compared to chemotherapy alone, while maintaining an acceptable level of safety. But it’s still unclear which strategy is the most cost-effective. The objective of the study was to compare the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) versus chemotherapy alone.Methods: A partitioned survival model with three states was constructed based on the RATIONALE-306 trial. The model’s time horizon was ten years, and its cycle was three weeks. Only direct medical costs were considered from the healthcare perspective in China. Calculations were performed on total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity and probabilistic sensitivity analysis (PSA) were performed to determine the uncertainty regarding model parameters.Results: Tislelizumab plus chemotherapy provided 1.35 QALYs for &dollar;26,450.77, while chemotherapy alone provided 0.89 QALY for &dollar;16,687.15. Compared to chemotherapy alone, tislelizumab had an ICER of &dollar;21,062.09/QALY. At the threshold of three times the Chinese GDP per capita (&dollar;38,253/QALY), the PSA indicated that tislelizumab had a 96.4% likelihood of being designated cost-effective. At the threshold of 1.5 times the Chinese GDP per capita (&dollar;19,126.5/QALY), the PSA indicated that tislelizumab had a probability of 48.7% of being designated cost-effective.Conclusion: Tislelizumab plus chemotherapy as the first treatment for patients with advanced or metastatic ESCC may be a cost-effective option compared to chemotherapy alone at 3 times Chinese GDP per capita.Keywords: esophageal squamous cell carcinoma, cost-effectiveness, partitioned survival model, tislelizumab

Ximing Peng,1,&ast; Xin Liu,2,&ast; Yanqing Yang,1,&ast; Mingwei Yu,1 Zhiwei Sun,1 Xiangru Chen,1 Keqiang Hu,1 Jing Yang,1 Shaotang Xiong,2 Bin Wang,2 Liya Ma,3 Zhenxing Wang,4 Hanxiao Cheng,5,&ast; Chuchao Zhou1,&ast; 1Department of Plastic Surgery, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, 430060, People’s Republic of China; 2Medical Aesthetic Department, The Second People’s Hospital of China Three Gorges University, The Second People’s Hospital of Yichang, Yichang, Hubei, People’s Republic of China; 3The Centre of Analysis and Measurement of Wuhan University, Wuhan University, Wuhan, 430072, People’s Republic of China; 4Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Plastic Surgery, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, 310006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanxiao Cheng; Chuchao Zhou, Email chxmomo@sina.com; chuchaozhou@163.comIntroduction: The formation of bone-like apatite (Ap) on natural polymers through biomimetic mineralization using simulated body fluid (SBF) can improve osteoconductivity and biocompatibility, while lowering immunological rejection. Nonetheless, the coating efficiency of the bone-like Ap layer on natural polymers requires improvement. Carbonyls (-COOH) and hydroxyls (-OH) are abundant in graphene oxide (GO), which may offer more active sites for biomimetic mineralization and promote the proliferation of rat bone marrow stromal cells (BMSCs).Methods: In this study, gelatin methacryloyl (GelMA) microgels were infused with GO (0, 0.5, 1, and 2 mg/mL) and embedded into microgels in SBF for 1, 7, and 14 days. Systematic in vitro and in vivo experiments were performed to evaluate the structure of the microgel and its effect on cell proliferation and ability to repair bone defects in rats.Results: The resulting GO-GelMA-Ap microgels displayed a porous, interconnected structure with uniformly coated surfaces in bone-like Ap, and the Ca/P ratio of the 1 mg/mL GO-GelMA-Ap group was comparable to that of natural bone tissue. Moreover, the 1 mg/mL GO-GelMA-Ap group exhibited a greater Ap abundance, enhanced proliferation of BMSCs in vitro and increased bone formation in vivo compared to the GelMA-Ap group.Discussion: Overall, this study offers a novel method for incorporating GO into microgels for bone tissue engineering to promote biomimetic mineralization.Graphical-Abstract: Keywords: graphene oxide, gelatin methacryloyl, bone-like apatite, biomimetic mineralization, simulated body fluid, bone repair

Tao Wang,1,2,&ast; Qianwen Yang,3,&ast; Yan Gao,2 Rongping Zhang,2 Chaoxin Zhou,2 Weifang Kong,1 Guojin Zhang,1 Xinyue Chen,4 Hong Pu,1 Lan Shang1 1Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Liangshan Yi Autonomous Prefecture, Xichang, Sichuan, People’s Republic of China; 3School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4CT Collaboration, Siemens-Healthineers, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Pu; Lan Shang, Department of Radiology, The First Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, Sichuan Province, 60072, People’s Republic of China, Tel +86 13882267217, Fax +86 87294280, Email ph196797@163.com; shanglan8282@163.comPurpose: This study aimed to investigate clinical features and computed tomography (CT) manifestations of rifampicin primary drug-resistant pulmonary tuberculosis in Liangshan Yi Autonomous Prefecture.Patients and Methods: A total of 100 inpatients with confirmed primary rifampicin-resistant pulmonary tuberculosis were recruited from January 2020 to December 2022 at an infectious disease hospital located in the Liangshan Yi Autonomous Prefecture. Additionally, 100 inpatients with confirmed drug-susceptible pulmonary tuberculosis during the same period were matched to the rifampicin-resistant group based on gender, age, and ethnicity. The clinical characteristics of the two groups were recorded separately. Furthermore, the CT manifestations in these patients were independently analyzed by three radiologists.Results: The results showed that comorbid diabetes mellitus was more prevalent in the drug-resistant tuberculosis (DR-TB) group than in the drug-susceptible tuberculosis (DS-TB) group (9% vs 0%, p=0.0032). In terms of imaging presentation, DR-TB patients exhibited a higher frequency of calcifications (55% vs 35.00%, p=0.0068), greater median number of cavities (5 vs 2, p=0.0027), and larger maximum cavity diameter (52.08± 25.55 mm vs 42.72± 17.48 mm, p=0.0097). Additionally, bilateral involvement was more common in DR-TB patients at the site of the lesion (89% vs 76%, p=0.0246), with a higher prevalence in the right middle (82% vs 68%, p=0.0332), right lower (82% vs 68%, p=0.0332), left upper (91% vs 77%, p=0.0113), and left lower lobes (92% vs 66%, p< 0.0001). Conversely, the involvement of only one lobe was less frequent in patients with DR-TB than in those with DS-TB (4% vs 13%, p=0.0398), whereas the involvement of all five lobes was more common (68% vs 51%, p=0.0209).Conclusion: Patients with DR-TB exhibit a higher prevalence of severe imaging manifestations, highlighting the importance of CT in the early detection and diagnosis of DR-TB.Keywords: drug-resistant tuberculosis, drug-susceptible tuberculosis, tuberculosis, comorbid diabetes mellitus

Jingjing Li,1,&ast; Yabing Liu,1,&ast; Wenxuan Zeng,2 Yanrun Wu,3 Wei Ao,4 Xiwei Yuan,1 Chuanyi Zhou1 1Department of Oncology, Yueyang People’s Hospital, Yueyang City, Hunan Province, 414000, People’s Republic of China; 2Department of Cardiovascular, Yueyang Central Hospital, Yueyang City, Hunan Province, 414000, People’s Republic of China; 3Department of Ultrasonic, Yueyang Central Hospital, Yueyang City, Hunan Province, 414000, People’s Republic of China; 4Department of Cardiovascular, Yueyang People’s Hospital, Yueyang City, Hunan Province, 414000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiwei Yuan; Chuanyi Zhou, Department of Oncology, Yueyang People’s Hospital, No. 263, Baling East Road, Yueyanglou District, Yueyang City, Hunan Province, People’s Republic of China, Email csj13590308660@126.com; Zzbc138092@126.comObjective: To analyze the correlation between the expression of circFAT1 in serum and immune cells in patients with non-small cell lung cancer (NSCLC).Methods: A total of 96 patients with NSCLC admitted to our hospital from November 2019 to November 2022 were regarded as the study subjects. In the meantime, 96 volunteers who had physical examination in our hospital were regarded as the control group. The expression level of circFAT1 in serum was detected by real-time fluorescence quantitative PCR. NSCLC cancer tissue (NSCLC group) and paracancerous tissue (tissue ≥ 2cm away from the focus) (paracancerous group) were collected during the operation, the expression of CD4+, CD8+ and Foxp3+ in tissues was determined by immunohistochemistry; the expression level of circFAT1 mRNA in NSCLC tissue was analyzed using the Ualcan database. Spearman correlation was applied to analyze the correlation between the expression of circFAT1 and immune cells (CD4+, Foxp3+, CD8+).Results: The level of circFAT1 in NSCLC tissue was higher than that in normal tissue (P < 0.05). Compared with the control group, the expression level of circFAT1 in serum of NSCLC group was obviously higher (P < 0.05). The expression level of circFAT1 was related to lymph node metastasis, TNM stage and differentiation (P < 0.05). Compared with the paracancerous group, the positive expression rate of CD8+ in NSCLC group was obviously lower, and the positive expression rates of CD4+ and Foxp3+ were obviously higher (P < 0.05). The expression of CD4+, Foxp3+ and CD8+ in NSCLC patients’ cancer tissue was related to lymph node metastasis, TNM stage and differentiation degree (P < 0.05). Spearman correlation analysis showed that circFAT1 was positively correlated with the expression of CD4+ and Foxp3+ and negatively correlated with the expression of CD8+ (P < 0.05).Conclusion: CircFAT1 is highly expressed in the serum of NSCLC patients and is closely related to immune cells.Keywords: non-small cell lung cancer, circFAT1, immune microenvironment, correlation

Chaoe Zhou,1 Liying Sun,2 Haixia Li,2 Lei Huang,2,&ast; Xinmin Liu1,&ast; 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinmin Liu, Department of Geriatrics, Peking University First Hospital, Beijing, 100034, People’s Republic of China, Tel +86-10-8357-2128, Email lxm2128@163.com Lei Huang, Department of Clinical Laboratory, Peking University First Hospital, Beijing, 100034, People’s Republic of China, Tel +86-10-8357-5546, Email leihuang2031@bjmu.edu.cnPurpose: Hospital-acquired pneumonia (HAP) caused by carbapenem-resistant K. pneumoniae (CRKP), especially in elderly patients, results in high morbidity and mortality. Studies on risk factors, mortality, and antimicrobial susceptibility of CRKP pulmonary infection among elderly patients are lacking.Patients and Methods: A retrospective case–control study was conducted from January 2019 to December 2021. The elderly inpatients (≥ 65 years) who were diagnosed with HAP caused by K. pneumoniae were enrolled. Clinical data were collected. Univariate and multivariate logistic regression analyses were used to identify risk factors. Propensity score matching was used to minimize the effect of potential confounding variables. Kaplan–Meier analysis was used to compare survival.Results: A total of 115 patients with CRKP infection and 78 patients with carbapenem-susceptible K. pneumoniae (CSKP) infection were recruited. There were four independent risk factors for CRKP infection: history of intensive care unit (ICU) stays from hospital admission to positive respiratory specimen culture for K. pneumoniae (odds ratio (OR)=2.530), Charlson comorbidity index score ≥ 3 (OR = 2.420), prior exposure to carbapenems (OR = 5.280), and prior K. pneumoniae infection or colonization in the preceding 3 years (OR = 18.529). The all-cause 30-day mortality was 22.3%, the mortality of CRKP and CSKP infection was 28.7% and 12.8%, respectively. Independent risk factors for mortality included: older age (OR = 1.107), immunocompromised patients (OR = 8.632), severe pneumonia (OR = 51.244), quick Sepsis-related Organ Failure Assessment (qSOFA) score ≥ 2 (OR = 6.187), exposure to tigecycline before infection (OR = 24.702), and prolonged ICU stay (OR = 0.987). Thirty-day mortality was significantly lower in patients receiving ceftazidime-avibactam (CAZ-AVI) containing regimens than patients receiving polymyxin B sulfate (PB) containing regimens (P = 0.048). qSOFA score had a good prognostic effect [area under receiver operating characteristic curve (AUROC) of 0.838].Conclusion: Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.Keywords: elderly, hospital-acquired pneumonia, CRKP, CSKP, ceftazidime-avibactam, qSOFA

Wenzhao Wang,1,2,&ast; Pan Liu,3,&ast; Boqing Zhang,4 Xingyu Gui,4 Xuan Pei,5 Ping Song,2 Xia Yu,6 Zhengdong Zhang,7,8 Changchun Zhou4 1Department of Orthopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 4National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Department of Clinical Laboratory, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 7School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 8Department of Orthopedics, the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Yu; Zhengdong Zhang, Email irisyue2021@uestc.edu.cn; doctorzzd@vip.qq.comPurpose: Large bone defects caused by congenital defects, infections, degenerative diseases, trauma, and tumors often require personalized shapes and rapid reconstruction of the bone tissue. Three-dimensional (3D)-printed bone tissue engineering scaffolds exhibit promising application potential. Fused deposition modeling (FDM) technology can flexibly select and prepare printed biomaterials and design and fabricate bionic microstructures to promote personalized large bone defect repair. FDM-3D printing technology was used to prepare polylactic acid (PLA)/nano β-tricalcium phosphate (TCP) composite bone tissue engineering scaffolds in this study. The ability of the bone-tissue-engineered scaffold to repair bone defects was evaluated in vivo and in vitro.Methods: PLA/nano-TCP composite bone tissue engineering scaffolds were prepared using FDM-3D printing technology. The characterization data of the scaffolds were obtained using relevant detection methods. The physical and chemical properties, biocompatibility, and in vitro osteogenic capacity of the scaffolds were investigated, and their bone repair capacity was evaluated using an in vivo animal model of rabbit femur bone defects.Results: The FDM-printed PLA/nano β-TCP composite scaffolds exhibited good personalized porosity and shape, and their osteogenic ability, biocompatibility, and bone repair ability in vivo were superior to those of pure PLA. The merits of biodegradable PLA and bioactive nano β-TCP ceramics were combined to improve the overall biological performance of the composites.Conclusion: The FDM-printed PLA/nano-β-TCP composite scaffold with a ratio of 7:3 exhibited good personalized porosity and shape, as well as good osteogenic ability, biocompatibility, and bone repair ability. This study provides a promising strategy for treating large bone defects.Keywords: fused deposition modeling, PLA/nano β-TCP, composited biomaterials, large bone defect, osteoinduction

Jincheng Xiao,1,&ast; Jing Wang,2,&ast; Chaoqun Zhou,3 Junpeng Luo4,5 1Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2Department of General Medicine, the First Medical Center, Department of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Pathology, Huaihe Hospital, Henan University, Henan University, Kaifeng, 475000, People’s Republic of China; 4Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, 475000, People’s Republic of China; 5Academy for Advanced Interdisciplinary Studies, Henan University, Zhengzhou, 450046, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junpeng Luo, Translational Medical Center of Huaihe Hospital, Henan University, 115 West Gate Street, Kaifeng, 475000, People’s Republic of China, Tel/Fax +86 371 23999999, Email hiccp@henu.edu.cnBackground: Studies have demonstrated that propionate metabolism-related genes (PMRGs) are associated with cancer progression. PMRGs are not known to be involved in Hepatocellular carcinoma (HCC).Methods: In this study, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were accessed for HCC-related transcriptome data and clinical information. First, DE-PMRGs were derived by intersecting PMRGs and DEGs between HCC tissues and normal controls. The clusterProfiler R package was then used to enrich DE-PMRGs. In addition, biomarkers of HCC were identified, and a prognostic model was developed. Using functional analysis and tumor microenvironment analysis, new insights were obtained into HCC. The expression of biomarkers was validated using quantitative real-time polymerase chain reaction (qRT-PCR).Results: 132 DE-PMRGs were obtained by intersecting 3690 DEGs and 291 PMRGs. Steroid and organic acid metabolism were associated with these genes. For the construction of the risk model for HCC samples, five biomarkers were identified, including Acyl-CoA dehydrogenase short chain (ACADS), CYP19A1, formiminotransferase cyclodeaminase (FTCD), glucose-6-phosphate dehydrogenase (G6PD), and glutamic-oxaloacetic transaminase (GOT2). ACADS, FTCD, and GOT2 were positive factors, whereas CYP19A1 and G6PD were negative. HCC patients with AUC greater than 0.6 were predicted to survive 1/2/3/4/5 years, indicating decent efficiency of the model. The probability of 1/3/5-survival for HCC was also predicted by the nomogram using the risk score, pathologic T stage, and cancer status. Moreover, functional enrichment analysis revealed the high-risk genes were associated with invasion and epithelial-mesenchymal transition. Significantly, immune cell infiltration and immune checkpoint expression were linked to HCC development.Conclusion: This study identified five biomarkers of propionate metabolism that can predict HCC prognosis. This finding may provide a deeper understanding of PMRG function in HCC.Keywords: Hepatocellular carcinoma, propionate metabolism-related genes, prognosis, biomarkers, tumor microenvironment

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

Ling Yang,1,2 Maolin Cao,3 Jing Tian,1 Peijin Cui,1 Ling Ai,3 Xue Li,4 Hua Li,5 Menghan Gao,1 Liang Fang,1,2,6 Libo Zhao,1,2 Fang Gong,2,6 Chanjuan Zhou1,3,4,6 1Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, People’s Republic of China; 3Department of General Practice, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Central Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Ophthalmology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Chongqing Clinical Research Center for Geriatric Disease, Chongqing, People’s Republic of ChinaCorrespondence: Fang Gong; Chanjuan Zhou, Yongchuan Hospital of Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan, Chongqing, 402160, People’s Republic of China, Email 1512367841@qq.com; chanjuanzhou@hospital.cqmu.edu.cnPurpose: The quality of life of worldwide adolescents has been seriously affected by depression. Notably, the inflammatory response is closely associated with the pathophysiology of depression. The present study applied a novel targeted proteomics technology, Olink proximity extension assay (PEA), to profile circulating immune-related proteins in adolescents with depression.Methods: In the present study, the expression levels of 92 inflammation-related proteins were compared between adolescents with depression (ADs) (n=15) and healthy controls (HCs) (n=15), using the OLINK PEA inflammation panel. We further validated 5 top proteins that were identified through KEGG and GO analyses between 40 HCs and 50 ADs, including CCL4, CXCL5, CXCL6, CXCL11, and IL-18 using enzyme linked immunosorbent assay (ELISA).Results: We identified 13 differentially expressed proteins between the two cohorts, including 5 up-regulated and 8 down-regulated proteins. Among them, the TRAIL protein levels were significantly negatively correlated with the HAMA-14 score (r=− 0.538, p= 0.038), and the levels of transforming growth factor α (TGF-α) were significantly associated with a change in appetite (r = -0.658, p = 0.008). After validation by ELISA, CCL4, CXCL5, CXCL11, and IL-18 showed significant changes between ADs and HCs (p < 0.05), while CXCL6 showed an up-regulated tendency in ADs (p=0.0673). The pooled diagnostic efficacy (area under the curve [AUC]) of these five inflammation markers in clinical diagnosis for adolescent depression was 0.819 (95% CI: 0.735– 0.904).Conclusion: We report a number of inflammation-related plasma biomarkers, which uncover a potential involvement of chemokines, cytokines, and cytokine receptors in adolescent depression. Their roles in the pathophysiology of depression need to be further elucidated.Keywords: olink proximity extension assay, biomarkers, adolescent depression, inflammation

Chengxu Zhou,1 Guilan Yu,1 Ying Meng,2 Ang Li3 1School of Business and Management, Jilin University, Changchun, People’s Republic of China; 2Yatai School of Business Administration, Jilin University of Finance and Economics, Changchun, People’s Republic of China; 3Dalian Base, China Southern Technic Branch, Dalian, People’s Republic of ChinaCorrespondence: Chengxu Zhou, School of Business and Management, Jilin University, Changchun, Jilin, 130015, People’s Republic of China, Tel +86 155 0001 9909, Email zhoucx17@mails.jlu.edu.cnPurpose: The dynamic and complex external environment calls for leaders to be both benevolent and authoritarian to cope with the mutually exclusive demands in the management process. But few research paid attention to the dark side of leaders’ inconsistent behaviors on employees’ work outcomes. Based on social information processing theory, this study investigated the impact of authoritarian-benevolent leadership on subordinates’ work engagement and explored the mediating role of leader-member exchange ambivalence and the moderating role of trait mindfulness.Methods: A two-wave time-lagged survey approach was employed and data from 309 employees from three Chinese companies were collected. R 4.2.1 and SPSS 26.0 were used to test our hypotheses.Results: The findings demonstrated how subordinates were influenced in their work engagement by authoritarian-benevolent leadership and leader-member exchange ambivalence and emphasized the value of maintaining a high level of trait mindfulness. This study indicated that (1) authoritarian-benevolent leadership was negatively associated with work engagement, which was mediated by leader-member exchange ambivalence; (2) subordinates’ trait mindfulness moderated the relationship between leader-member exchange ambivalence and work engagement; (3) the indirect effect of authoritarian-benevolent leadership on subordinates’ work engagement through leader-member exchange ambivalence was moderated by subordinates’ trait mindfulness.Conclusion: This study reveals the dark side of authoritarian-benevolent leadership and deepens our understanding of the mechanism underlying the effect of authoritarian-benevolent leadership on subordinates’ work engagement from a new theoretical perspective. Practical implications are provided for managers to effectively develop authoritarian-benevolent leadership skills and improve subordinates’ work engagement.Keywords: authoritarian-benevolent leadership, work engagement, leader-member exchange ambivalence, trait mindfulness

Hang Lin,1,2 Cui Zhou,1 Kai-Hang Yu,3 Yi-Shuai Lin,1 Ling-Bo Wang,1 Ying Zhang,1 Shi-Xing Liu,1 Wen-Ya Xu,1 Yao Sun,1 Tie-Li Zhou,1 Jian-Ming Cao,4 Jian-Zhong Ye1 1Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenhzou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 3Pathology Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Tie-Li Zhou; Jian-Zhong Ye, Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, 325000, People’s Republic of China, Email wyztli@163.com; jzye89@163.comObjective: Acinetobacter baumannii is a hazardous bacterium that causes hospital-acquired nosocomial infections, and the advent of multidrug-resistant A. baumannii (MDR-AB) strains is concerning. Novel antibacterial therapeutic strategies must be developed. The biological effects of glabridin on MDR-AB were investigated in this study.Methods: The minimum inhibitory concentrations (MICs) of glabridin against eight clinical MDR-AB strains were determined using the broth microdilution technique. Crystal violet staining was used to assess biofilm development, which has significant contribution to bacterial resistance. Swarming motility was measured according to surface growth zone of MDR-AB on LB agar medium. qRT-PCR was used to evaluate the expression of quorum sensing genes abaI and abaR. Glabridin and routinely used therapeutic antimicrobial agents were tested for synergistic action using the checkerboard method.Results: According to our findings, glabridin suppressed MDR-AB growth at high doses (512– 1024 μg/mL). The 1/4 MIC of glabridin significantly decreased MDR-AB biofilm formation by 19.98% (P < 0.05), inhibited MDR-AB motility by 44.27% (P < 0.05), whereas the 1/2 MIC of glabridin dramatically reduced MDR-AB biofilm development by 27.43% (P < 0.01), suppressed MDR-AB motility by 50.64% (P < 0.05). Mechanistically, glabridin substantially downregulated the expression of quorum sensing-related genes abaI and abaR by up to 39.12% (P < 0.001) and 25.19% (P < 0.01), respectively. However, no synergistic effect between glabridin and antibacterial drugs was found.Conclusion: Glabridin might be a quorum sensing inhibitor that inhibits MDR-AB biofilm development and swarming motility.Keywords: Acinetobacter baumannii, multidrug-resistance, glabridin, quorum sensing

Tianyou Chen,1,&ast; Chong Liu,1 Zide Zhang,2 Tuo Liang,2 Jichong Zhu,1 Chenxing Zhou,1 Shaofeng Wu,1 Yuanlin Yao,1,&ast; Chengqian Huang,1 Bin Zhang,1 Sitan Feng,1 Zequn Wang,1 Shengsheng Huang,1 Xuhua Sun,1 Liyi Chen,1 Xinli Zhan1 1Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Spine Ward, Liuzhou People’s Hospital, Liuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Zhan, Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email zhanxinli@stu.gxmu.edu.cnObjective: The objective of this study was to utilize machine learning techniques to analyze perioperative factors and identify blood glucose levels that can predict the occurrence of surgical site infection following posterior lumbar spinal surgery.Methods: A total of 4019 patients receiving lumbar internal fixation surgery from an institute were enrolled between June 2012 and February 2021. First, the filtered data were randomized into the test and verification groups. Second, in the test group, specific variables were screened using logistic regression analysis, Lasso regression analysis, support vector machine, and random forest. Specific variables obtained using the four methods were intersected, and a dynamic model was constructed. ROC and calibration curves were constructed to assess model performance. Finally, internal model performance was verified in the verification group using ROC and calibration curves.Results: The data from 4019 patients were collected. In total, 1327 eligible cases were selected. By combining logistic regression analysis with three machine learning algorithms, this study identified four predictors associated with SSI, namely Modic changes, sebum thickness, hemoglobin, and glucose. Using this information, a prediction model was developed and visually represented. Then, we constructed ROC and calibration curves using the test group; the area under the ROC curve was 0.988. Further, calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index of our model was 0.986 (95% CI 0.981– 0.994). Finally, we used the validation group to validate the model internally; the AUC was 0.987. Calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index was 0.982 (95% CI 0.974– 0.999).Conclusion: Logistic regression analysis and machine learning were employed to select four risk factors: Modic changes, sebum thickness, hemoglobin, and glucose. Then, a dynamic prediction model was constructed to help clinicians simplify the monitoring and prevention of SSI.Keywords: surgical site infection, lumbar spine surgery, machine learning, blood glucose, dynamic prediction model

Fei Wu,1,2,&ast; Haitao Sun,1,2,&ast; Zhang Shi,1,2 Changwu Zhou,1– 3 Peng Huang,1,2 Yuyao Xiao,1,2 Chun Yang,1,2 Mengsu Zeng1– 3 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengsu Zeng, Department of Radiology, Zhongshan Hospital, Fudan University; Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 13501922963, Email zeng.mengsu@zs-hospital.sh.cn Chun Yang, Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18702135336, Email dryangchun@hotmail.comObjective: To determine the preoperative clinicoradiological factors to predict microvascular invasion (MVI) in patients with resectable multinodular hepatocellular carcinoma (mHCC), and further to establish and validate a stratified risk scoring system.Methods: Two hundred and seventy-three patients with pathologically confirmed mHCC (≥ 2 lesions) without major vascular invasion and biliary tract tumor thrombosis, who underwent preoperative contrast-enhanced MRI and hepatectomy, were consecutively enrolled (training/validation cohort=193/80). Preoperative clinicoradiological variables were collected and analyzed. The multivariable logistic regression was performed to determine the independent predictors of MVI and create a risk score system. The C-index, calibration curve and decision curve were used to evaluate the performance of the risk score. A risk score-based prognostic stratification system was performed in mHCC patients. The risk score system was further verified in the validation cohort.Results: AFP > 400 ng/mL, presence of satellite nodule, mosaic architecture and increased total tumor diameter were independent predictors of MVI while fat in mass was an independent protective factor of MVI. The risk score yielded satisfactory C-index values (training/validation cohort: 0.777/0.758) and fitted well in calibration curves. Decision curve analysis further confirmed its clinical utility. Based on the risk score, mHCC patients were stratified into high-/low-MVI-risk subgroups with significantly different recurrence-free survival (both P < 0.001).Conclusion: The presented risk score incorporating clinicoradiological parameters could stratify mHCC patients into high-risk and low-risk subgroups and predict prognosis in patients with resectable mHCC.Keywords: hepatocellular carcinoma, prognosis, magnetic resonance imaging, statistical model

Yuyi Zhang,1 Suzhen Wang,1 Chunmei Zhou,1 Yao Zhang,2 Jue Pan,2 Baishen Pan,1 Beili Wang,1 Bijie Hu,2 Wei Guo1 1Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Infectious Disease, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Wei Guo, Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel/Fax +86-21-64041990-2376, Email guo.wei@zs-hospital.sh.cn Bijie Hu, Department of Infectious Disease, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel/Fax +86-21-64041990-2328, Email hu.bijie@zs-hospital.sh.cnBackground: Aspergillus species are becoming a major public health concern worldwide due to the increase in the incidence of aspergillosis and emergence of antifungal resistance. In this study, we surveyed all Aspergillus species isolated from aspergillosis patients in Zhongshan Hospital Fudan University, Shanghai, China, from 2019 to 2021.Methods: We characterized the susceptibility profiles of these Aspergillus species to medical azoles (voriconazole, itraconazole and posaconazole) using YeastOneTM broth microdilution system. To determine the underlying antifungal resistance mechanisms in azole-resistant A. fumigatus (ARAf) isolates, we characterized mutations in the cyp51A gene. Genotypic diversity of sampled A. fumigatus was investigated using CSP-typing.Results: A total of 112 Aspergillus isolates (81 A. fumigatus, 17 A. flavus, 5 A. niger, 2 A. terreus, 2 A. lentulus, 2 A. oryzae, 1 A. nidulans, 1 A. versicolor and 1 A. sydowii) from 105 patients diagnosed with aspergillosis (including proven or probable invasive aspergillosis, chronic pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and cutaneous aspergillosis) were obtained. Eight isolates (7 A. fumigatus and 1 A. niger) from seven patients were either azole non-susceptible or non-wild type. Azole non-susceptible or non-wild type rate was 7.1%/isolate and 6.7%/patient analysed. Four ARAf harbored TR34/L98H mutation, whereas one carried TR46/Y121F/T289A allele. The 81 A. fumigatus isolates were spread across 8 CSP types with t01 to be the predominant type (53.1%). ARAf isolates were distributed over CSP types t01, t02, t04A and t11.Conclusion: Results from this study provided us with an understanding of the antifungal resistance and related characteristics of Aspergillus species in Eastern China. Further comparisons of our results with those in other countries reflect potential clonal expansion of A. fumigatus in our region. Further surveillance study is warranted to guide antifungal therapy and for epidemiological purposes.Keywords: Aspergillus fumigatus, aspergillosis, antifungal susceptibility profile, non-susceptible, non-wild type, CSP-typing

Jiarui Zhang,1,&ast; Yichun Qin,2,&ast; Chen Zhou,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Hui-Guo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Adila Aili,1 Lige Peng,1 Yu Liu,1 Jiaqi Pu,1 Qun Yi,1,13,&ast; Haixia Zhou1,&ast; 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiujiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China; 13Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou; Qun Yi, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cn; yiqun925@126.comBackground: High blood urea nitrogen (BUN) is observed in a subset of patients with acute exacerbation of COPD (AECOPD) and may be linked to clinical outcome, but findings from previous studies have been inconsistent.Methods: We performed a retrospective analysis of patients prospectively enrolled in the MAGNET AECOPD Registry study (ChiCTR2100044625). Receiver operating characteristic (ROC) was used to determine the level of BUN that discriminated survivors and non-survivors. Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the impact of BUN on adverse outcomes.Results: Overall, 13,431 consecutive inpatients with AECOPD were included in this study, of whom 173 died, with the mortality of 1.29%. The non-survivors had higher levels of BUN compared with the survivors [9.5 (6.8– 15.3) vs 5.6 (4.3– 7.5) mmol/L, P < 0.001]. ROC curve analysis showed that the optimal cutoff of BUN level was 7.30 mmol/L for in-hospital mortality (AUC: 0.782; 95% CI: 0.748– 0.816; P < 0.001). After multivariate analysis, BUN level ≥ 7.3 mmol/L was an independent risk factor for in-hospital mortality (HR = 2.099; 95% CI: 1.378– 3.197, P = 0.001), also for invasive mechanical ventilation (HR = 1.540; 95% CI: 1.199– 1.977, P = 0.001) and intensive care unit admission (HR = 1.344; 95% CI: 1.117– 1.617, P = 0.002). Other independent prognostic factors for in-hospital mortality including age, renal dysfunction, heart failure, diastolic blood pressure, pulse rate, PaCO2 and D-dimer.Conclusion: BUN is an independent risk factor for in-hospital mortality in inpatients with AECOPD and may be used to identify serious (or severe) patients and guide the management of AECOPD.Clinical Trial Registration: MAGNET AECOPD; Chinese Clinical Trail Registry NO.: ChiCTR2100044625; Registered March 2021, URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: AECOPD, inpatients, blood urea nitrogen, mortality, adverse outcomes

YiFu Tian,1 CaiXia Zhou,1 XiaoYang Bu,1 Qian Lv,1 Qin Huang1,2 1Department of Physiology of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education & School of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Qin Huang, Department of Physiology, Guangxi Medical University, Building 102, 22 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email hqgxmu@163.comBackground: Inflammation plays a crucial role in the development of diabetic cardiomyopathy (DCM), including inflammation caused by high-glucose and high-lipid (HGHL). Targeting inflammation may provide a useful strategy for preventing and treating DCM. Puerarin has been shown to reduce the inflammation, apoptosis and hypertrophy of cardiomyocytes induced by HGHL, in which this study aims to investigate the underlying mechanisms.Methods: H9c2 cardiomyocytes cultured with HGHL were used to establish a cell model of DCM. Puerarin was then placed to these cells for 24 hours. The effects of HGHL and puerarin on cell viability and apoptosis were investigated by the Cell Proliferation, Toxicity Assay Kit (CCK-8) and flow cytometry. Morphological changes of cardiomyocytes was observed by HE staining. CAV3 proteins in H9c2 cardiomyocytes were altered by transient transfection of CAV3 siRNA. IL-6 was detected by ELISA. The Western blot was performed to determine the CAV3, Bcl-2, Bax, pro-Caspase-3, cleaved-Caspase-3, NF-κB (p65) and p38MAPK proteins.Results: Puerarin treatment reversed the cells viability, hypertrophy in morphology, inflammation (showed by p-p38 and p-p65 and IL-6) and apoptosis-related damage (showed by cleaved-Caspase-3/pro-Caspase-3/Bax, Bcl-2 and flow cytometry) of the H9c2 cardiomyocyte caused by HGHL. Puerarin treatment also restored the decrease of CAV3 proteins of the H9c2 cardiomyocyte caused by HGHL. When silenced the expression of CAV3 proteins with SiRNA, puerarin failed to decreased p-p38 and p-p65 and IL-6, and could not reversed cell viability and morphological damage. In contrast to the simple CAV3 silenced group, the CAV3 silenced with NF-κB pathway or p38MAPK pathway inhibitors, significantly downregulated the p-p38, p-p65 and IL-6.Conclusion: Puerarin upregulated CAV3 protein expression in H9c2 cardiomyocytes and inhibited the NF-κB and p38MAPK pathways, thereby reducing HGHL-induced inflammation and may related to the apoptosis and hypertrophy of cardiomyocytes.Keywords: puerarin, cardiomyocyte, inflammation, caveolin-3, siRNA, NF-κB, p38MAPK

Can Zhou,&ast; Chunting Hua,&ast; Qichang Liang,&ast; Mus’ab Al Rudaisat, Siji Chen, Yinjing Song, Jiang Zhu, Hao Cheng Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Cheng; Jiang Zhu, Email chenghao1@zju.edu.cn; jzhu1@zju.edu.cnBackground: As a keratolytic, salicylic acid (SA) can be topically applied in various formulations and doses in dermatology. Supramolecular SA hydrogel, a new SA formulation with higher bioavailability, is developed and commercially available nowadays. However, there still remain concerns that the long-term and continual application of SA at low concentrations may jeopardize the cutaneous barrier properties.Aim of the Study: To reveal the long-term effects of 0.5– 5% supramolecular SA hydrogel on the skin barrier in normal mice models.Materials and Methods: The 0.5%, 1%, 2%, and 5% supramolecular SA hydrogel or hydrogel vehicle without SA was applied to mice’s shaved dorsal skin once per day respectively. Tissue samples of the dorsal skin were harvested on day 14 and 28 of the serial application of SA for histopathological observation and transcriptomic analysis.Results: Following topical supramolecular SA hydrogel therapy with various concentrations of SA (0.5%, 1%, 2%, and 5%) for 14 days and 28 days, there were no obvious macroscopic signs of impaired cutaneous health and no inflammatory or degenerative abnormalities were observed in histological results. Additionally, the transcriptomic analysis revealed that on day 14, SA dramatically altered the expression of genes related to the extracellular matrix structural constituent. And on day 28, SA regulated gene expression profiles of keratinization, cornified envelope, and lipid metabolism remarkably. Furthermore, the expression of skin barrier related genes was significantly elevated after the application of SA based on RNA-seq results, and this is likely to be associated with the PPAR signaling pathway according to the enrichment analysis.Conclusion: Our findings demonstrated that the sustained topical administration of the 0.5– 5% supramolecular SA hydrogel for up to 28 days did no harm to normal murine skin and upregulated the expression of genes related to the epidermal barrier.Keywords: supramolecular salicylic acid hydrogel, skin barrier, PPAR signaling pathway, transcriptomic analysis

Jiaying Li,1,&ast; Xiuqin Ma,1,&ast; Xuetao Zeng,1,2 Chen Zhou,1 Taofeng Zhu1 1Department of Respiratory and Critical Care Medicine, The Yixing Hospital Affiliated to Jiangsu University, Yixing, Jiangsu, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated Hospital to Jiangnan University, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taofeng Zhu, Department of Respiratory and Critical Care Medicine, The Yixing Hospital Affiliated to Jiangsu University, No. 75 Tongzhenguan Road, Yixing, Jiangsu, 214200, People’s Republic of China, Tel +86-510-879210911, Fax +86-510-87921110, Email staff1639@yxph.comObjective: This study aimed to explore the risk factors for readmission within 90 d in Chronic Obstructive Pulmonary Disease (COPD) patients with frailty and construct a clinical warning model.Methods: COPD patients with frailty hospitalized in the Department of Respiratory and Critical Care Medicine of Yixing Hospital, Affiliated to Jiangsu University, were retrospectively collected from January 1, 2020, to June 30, 2022. Patients were divided into readmission and control groups according to readmission within 90 d. The clinical data of the two groups were evaluated by univariate and multivariate logistic regression analyses to identify readmission risk factors within 90 d in COPD patients with frailty. Then, a risk quantitative early warning model was constructed. Finally, the model’s prediction efficiency was evaluated, and external verification was carried out.Results: The multivariate logistic regression analysis showed that BMI, number of hospitalizations in the past year ≥ 2, CCI, REFS, and 4MGS were independent risk factors for readmission within 90 d in COPD patients with frailty. The early warning model for these patients was established as follows: Logit (p) = − 1.896 + (− 0.166 × BMI) + (0.969 × number of hospitalizations in the past year ≥ 2) + (0.265 × CCI) + (0.405 × REFS) + (− 3.209 × 4MGS), and presented an area under the ROC curve (AUC) of 0.744 [95% CI: 0.687– 0.801]. The AUC of the external validation cohort was 0.737 (95% CI: 0.648– 0.826), and the AUC of the LACE warning model was 0.657 (95% CI:0.552– 0.762).Conclusion: The BMI, number of hospitalizations in the past year ≥ 2, CCI, REFS, and 4MGS were independent risk factors for readmission within 90 d in COPD patients with frailty. The early warning model presented a moderate predictive value for assessing the risk of readmission within 90 d in these patients.Keywords: chronic obstructive pulmonary disease, frailty, readmission, risk factors, warning model

Ling Peng,1,2,&ast; Hong You,2,&ast; Mei-yu Xu,2 Zhou-yu Dong,2 Min Liu,2 Wen-jing Jin,2 Chao Zhou2 1Department of Critical Care Medicine, Qiannan Buyi and Miao Autonomous Prefecture People’s Hospital, Guizhou, People’s Republic of China; 2Department of Respiratory Medicine, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Zhou, Department of Respiratory Medicine, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, No. 43 DongMen Street. Pudong new District, Shanghai, 201399, People’s Republic of China, Tel +86-21-68019069, Email zhou2000sh@163.comBackground: Chronic obstructive pulmonary disease (COPD) has higher mortality when developing to acute exacerbation (AECOPD); hence, the early intervention of COPD is critical for preventing AECOPD. Exploring the serum metabolites associated with acute exacerbation in patients with COPD will contribute to the early intervention of COPD.Methods: In the study, a non-targeted metabolomics strategy combined with multivariate statistical methods was performed to explore the metabolic profiling of COPD developing acute exacerbation, to screen the potential metabolites associated with AECOPD and to analyze the potential value of these metabolites in predicting the development of COPD.Results: Serum lysine, glutamine, 3-hydroxybutyrate, pyruvate and glutamate levels were significantly higher, while 1-methylhistidine, isoleucine, choline, valine, alanine, histidine and leucine levels were significantly lower in AECOPD patients, compared with stable COPD patients after normalization based on the healthy controls. Moreover, eight metabolic pathways were significantly altered (P< 0.05) in the serum of AECOPD patients compared with the stable COPD population, including purine metabolism, glutamine and glutamate metabolism, arginine biosynthesis, butyrate metabolism, ketone body synthesis and degradation, and linoleic acid metabolism. In addition, the correlation analysis between metabolites and AECOPD patients demonstrated that an M-score based on a weighted sum of concentrations of four metabolites including pyruvate, isoleucine, 1-methylhistidine and glutamine were significantly associated with the acute exacerbation of pulmonary ventilation function in COPD patients.Conclusion: Altogether, the metabolite score based on a weighted sum of concentrations of four serum metabolites was associated with an increased risk of COPD developing acute exacerbation, which will provide a new insight for the understanding of COPD development.Keywords: COPD, AECOPD, acute exacerbation, metabolomics, metabolites

Cheng Zhou,1,&ast; Zhang-Fu Yang,1,&ast; Bao-Ye Sun,1,&ast; Yong Yi,1 Zheng Wang,1 Jian Zhou,1 Jia Fan,1 Wei Gan,1 Ning Ren,1,2 Shuang-Jian Qiu1 1Department of Liver Surgery and Transplantation & Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Institute of Fudan Minhang Academic Health System & Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuang-Jian Qiu, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200030, People’s Republic of China, Tel +86 13916625289, Email qiu.shuangjian@zs-hospital.sh.cnPurpose: Immunogenic cell death (ICD) is a cell death modality that plays a vital role in anticancer therapy. In this study, we investigated whether lenvatinib induces ICD in hepatocellular carcinoma and how it affects cancer cell behavior.Patients and Methods: Hepatoma cells were treated with 0.5 μM lenvatinib for two weeks, and damage-associated molecular patterns were assessed using the expression of calreticulin, high mobility group box 1, and ATP secretion. Transcriptome sequencing was performed to investigate the effects of lenvatinib on hepatocellular carcinoma. Additionally, CU CPT 4A and TAK-242 were used to inhibit TLR3 and TLR4 expressions, respectively. Flow cytometry was used to assess PD-L1 expression. Kaplan–Meier and Cox regression models were applied for prognosis assessment.Results: After treatment with lenvatinib, there was a significant increase in ICD-associated damage-associated molecular patterns, such as calreticulin on the cell membrane, extracellular ATP, and high mobility group box 1, in hepatoma cells. Following treatment with lenvatinib, there was a significant increase in the downstream immunogenic cell death receptors, including TLR3 and TLR4. Furthermore, lenvatinib increased the expression of PD-L1, which was later inhibited by TLR4. Interestingly, inhibiting TLR3 in MHCC-97H and Huh7 cells strengthened their proliferative capacity. Moreover, TLR3 inhibition was identified as an independent risk factor for overall survival and recurrence-free survival in patients with hepatocellular carcinoma.Conclusion: Our study revealed that lenvatinib induced ICD in hepatocellular carcinoma and upregulated PD-L1 expression through TLR4 while promoting cell apoptosis through TLR3. Antibodies against PD-1/PD-L1 can enhance the efficacy of lenvatinib in the management of hepatocellular carcinoma.Graphical Abstract: Keywords: hepatocellular carcinoma, immunogenic cell death, lenvatinib, toll-like receptor

Gang Xu,1 Weizhen Tang,1 Chaosheng Zhou,1 Jie Xu,1 Chao Cheng,1 Weiwei Gong,2,3 Shihong Dong,2 Yu Zhang1 1Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 200072, People’s Republic of China; 2Department of Rehabilitation Medicine, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Department of Rehabilitation Medicine, Shanghai First Rehabilitation Hospital, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Gang Xu, Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, 301 Middle Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +8621-66306496, Fax +8621-66301051, Email sykfsci@126.comPurpose: To evaluate the efficacy and pain fluctuations of methylcobalamin in combination with lidocaine local injection treatment for subacute herpetic neuralgia (SHN).Methods: Seventy-nine women (60.4 ± 2.7 years) with thoracic SHN were enrolled and randomized to receive a combination of methylcobalamin and lidocaine local injection (MI, N=40), or a combination of lidocaine patch 5% and oral methylcobalamin (PO, N=39) for four weeks. Repeated-measures analyses of variance were used to evaluate the effect on pain levels. Generalized estimation equations were used to analyze the cause-effect relationship between pain fluctuations and influencing factors.Results: At the treatment endpoint, the group, treatment time, and group interacted with treatment time effects of the pain scores and area were statistically significant (P< 0.001), The pain scores were 2.9 ± 0.9 (MI) and 4.3 ± 1.5 (PO). 80.00% (MI) or 28.21% (PO) of patients had pain scores ≤ 3, the odds ratio was 2.84 (95% CI: 1.68 to 4.79). The incidence of postherpetic neuralgia was 5.0% (2/40) at 3 months. Pain fluctuated repeatedly during treatment. The pain fluctuation increased from 8.75 log folds in the afternoon, to 79.85 log folds at night. With the ADLs level increasing from 1 to 3, the pain fluctuated from 4.28 to 17.70 log folds. Allodynia, itching, sleep quality, and ADLs were the significant influencing factors (P< 0.05).Conclusion: This study validated the efficacy of methylcobalamin combined with lidocaine for SHN, and confirmed that pain levels in patients with SHN had an obvious circadian rhythm. ADLs were an important cause of pain fluctuations.Keywords: subacute herpetic neuralgia, methylcobalamin, lidocaine, pain fluctuation, activities of daily living

Yujing Zhang, Jianzhong Zhang, Cheng Zhou Department of Dermatology, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Cheng Zhou, Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, People’s Republic of China, Tel +86-10-88325472, Fax +86 10-68318386, Email chengzhou@live.cnAbstract: Perinevoid alopecia (PA) is a rare variant of alopecia areata (AA) associated with a central pigmented nevus. In this study, we reported two cases of PA and reviewed 14 cases from 11 studies in the literature. In one of our cases, PA was combined with a halo nevus and white terminal hairs were spared in the hair loss patch, which was rarely reported in the literature. It is implicated that antigens from melanocytes might be involved in the development of AA in PA.Keywords: alopecia areata, hair loss, nevus, halo nevus

Crystal Zhou,1 Abhinav Vempati,1 Curtis Tam,1 Jeffrey Khong,2 Ruslan Vasilev,1 Kevin Tam,1 Sanam Hazany,1 Salar Hazany1 1Scar Healing Institute, Los Angeles, CA, USA; 2Johns Hopkins School of Medicine, Baltimore, MD, USACorrespondence: Crystal Zhou, Scar Healing Institute, Los Angeles, CA, USA, Tel +1 424 225 2435, Fax +1 310 571 8435, Email info@shi.orgAbstract: Post-acne scarring is a common consequence of acne vulgaris with no universal cure. Although there have been many recent advances to address acne scars physically, there is still a lack of research that investigates their psychosocial impacts. Our comprehensive PubMed search presents an overview of existing information to highlight known sources of mental distress caused by post-acne scarring, both related to and independent of the psychosocial detriments caused early on by active acne. The literature indicates that acne scarring is a distinct condition from acne vulgaris and therefore requires a comprehensive clinical approach unique from those available for active acne.Keywords: acne scar, quality of life, psychosocial, social stigma, self-esteem, mental health

Yubo Li,1– 4 Xiaoyan Ni,2– 4 Xinai Liu,1 Chun Yang,2– 4 Yi Wang,2,4 Xin Lu,2– 4 Changwu Zhou2– 4 1Department of MRI, Henan Provincial Hospital of Traditional Chinese Medicine (the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, People’s Republic of China; 2Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 4Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Xin Lu; Changwu Zhou, Shanghai Institute of Medical Imaging; Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18702135336 ; +86 13912121145, Email luxcn@163.com; changwu83@163.comObjective: The prognostic value of the Liver Imaging Reporting and Data System (LI-RADS) 2018 in differentiating hepatocellular carcinoma (HCC) from other primary liver cancers (PLC) with cirrhosis is unclear. We aim to evaluate the value of LI-RADS 2018 with agent-enhanced MRI in the postoperative prognosis of PLC patients with cirrhosis.Methods: Between 2016 and 2021, 432 patients with cirrhosis and surgically proven single primary liver cancer were retrospectively evaluated. Two radiologists evaluated the preoperative MRI features independently and assigned each lesion a LI-RADS category. Overall survival (OS), recurrence-free survival (RFS), and their associated factors were evaluated by using the Kaplan-Meier method, Log rank test, and Cox proportional hazards model.Results: The mean age of 432 patients (239 HCCs, 93 ICCs, and 100 cHCC-CCAs) was 57.27± 10.92 years. The LR-M category showed poorer OS and RFS than the LR-4 or LR-5 category did for all primary liver cancers (P < 0.001 for both), and so did HCCs with tumor size less than 30mm (P =0.003 and P =0.04, respectively). In the multivariable analysis, the LI-RADS category and tumor size > 30 mm had independent correlations with OS and RFS (all P < 0.05). Multivariable Cox analysis identified rim arterial phase hyperenhancement (APHE) as independent determinants of poor OS and RFS in primary liver cancers (all P < 0.05).Conclusion: The LI-RADS categories can predict the postsurgical prognosis of primary liver cancers independently.Keywords: hepatocellular carcinoma, magnetic resonance imaging, prognosis, liver cirrhosis

Wang H, Zhou C, Su Y, Gou K, Geng X, Qiu X. Drug Des Devel Ther. 2021;15:4865–4873. The authors have informed the journal that ripretinib was used in this study, not erdafitinib as indicated in parts of the paper. Namely, on page 4865, Abstract, Results section; page 4868, Animal Experiments and Pharmacokinetics Study sections; page 4872, Pharmacokinetics Effects and Conclusions sections. The authors have also advised on page 4867, Materials and Methods, Chemicals Materials section, third line from the bottom, the text “Itraconazole” should read “voriconazole”. The authors apologize for any confusion this may have caused.

Jiaqi Pu,1,&ast; Qun Yi,1,2,&ast; Yuanming Luo,3 Hailong Wei,4 Huiqing Ge,5 Huiguo Liu,6 Xianhua Li,7 Jianchu Zhang,8 Pinhua Pan,9 Hui Zhou,10 Chen Zhou,11 Mengqiu Yi,12 Lina Cheng,12 Liang Liu,10 Jiarui Zhang,1 Lige Peng,1 Adila Aili,1 Yu Liu,1 Haixia Zhou1 On behalf of the MAGNET AECOPD Registry Investigators1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, Cancer Hospital Affiliate to School of Medicine, UESTC, Chengdu, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, the First People’s Hospital of Neijiang City, Neijiang, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, People’s Republic of China; 11West China School of Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 12Department of Emergency, First People’s Hospital of Jiujiang, Jiu Jiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cnPurpose: The prognostic value of blood eosinophils in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains controversial. This study aimed to evaluate whether blood eosinophils could predict in-hospital mortality and other adverse outcomes in inpatients with AECOPD.Methods: The patients hospitalized for AECOPD were prospectively enrolled from ten medical centers in China. Peripheral blood eosinophils were detected on admission, and the patients were divided into eosinophilic and non-eosinophilic groups with 2% as the cutoff value. The primary outcome was all-cause in-hospital mortality.Results: A total of 12,831 AECOPD inpatients were included. The non-eosinophilic group was associated with higher in-hospital mortality than the eosinophilic group in the overall cohort (1.8% vs 0.7%, P < 0.001), the subgroup with pneumonia (2.3% vs 0.9%, P = 0.016) or with respiratory failure (2.2% vs 1.1%, P = 0.009), but not in the subgroup with ICU admission (8.4% vs 4.5%, P = 0.080). The lack of association still remained even after adjusting for confounding factors in subgroup with ICU admission. Being consistent across the overall cohort and all subgroups, non-eosinophilic AECOPD was also related to greater rates of invasive mechanical ventilation (4.3% vs 1.3%, P < 0.001), ICU admission (8.9% vs 4.2%, P < 0.001), and, unexpectedly, systemic corticosteroid usage (45.3% vs 31.7%, P < 0.001). Non-eosinophilic AECOPD was associated with longer hospital stay in the overall cohort and subgroup with respiratory failure (both P < 0.001) but not in those with pneumonia (P = 0.341) or ICU admission (P = 0.934).Conclusion: Peripheral blood eosinophils on admission may be used as an effective biomarker to predict in-hospital mortality in most AECOPD inpatients, but not in patients admitted into ICU. Eosinophil-guided corticosteroid therapy should be further studied to better guide the administration of corticosteroids in clinical practice.Keywords: acute exacerbation of chronic obstructive pulmonary disease, peripheral blood eosinophils, inpatients, in-hospital mortality, clinical outcomes

Peng Huang,1,2,&ast; Xiaoyan Ni,1,2,&ast; Changwu Zhou,1– 3 Zhang Shi,1,2 Fei Wu,1,2 Yuyao Xiao,1,2 Chun Yang,1,2 Mengsu Zeng1– 3 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengsu Zeng, Shanghai Institute of Medical Imaging, Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 13501922963, Email zeng.mengsu@zs-hospital.sh.cn Chun Yang, Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18702135336, Email dryangchun@hotmail.comObjective: To compare the pathologic diagnosis and survival of patients with subcentimeter and 1– 2 cm nodules that present with diagnostic hallmarks of hepatocellular carcinoma (HCC).Methods: Diagnostic hallmarks of HCC were defined as hyperintensity on T2 weighted imaging, restricted diffusion, arterial phase hyperenhancement, washout on portal venous phase, and hypointensity on hepatobiliary phase. We retrospectively included 139 patients undergoing curative resection with single nodules ≤ 2 cm that present imaging features described above on gadoxetic acid-enhanced MRI. The final diagnosis was confirmed by histopathological assessment. Recurrence-free survival (RFS) was compared using Kaplan–Meier analysis with the Log-rank test. Factors associated with overall and early recurrence were identified using Cox regression analysis.Results: Among 139 nodules (49 nodules < 1 cm), there was no significant difference in the percentage of HCC between subcentimeter and 1– 2 cm nodules (94.0% vs 94.4%, P > 0.999). Microvascular invasion (MVI) was less common in subcentimeter HCC (4.3% vs 17.6%, P = 0.032). There were 27 recurrences during a median follow-up time of 46.7 months. Patients with subcentimeter HCC achieved less recurrence, with a 5-year RFS rate of 87.3%. The MVI-positive patients had more early and overall recurrence. A tumor size < 1 cm was associated with lower overall recurrence (HR, 0.336; P = 0.047). No factors were independently associated with early recurrence.Conclusion: Subcentimeter nodules with diagnostic hallmarks of HCC are highly associated with HCC diagnosis and achieve less tumor recurrence after resection. Early diagnosis and treatment of subcentimeter HCC may be more appropriate.Keywords: carcinoma, hepatocellular, magnetic resonance imaging, gadolinium ethoxybenzyl DTPA

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

Abhinav Vempati,1 Crystal Zhou,1 Curtis Tam,1 Jeffrey Khong,2 Aaron Rubanowitz,3 Kevin Tam,1 Sarah Hazany,1 Ruslan Vasilev,1 Salar Hazany1 1Scar Healing Institute, Los Angeles, CA, USA; 2Johns Hopkins School of Medicine, Baltimore, MD, USA; 3Geisel School of Medicine, Hanover, NH, USACorrespondence: Abhinav Vempati, Scar Healing Institute, Los Angeles, CA, USA, Tel +1 424 225 2453, Fax +1 310 571 8435, Email info@shi.orgAbstract: Subcutaneous incisionless surgery, also known as subcision, is a minimally invasive procedure that is commonly indicated for the treatment of atrophic acne scars. In recent years, many new techniques have been developed to maximize results from this procedure. This review article aims to identify an updated list of instruments and combinatorial treatments available for atrophic acne scar patients undergoing subcision. We constructed a comprehensive PubMed search term and performed triple-blinded screening on all resulting studies for mentions of subcision as indicated by acne scarring. Our results show that there are four main categories of subcision tools that are commonly employed to treat atrophic acne scars: needles, cannulas, wires, and blunt-blade instruments. Usage of these devices varies by scar depth, personal preference, and combinatorial treatment options. Overall, subcision is a particularly effective treatment for atrophic acne scars, and there is vast potential for further innovation with this technique.Keywords: subcutaneous incisionless surgery, acne scar, depressed scars, CROSS, Taylor liberator

Mengxin Xu,1 Changrui Qian,2 Huaiyu Jia,1 Luozhu Feng,3 Shiyi Shi,1 Ying Zhang,3 Lingbo Wang,1 Jianming Cao,3 Tieli Zhou,1 Cui Zhou1 1Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, People’s Republic of China; 2School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Medical Laboratory Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Tieli Zhou; Cui Zhou, Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325035, People’s Republic of China, Tel +86 0577 8668 9885, Email wyztli@163.com; ZHOUCUI0826@163.comIntroduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a serious threat to human public health. Ceftazidime–avibactam (CZA) is currently one of the few effective antibiotics for carbapenem-resistant Enterobacteriaceae (CRE).Methods and Results: Here, we analyzed two longitudinal Klebsiella pneumoniae clinical isolates (FK8578, FK8695) that were isolated from an ICU patient during antimicrobial treatment. Broth microdilution method, whole-genome sequencing (WGS) and comparative genomic analysis were used to elucidate the dynamics and mechanisms of antibiotic resistance. String test, quantification of capsule, biofilm inhibition test and Galleria mellonella (G. mellonella) infection model were used to explore the changes in virulence of the two clinical isolates. During antibiotic treatment, CRKP FK8578 underwent a series of drug resistance and virulence changes, including CZA resistance, carbapenem susceptibility and virulence attenuation. The results of WGS showed that mutation of blaKPC-2 to blaKPC-33 was responsible for the change of drug resistance phenotype between FK8578 and FK8695. pLVPK-like virulence plasmid without siderophore synthesis operon was identified in the two strains. On the other hand, the loss of hypermucoviscosity phenotype in the FK8695 strain may be related to a single nucleotide deletion of the rmpA gene, which would further lead to a decrease in virulence. Virulence results showed that compared with FK8578, FK8695 was negative in the string test, with decreased capsular production, smaller amounts of biofilm formation and higher survival rate of G. mellonella.Conclusion: This is the first report of CZA resistance and decreased virulence in ST11 CRKP strains during antimicrobial treatment. It is urgent to monitor CZA resistance and timely adjust anti-infective treatment strategies.Keywords: ceftazidime–avibactam, carbapenem-resistantKlebsiella pneumoniae, whole-genome sequencing, hypermucoviscosity, pLVPK-like plasmid, virulence attenuation

Zhiguo Zhang,1,2,&ast; Fangda Fu,1,2,&ast; Yishan Bian,1,2,&ast; Huihao Zhang,1,2 Sai Yao,1,2 Chengcong Zhou,1,2 Yuying Ge,2 Huan Luo,3 Yuying Chen,4 Weifeng Ji,1 Kun Tian,1 Ming Yue,5 Weibin Du,6 Hongting Jin,1 Peijian Tong,1 Chengliang Wu,1,2 Hongfeng Ruan1,2 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 6Research Institute of Orthopedics, The Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that α-Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure.Objective: To determine whether α-Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between α-Chaconine and OA progression.Methods: We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 μM α-Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1β, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence.Results: We found that α-Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, α-Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that α-Chaconine stimulated NF-κB signaling by promoting I-κB α phosphorylation and p65 nuclear translocation.Conclusion: Collectively, our findings raise the possibility that α-Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.Graphical Abstract: Keywords: α-Chaconine, osteoarthritis, pyroptosis, nerve ingrowth, NF-κB signaling

Chen Zhou,1,&ast; Yujie Guang,1,&ast; Yuanming Luo,2 Huiqing Ge,3 Hailong Wei,4 Huiguo Liu,5 Jianchu Zhang,6 Pinhua Pan,7 Jiarui Zhang,8 Lige Peng,8 Adila Aili,8 Yu Liu,8 Jiaqi Pu,8 Xia Zhong,1 Yixi Wang,1 Qun Yi,8,9 Haixia Zhou8 On behalf of the MAGNET AECOPD Registry Investigators1West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 9Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, Cancer Hospital Affiliate to School of Medicine, UESTC, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86-28-85422571, Fax +86-28-85422571, Email zhouhaixia@wchscu.cnBackground: The optimal tool for risk prediction of venous thromboembolism (VTE) in inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is still unknown. This study aimed to evaluate whether D-dimer could predict the risk of VTE in inpatients with AECOPD compared to the Padua Prediction Score (PPS).Methods: Inpatients with AECOPD were prospectively enrolled from seven medical centers in China between December 2018 and June 2020. On admission, D-dimer was detected, PPS was calculated for each patient, and the incidence of 2-month VTE was investigated. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer and PPS on VTE development, and the best cut-off value for both methods was evaluated through the Youden index.Results: Among the 4468 eligible patients with AECOPD, 90 patients (2.01%) developed VTE within 2 months after admission. The area under the receiver operating characteristic curves (AUCs) of D-dimer for predicting VTE were significantly higher than those of the PPS both in the overall cohort (0.724, 95% CI 0.672– 0.776 vs 0.620, 95% CI 0.562– 0.679; P< 0.05) and the subgroup of patients without thromboprophylaxis (0.747, 95% CI 0.695– 0.799 vs 0.640, 95% CI 0.582– 0.698; P< 0.05). By calculating the Youden Index, the best cut-off value of D-dimer was determined to be 0.96 mg/L with an AUC of 0.689, which was also significantly better than that of the PPS with the best cut-off value of 2 (AUC 0.581, P=0.007). After the combination of D-dimer with PPS, the AUC (0.621) failed to surpass D-dimer alone (P=0.104).Conclusion: D-dimer has a superior predictive value for VTE over PPS in inpatients with AECOPD, which might be a better choice to guide thromboprophylaxis in inpatients with AECOPD due to its effectiveness and convenience.Clinical Trial Registration: Chinese Clinical Trail Registry NO. ChiCTR2100044625; URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: acute exacerbation of chronic obstructive pulmonary disease, inpatients, D-dimer, Padua Prediction Score, venous thromboembolism

Xiaoling Zhang1 &ast;, Zhaohui Li2 &ast;, Linlin Han3 &ast;, Zheng Lv,4 Yuee Teng,5 Xiujie Cui,6 Caiyun Zhou,7 Hongwei Wu,8 Wei Fang,8 Lingzhi Xu,1 Shanshan Zhao,1 Chen Song,1 Yuanyuan Zheng,1 Tianqi Gao,1 Man Li1 1Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Oncology, Anshan Cancer Hospital, Anshan, People’s Republic of China; 3Health Management Center, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of China; 4Department of Oncology, The First Hospital of Jilin University, Changchun, People’s Republic of China; 5Department of Oncology, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 6Department of Oncology, Chaoyang Center Hospital, Chaoyang, People’s Republic of China; 7Department of Oncology, Huludao Center Hospital, Huludao, People’s Republic of China; 8Department of Oncology, Yingkou Center Hospital, Yingkou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Man Li, Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China, Tel +86-0411-84671291, Fax +86-411-84672130, Email man_li@dmu.edu.cnPurpose: Pyrotinib, a novel human epidermal growth factor receptor 2 (HER2)-targeted tyrosine kinase inhibitor (TKI), has led to remarkable survival outcomes in HER2-positive advanced breast cancer (ABC) in clinical trials and was approved for second-line standards of treatment for HER2+ ABC in China. However, the clinical trials could not fully reflect reality of clinical practice, and predictive factors were still lacking. This study aimed to assess the actual efficacy and safety of pyrotinib in HER2+ ABC in real-world setting.Patients and Methods: In this multicenter, retrospective, observational real-world study, we analyzed 171 patients with HER2+ ABC, who received pyrotinib-based treatment from November 2017 to November 2020. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety.Results: Up to November 30, 2021, the median PFS (mPFS) was 12.0 months for all patients. One hundred and sixty-two patients (94.7%) with measurable lesions had been included in efficacy assessment. The ORR and CBR were 45.1% and 81.5%, respectively. A significantly longer PFS was reported in patients who received pyrotinib as first-line treatment, had the ECOG-PS of 0– 1, as well as those who were lapatinib-naive. In addition, multivariable analysis indicated that ECOG-PS of 2– 4, positive hormone receptor (HR) status, and presence of visceral metastasis were independent negative predictors of PFS. As far as we know, this study first reported the survival outcome of pyrotinib cross-line treatment, with a mPFS of 5.0 months. All grades of adverse events (AEs) occurred in 171 patients (100%), and the most common AE was diarrhea (86.5%).Conclusion: This study further demonstrated the outstanding efficacy and safety of pyrotinib and reported the potential predictors of survival in HER2+ ABC.Keywords: breast cancer, tyrosine kinase inhibitors, prognostic factor, targeted therapy

Zhong-Han Fang,1,2 Hong-Lin Liao,1,2 Qing-Feng Tang,1,2 Ya-Jing Liu,1,2 Yan-Yan Zhang,1,2 Jiu Lin,1,2 Hao-Peng Yu,3 Cheng Zhou,4 Chun-Jie Li,1,5 Fei Liu,1,2,&ast; Jie-Fei Shen1,2,&ast; 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Liu; Jie-Fei Shen, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Email liufei.hxkq@scu.edu.cn; shenjiefei@scu.edu.cnBackground: Recent studies have demonstrated the contribution of non-coding RNAs (ncRNAs) to neuropathic pain. However, the expression profile of ncRNAs in the trigeminal ganglion (TG) and their functional mechanism underlying trigeminal neuropathic pain are still unclear.Methods: In the present study, the trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve (CCI-ION) was used to study the expression profile and potential regulatory mechanism of miRNAs, lncRNAs, circRNAs, and mRNAs in the TG by RNA-sequencing (RNA-seq) and bioinformatics analysis. CCI-ION mice suffered from mechanical allodynia from 3 days to 28 days after surgery.Results: The RNA-seq results discovered 67 miRNAs, 216 lncRNAs, 14 circRNAs, 595 mRNAs, and 421 genes were differentially expressed (DE) in the TG of CCI-ION mice 7 days after surgery. And 39 DEGs were known pain genes. Besides, 5 and 35 pain-related DE mRNAs could be targeted by 6 DE miRNAs and 107 DE lncRNAs, respectively. And 23 pain-related DEGs had protein–protein interactions (PPI) with each other. GO analysis indicated membrane-related cell components and binding-related molecular functions were significantly enriched. KEGG analysis showed that nociception-related signaling pathways were significantly enriched for DE ncRNAs and DEGs. Finally, the competing endogenous RNA (ceRNA) regulatory network of DE lncRNA/DE circRNA-DE miRNA-DE mRNA existed in the TG of mice with trigeminal neuropathic pain.Conclusion: Our findings demonstrate ncRNAs are involved in the development of trigeminal neuropathic pain, possibly through the ceRNA mechanism, which brings a new bright into the study of trigeminal neuropathic pain and the development of novel treatments targeting ncRNAs.Keywords: trigeminal neuropathic pain, non-coding RNAs, RNA-sequencing, trigeminal ganglion, trigeminal nerve injury, bioinformatics

Tianyu Tan,1 Chao Zhou,1 Rongrong Lu,1 Cheng Chen,2 Chongyang Bai,1 Long Li,1 Guohui Wu1 1Chongqing Center for Disease Control and Prevention, Chongqing, 400042, People’s Republic of China; 2Chongqing Jiulongpo District Center for Disease Control and Prevention, Chongqing, 400039, People’s Republic of ChinaCorrespondence: Guohui Wu, Chongqing Center for Disease Control and Prevention, No. 8, Changjiang 2nd Road, Chongqing, 400042, People’s Republic of China, Tel +8602368801491, Email wgh68803652@163.comPurpose: This study aimed to assess the proportion of depression and its associated factors among men living with HIV/AIDS and aged 50 and over in Chongqing, China.Methods: This cross-sectional study included 774 men diagnosed as HIV/AIDS and aged 50 and over in four regions. Data were collected through face-to-face interviews with a structured questionnaire. Multivariate logistic regression analysis was performed to identify factors associated with depression. A two-tailed P-value less than 0.05 was considered as statistical significance.Results: A total of 293 participants (37.9%) reported depressive symptoms. Results from multivariate logistic regression suggested that individuals aged ≥ 70 (AOR = 1.99, 95% CI: 1.28– 3.08) and those living in rural areas (AOR = 2.79, 95% CI: 1.96– 3.97) were associated with higher odds of depression, while those being employed (AOR = 0.50, 95% CI: 0.32– 0.80) and with monthly income > 3000 CNY (AOR = 0.47, 95% CI: 0.30– 3.74) had lower odds of depression.Conclusion: Our findings indicate a high prevalence of depression among older men living with HIV/AIDS in Chongqing, China. Age, residence, employment, and income have been identified as potential risk factors of depressive symptoms. Mental-health intervention initiatives should be tailored to target adults with a higher risk of depression.Keywords: depression, China, older male, HIV/AIDS, influencing factors