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Jifeng Li,1 Dongxiao Zhang,1 Jing Hu,1 Jianchun Cui,2 Khattak Mazher Mansoor2 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Liaoning Provincial People’s Hospital (Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University), Shenyang, People’s Republic of ChinaCorrespondence: Dongxiao Zhang, Department of Galactophore, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23, Art Museum Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +8617864190977, Email morningdong@163.comObjective: This study aims to systematically evaluate the effectiveness and safety of acupuncture in treating mammary hyperplasia.Methods: A comprehensive search was conducted in various databases, including PubMed, Web of Science, Cochrane Library, Embase, SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP Database, from their inception until July 2023. Only randomized controlled trials (RCTs) researching the use of acupuncture for mammary hyperplasia were included. Quality assessment and data analysis were performed using RevMan 5.3 software.Results: Eight RCTs, comprising 573 patients, were included in this analysis. The meta-analysis revealed that in the acupuncture group, the experimental group was better than the control group in improving breast pain, breast lump extent, and the texture of breast lump (P=0.0007, I2=61%; P=0.02, I2=0%; P=0.0002, I2=0%). We found that both could be improved, but after statistical analysis, there was no significant advantage in the acupuncture group compared with the patent Chinese medicine group (p> 0.05).Conclusion: Acupuncture appears to be an effective and safe treatment for mammary hyperplasia, providing pain relief and reducing mass volume, texture, and extent. However, the insufficient quality of the available evidence indicates the need for further methodologically rigorous and convincingly designed studies to determine the efficacy and safety of acupuncture in the treatment of breast hyperplasia.Keywords: acupuncture, mammary hyperplasia, efficacy, meta-analysis, review, safety

Dongdong Zhang,1 Jie Bai2 1Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 2Department of Neurology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, People’s Republic of ChinaCorrespondence: Dongdong Zhang, Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Jiefang Road No. 15, Xiangyang, Hubei, 441000, People’s Republic of China, Tel +8615072278600, Email zhangdongdong@whu.edu.cnBackground: Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common adverse reaction during cancer treatment, typically characterized by numbness and paresthesias. This study aimed to report a rare case of VIPN with an atypical genotype, manifesting as grade 3 weakness of the lower limbs.Case Presentation: A 19-year-old man, diagnosed with alveolar rhabdomyosarcoma for 8 months, was transferred to our hospital for further treatment after the failure of first-line treatment. He developed severe long-standing weakness in both lower limbs and could not walk after four sessions of second-line chemotherapy. The diagnosis of VIPN was confirmed based on the patient’s physical examination, imaging studies, electromyogram results, and treatment history. Furthermore, the pharmacogenetic analysis indicated that the patient harbored CYP3A4 rs2740574 TT genotypes.Conclusion: We have reported for the first time a VIPN patient whose main clinical manifestation is severe weakness in both lower limbs, accompanied by the CYP3A4 rs2740574 TT phenotype. This case may provide new information on the phenotypic features of VIPN, and may help to better understand the disease pathogenesis and contributing factors.Keywords: vincristine, vincristine-induced peripheral neuropathy, CYP3A rs2740574 TT genotype

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

Ryan Kipp,1 Lee-or Herzog,2 Rahul Khanna,3 Dongyu Zhang3 1Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 2Franchise Health Economics and Market Access, Johnson and Johnson, Irvine, CA, USA; 3MedTech Epidemiology and Data Sciences, Johnson and Johnson, New Brunswick, NJ, USACorrespondence: Ryan Kipp, Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI, 53792, USA, Tel +608-265-4188, Email rtkipp@medicine.wisc.eduBackground: Atrial fibrillation (AF) is associated with considerable morbidity and mortality. Timely management and treatment are critical in alleviating AF disease burden. There is significant heterogeneity in patterns of AF care. It is unclear whether there are racial and ethnic differences in treatment of AF following antiarrhythmic drug (AAD) prescription.Methods: Using the Optum Clinformatics Data Mart-Socioeconomic Status database from January, 2009, through March, 2022, multivariable logistic regression techniques were used to examine the impact of race and ethnicity on rate of AAD initiation, as well as receipt of catheter ablation within two years of initiation. We compared AAD discontinuation rate by race and ethnicity groups using Cox regression models. Log-rank analyses were used to examine the rate of AF-related hospitalization.Results: Among 143,281 patients identified with newly diagnosed AF, 30,019 patients (21%) were initiated on an AAD within 90 days. Patients identified as Non-Hispanic Black (NHB) were significantly less likely to receive an AAD compared to Non-Hispanic White patients (NHW) (Odds Ratio [OR] 0.90, 95% confidence interval [CI] 0.85– 0.94). Compared to NHW, Hispanic (Hazard Ratio [HR] 1.08, 95% CI 1.02– 1.14) and Asian patients (HR 1.17, 95% CI 1.06– 1.29) have a higher rate of AAD discontinuation. Following AAD initiation, NHB patients were significantly more likely to have an AF-related hospitalization (p < 0.01). However, NHB patients were significantly less likely to receive ablation compared to NHW (HR 0.83, 95% CI 0.70– 0.97), and less likely to change AAD (p < 0.01).Conclusion: Patients identified as NHB are 10% less likely to receive an AAD for treatment of newly diagnosed AF. Compared to NHW, Hispanic and Asian patients were more likely to discontinue AAD treatment. Once initiated on an AAD, NHB patients were significantly more likely to have an AF -related hospitalization, but were 17% less likely to receive ablation compared to NHW patients. The etiology of, and interventions to reduce, these disparities require further investigation.Keywords: atrial fibrillation, cardiovascular disease, health disparity, epidemiology, real-world data

Daya Zhang,1,&ast; Fen-jiao Mao,1,&ast; Shimei Huang,1,&ast; Chen Chen,1 Da Li,1 Fan Zeng,1 Feihu Bai2,3 1Graduate School, Hainan Medical University, Haikou, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 3The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feihu Bai, Chief Physician and Professor of the Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, &num;368, Longhua District, Haikou, Hainan Province, People’s Republic of China, Tel +86-18995181963, Fax +86-89866809168, Email baifeihu_hy@163.comPurpose: Recurrence rate of Helicobacter pylori (H. pylori) infection after successful eradication have gained attention. This study was to assess the recurrence rate of H. pylori infection after successful eradication in the southern coastal provinces of China and to analyze its factors.Patients and Methods: 975 patients with upper gastrointestinal symptoms who were diagnosed with H. pylori infection using the 13C or 14C-urea breath test (UBT) underwent eradication treatment between August 2021 and December 2022. After eight to twelve weeks, repeat UBT was performed. Besides, 824 patients with successful eradication underwent a repeat UBT by completing questionnaires after a year. The 1-year recurrence rate was calculated, and the differences were analyzed based on baseline data, sociological characteristics, and lifestyle.Results: A total of 734 patients completed the 1-year follow-up, out of which 26 (3.5%) patients experienced a recurrence of H. pylori infection. Exposure to other individuals infected with H. pylori (χ2=12.852, P< 0.001), poor hygiene conditions at dining out places (χ2=6.839, P=0.009), frequent dining out (χ2=24.315, P< 0.001), smoking (χ2=7.510, P=0.006), consumption of non-purified water (χ2=16.437, P< 0.001), consumption of pickled foods (χ2=5.682, P=0.017), irregular meal patterns (χ2=16.877, P< 0.001) and age (χ2=9.195, P=0.010) were significant factors for H. pylori infection recurrence. Exposure to other individuals infected with H. pylori, poor hygiene conditions at dining out places, consumption of non-purified water, frequent dining out and irregular meal patterns were independent risk factors (P=0.022, 0.016, 0.002, < 0.001, < 0.001; 95% CI 0.146– 0.861, 0.121– 0.806, 1.715– 10.845, 0.085– 0.521, 2.291– 14.556).Conclusion: The one-year recurrence rate of H. pylori infection post-eradication in the southern coastal provinces of China is 3.5%. Contacting with infected individuals, poor hygiene in dining places, consumption of non-purified water, frequent dining out, and irregular meal patterns were identified as significant independent factors influencing H. pylori recurrence.Keywords: Helicobacter pylori, successful eradication, Southern Coastal Provinces of China, risk factors, 1-year follow-up

Jiaru Wang,1 Peiyao Jia,2 Dong Zhang,2 Ying Zhao,2,3 Xin Sui,1 Zhengyu Jin,1,&ast; Wei Song1,&ast; 1Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Song, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Tel/Fax +86 10 69159525, Email cjr.songwei@vip.163.comPurpose: To explore the clinical characteristics, diagnosis, and treatment of family outbreak of psittacosis and to improve the success rate of treatment.Patients and Methods: The clinical characteristics, diagnosis, treatment, and outcome of family outbreak of psittacosis, which consists three patients, diagnosed by clinical analysis and metagenomic next-generation sequencing (mNGS) in our hospital were analyzed retrospectively.Results: We report on three instances of clustered atypical pneumonia, which were caused by Chlamydia psittaci during the COVID-19 pandemic. All patients exhibited symptoms of fever and cough, while one patient also experienced gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Laboratory tests indicated no significant increase in leukocytes and neutrophils, but a mild increase in C-reactive protein was observed in all three patients. Chest computed tomography (CT) scans revealed a consolidation shadow in a unilateral lung lobe in all three patients. Both patients were treated with empirical moxifloxacin, yielding unsatisfactory outcomes. mNGS was conducted on sputum samples from one adult patient, revealing the presence of Chlamydia psittaci. Additional doxycycline was prescribed immediately, and then the patients’ temperatures were stabilized, and the lesion in chest CT was absorbed. The pediatric patient exhibited less severe symptoms compared to the adult patients and exhibited a favorable response to azithromycin administration.Conclusion: This study reports a cluster of a family outbreak of atypical pneumonia caused by C. psittaci in China. The occurrence of a family outbreak during the COVID-19 pandemic may be attributed to familial aggregation resulting from the epidemic. The three cases reported in this study did not experience severe complications, which can be attributed to the prompt medical intervention and swift diagnosis. This finding implies the need to enhance patients’ awareness and vigilance towards their health. Additionally, mNGS emerges as a valuable technique for accurately identifying pathogens causing pulmonary infections.Keywords: psittacosis, outbreak, COVID-19, metagenomic next-generation sequencing, pneumonia

Yu Gao,1 Min Fan,1 Yu Li,1 Shaochen Zhao,2 Wei Chen,1 Donghuan Zhang,1 Xifu Zheng1,3 1School of Psychology, South China Normal University, Guangzhou, 510663, People’s Republic of China; 2Guangdong-Hongkong-Macao Policing Model Innovation Research Center, China People’s Police University, Guangzhou, 510663, People’s Republic of China; 3Key Laboratory of Brain, Cognition, and Education Sciences, Ministry of Education, Guangzhou, 510663, People’s Republic of ChinaCorrespondence: Xifu Zheng, School of Psychology, South China Normal University, Guangzhou, 510663, People’s Republic of China, Email zhengxifu@m.scnu.edu.cnObjective: The study aimed to examine the roles of anxiety and intolerance of uncertainty (IU) in conditioned fear learning under an uncertain context induced by the contingency reversal of the association between the conditioned stimulus and the unconditioned stimulus (CS-US).Methods: The study sample comprised 53 participants, randomly divided into two groups: a non-instruction group and an instruction group. The experimental procedure encompassed five stages: pre-acquisition, acquisition, generalization, reversal acquisition, and reversal generalization. Our study primarily focused on analyzing a moderated mediation model.Results: In the instructed group, we observed that the reversed fear generalization response was directly influenced by the pre-reversal fear generalization response, while also being indirectly mediated by the IU factor. However, in the non-instructed group, we did not find a significant mediating effect of IU. Moreover, we noted that the mediation of IU was contingent on the instructional information. It is noteworthy that anxiety did not exhibit a discernible role in conditioned fear within the uncertainty condition in our study.Conclusion: The findings provide novel insights into fear-related phenomena, emphasizing the intricate interplay between individual traits and fear generalization under conditions of uncertainty. They contribute to understanding the mechanisms of emotional and cognitive interactions in uncertain conditions.Keywords: associations learning, fear generalization, instructional learning, moderated mediation model

Qi Wang,1– 3,&ast; Jiaxin Dong,4,&ast; Mengxian Du,1,3,&ast; Xinna Liu,1– 3 Shiqi Zhang,1 Di Zhang,1,3 Wanyun Qin,1,3 Xikun Xu,1,2 Xianghui Li,1,3 Ruidong Su,1,2 Leyi Qiu,1,2 Baoqiang Li,4,5 Huiping Yuan1 1Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry Education, Harbin, People’s Republic of China; 3Future Medical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, People’s Republic of China; 5Laboratory of Dynamics and Extreme Characteristics of Promising Nanostructured Materials, Saint Petersburg State University, St. Petersburg, Russia&ast;These authors contributed equally to this workCorrespondence: Huiping Yuan, Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China, Email yuanhp2013@126.com Baoqiang Li, Institute for Advanced Ceramics, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150081, People’s Republic of China, Email libq@hit.edu.cnIntroduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications.Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined.Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function.Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy. Keywords: retina, ischemia/reperfusion injury, rapamycin, carbon dots, microglial polarization, autophagy

Zhen Xiao,1,2 Simin Yu,1 Deng Zhang,1 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Chunming Li, Email chunminglincu@163.comBackground: Capsaicin is the main compound found in chili pepper and has complex pharmacologic effects. This study aimed to elucidate the mechanism of the effect of capsaicin on physiological processes by analyzing changes in metabolites and metabolic pathways.Methods: Female C57BL/6 mice were divided into two groups(n = 10/group) and fed with capsaicin-soybean oil solution(group T) or soybean oil(group C) for 6 weeks. Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was undertaken to assess plasma and skin metabolic profile changes and identify differential metabolites through multivariate analysis.Results: According to the OPLS-DA score plots, the plasma and skin metabolic profiles in the group T and group C were significantly separated. In plasma, 38 significant differential metabolites were identified. KEGG pathway enrichment analysis revealed that the most significant plasma metabolic pathways included pyruvate metabolism and ABC transporters. In skin, seven significant differential metabolites were found. Four metabolic pathways with p values < 0.05 were detected, including sphingolipid metabolism, sphingolipid signaling pathway, apoptosis, and necroptosis.Conclusion: These findings will provide metabolomic insights to assess the physiological functions of capsaicin and contribute to a better understanding of the potential effects of a capsaicin-rich diet on health.Keywords: capsaicin, UHPLC-QTOF-MS, metabolomics, plasma, skin

Dan Li,1,2,&ast; Donglin Zhang,3,&ast; Minjuan Wang,2 Jianfeng Hao,2 Yongquan Shi,4 Dake Chu1,5 1Graduate School, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Scientific Research Management Department, The Third Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 3General Medicine Department, The First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 4State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, People’s Republic of China; 5Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dake Chu, Graduate School, Xi’an Jiaotong University, No. 28 Xianning West Road, Xi’an, Shaanxi Province, 710049, People’s Republic of China, Tel/Fax +86-2985323922, Email chudake@xjtu.edu.cnPurpose: We conducted a multicenter cross-sectional study in central and western China to explore the association between inflammatory diet and stomach cancer odds.Patients and Methods: Participants from five hospitals in the central and western regions were collected. All participants completed the questionnaire we provided before the gastroscopy examination, which includes inquiries about risk factors for stomach cancer and food frequency. All participants underwent gastroscopy, and a mucosal biopsy was confirmed pathologically. Pathological findings were classified as chronic gastritis group, precancerous lesions group and stomach cancer group. Dietary Inflammatory Index (DII) scores were calculated based on the frequency of food occurrences in the questionnaire, and finally SPSS was used to calculate the correlation between variables.Results: A total of 1162 patients were included in this study, including 668 cases of chronic gastritis, 411 cases of precancerous lesions, and 83 cases of cancer. A single factor analysis was conducted to examine the risk factors of stomach cancer, revealing a significant association between a pro-inflammatory diet and the stomach cancer odds (p value < 0.05). The results of binary classification analysis further confirmed that a pro-inflammatory diet is a risk factor for stomach cancer 【odds ratio (OR) =7.400)】. Moreover, correlation analysis demonstrated a positive correlation between the severity of gastric mucosal diseases and an inflammatory diet (including anti-inflammatory and pro-inflammatory diets) (rs=0.274, p-value < 0.001).Conclusion: Pro-Inflammatory diet is a risk factor for stomach cancer, and may accelerate the progression of stomach mucosal disease.Keywords: stomach cancer, chronic gastritis, precancerous lesions, dietary inflammatory index, pro-inflammatory diet

Miaomiao Sun,1– 3,&ast; Fuquan Wang,1– 3,&ast; Haopeng Li,1– 3 Mengyu Li,1– 3 Yu Wang,1– 3 Chenchen Wang,1– 3 Yan Zhang,1– 3 Dingyu Zhang,1– 4 Jianhua Li,5 Shanglong Yao1– 3 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, 430022, People’s Republic of China; 4Wuhan Jinyintan Hospital, Wuhan, 430023, People’s Republic of China; 5Department of Critical Care Medicine, Chongqing University Jiangjin Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanglong Yao; Jianhua Li, Email yaoshanglong@hust.edu.cn; jianhuali2022@cqu.edu.cnBackground: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation.Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay.Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1β and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1β also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1’s protective effects in septic mice.Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.Keywords: Maresin-1, pyroptosis, AMPK/SIRT3, endoplasmic reticulum stress, sepsis-associated acute kidney injury, inflammation

Fei Wang,1,2 Chun Yue Yan,3 Yuan Qin,4 Zheng Ming Wang,1 Dan Liu,1 Ying He,1 Ming Yang,2 Li Wen,1 Dong Zhang1 1Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 2Department of Medical Imaging, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China; 3Department of Emergency Medicine, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China; 4Department of Radiology, Chongqing University Three Gorges Hospital, Chongqing, 404031, People’s Republic of ChinaCorrespondence: Dong Zhang, Department of Radiology, Xin Qiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86-23-68774676, Email hszhangd@tmmu.edu.cnBackground: Currently, it is still confused whether preoperative aminotransferase-to-platelet ratio (APRI) and gamma-glutamyl transferase-to-platelet ratio (GPR) can predict microvascular invasion (MVI) in solitary hepatocellular carcinoma (HCC). We aimed to develop and validate a machine-learning integration model for predicting MVI using APRI, GPR and gadoxetic acid disodium (Gd-EOB-DTPA) enhanced MRI.Methods: A total of 314 patients from XinQiao Hospital of Army Medical University were divided chronologically into training set (n = 220) and internal validation set (n = 94), and recurrence-free survival was determined to follow up after surgery. Seventy-three patients from Chongqing University Three Gorges Hospital and Luzhou People’s Hospital served as external validation set. Overall, 387 patients with solitary HCC were analyzed as whole dataset set. Least absolute shrinkage and selection operator, tenfold cross-validation and multivariate logistic regression were used to gradually filter features. Six machine-learning models and an ensemble of the all models (ENS) were built. The area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate model’s performance.Results: APRI, GPR, HBPratio3 ([liver SI‒tumor SI]/liver SI), PLT, peritumoral enhancement, non-smooth margin and peritumoral hypointensity were independent risk factors for MVI. Six machine-learning models showed good performance for predicting MVI in training set (AUCs range, 0.793– 0.875), internal validation set (0.715– 0.832), external validation set (0.636– 0.746) and whole dataset set (0.756– 0.850). The ENS achieved the highest AUCs (0.879 vs 0.858 vs 0.839 vs 0.851) in four cohorts with excellent calibration and more net benefit. Subgroup analysis indicated that ENS obtained excellent AUCs (0.900 vs 0.809 vs 0.865 vs 0.908) in HCC > 5cm, ≤ 5cm, ≤ 3cm and ≤ 2cm cohorts. Kaplan‒Meier survival curves indicated that ENS achieved excellent stratification for MVI status.Conclusion: The APRI and GPR may be new potential biomarkers for predicting MVI of HCC. The ENS achieved optimal performance for predicting MVI in different sizes HCC and may aid in the individualized selection of surgical procedures.Keywords: hepatocellular carcinoma, microvascular invasion, inflammatory biomarker, magnetic resonance imaging, machine learning

Chunhong Li,1,&ast; Zhen Wang,1,&ast; Yifeng Zhang,1 Yuqing Zhu,1 Maochang Xu,1 Hui Lei,1 Dan Zhang1,2 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Green Pharmaceutical Technology Key Laboratory of Luzhou, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Lei; Dan Zhang, Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, 1-1 Xianglin Road, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 17360593759 ; +86 18982700067, Email huilei@swmu.edu.cn; zhangdan@swmu.edu.cnPurpose: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them.Methods: Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM). Folic acid was further introduced to modify liposomes as the targeting moiety (F/CL@BM). We established a novel NIH3T3+4T1 co-culture model to mimic the tumor microenvironment and assessed the nanocarrier’s inhibitory effects on CAFs-induced drug resistance and migration in the co-culture model. The in vivo biological distribution, fluorescence imaging, biological safety evaluation, and combined therapeutic effect evaluation of the nanocarrier were carried out based on a triple-negative breast cancer model.Results: In the present study, a novel multifunctional nano-formulation was designed by combining the advantages of sequential release, co-loading of tretinoin and betulinic acid, and folic acid-mediated active targeting. As expected, the nano-formulation exhibited enhanced cytotoxicity in different cellular models and effectively increased drug accumulation at the tumor site by disrupting the cellular barrier composed of CAFs by tretinoin. Notably, the co-loaded nano-formulations proved to be more potent in inhibiting tumor growth in mice and also showed better anti-metastatic effects in lung metastasis models compared to the formulations with either drug alone. This novel drug delivery system has the potential to be used to develop more effective cancer therapies.Conclusion: Targeting CAFs with celastrol sensitizes tumor cells to chemotherapy, increasing the efficacy of betulinic acid. The combination of drugs targeting tumor cells and CAFs may lead to more effective therapies against various cancers.Keywords: liposomes, targeted delivery, triple-negative breast cancer, anti-tumor, combination therapy, sequential drug delivery

Jiancao Ding,1 Ying Sun,2 Kan Zhang,2 Wei Huang,2 Mei Tang,2 Dai Zhang,2 Yunli Xing2 1Department of Geriatrics, First People’s Hospital of Zigong, Sichuan, People’s Republic of China; 2Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yunli Xing, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 13121181469, Fax +86 10 6313 8040, Email xingyunli1976@126.comObjective: This study explored whether anticoagulation is safe for frail and non-frail elderly patients who have nonvalvular atrial fibrillation (NVAF).Methods: At hospital discharge, the anticoagulant regimen and frailty status were recorded for 361 elderly patients (aged ≥ 75 y) with NVAF. The patients were followed for 12 months. The endpoints included occurrence of thrombosis; bleeding; all-cause death; and cardiovascular events.Results: At hospital discharge, frailty affected 50.42% of the population and the anticoagulation rate was 44.04%. At discharge, age (OR 0.948, P = 0.006), paroxysmal NVAF (OR 0.384, P < 0.001), and bleeding history (OR 0.396, P = 0.001) were associated with a decrease in rate of receiving anticoagulation, while thrombotic events during hospitalization (OR 2.281, P = 0.021) were associated with an increase. Relative to non-frail patients, those with frailty showed a higher rate of ischemic stroke (5.33% cf. 3.01%), bleeding (P = 0.006) events, and all-cause mortality (P = 0.001). Relative to the group without anticoagulation, in those with anticoagulation the rate of thrombotic events was lower (6.99 cf. 10.98%) and bleeding events were higher (20.98 cf. 12.72%), but the risk of major bleeding was comparable.Conclusion: In the elderly patients with NVAF, the decision toward anticoagulation therapy at hospital discharge was influenced by age, bleeding history, paroxysmal atrial fibrillation diagnosis, and absence of thrombosis. Frail patients were at greater risk of bleeding and all-cause mortality. Anticoagulation tended to reduce the risk of thrombotic events.Keywords: elderly, non-valvular atrial fibrillation, frailty, anticoagulation

Xing Wang,&ast; Dong Zhang,&ast; Qingxia Lin, Changying Niu, Huiping Fan, Mogen Zhang, Xiangfeng Yuan, Weiyuan Ma Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangfeng Yuan; Weiyuan Ma, Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of China, Tel +86-536-3081272, Email nsmcyxf@126.com; fymaweiyuan@wfmc.edu.cnAbstract: Acquired digital fibrokeratoma (ADF) is rare in clinical practice and is easily misdiagnosed. Herein, 5 cases of patients (3 males and 2 females) with ADF are reported. The mean age at onset was 42.6 years, and the mean disease duration was 3 years. Four patients had ADF on the hands, and 1 patient had ADF on the foot. The clinical manifestations were all solitary, skin-colored papules, with a firm texture and smooth surface, protruding from the skin surface. In 3 patients, ADF manifested as columnar protrusions, and in 2 patients, ADF manifested as dome-shaped protrusions. For all 5 patients, the diameters of the lesions were < 1 cm. Clinically, all 5 patients were misdiagnosed (ie, eccrine poroma (EP), common warts, rudimentary polydactyly, pyogenic granuloma (PG), and acral fibroma). All cases of ADF were confirmed by histopathology. The histopathological manifestations of ADF were as follows: finger-like protrusions on the skin surface; collagen fiber bundles running vertically to the epidermis seen in the dermis; and thick red-stained collagen fibers connected with the normal dermal connective tissue below. All 5 patients underwent surgical resection; the distance between the incision margin and the edge of the tumor was 2– 3 mm, and the surgical depth was the deep dermis. No recurrence was observed in more than half a year of follow-up after surgery.Keywords: acquired digital fibrokeratoma, clinical manifestation, histopathology, surgical resection

Xiuping Wang,1 Xiaoliang Ouyang,2 Deng Zhang,1 Yunxia Zhu,1 Liang Wu,1 Zhen Xiao,3 Simin Yu,1 Wei Li,2 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Plastic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Tel/Fax +86 791 86278821, Email chunminglincu@163.comPurpose: Porokeratosis (PK) is a chronic autosomal-dominant cutaneous keratinization disorder exhibiting clinical and genetic heterogeneity. Mevalonate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), phosphomevalonate kinase(PMVK), and mevalonate kinase genes(MVK), which encode the mevalonate pathway, are disease-causing genes in PK.Patients and Methods: Data and blood samples were collected from two Chinese families and five sporadic patients with porokeratosis. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients.Results: Five heterozygous mutations were identified, including a novel FDPS stop-gain mutation c.438T>G (p.Tyr146Ter), a novel MVD missense mutation c.683G>C (p.R228P), and three previously reported MVD mutations: c.746T>C (p.F249S), c.875A>G (p.N292S), and c.1111_1113del (p.371_371del). The novel FDPS c.438T>G mutation was predicted as “disease-causing” (p = 1) by Mutation Taster. The other novel MVD c.683G>C was also predicted as “deleterious” (score = 0.00) by Sorting Intolerant From Tolerant (SIFT), “probably damaging” (score = 1) by PolyPhen2, and “disease-causing” (p = 0.999) by Mutation Taster.Conclusion: Our results extended the mutation spectrum of mevalonate pathway genes in porokeratosis and provided useful strategies for a more accurate diagnosis and genetic counseling.Keywords: porokeratosis, mutation, MVD, FDPS, genetics

Xiaoju Huang,1– 3 Mengmeng Wang,1– 3 Dan Zhang,1– 3 Chen Zhang,4 Pian Liu1– 3 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, 430022, People’s Republic of China; 4Liver Transplant Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Chen Zhang; Pian Liu, Email zhang_chen@hust.edu.cn; liupianamazing@126.comAbstract: Hepatocellular carcinoma is the prevailing malignant neoplasm affecting the liver, often diagnosed at an advanced stage and associated with an unfavorable overall prognosis. Sorafenib and Lenvatinib have emerged as first-line therapeutic drugs for advanced hepatocellular carcinoma, improving the prognosis for these patients. Nevertheless, the issue of tyrosine kinase inhibitor (TKI) resistance poses a substantial obstacle in the management of advanced hepatocellular carcinoma. The pathogenesis and advancement of hepatocellular carcinoma exhibit a close association with metabolic reprogramming, yet the attention given to lipid metabolism dysregulation in hepatocellular carcinoma development remains relatively restricted. This review summarizes the potential significance and research progress of lipid metabolism dysfunction in Sorafenib and Lenvatinib resistance in hepatocellular carcinoma. Targeting hepatocellular carcinoma lipid metabolism holds promising potential as an effective strategy to overcome hepatocellular carcinoma drug resistance in the future.Keywords: hepatocellular carcinoma, lipid metabolism, sorafenib, lenvatinib, targeted drug resistance

Xian Ding,1,&ast; Wenqi Liang,2,&ast; Hongjuan Xia,1,&ast; Yuee Liu,2 Shuxiong Liu,1 Xinyu Xia,1 Xiaoli Zhu,1 Yongyan Pei,3 Dewen Zhang4 1Department of Emergency, Third Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Emergency, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, People’s Republic of China; 4Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongyan Pei, School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, No. 9-13, Zhongshan Campus, No. 13, Changmingshui Avenue, Wuguishan, Zhongshan City, Guangdong Province, People’s Republic of China, Email peiyongyan@gdpu.edu.cn Dewen Zhang, Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, People’s Republic of China, Email zhangdewen120@hotmail.comBackground: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis.Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan–Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit.Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress.Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.Keywords: sepsis, immune-related lncRNA, lncRNA-mRNA, PRKCQ-AS1, prognosis and progress

Haiyan Song,1,2 Hui Zhang,1 Ding Zhang,1 Bo Liu,2 Pengcheng Wang,3 Yanyan Liu,1,4,5 Jiabin Li,1,4– 6 Ying Ye1 1Department of Infectious Disease, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Infectious Disease, the 901st Hospital, Hefei, Anhui, People’s Republic of China; 3Department of Clinical Laboratory, the 901st Hospital, Hefei, Anhui, People’s Republic of China; 4Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People’s Republic of China; 5Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 6Department of Infectious Diseases, the Chaohu Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Ying Ye; Jiabin Li, Tel +86-551-62922713, Fax +86-551-62922281, Email yeying2@139.com; lijiabin@ahmu.edu.cnPurpose: This study aims to establish a valuable risk prediction model for mortality in patients with Acinetobacter baumannii (A. baumannii).Patients and Methods: The 622 patients with A. baumannii infection from the First Affiliated Hospital of Anhui Medical University were enrolled as the study cohort. Univariate and multivariate logistic regression analysis was used to preliminarily screen the independent risk factors of death caused by A. baumannii infection, followed by LASSO regression analysis to determine the risk factors. According to the calculated regression coefficient, the Nomogram death prediction model is established. The area under the curve (AUC) and decision curve analysis (DCA) of the operating characteristic (ROC) curve of the subjects are used to evaluate the discrimination of the established prediction model. The calibration degree of the prediction model is represented by a calibration chart. A validation cohort that consisted of 477 patients admitted to the 901st Hospital was also included.Results: Our results revealed that the source of infection, carbapenem-resistant A. baumannii, mechanical ventilation, serum albumin value, and Charlson comorbidity index were independent risk factors for death caused by A. baumannii infection. The AUC value of ROC curves of study cohort and validation cohort were 0.76 and 0.69, respectively. The probability range (30– 80%) indicated a high net income of the modified model and strong capacity of discrimination. The calibration curve obtained by analysis swings up and down around the 45 diagonal line, which shows that the calibration degree of the prediction model is very high.Conclusion: In this study, we have reconstructed a risk prediction model for mortality in patients with A. baumannii infections. This model provides useful information to predict the risk of death in patients with A. baumannii infection, but the specificity is not optimistic. If this prediction model is wanted to be applied to clinical practice, more analysis and research are necessary.Keywords: A. baumannii, prediction model, risk factors, carbapenem resistance

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

Yong-Kang Gui,1,2,&ast; Xiao-Hui Zeng,1,2,&ast; Rui Xiao,3 Wen-Feng Xi,1– 3 Dan Zhang,1– 3 Yang Liu,1,2 Si-Hui Zhu,1,2 Xin Da,1,2 De-Wen Shi,1,2 Xu-Dong Hu,1,2 Guang-Hong Xu1,2 1Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 3Department of Anesthesiology, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui, 236113, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guang-Hong Xu, 230032, Tel +86 13856949535, Fax +86 0551 62923704, Email xuguanghong2004@163.comPurpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of μ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine.Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil.Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group.Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.Keywords: spinal anesthesia, respiratory depression, median effective dose, sufentanil, dezocine

Jinpei Song,1,&ast; Kai Feng,1,2,&ast; Dian Zhang,1 Shengnan Wang,1,3 Wei Wang,1 Yongxin Li1 1Institute of Psychology and Behaviour, Henan University, Kaifeng, Henan, People’s Republic of China; 2Academic Affairs Office, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, People’s Republic of China; 3Mental Health Service Center, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongxin Li, Email liyongxin@henu.edu.cnBackground: Entering university is a big change in life. It can cause a lot of stress for new students. Stress can affect their mental health in a negative way. Mental health literacy is the knowledge and skills to deal with mental health issues. It can help new students cope better with stress and improve their mental health.Objective: To investigate the status of mental health literacy, overall adaptation, and mental health of university freshers, and to explore the influence of mental health literacy on the overall adaptation and mental health, as well as the mediating role of overall adaptation.Methods: The undergraduate freshers of 2022 from a comprehensive university in Henan Province were selected as the research participants using a cluster sampling method and were investigated by the general information questionnaire, mental health literacy scale (MHLS), the university student overall adaptation questionnaire (CSOAQ) and university personality inventory (UPI).Results: (1) The detection rate of mental health problems among freshers was 22.39%, and the mental health literacy (112.26 ± 9.66), overall adaptation (3.93 ± 0.93), mental health (10.90 ± 10.51) of freshers had significant differences in demographic variables. (2) Mental health literacy was significantly positively correlated with overall adaptation and mental health, and overall adaptation was significantly positively correlated with mental health. (3) Overall adaptation plays a mediating role in the impact of mental health literacy on mental health. (4) Gender plays a moderating role in the effects of overall adaptation on mental health.Conclusion: The mental health literacy of university freshers could not only directly predict their mental health but also indirectly affect their mental health through overall adaptation, which is more significant among women.Keywords: university freshers, mental health literacy, overall adaptation, mental health, gender

Hanbing Song,&ast; Hongpeng Liu,&ast; XiaoDong Li, Bing Lv, Zonghan Tang, Qipeng Chen, Danqi Zhang, Fei Wang Department of Orthopedics, Heilongjiang University of Traditional Chinese Medicine, Harbin, 150000, Heilongjiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Danqi Zhang; Fei Wang, Surgery Building, Department of Orthopedics, Heilongjiang University of Traditional Chinese Medicine, No. 26 Heping Road, Xiangfang District, Harbin, Heilongjiang Province, People’s Republic of China, Email hljzymzdq@163.com; wangfei631@126.comBackground: This study aims to identify new therapeutic targets and explore the molecular mechanism of ankylosing spondylitis (AS), a rheumatic immune disease that mainly affects the sacroiliac and spinal joints. Despite extensive research, the exact cause of AS is still unknown. The research team utilized a bioinformatics approach to achieve their objectives.Methods: The GSE73754 dataset was downloaded from GEO database. Autophagy-related genes (ARGs) were collected from the Human Autophagy-dedicated Database. The limma package was used to screen for differentially expressed genes (DEGs), which were then intersected with the autophagy-related genes (ARGs) to identify differentially expressed autophagy-related genes (DEARGs). Subsequently, the DEARGs associated with AS were subjected to GO-BP and KEGG enrichment analyses using the clusterProfiler package. Core genes were identified using the cytoHubba plug-in of Cytoscape and were validated by clinical blood samples. Additionally, the Cell algorithm was utilized to evaluate the proportion of immune cell infiltration.Results: A total of 29 DEARGs were identified, which were found to be mainly enriched in autophagy, apoptosis, and necroptosis through functional enrichment analysis. Two core genes, HSPA5 and SQSTM1, were confirmed to have diagnostic value in AS. Immune cell infiltration analysis revealed CD8+ T cells, CD8+ T effector memory (Tem), natural killer (NK) cells, T gamma delta (Tgd) cells, and T-helper 1 (Th1) cells as major participants in AS development. Furthermore, HSPA5 expression was significantly correlated with Th1 cells, CD8+ T cells, CD4+ memory cells, and macrophages.Conclusion: This study suggested that HSPA5 and SQSTM1 can serve as useful diagnostic biomarkers for AS. These findings lay the foundation for identifying crucial mRNAs in the whole blood of AS patients, which may aid in the development of novel markers for AS.Keywords: diagnostic biomarkers, autophagy, immune cell, ankylosing spondylitis

Mingxiang Cai,1,&ast; Huizhen Peng,1,&ast; Minyi Liu,1,&ast; Maohua Huang,2,3 Wen Zheng,1 Guilan Zhang,1 Wenjia Lai,1 Chufang Liao,1 Lizhao Cai,1 Dongmei Zhang,2,3 Xiangning Liu1 1The First Affiliated Hospital of Jinan University, School of Stomatology, Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, 510630, People’s Republic of China; 2College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangning Liu, The First Affiliated Hospital of Jinan University, School of Stomatology, Clinical Research Platform for Interdiscipline of Stomatology, Jinan University, Guangzhou, 510630, People’s Republic of China, Email liuxiangning@jnu.edu.cn Dongmei Zhang, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China, Email dmzhang701@jnu.edu.cnPurpose: Blood vessels distribute cells, oxygen, and nutrients throughout the body to support tissue growth and balance. Pericytes and endothelial cells form the inner wall of blood vessels, crucial for organ development and tissue homeostasis by producing paracrine signaling molecules. In the skeletal system, pericyte-derived vascular factors along with angiogenic factors released by bone cells regulate angiogenesis and bone formation. Although the involvement of angiogenic factors and skeletal blood vessels in bone homeostasis is relatively clear, the role of pericytes and the underlying mechanisms remain unknown. Here, our objective was to elucidate the significance of pericytes in regulating osteoclast differentiation.Methods: We used tissue staining to detect the coverage of pericytes and osteoclasts in femoral tissues of osteoporotic mice and mice of different ages, analyzing their correlation. We developed mice with conditionally deleted pericytes, observing changes in bone mass and osteoclast activity using micro-computer tomography and tissue staining to detect the regulatory effect of pericytes on osteoclasts. Pericytes-derived exosomes (PC-EVs) were collected and co-cultured with monocytes that induce osteoclast differentiation to detect the effect of the former on the exosomes. Finally, the specific mechanism of PC-EVs regulating osteoclast differentiation was verified using RNA sequencing and Western blotting.Results: Our study indicates a significant correlation between pericytes and age-related bone resorption. Conditional deletion of pericytes activated bone resorption and led to osteopenia in vivo. We discovered that PC-EVs inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, which is mediated by tumor necrosis factor receptor-associated factor 3 (Traf3), negatively regulating osteoclast development and bone resorption. Silencing Traf3 in PC-EVs canceled their inhibitory effect on osteoclast differentiation.Conclusion: Our study provides a novel perspective into the regulatory role of pericytes on bone resorption and may provide potential strategies for developing novel anti-bone resorption therapies. Keywords: pericytes, exosomes, bone resorption, Traf3

Dongyan Chai,1,2,&ast; Zhihui Liu,3,&ast; Liuyi Wang,3 Hongyan Duan,2,3 Chenglong Zhao,1 Chengyang Xu,2 Dongyan Zhang,1 Qiongrui Zhao,4 Peizhi Ma1 1Department of Pharmacy, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan People’s Republic of China; 2International Medical Center of Henan Province, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of General Practice, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 4Department of Clinical Research Service Center, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peizhi Ma, Department of Pharmacy, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Weiwu Road 7, Zhengzhou, Henan, People’s Republic of China, Tel +86 18538298188, Fax +86 037165580803, Email ma18539298188@163.comBackground: Implementing medication reconciliation (MR) was complex and challenging because of the variability in the guidance provided for conducting. The processes of MR adopted in China were different from that recommended by the World Health Organization. A pilot study to inform the design of a future randomized controlled trial to determine the effectiveness of these two workflows was undertaken.Methods: Patients taking at least one home/regular medication for hypertension, diabetes, or coronary heart disease were recruited at admission, and then were randomized using a computer-generated random number in a closed envelope. In the study group, the pharmacist reviewed electronic medical record systems before communication with patients. In the control group, pharmacists communicated with patients at patient’s admission. The time investment of pharmacists for MR process, the number of unintended medication discrepancies, and physician acceptance were tested as outcome measures.Results: One hundred and forty adult patients were randomized, of which 66 patients in the intervention received MR within 24 hours, while 58 patients in control received MR at some point during admission. The most common condition in the study group was hypertension (coronary heart disease in the control group). The workflow of the study group can save an average 7 minutes per patient compared with the WHO recommended process [17.5 minutes (IQR 14.00, 28.25) vs 24.5 minutes (IQR17.75, 35.25), p = 0.004]. The number of unintended discrepancies was 42 in the study group and 34 in the control group (p = 0.33). Physicians’ acceptance in the study and control groups were 87.5% and 92.3%, respectively (p = 0.87).Conclusion: The results suggest that changes in outcome measures were in the appropriate direction and that the time limit for implementing MR can be set within 48 hours. A future multi-centre RCT study to determine the effectiveness of MR is feasible and warranted.Keywords: medication reconciliation, workflow, prospective studies, pharmacist, randomized controlled trial

Jun Wang,1,&ast; Hongmei Chen,2,&ast; Lin Yang,2 Xiuli Yu,3 Dandan Zhang,3 Qinghua Zhao,1 Mingzhao Xiao4 1Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Qinggang Senior Care Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingzhao Xiao, Department of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +8613608399433, Fax +86-23-89012206, Email mingzhaoxiao@cqmu.edu.cnAbstract: This paper aims to describe a randomized controlled trial protocol evaluating the effectiveness, cost, and process of a stress process model-based program in dementia caregiving (DeCare-SPM) for family caregivers. Family caregivers of individuals with dementia will be recruited from memory clinics and community settings and randomly assigned to either DeCare-SPM or usual care. DeCare-SPM comprises three face-to-face sessions (ie, problem-based coping, emotion-based coping, meaning-based coping), and a fourth session (ie, social support) including weekly telephone-based consultation for four weeks and then monthly face-to-face boosters. Outcomes will be measured at baseline (T0), and at one (T1), three (T2), and six months (T3). The primary outcome is positive aspects of caregiving and secondary outcomes are caregiving (ie, sense of competence, caregiver burden, social support, anxiety, depression, and quality of life), dementia-related (ie, care dependency, neuropsychiatric symptoms, and quality of life), and stress-related biomarkers of blood and saliva. In addition, process and economic evaluations will be performed. Mixed-effects models will be used to assess intervention effects. Content analysis will be performed on the qualitative data. This paper described the protocol for comprehensive evaluation of the effectiveness, cost, and process of the theory-driven DeCare-SPM to inform how and why interventions work. It highlights the need to reduce challenges and enhance the positive aspects of dementia care. The DeCare-SPM will provide evidence-based insights into how to support and empower family caregivers in their important roles, thereby, leading to improved dementia care.Keywords: Alzheimer’s disease, stress coping, informal caregivers, community, psychosocial

Weimin Fang,1,2,&ast; Jinghao Wang,3,&ast; Xiaocong Ma,1,2 Ni Shao,1,2 Kunlin Ye,1,2 Dong Zhang,1,2 Changzheng Shi,1,2 Liangping Luo1,2 1Medical Imaging Center, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changzheng Shi, Medical Imaging Center, The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China, Email tsczcn@jnu.edu.cn Liangping Luo, Medical Imaging Center, The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China. Department of Radiology, The Fifth Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China, Email tluolp@jnu.edu.cnBackground: Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor has demonstrated promising efficacy in patients with triple-negative breast cancer (TNBC) carrying breast cancer gene (BRCA) mutations. However, its impact on BRCA wild-type (BRCAwt) TNBC is limited. Hence, it is crucial to sensitize BRCAwt TNBC cells to olaparib for effective clinical practice. Novobiocin, a DNA polymerase theta (POLθ) inhibitor, exhibits sensitivity towards BRCA-mutated cancer cells that have acquired resistance to PARP inhibitors. Although both of these DNA repair inhibitors demonstrate therapeutic efficacy in BRCA-mutated cancers, their nanomedicine formulations’ antitumor effects on wild-type cancer remain unclear. Furthermore, ensuring effective drug accumulation and release at the cancer site is essential for the clinical application of olaparib.Materials and Methods: Herein, we designed a progressively disassembled nanosystem of DNA repair inhibitors as a novel strategy to enhance the effectiveness of olaparib in BRCAwt TNBC. The nanosystem enabled synergistic delivery of two DNA repair inhibitors olaparib and novobiocin, within an ultrathin silica framework interconnected by disulfide bonds.Results: The designed nanosystem demonstrated remarkable capabilities, including long-term molecular storage and specific drug release triggered by the tumor microenvironment. Furthermore, the nanosystem exhibited potent inhibitory effects on cell viability, enhanced accumulation of DNA damage, and promotion of apoptosis in BRCAwt TNBC cells. Additionally, the nanosystem effectively accumulated within BRCAwt TNBC, leading to significant growth inhibition and displaying vascular regulatory abilities as assessed by magnetic resonance imaging (MRI).Conclusion: Our results provided the inaugural evidence showcasing the potential of a progressively disassembled nanosystem of DNA repair inhibitors, as a promising strategy for the treatment of BRCA wild-type triple-negative breast cancer.Keywords: olaparib, novobiocin, tumor microenvironment, disulfide bonds, drug release, magnetic resonance

Yifei Zeng,1,2 Dongxiao Zhang,1 Na Fu,1 Wenjie Zhao,1 Qiao Huang,1 Jianchun Cui,3 Yunru Chen,4 Zhaolan Liu,4 Xiaojun Zhang,5 Shiyun Zhang,6 Khattak Mazher Mansoor3 1Department of Galactophore, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Liaoning Provincial People’s Hospital (Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University), Shenyang, People’s Republic of China; 4Centre for Evidence-Based Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 6Guang’ Anmen Hospital, China Academy of Chinese Medical Science, Beijing, People’s Republic of ChinaCorrespondence: Dongxiao Zhang, Department of Galactophore, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23, Art Museum Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +86 17862968916, Email morningdong@163.comBackground: This study aimed to explore the risk factors and clinical characteristics of granulomatous mastitis (GM) using a case-control study and establish and validate a clinical prediction model (nomogram).Methods: This retrospective case-control study was conducted in three hospitals in China from June 2017 to December 2021. A total of 1634 GM patients and 186 healthy women during the same period were included and randomly divided into the modeling and validation groups in a 7:3 ratio. To identify the independent risk factors of GM, univariate and multivariate logistic analyses were conducted and used to develop a nomogram. The prediction model was internally and externally validated using the Bootstrap technique and validation cohort. The receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the prediction model. Decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical significance of the model.Results: The average age of GM patients was 33.14 years (mainly 20– 40). The incidence was high within five years from delivery and mainly occurred in the unilateral breast. The majority of the patients exhibited local skin alterations, while some also presented with systemic symptoms. On multivariate logistic analysis, age, high prolactin level, sex hormone intake, breast trauma, nipple discharge or invagination, and depression were independent risk factors for GM. The mean area under the curve (AUC) in the modeling and validation groups were 0.899 and 0.889. The internal and external validation demonstrated the model’s predictive ability and clinical value.Conclusion: Lactation-related factors are the main risk factors of GM, leading to milk stasis or increased ductal secretion. Meanwhile, hormone disorders could affect the secretion and expansion of mammary ducts. All these factors can obstruct or injure the duct, inducing inflammatory reactions and immune responses. Additionally, blunt trauma, depressed mood, and diet preference can accelerate the process. The nomogram can effectively predict the risk of GM.Keywords: granulomatous mastitis, risk factors, case-control study, nomogram, prediction model

Dong Zhang,1,2 Siwei Duan,3 Zhangyou He,4 Zeming Zhu,3 Zhiping Li,3 Qincheng Yi,4 Tiantian Cai,1,2 Juanjuan Li,1,2 Nan Chen,1,2 Shaoju Guo1,2 1Gastrointestinal Ward, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Gastrointestinal Ward, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, People’s Republic of China; 3Institute of Gastroenterology, Science and Technology Innovation Center of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Shaoju Guo, Gastrointestinal Ward, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China, Tel +86-0755-82571384, Email gsj1080@163.comPurpose: This study was conducted to explore the mechanism of Sijunzi Decoction (SJZ) in the treatment of ulcerative colitis (UC).Methods: The study aimed to investigate the active components and targets of SJZ in the treatment of UC by screening databases such as TCMSP, GeneCards, OMIM, Distinct, TTD, and Drugbank. An online Venn tool, Cytoscape 3.7.2, and Autodock Tools were used to analyze the components and targets. The study also used a mouse model of UC to further investigate the effects of SJZ. HE staining, immunofluorescence, ELISA, qPCR, and Western blot were used to detect various indices.Results: Eighty-three active components and 112 action targets were identified from SJZ, including 67 targets for treating UC-related NETs. The five core targets identified were AKT1, JUN, IL1B, PTGS2, and TNF, and molecular docking studies indicated that the five targets were well-docked with ginsenoside Rh2, isoflavones, and formononetin. Animal experiments demonstrated that SJZ could alleviate various parameters such as weight, colon length, spleen index, disease activity index, and intestinal pathology of the UC mice. Immunofluorescence and Western blot showed that SJZ could reduce the expression of IL1B and TNF in intestinal neutrophils while increasing the expression of Occludin. Cellular immunofluorescence suggests that SJZ can reduce the expression of TNF and IL1B in NETs. The qPCR results also suggested that SJZ could inhibit TNF signal. Furthermore, ELISA results suggested that SJZ could inhibit the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while promoting the expression of anti-inflammatory cytokines (IL-10, IL-37, TGF-β).Conclusion: SJZ treats UC by reducing the content of intestinal NETs, with primary targets on the NETs being IL1B and TNFand suppress TNF signal. The practical components of SJZ may be ginsenoside Rh2, isoflavones, and formononetin.Graphical Abstract: Keywords: ulcerative colitis, Sijunzi decoction, network pharmacology, IL1B, TNF

Dandan Zhang,1– 3,&ast; Xiaoxuan Yu,4,&ast; Qian Lin,1,3 Ying Xia,2 Guyi Wang,2 Jianhua Zhang,3 Yanyi Yang2 1Office of Pediatrics, Pediatric College, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Music Education, Shanghai Conservatory of Music, Shanghai, People’s Republic of China; 3Shanghai Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4College of Basic Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyi Yang; Jianhua Zhang, Email proyyy666@163.com; zjh12195@126.comAbstract: Music therapy (MT) is a common modality that performs a complementary and integrative role along with standard treatments for many pediatric diseases. This article briefly reviewed the effects of MT on children aged 5– 11 years old and adolescents with asthma from previous studies, specified its functional target towards asthma symptoms, and sorted out the design and investigation of selected research. Medline/PubMed, Embase, SportDis-cus, Cochrane Library, Teacher Reference Centre, Web of Science, Academic Search Complete, PsycARTICLES, and Scopus were queried for experimental and observational studies published between 1990 and 2021. Then, researchers showed that MT lessened patients’ asthma symptoms, improved medication compliance, pulmonary function, and quality of life, and helped children and their parents manage anxiety and depression. This article may serve as a reference for clinical research for pediatric asthma therapies and lay the foundation for future research on MT and its clinical practice.Keywords: pediatric asthma, music therapy, breath exercise, sing and play the wind instruments

Renke Chen,1,&ast; Mengxiao Xie,2,&ast; Shenlong Wang,1 Fei Yu,2– 4 Dan Zhang,2– 4 Lingjun Yuan,2 Jieyuan Zheng,2 Jingchao Wang,2 Jieting Zhou,2 Binxiao Li,2 Shufa Zheng,2– 4 Yongsheng Fan,1 Dongsheng Han2– 4 1The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Key Laboratory of Clinical in vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China; 4Institute of Laboratory Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Han, Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email hands@zju.edu.cn Yongsheng Fan, School of Basic Medical Sciences, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email fyszjtcm@163.comBackground: Metagenomic next-generation sequencing (mNGS) is a promising tool for improving antimicrobial therapy and infection control decision-making in complex infections. Secondary infection surveillance using mNGS in COVID-19 patients has rarely been reported.Methods: Respiratory pathogen and antibiotic resistance prediction were evaluated by BALF mNGS for 192 hospitalized COVID-19 patients between December 2022 and February 2023.Results: Secondary infection was confirmed in 83.3% (160/192) of the COVID-19 patients, with bacterial infections (45%, 72/160) predominating, followed by mixed bacterial and fungal infections (20%, 32/160), and fungal infections (17.5%, 28/160). The incidence of bacterial or viral secondary infection was significantly higher in patients who were admitted to the ICU, received mechanical ventilation, or developed severe pneumonia (all p< 0.05). Klebsiella pneumoniae (n=30, 8.4%) was the most prevalent pathogen associated with secondary infection followed by Acinetobacter baumannii (n=29, 8.1%), Candida albicans (n=29, 8.1%), Aspergillus fumigatus (n=27, 7.6%), human herpes simplex virus type 1 (n=23, 6.4%), Staphylococcus aureus (n=20, 5.6%) and Pneumocystis jiroveci (n=14, 3.9%). The overall concordance between the resistance genes detected by mNGS and the reported phenotypic resistance in 69 samples containing five clinically important pathogens (ie, K. pneumoniae, A. baumannii, S. aureus, P. aeruginosa and E. coli) that caused secondary infection was 85.5% (59/69).Conclusion: mNGS can detect pathogens causing secondary infection and predict antimicrobial resistance for COVID19 patients. This is crucial for initiating targeted treatment and rapidly detect unsuspected spread of multidrug-resistant pathogens.Keywords: COVID-19, SARS-CoV-2, metagenomic next-generation sequencing, antibiotic resistance

Yonghong Gao,1 Yan Wang,1 Dandan Zhang,2 Tingting Wu,1 Qingwei Li1 1Department of Cardiology, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of China; 2Department of General Practice, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of ChinaCorrespondence: Qingwei Li, Department of Cardiology, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of China, Email tel18930810663@163.comBackground: In the general population of the United States (U.S.), the relationship between dietary inflammatory index (DII) and mortality (all-cause, cardiovascular disease (CVD)-related, and cancer-related) is still unclear. Therefore, in this research, we examined the association of DII with mortality caused by all-cause, CVD-related, and cancer-related causes.Methods: Data from the National Health and Nutrition Examination Survey (NHANES) from 1999– 2018 was used for exploring the link between DII and all-cause, CVD-related, and cancer-related mortality through the use of Cox proportional hazard models and restricted cubic spline model. In addition, subgroup analyses were further performed.Results: The study included 29,013 individuals from the NHANES from 1999 to 2018. The DII scores were nominated as low (T1: − 5.281– 0.724), medium (T2: 0.725– 2.513), and high-grade inflammation (T3: 2.514– 5.795), with T1 serving as the reference group. The linear positive correlation between DII and all-cause and CVD-related mortality was studied using Cox regression analysis. In the full-adjusted model, as compared with the individuals with T1 DII scores, adjusted odds ratios with 95% confidence intervals for all-cause and CVD-related mortality were 1.149 (1.059, 1.247), and 1.186 (1.084, 1.297), as well as 1.197 (1.032, 1.387), and 1.198 (1.019, 1.409), respectively. However, there was no statistical significance between DII and cancer-related mortality. The RCS plot also showed a significant increase in all-cause and CVD-related mortality with increased DII. Nevertheless, as DII scores increased, cancer-related mortality first increased and then decreased.Conclusion: All-cause and CVD-related mortality are linked independently to high DII scores, independently. Further study of the association of DII scores with mortality caused by all-cause, CVD-related, and cancer-related causes is necessary to explore.Keywords: all-cause mortality, cancer-related mortality, cardiovascular disease-related mortality, dietary inflammation index, National Health and Nutrition Examination Survey

Daya Zhang,1,&ast; ZhengJin Liu,2,&ast; Feihu Bai2,3 1Graduate School, Hainan Medical University, Haikou, People’s Republic of China; 2Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 3The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feihu Bai, Chief Physician and Professor of Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, &num;368, Longhua District, Haikou, Hainan Province, 570216, People’s Republic of China, Tel +86-18995181963, Fax +86898-66809168, Email 328473521@qq.comAbstract: Alcoholic liver disease (ALD)—one of the most common liver diseases — involves a wide range of disorders, including asymptomatic hepatic steatosis, alcoholic hepatitis (AH), liver fibrosis, and cirrhosis. Alcohol consumption induces a weakened gut barrier and changes in the composition of the gut microbiota. The presence of CYP2E1 and its elevated levels in the gastrointestinal tract after alcohol exposure lead to elevated levels of ROS and acetaldehyde, inducing inflammation and oxidative damage in the gut. At the same time, the influx of harmful molecules such as the bacterial endotoxin LPS and peptidogly from gut dysbiosis can induce intestinal inflammation and oxidative damage, further compromising the intestinal mucosal barrier. In this process, various oxidative stress-mediated post-translational modifications (PTMs) play an important role in the integrity of the barrier, eg, the presence of acetaldehyde will result in the sustained phosphorylation of several paracellular proteins (occludin and zona occludens-1), which can lead to intestinal leakage. Eventually, persistent oxidative stress, LPS infiltration and hepatocyte damage through the enterohepatic circulation will lead to hepatic stellate cell activation and hepatic fibrosis. In addition, probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), bioengineered bacteria, gut-restricted FXR agonists and others are promising therapeutic approaches that can alter gut microbiota composition to improve ALD. In the future, there will be new challenges to study the interactions between the genetics of individuals with ALD and their gut microbiome, to provide personalized interventions targeting the gut-liver axis, and to develop better techniques to measure microbial communities and metabolites in the body.Keywords: alcoholic liver disease, gut dysbiosis, modulators

Minglei Ma, Tao Jiang, Dongxue Zhang, Xiaoai Yao, Zhen Wen, Lei Xiu Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Tao Jiang, Email jiangtao@bjsjth.cnObjective: To investigate the association of bedtime with the risk of early-onset diabetes mellitus (DM) and islet beta cell function.Methods: 138 participants with treat-naïve DM were included in this study. All participants underwent a 75g oral glucose tolerance test. Sleep habit was obtained through a standardized questionnaire. Bedtime was categorized as < 22:00, 22:00– 24:00, and ≥ 24:00 in this study. Multivariate logistic regression and multiple linear regression were used to estimate the association between bedtime and risk of early-onset DM and islet beta cell function, respectively.Results: Patients with early-onset DM had a later bedtime than those with late-onset DM. Individuals with bedtime ≥ 24:00 had a higher prevalence of early-onset DM than those with bedtime at 22:00– 24:00 and < 22:00 (51.2% vs 29.3% vs 14.3%, respectively, p = 0.028). The multivariate logistic regression showed that per hour later in bedtime was associated with a 52% increased risk of early-onset DM (p = 0.023). Patients with bedtime after 24:00 had a 146% increased risk of early-onset DM compared to those went to bed between 22:00 to 24:00 (OR = 2.46, 95% CI 1.05 to 5.77, p = 0.039). The multiple linear regression showed that bedtime was independently negatively correlated with late-phase insulin secretion (assessed by disposition index, DI120).Conclusion: Later bedtime was associated with worse late-phase insulin secretion and may be a risk factor for early-onset DM. Proper bedtime to lower risk of early-onset DM deserves further investigation.Keywords: diabetes mellitus, early-onset, sleep, bedtime, islet beta cell function

Deng Zhang,1 Simin Yu,1 Xiaoliang Ou Yang,1 Xiuping Wang,1 Yunxia Zhu,1 Zhen Xiao,2 Yanping Tan,3 Liang Wu,1 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of China; 3Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email chunminglincu@163.comBackground: Acne vulgaris (AV) is a common inflammatory disorder involving the pilosebaceous unit. The study aimed to explore the plasma lipidome signatures and identify specific lipid biomarkers in moderate-to-severe acne patients.Patients and Methods: Untargeted plasma lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was employed on 30 moderate-to-severe acne patients aged between 16– 25 years and 30 healthy controls. Multivariate data analyses were used to identify the distinguishing lipid metabolites.Results: All 1449 species of 37 lipid subclasses were identified from the MS data. There were apparent differences in plasma lipid profiles between acne groups and control groups. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 26 significantly different lipid metabolites were identified. These metabolites consisted mainly of glycerophospholipids (GPs), sphingolipids (SPs), and glycerolipids (GLs). Combining with AUC≥ 0.800 as the elected criteria, we obtained five differential lipids with good diagnostic performance for acne severity, including 2 sphingomyelins (SM), 1 phosphatidylglycerol (PG), 1 trihexosylceramide (Hex3Cer), and 1 Phosphatidylcholine (PC). Among them, PG (44:0) had the highest AUC values.Conclusion: Our study revealed the plasma lipidome signature of patients with moderate-to-severe acne. The results will provide a novel light into the perturbed lipid metabolism leading to the development of acne.Keywords: moderate-to-severe acne, lipidomics, sphingolipids, glycerophospholipids

Yuxin Tan,1 Xiuyun Lin,1,2 Hui Chen,1 Min Xu,1 Yingying Tang,1 Pengfei Gao,1 Wei Ren,1 Di Zhang1 1Faculty of Psychology, Beijing Normal University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Applied Experimental Psychology, Faculty of Psychology, Beijing Normal University, Beijing, People’s Republic of ChinaCorrespondence: Xiuyun Lin, Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of China, Email linxy@bnu.edu.cnIntroduction: During emergencies, individuals and communities often react in a variety of ways, including panic response. However, the study of panic response is limited due to narrow assessment tools that measure only one or two dimensions of human response (eg, physiology, cognition, emotion, and behavior). To address this limitation and to explore the risk and protective factors of panic response during the global spread of the Coronavirus Disease 2019 (COVID-19), the current study developed and evaluated the Panic Response Scale (PRS).Methods: Four samples were recruited for the following purposes: interview analysis (n = 26); item analysis and exploratory factor analysis (n = 604); confirmatory factor analysis and reliability analysis (n = 603); and retest reliability, validity analysis, and regression analysis (n = 349).Results: The PRS consists of 21 items with four subscales: Physical Discomfort, Anxious Fluster, Sensitive Depression, and Excessive Prevention. Each of these subscales demonstrated good internal consistency (rs > 0.73), test-retest reliability (rs > 0.77), criterion validity (r = 0.69, p < 0.01), and convergent validity (rs = 0.31– 0.65, p < 0.01). Regression analysis revealed significant predicting effects of COVID-19 knowledge and neuroticism on panic response. Additionally, cognitive reappraisal moderated the association between neuroticism and panic response.Discussion: Following a traumatic event, the PRS offers a potential tool for identifying individuals in need of mental health services. Moreover, during the COVID-19 pandemic, knowledge and neuroticism served as risk factors for heightened panic response, while cognitive reappraisal served as a protective factor for coping with panic response.Keywords: COVID-19, panic response, knowledge, neuroticism, cognitive reappraisal

Yifei Zeng,1,2 Dongxiao Zhang,1 Wenjie Zhao,1 Na Fu,1 Qiao Huang,1 Shuqi Li,2 Chang Gao,2 Jiale Yu2 1Department of Galactophore, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Dongxiao Zhang, Department of Galactophore, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23, Art Museum Back Street, Dongcheng District, Beijing, People’s Republic of China, Tel +86 13811077684, Email morningdong@163.comBackground: Despite the rising incidence rate of granulomatous lobular mastitis (GLM), uncertainties persist about its etiologic and predisposing factors to guide clinical treatment and early prevention. The objective of this study is to explore the predisposing factors for GLM.Patients and methods: This case-control study was conducted from 2018 to 2021 at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Patients with GLM (cases) were matched with healthy examinees (controls) in a 1:1 ratio according to gender and living area. We analyzed their demographic features and investigated 75 factors that may be relevant to GLM using a standard questionnaire. Univariate and multivariable binary conditional logistic regression analyses were used to compare the differences between the two groups and evaluate the predisposing factors that may induce GLM.Results: There were 594 female GLM patients and 594 matched controls included in the study. The average age of the cases was 32.78 years (mainly 20 to 40). The incidence was high within five years after childbirth, and lesions were mainly in the unilateral breast. Univariate and multivariable conditional logistic regression analyses obtained six relevant factors and six high-risk factors. The six relevant factors included age, marriage, emotional abnormality, high prolactin, psychiatric drug intake, and sex hormone intake. Additionally, the independent high-risk factors for GLM included gestation, nipple invagination, blunt trauma, non-iatrogenic massage, lactation disorder, and nipple discharge (odds ratio (OR)=17.378, 8.518, 4.887, 3.116, 2.522, 1.685, P< 0.05). Menopause was an independent protective factor (OR=0.249, P< 0.05).Conclusion: The factors that increase milk and secretion production in the mammary duct are the main risk factors of GLM, especially when the nipples are invaginated. These factors can obstruct the duct and induce inflammation. Additionally, hormonal disorders, extrinsic trauma, and emotional abnormalities can accelerate the occurrence of GLM.Keywords: granulomatous lobular mastitis, GLM, predisposing factor, risk factor, case-control study, etiology

Xiaosu Wang,&ast; Dan Zhang,&ast; Zheng Dai, Jingdan Yu, Qichao Li, Litao Zhang Department of Clinical Laboratory, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, 430056, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Zhang, Email dandanzhangnihao@126.comIntroduction: W. confusa has been known to cause various human infections. It is naturally resistant to vancomycin and is difficult to identify using traditional methods, which may lead to misidentification and delay treatment.Case Presentation: We present a case of a 42-year-old male patient with gastrointestinal bleeding and coronary heart disease who developed sepsis caused by Weissella confusa. The patient’s blood cultures showed the presence of gram-positive coccobacilli, later identified as W. confusa through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing revealed that W. confusa had low minimum inhibitory concentrations (MICs) for some drugs (eg, ampicillin) and higher MICs for others (eg, cefotaxime). Empirical treatment with vancomycin was initially started, but after obtaining the identification and susceptibility results, the treatment was switched to meropenem combined with daptomycin, resulting in a successful outcome.Conclusion: Weissella confusa bacteremia is relatively rare, and accurate pathogenic diagnosis is essential for effective clinical treatment.Keywords: Weissella confusa, bacterial identification, 16S rRNA, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Hazrat Bilal,1 Dongxing Zhang,2,3 Muhammad Shafiq,4 Muhammad Nadeem Khan,5 Canhua Chen,6 Sabir Khan,1 Qian Wang,1,7 Lin Cai,1 Muhammad Awais,8 Haibin Hu,9 Yuebin Zeng1,10 1Department of Dermatology, Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Department of Dermatology, Meizhou Dongshan Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China; 3Department of Dermatology, Meizhou People’s Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China; 4Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, People’s Republic of China; 5Faculty of Biological Sciences, Department of Microbiology, Quaid-I-Azam University, Islamabad, 45320, Pakistan; 6Clinical Laboratory, Meizhou People’s Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China; 7Department of Medical-Surgical and Experimental Sciences University of Sassari Neurology Unit, Azienda Ospedaliera Universitaria (AOU), Sassari, Italy; 8Department of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 9The First Clinical Medical college, Guangdong Medical University, Zhanjiang, 523808, People’s Republic of China; 10Department of Dermatology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610021, People’s Republic of ChinaCorrespondence: Yuebin Zeng, Tel +8618607549813, Email zeng_yb@163.comObjective: Cryptococcosis is a fatal infection that can affect both immunocompetent and immunocompromised patients, and it is little understood in China’s various regions. This research aimed to look at the epidemiology, risk factors, and antifungal susceptibility pattern of Cryptococcus neoformans in eastern Guangdong, China.Methods: A six-year (2016– 2022) retrospective study was conducted at Meizhou People’s Hospital, China. Demographical, clinical, and laboratory data of cryptococcal patients were collected from hospital records and statistically analyzed using the chi-square and ANOVA tests.Results: Overall, 170 cryptococcal infections were recorded, of which meningitis accounted for 78 (45.88%), cryptococcemia for 50 (29.41%), and pneumonia for 42 (24.7%). The number of cases increased 8-fold during the study duration. The median age of patients was 58 years (Inter quartile range: 47– 66), and the high proportion of cases was from the male population (n = 121, 71.17%). The underlying diseases were identified only in 60 (35.29%) patients, of which 26 (15.29%) were severely immunocompromised, and 26 (15.29%) others were mildly immunocompromised. A statistically significant difference was reported for chronic renal failure, and anemia (p < 0.05) persisted in cases of three infection types. A high number of non-wild type (NWT) isolates were found against amphotericin B (n=13/145, 8.96%), followed by itraconazole (n=7/136, 5.15%) and voriconazole (n=4/158, 2.53%). Only six isolates (3.79%) were multidrug-resistant, four of which were from cryptococcemia patients. Compared to meningitis and pneumonia, cryptococcemia revealed a higher percentage of NWT isolates (p < 0.05).Conclusion: In high-risk populations, cryptococcal infections require ongoing monitoring and management.Keywords: cryptococcosis, Cryptococcus neoformans, epidemiology, risk factors, antifungal susceptibility

Dong Zhang,1 Yan Qu,2 Changlin Sui,2 Meiling Li,1 Yanmei Yuan,1 Ningning Wang,1 Weiyuan Ma1 1Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Weiyuan Ma, Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China, Email fymaweiyuan@wfmc.edu.cnBackground: Condyloma cuminata (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, which is prone to recurrence and difficult to cure in the short term. CD207 is a C-type lectin receptor that is specifically expressed on the surface of Langerhans cells (LCs) and is considered as an LC-specific immunohistochemical marker. The main purpose of this study is to explore the correlation between the expression of CD207 in CA skin lesions and the duration of CA disease course and frequency of recurrence, in order to provide new prognostic markers for CA to clinicians.Materials and Methods: A total of 40 male patients with CA and their skin lesions were collected, as well as 40 healthy male penile tissue samples. The skin lesions of CA were clinically and histologically confirmed by acetic acid test. The expression of CD207 in epidermal tissues was detected using immunohistochemistry. The difference in the number of CD207 positive cells between CA skin lesions and healthy skin controls was compared, and the association between the number of CD207 positive cells in CA skin lesions and the duration of disease course and the frequency of recurrence was determined through Spearman correlation analysis.Conclusion: In CA skin lesions, CD207 positive cells were found to have morphological abnormalities and the number of cells was significantly reduced compared to healthy skin, suggesting that there may be antigen presentation dysfunction in CA skin lesions, which may be the reason for the prolonged and unresolved condition of the disease. The fewer CD207 positive cells in CA skin lesions, the longer the disease course and the more frequent the recurrence, therefore, the expression level of CD207 can be used as a new prognostic marker for predicting the outcome of CA.Keywords: condyloma acuminata, CD207, langerhans cells, prognosis, biomarker

Xiaonan Chen,1 Dong Zhang,2 Teng Wang,3 Weiyuan Ma2 1Department of Hematology, Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of China; 3Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Teng Wang, Qilu Hospital of Shandong University, Jinan, People’s Republic of China, Tel +86-531-82169361, Email wt10113277@163.com Weiyuan Ma, Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of China, Tel +86-536-3081272, Email fymaweiyuan@wfmc.edu.cnAbstract: Mycobacterium marinum is an atypical bacterium, and skin infections caused by it are relatively rare, usually occurring in workers engaged in seafood processing and housewives who clean and prepare fish for consumption. The infection often occurs after the skin is punctured by fish scales, spines, etc. The JAK/STAT signaling pathway is closely related to the human immune response to infections. Therefore, JAK inhibitors may induce and exacerbate various infections in clinical practice. This article reports a case of mycobacterium marinum skin infection in the left upper limb of a female patient with chronic idiopathic myelofibrosis during treatment with ruxolitinib. The patient denied being punctured or scratched by fish scales or spines. Clinical manifestations included multiple infiltrative erythemas and subcutaneous nodules in the thumb and forearm. Histopathological examination showed infiltration of mixed acute and chronic inflammatory cells in the subcutaneous tissue. The diagnosis was ultimately confirmed by NGS sequencing. The patient was cured after taking moxifloxacin and clarithromycin for 10 months. Infection is a common adverse reaction of JAK inhibitors, but no literature has reported on mycobacterium marinum skin infections occurring during JAK inhibitor treatment, which is relatively rare. As the clinical application of JAK inhibitors becomes more widespread, the skin infections they cause may present in various forms and require the attention of clinicians.Keywords: ruxolitinib, JAK inhibitors, Mycobacterium marinum, skin, infection

Deng Zhang,1 Zhen Xiao,2 Xiaoliang Ouyang,1 Xiuping Wang,1 Yunxia Zhu,1 Simin Yu,1 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Tel/Fax +86 791 86278821, Email chunminglincu@163.comPurpose: Hailey–Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited blistering dermatosis. Pathogenic variants in ATP2C1 have been associated with HHD since 2000. This study aimed to identify the mutations in the ATP2C1 gene in two Chinese pedigrees and two sporadic cases with HHD.Patients and Methods: Two Chinese pedigrees and two sporadic cases were included in this study. Whole-exome sequencing and Sanger sequencing were performed to detect the mutation of the ATP2C1 gene. Predictions of protein structure and function were performed using bioinformatics tools, including Mutation Taster, Polyphen-2, SIFT, and Swiss-Model.Results: In this study, we detected three heterozygous mutations, including novel compound mutations of (c.1840– 4delA and c.1840_1844delGTTGC), splice site mutation of c.1570+3A>C, and a previously known nonsense mutation c.1402C>T in the ATP2C1 gene. Combined with our previous study, ten patients with c.1402C>T mutation in the ATP2C1 gene have been identified, and all these patients originated from Jiangxi Province.Conclusion: c.1402C>T mutation in the ATP2C1 gene was considered a regional highly prevalent mutation in the Chinese population with HHD. The results added new variants to the database of ATP2C1 mutations associated with HHD.Keywords: Hailey–Hailey disease, novel mutation, ATP2C1, Chinese pedigree, Sanger sequencing

Yang Wang,1,&ast; Zheng Wang,1,&ast; Xiao Wu,1,&ast; Song Zhu,2,&ast; Qiru Guo,1 Zhong Jin,1 Zixian Chen,3 Delai Zhang,2 Wangming Hu,1 Huan Xu,1 Liangqin Shi,1 Lan Yang,1 Yong Wang1 1College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Wang, College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Tel +86 18280350393, Email yongwang1008@hotmail.com; wangyong@cdutcm.edu.cnPurpose: Dysfunction of endothelium is associated with multiple pathological vascular diseases. However, how to regulate reendothelialization after vascular injury is not well defined. This study aims to determine whether and how Paeonol controls reendothelialization following artery injury.Methods: The endothelium of murine carotid artery was denuded by catheter guide wires injury. H&E staining and IF staining were performed to determine whether Paeonol is critical for reendothelialization. BRDU Incorporation Assay, Boyden Chamber Migration Assay, Tube Formation Assay, and Spheroid Sprouting Assay were used to investigate whether Paeonol is involved in regulating proliferation and migration of endothelial cells. The underlying mechanism of how Paeonol regulates reendothelialization was determined by Molecular docking simulation and CO-IP Assay.Results: Paeonol treatment significantly inhibits neointima formation in carotid artery ligation model by promoting proliferation and migration of endothelial cells. Mechanistically, Paeonol enhances c-Myc expression, consequently interacts with VEGFR2 results in activating VEGF signaling pathway, and eventually promotes reendothelialization after vascular injury.Conclusion: Our data demonstrated that Paeonol plays a critical role in regulating vascular reendothelialization, which may be therapeutically used for treatment of pathological vascular diseases.Graphical Abstract: Keywords: Paeonol, c-Myc, VEGFR2, vascular injury, reendothelialization

Song Guo,1,&ast; Di Zhang,2,&ast; Shan Zhao,1 Huan Zhang,1 Yijuan Sun,3 Li Yan1 1Gynecology Department, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 2Obstetrics Department, Shandong Provincial Third Hospital, Jinan, Shandong Province, People’s Republic of China; 3Shanghai Ji Ai Genetics & In vitro Fertilization Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yijuan Sun, Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, NO. 352 Dalin Road, Shanghai, 200011, People’s Republic of China, Tel +86-21-6345-5468, Fax +86-21-33180478, Email xiaowei2987415@163.com Li Yan, Gynecology Department, The First Affiliated Hospital of Shandong First Medical University, No. 16766 Jingshi Road, Jinan, 250014, Shandong Province, People’s Republic of China, Tel +86-531-89268763, Fax +86-531-82963647, Email yanliqy@163.comBackground: It is well established that female fertility declines with age, primarily because of loss of ovarian function. However, few studies have clarified the relationship between increasing age and endometrial receptivity. Here, we aimed to study the impact of age on endometrial receptivity, meanwhile, we examined the expression of endometrial mesenchymal stem cell (eMSC) surface markers (CD146 and PDGF-Rβ), essential for endometrial development and re-growth, in different age groups.Methods: Participants were enrolled in this study between October 2020 and July 2021. All 31 patients were divided into three age groups; early (30– 39 years old, n=10), intermediate (40– 49 years old, n=12) and advanced (≥ 50 years old, n=9). We assessed localization and expression of CD146 and PDGF-Rβ by immunofluorescence and further analyzed selected endometrial receptivity markers (Homeobox A10 HOXA10, leukemia inhibitory factor LIF and osteopontin) and steroid hormone receptors by immunohistochemistry.Results: There were no significant differences in expression of HOXA10 and OPN (p> 0.05) among the three groups. However, we found a significant difference in LIF expression between the early and advanced age groups, with higher expression noted in the latter group (p=0.02). Similarly, estrogen receptor (ER) and progesterone receptor (PR) expression were significantly increased (p=0.01 and p=0.01, respectively) in the advanced age group compared with the early age group. There were no significant difference in CD146 and PDGF-Rβ expression among the three groups (p> 0.05).Conclusion: These results suggest that the age of the patient does not influence their endometrial receptivity. So, this study serves to increase our understanding of the impact of age and eMSCs on endometrial receptivity and expands the etiology of age-related infertility.Keywords: age, endometrial receptivity, endometrial mesenchymal stem cells

Daya Zhang,1,&ast; Lijun Zhang,2,&ast; Shiju Chen,1,&ast; Runxiang Chen,1 Xiaodong Zhang,1 Feihu Bai3,4 1Graduate School, Hainan Medical University, Haikou, People’s Republic of China; 2Medical Examination Center, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 3Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 4The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feihu Bai, Chief Physician and Professor of Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, &num;368, Longhua District, Haikou, Hainan Province, People’s Republic of China, Tel +86-18995181963, Fax +86 898-66809168, Email 328473521@qq.comBackground: The prevalence of metabolism-related fatty liver disease (MAFLD) has been rarely reported in hospital staffs. The aim of this study was to assess the prevalence and risk factors for MAFLD in hospital staffs aged ≥ 18 years.Methods: Based on type B ultrasonic, hospital staffs who underwent medical examinations at the second Affiliated Hospital of Hainan Medical University from January 2022 to March 2022 were classified into health control group (661 subjects) and MAFLD group (223 subjects), demographic, biochemical and blood examination information were compared between 2 groups. Independent risk factors for MAFLD were determined by logistic regression. Predictive values of risk factors of MAFLD were evaluated by receiver operating characteristic (ROC) curves.Results: The prevalence of MAFLD was 33.7%. Older age (OR=1.08, p< 0.001), H. pylori infection (OR=0.234, p=0.02), triglyceride-glucose (TyG) (OR=7.001, p< 0.001), low-density lipoprotein cholesterol (LDL-C) (OR=2.076, p= 0.028), red blood cell (RBC) (OR=2.386, p=0.001), eating out (OR=0.048, p=0.001), regular exercise (OR=23.017, p< 0.001), and overweight (OR=3.891, p= 0.003) were independently associated factors for MAFLD. The AUC of model predicting MAFLD is 0.910 [95% CI (0.886, 0.934)], with 0.794 sensitivity, 0.908 specificity. The diagnostic value of model was higher in the female MAFLD group after stratified analysis according to gender. The model showed that TyG was the factor contributing more to MAFLD. The diagnostic value of TyG was higher in the female MAFLD group than male MAFLD group.Conclusion: The prevalence of MAFLD among hospital staffs was 33.7%. TyG can be used to predict MAFLD especially for female hospital staffs for early intervention.Keywords: metabolic-associated fatty liver disease, MAFLD, hospital staffs, risk factors, triglyceride-glucose index, TyG, red blood cell, RBC, H. pylori infection

Renjie Li,1 Tingting Li,1 Yang Xie,1 Shuang Zhai,1 Yang Qu,1 Dan Zhang,1 Liwei Zou,2 Yajuan Yang,2 Xiaoyan Wu,1,2 Fangbiao Tao,1,2 Shuman Tao2,3 1Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2MOE Key Laboratory of Population Health Across Life Cycle; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, 230032, People’s Republic of China; 3Department of Ophthalmology, The Second Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Shuman Tao, Email Shumantao@126.comPurpose: Smartphone use could lead to being physically inactive and a greater risk for health problems, such as inflammation. However, the associations between smartphone use, physical activity (PA), and systemic low-grade inflammation remained unclear. This study aimed to examine the potential mediating effect of PA on the association between smartphone use and inflammation.Patients and Methods: A two-year follow-up study was conducted between April 2019 and April 2021. Duration of smartphone use, smartphone dependence and PA were assessed by a self-administered questionnaire. Laboratory analysis of blood samples was performed to evaluate the levels of TNF-α, IL-6, IL-1β, and CRP as biomarkers of systemic inflammation. The correlations between smartphone use, PA, and inflammation were analyzed using Pearson correlation. Structural equation modelling was used to analyze the potential mediating effect of PA on the associations between smartphone use and inflammation.Results: A total of 210 participants were included with a mean (standard deviation) age of 18.7 (1.0) years, 82 (39%) of whom were males. Smartphone dependence was negatively associated with the total PA level (r=− 0.18, P< 0.01). PA mediated the associations between the duration of smartphone use and smartphone dependence with inflammatory markers. Specifically, as PA decreased, the duration of smartphone use was more negatively associated with TNF-α (ab=− 0.027; 95% CI: − 0.052, − 0.007) and more positively correlated to IL-6 (ab=0.020; 95% CI: 0.001, 0.046) and CRP (ab=0.038; 95% CI: 0.004, 0.086); smartphone dependency was more negatively associated with TNF-α (ab=− 0.139; 95% CI: − 0.288, − 0.017) and more positively related to CRP (ab=0.206; 95% CI: 0.020, 0.421).Conclusion: Our study illustrates that there are no direct associations between smartphone use and systemic low-grade inflammation, however, PA level plays a weak but significant mediating effect on the associations between smartphone use and inflammation among college students.Keywords: smartphone, inflammation, physical activity, mediating role, follow-up

Yi Zhang,1,&ast; Jin Cao,2,&ast; Minghui Jian,1 Zhixiao Zhou,2 Nadia Anwar,2 Lan Xiao,3,4 Yaping Ma,2 Dingmei Zhang,2 Jun Zhang,2 Xin Wang1– 4 1Department of Hygiene Toxicology, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 2Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, People’s Republic of China; 3School of Mechanical, Medical and Process Engineering, Centre for Biomedical Technologies, Queensland University of Technology, Brisbane, QLD, 4059, Australia; 4Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, Brisbane, QLD, 4059, Australia&ast;These authors contributed equally to this workCorrespondence: Xin Wang, Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, People’s Republic of China, Tel +86 136 3928 8558, Fax +86-851-2860 8903, Email lchwx@aliyun.comBackground: Despite the inherent regenerative ability of bone, large bone defect regeneration remains a major clinical challenge for orthopedic surgery. Therapeutic strategies medicated by M2 phenotypic macrophages or M2 macrophage inducer have been widely used to promote tissue remodeling. In this study, ultrasound-responsive bioactive microdroplets (MDs) encapsulated with bioactive molecule interleukin-4 (IL4, hereafter designated MDs-IL4) were fabricated to regulate macrophage polarization and potentiate the osteogenic differentiation of human mesenchymal stem cells (hBMSCs).Materials and Methods: The MTT assay, live and dead staining, and phalloidin/DAPI dual staining were used to evaluate biocompatibility in vitro. H&E staining was used to evaluate biocompatibility in vivo. Inflammatory macrophages were further induced via lipopolysaccharide (LPS) stimulation to mimic the pro-inflammatory condition. The immunoregulatory role of the MDs-IL4 was tested via macrophage phenotypic marker gene expression, pro-inflammatory cytokine level, cell morphological analysis, and immunofluorescence staining, etc. The immune-osteogenic response of hBMSCs via macrophages and hBMSCs interactions was further investigated in vitro.Results: The bioactive MDs-IL4 scaffold showed good cytocompatibility in RAW 264.7 macrophages and hBMSCs. The results confirmed that the bioactive MDs-IL4 scaffold could reduce inflammatory phenotypic macrophages, as evidenced by changing in morphological features, reduction in pro-inflammatory marker gene expression, increase of M2 phenotypic marker genes, and inhibition of pro-inflammatory cytokine secretion. Additionally, our results indicate that the bioactive MDs-IL4 could significantly enhance the osteogenic differentiation of hBMSCs via its potential immunomodulatory properties.Conclusion: Our results demonstrate that the bioactive MDs-IL4 scaffold could be used as novel carrier system for other pro-osteogenic molecules, thus having potential applications in bone tissue regeneration.Keywords: IL-4, bioactive microdroplets, biocompatibility, macrophages, immunoregulation, osteogenesis

Chunxia Shi, Pan Cao, Yukun Wang, Qingqi Zhang, Danmei Zhang, Yao Wang, Luwen Wang, Zuojiong Gong Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Zuojiong Gong, Department of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Email zjgong@163.comAbstract: PANoptosis is a new cell death proposed by Malireddi et al in 2019, which is characterized by pyroptosis, apoptosis and necroptosis, but cannot be explained by any of them alone. The interaction between pyroptosis, apoptosis and necroptosis is involved in PANoptosis. In this review, from the perspective of PANoptosis, we focus on the relationship between pyroptosis, apoptosis and necroptosis, the key molecules in the process of PANoptosis and the formation of PANoptosome, as well as the role of PANoptosis in diseases. We aim to understand the mechanism of PANoptosis and provide a basis for targeted intervention of PANoptosis-related molecules to treat human diseases.Keywords: PANoptosis, pyroptosis, apoptosis, necroptosis

Minglei Ma, Tao Jiang, Zhen Wen, Dongxue Zhang, Lei Xiu Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Tao Jiang, Email jiangtao@bjsjth.cnObjective: To assess the correlation between body components with insulin resistance (IR) and islet beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM) or pre-diabetes mellitus (pre-DM) and to explore whether this correlation differs in males and females.Methods: 111 newly diagnosed diabetic or pre-diabetic patients were recruited in this cross-sectional study. 75g oral glucose tolerance test was used to determine the diagnosis of DM or pre-DM. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI30) was calculated to assess IR and islet beta cell function, respectively. Whole-body and regional lean mass (LM) and fat mass (FM) were obtained by dual-energy X-ray absorptiometry (DEXA). Partial correlation and multiple linear regression analyses were used to determine the associations between body composition, IR, and islet beta cell function.Results: More body fat and appendicular fat was observed in female patients than in male, though with similar BMI. Legs fat % was negatively correlated with HOMA-IR, whereas legs lean % was positively associated with HOMA-IR in females (r = − 0.673, p = 0.017; r =0.664, p = 0.018, respectively). The regression analysis showed that legs LM was positively correlated with HOMA-IR in females. However, in male patients, android FM was positively correlated with HOMA-IR (r = 0.462, p = 0.007), and trunk LM was negatively associated with DI30 (r = − 0.458, p = 0.007). Nevertheless, no significant correlation was observed between body composition and islet beta cell function in female patients.Conclusion: Android FM was positively correlated with IR only in male patients but not in females. Besides, relative legs fat and LM were independently associated with IR in female patients but not in males. Further studies are needed to explore the underlying mechanism.Keywords: body composition, diabetes mellitus, insulin resistance, islet beta cell function

Sheng Ye,1 Huichun Xiao,1 Jian Chen,1 Di Zhang,1 Li Qi,1 Ting Peng,2 Yanyang Gao,2 Qianbing Zhang,3 Jinqing Qu,2 Lei Wang,4 Ruiyuan Liu1 1Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 3Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, People’s Republic of ChinaCorrespondence: Jinqing Qu; Ruiyuan Liu, Email cejqqu@scut.edu.cn; ruiyliu@smu.edu.cnIntroduction: The high concentration of glutathione (GSH) and hydrogen peroxide (H2O2) levels within the tumor microenvironment (TME) are the major obstacle to induce the unsatisfactory anticancer treatment efficiency. The synergistic cancer therapy strategies of the combination the GSH depletion enhanced chemodynamic therapy (CDT) with photothermal therapy (PTT) have been proved to be the promising method to significantly improve the therapeutic efficacy.Methods: The copperphosphotungstate was incorporated into polyanilines to design copperphosphotungstate doped polyaniline nanorods (CuPW@PANI Nanorods) via chemical oxidant polymerization of aniline. The low long-term toxicity and biocompatibility were evaluated. Both in vitro and in vivo experiments were carried out to confirm the GSH depletion enhanced CDT/NIR-II PTT synergistic therapy.Results: CuPW@PANI Nanorods feature biosafety and biocompatibility, strong NIR-II absorbance, and high photothermal-conversion efficiency (45.14%) in NIR-II bio-window, making them highly applicable for photoacoustic imaging and NIR-II PTT. Moreover, CuPW@PANI Nanorods could consume endogenous GSH to disrupt redox homeostasis and perform a Fenton-like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Furthermore, NIR-II photothermal-induced local hyperthermia accelerates •OH generation to enhance CDT, which realizes high therapeutic efficacy in vivo.Conclusion: This study provides a proof of concept of GSH-depletion augmented chemodynamic/NIR-II photothermal therapy.Keywords: copperphosphotungstate, NIR-II absorption nanorods, NIR-II photothermal therapy, GSH depletion, chemodynamic therapy, synergistic therapy