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Haoyang Xin,1,&ast; Man Wang,2,&ast; Shuo Wang,3 Haiyan Han,3 Nan Jiang1 1Department of Nephrology and Rheumatology, Second Affiliated Hospital of Tianjin University of TCM, Tianjin, People’s Republic of China; 2Department of Pharmacy, Tianjin Forth Central Hospital, Tianjin, People’s Republic of China; 3Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Jiang, Department of Nephrology and Rheumatology, Second Affiliated Hospital of Tianjin University of TCM, No. 69, Zengchan Street, Hebei District, Tianjin, 300250, People’s Republic of China, Tel +86 18622997255, Email jingnan_jn@126.comObjective: This study aimed to explore the potential active components and therapeutic targets of Shentong Zhuyu Decoction (SZD) in the treatment of ankylosing spondylitis (AS) through network pharmacology and animal experiments.Methods: Targets for AS and related pathways were obtained by network pharmacology, and the pathways with the best binding affinity in molecular docking were verified by animal experiments.Results: The network pharmacology analysis found 248 chemical components, 1068 drug targets and 803 AS-related targets in SZD. After intersection targets analysis, 116 common drug–disease targets were obtained, and matrix metalloproteinase-9, nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) and cytochrome P450 2D6 were identified as the key targets of SZD for the treatment of AS. A total of 2152 biological processes, 38 cellular component expressions and 150 molecular function terms were obtained in gene ontology enrichment analysis, and 153 Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathways were obtained in KEGG enrichment analysis. Molecular docking analysis showed that the absolute binding energies of glypallichalcone and NLRP3, quercetin and NLRP3 and kaempferol and NLRP3 were > 7. Animal experiments showed that the expressions of NLRP3, Caspase-1, interleukin (IL)-1β and IL-18 were significantly increased in the model group and the treatment group compared with those in the blank group, and the expression levels in the treatment group were significantly decreased compared with those in the model group (p < 0.05).Conclusion: The active components in SZD, such as baicalin, quercetin, kaempferol and glypallichalcone, may reduce the expression of IL-1β and IL-18 via the NLRP3/Caspase-1 signalling pathway to inhibit the development and progression of inflammation and play a role in the treatment of AS.Keywords: Shentong Zhuyu Decoction, ankylosing spondylitis, network pharmacology, mechanism of action

Haoming Luo,1,2,&ast; Miao Guo,3,4,&ast; Mingxing Li,1 Yueshui Zhao,1 Jing Shen,1 Fukuan Du,1 Yu Chen,1 Shuai Deng,1 Yuhong Sun,1 Li Gu,1 Wanping Li,1 Xiaobing Li,1 Meijuan Chen,1 Zhangang Xiao,1,5,6 Shengpeng Wang,3,4 Xu Wu1,7 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2Department of Pharmacy, Three Gorges University Hospital of Traditional Chinese Medicine & Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei, 443003, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 4Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 5Department of Pharmacy, Gulin County Hospital of Traditional Chinese Medicine, Luzhou, Sichuan, 646500, People’s Republic of China; 6School of Pharmacy, Sichuan College of Traditional Chinese Medicine, Mianyang, Sichuan, 621000, People’s Republic of China; 7Department of Paediatric Care, Luzhou People’s Hospital, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengpeng Wang, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China, Email swang@um.edu.mo Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@swmu.edu.cnIntroduction: Rhodiola species have been utilized as functional foods in Asia and Europe for promoting health. Research has demonstrated that Rhodiola has the potential to alleviate inflammatory bowel disease (IBD) in animal models. However, the specific active components and the underlying mechanism for ameliorating intestinal damage remain unclear. This study aims to explore the relieving effect of Rosavin (Rov), a known active constituent of Rhodiola, in IBD and the regulatory mechanisms.Methods: The therapeutic effect of Rov was evaluated using a murine model of acute colitis induced by dextran sulfate sodium salt (DSS). Inflammatory cytokines and neutrophil activation markers were measured by corresponding kits. Immunohistochemistry, immunofluorescence, TUNEL, and EdU assays were applied to investigate the tight conjunction proteins expression, epithelial marker expression, number of apoptotic cells, and epithelial proliferation, respectively. The protection effect of Rov on gut epithelial injury was assessed using TNF-α-induced intestinal organoids. Additinally, RNA sequencing was applied to observe the genetic alteration profile in these intestinal organoids.Results: Oral administration of Rov significantly attenuated weight loss and restored colon length in mice. Notably, Rov treatment led to decreased levels of pro-inflammatory cytokines and neutrophil activation markers while increasing anti-inflammatory factors. Importantly, Rov restored intestinal despair by increasing the number of Lgr5+ stem cells, Lyz1+ Paneth cells and Muc2+ goblet cells in intestines of colitis mice, displaying reduced epithelial apoptosis and recovered barrier function. In TNF-α-induced intestinal organoids, Rov facilitated epithelial cell differentiation and protected against TNF-α-induced damage. RNA sequencing revealed upregulation in the gene expression associated with epithelial cells (including Lgr5+, Lyz1+ and Muc2+ cells) proliferation and defensin secretion, unveiling the protective mechanisms of Rov on the intestinal epithelial barrier.Discussion: Rov holds potential as a natural prophylactic agent against IBD, with its protective action on the intestinal epithelium being crucial for its therapeutic efficacy. Keywords: rosavin, colitis, inflammatory bowel disease, organoid, intestinal stem cell

Juan Li,1,&ast; Shu Wang,2,&ast; Chaoping Ma,1,&ast; Ning Ning,3,&ast; Yingying Huang,1,4,&ast; Min Jiao,1 Jiyuan Zhang,1 Wenwu Sun,3 Jiaoyan Li,3 Bing Zhao,3 Enqiang Mao,3 Zaiqian Che,3 Chengjin Gao1 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Intensive Care Medicine, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400016, People’s Republic of China; 3Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 4Dementia Research Center, Macquarie University, Sydney, Australia&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, People’s Republic of China, Email gaochengjin@xinhuamed.com.cn Zaiqian Che, Departments of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email chezaiqian@163.comPurpose: New-onset atrial fibrillation (NOAF) and sepsis-induced coagulopathy (SIC) are severe complications in septic patients. However, the relationship between NOAF and SIC score has not been clearly defined. This study aims to investigate the association between SIC score and NOAF, as well as their effect on mortality in sepsis.Patients and Methods: This study was a two-center retrospective analysis. Medical data were collected from patients diagnosed with sepsis. The patients were divided into NOAF and non-NOAF groups, and the SIC score was calculated for each group. Univariable and multivariable logistic regression analyses were performed to explore the relationship between the SIC score and NOAF, as well as their effects on mortality. The Kaplan-Meier curve was used to assess the survival rate.Results: A total of 2,280 septic patients were included, with 132 (5.7%) suffering from NOAF. Multivariable logistic regression analyses indicated that age, gender, the Acute Physiology and Chronic Health Evaluation II score (APACHE II), heart rate, renal failure, stroke, chronic obstructive pulmonary disease (COPD), and the SIC score were independent risk factors for NOAF in sepsis. Moreover, NOAF was associated with an increased risk of in-hospital mortality, 28-day mortality, and 90-day mortality. These results were consistent across subgroup analyses.Conclusion: The SIC score was an independent risk factor for NOAF in septic patients, and NOAF was an independent risk factor for predicting mortality.Keywords: sepsis, sepsis-induced coagulopathy, new-onset atrial fibrillation, association, mortality

Sheng Wang,1– 3,&ast; Wufei Ye,1,3,&ast; Kui Yang,1,3 Xiongwen Lv,2 Jiajie Luan1,3 1Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, 241001, People’s Republic of China; 2The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3School of Pharmacy, Wannan Medical College, Wuhu, Anhui, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiongwen Lv, The Key Laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China, Email xiongwen_lv2019@163.com Jiajie Luan, Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, 241001, People’s Republic of China, Email luanjiajie775@163.comObjective: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer. Hypoxia can be involved in HCC tumor growth, invasion and metastasis through inducing angiogenesis. Nevertheless, the assessment of the impact of hypoxia and angiogenesis on the prognosis of HCC remains inadequate.Methods: According to hypoxia-angiogenesis-related genes (HARGs) expression information and clinical data from patients within the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, we constructed a prognostic model (HARG-score) using bioinformatic tools. In addition to assessing the predictive ability of this prognostic model in both Liver Cancer-Riken-Japan (LIRI-JP) and GSE14520 cohorts, we analyzed the correlation between HARG-score and clinical characteristics, immune infiltration and immunotherapy efficacy. Moreover, we investigated the exact role and underlying mechanism of key HARGs through molecular experiments.Results: We constructed a 5-gene prognostic model HARG-score consisting of hypoxia-inducible lipid droplet-associated (HILPDA), erythropoietin (EPO), solute carrier family 2 member 1 (SLC2A1), proteasome subunit alpha type 7 (PSMA7) and cAMP responsive element-binding protein 1 (CREB1) through differentially expressed HARGs. The findings demonstrated that HARG-score was a good predictor of the prognosis of HCC patients from distinct cohorts and was correlated with clinical characteristics and immune infiltration. Furthermore, the HARG-score was identified as an independent prognostic factor. Lower HARG-score implied greater immunotherapy efficacy and better response. The expression and prognostic significance of these 5 genes were additionally validated in clinical data. In addition, experimental data revealed that the key gene HILPDA contributes to the progression of HCC through facilitating angiogenesis and affecting the expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA4).Conclusion: HARG-score has promising applications in prognosis prediction of HCC patients, in which HILPDA may be a latent prognostic biomarker and therapeutic target, providing a foundation for further research and treatment of HCC.Keywords: hepatocellular carcinoma, hypoxia-angiogenesis, HILPDA, prognosis, immunotherapy efficacy

Xueen Liu,1 Fang Pan,1 Qingmei Wang,1 Shuai Wang,1 Jiale Zhang2 1Department of Nursing, Beijing Hepingli Hospital, Beijing, People’s Republic of China; 2Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Jiale Zhang, Email zhang_tcm@163.comAbstract: Myofascial as a holistic structure emphasizes a holistic approach to intervention and treatment of fascial-related disorders such as neck pain (NP), low back pain (LBP), and knee pain. There are currently adverse effects of medication for diseases related to myofascial. Traditional Chinese rehabilitation exercise (TCRE) is a practical approach to traditional Chinese medicine and is a valuable option for intervening in myofascial-related pain. This article found some research evidence for Baduanjin, Wuqinxi, and Yijinjing in clinical studies of myofascial chain-related pain. The article summarizes the current evidence and finds that TCRE can enhance limb movement function through breathing and slow movements, increase joint movement and flexibility, and reduce joint pathology and stress-induced pain. As for future directions, focus on TCRE in improving the health of older adults and treating long-COVID syndrome, and integrate robotic and TCRE training to frame safe and effective exercise models. Relevant studies have already been registered in the Clinical Trials Registry, and some clinical study protocols have been published. TCRE can be an alternative nonpharmacological rehabilitation therapy to alleviate chronic rheumatic pain symptoms and augment public health management.Keywords: traditional Chinese rehabilitation exercise, pain, myofascial chain, rehabilitation

Yapu Liu, Yuanyuan Su, Zhonghao Luan, Xiuwei Hou, Guangliang Wu, Yonghui Xu, Songmao Wang, Lifeng Gao, Xiaochen Zheng Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, Luohe, People’s Republic of ChinaCorrespondence: Yapu Liu, Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, 463 Haihe Avenue, Luohe, 462300, People’s Republic of China, Tel/Fax +86-0395-6162312, Email 460547380@qq.comPurpose: To introduce the surgical methods and clinical results of percutaneous vertebroplasty (PVP) combined with hollow screw placement as a treatment for patients with Kummell’s disease and pedicle rupture.Methods: From January 2020 to January 2023, a total of 10 patients with Kummell’s disease and pedicle rupture confirmed via imaging underwent three-column intensive therapy using hollow screws combined with PVP. There were two males and eight females with an average age 75.7± 6.11 years old. The time of operation, bone cement injection amount, bone cement leakage during operation were recorded. X-ray and CT were reexamined after operation. The improvement in quality of life was assessed using the Oswestry Disability Index (ODI), and the improvement in low back pain was assessed using the visual analogue scale (VAS).Results: Hollow screw placement combined with PVP was successfully performed in all patients. The average operation time was 39.2± 5.1 min, and the average volume of bone cement injected was 5.85± 0.83mL. No leakage of bone cement into spinal canal occurred.The mean preoperative ODI score was 75.70± 4.39, but this decreased significantly postoperatively(P< 0.05), being 37.70± 6.95 at 1 day and 26.40± 4.90, 23.70± 4.87, 21.70± 5.46, and 20.50± 4.21 at 1, 3, 6, and 12 months after the operation, respectively. The mean VAS pain score before the operation was 8.35± 0.63, but the symptoms of back pain were significantly relieved after operation(P< 0.05). The mean VAS scores 1 day and 1, 3, 6, and 12 months after the operation were 3.45± 0.47, 2.55± 0.60, 1.89± 0.48, 1.50± 0.27, and 1.12± 0.20, respectively.Conclusion: Hollow screw placement combined with percutaneous vertebroplasty serves as a valuable three-column intensive treatment for patients with Kummell’s disease and pedicle rupture. This procedure has the advantages of minimal trauma, less pain and quick recovery. The strong anchoring of bone cement and hollow screws provides stable and firm healing conditions for vertebral and pedicle fractures.Keywords: three-column enhancement, PVP, hollow screw, Kummell’s disease, pedicle rupture

Pair Ahmed Jiko,1 Mahathir Mohammad,1 Fahmida Tasnim Richi,2 Md. Anisul Islam,3 Safaet Alam,2,4 Mohammad Abdullah Taher,2,5 Chuxiao Shao,6 Shuanghu Wang,6 Peiwu Geng,6 Abdullah Al Mamun6 1Department of Chemistry, Chittagong University of Engineering & Technology, Chittagong, 4349, Bangladesh; 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh; 3Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4202, Bangladesh; 4Chemical Research Division, BCSIR Dhaka Laboratories, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, 1205, Bangladesh; 5Bangladesh Reference Institute for Chemical Measurements (BRiCM), Laboratory Road, Dhaka, 1205, Bangladesh; 6Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of ChinaCorrespondence: Abdullah Al Mamun, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Tel +86-19715780050, Email pharmaalmamun@yahoo.comBackground: Shirakiopsis indica (Willd)., commonly known as Sa-Mor-Ta-Lay in Thailand, is a mangrove plant belonging to the Euphorbiaceae family. As mangrove plants’ medicinal potentials are less explored, this study sought to qualitatively and quantitatively verify the bioactive components of Shirakiopsis indica fruits methanolic extract (SIF-ME) at the side of its analgesic, anti-inflammatory and anti-oxidant effects followed by in-silico studies.Methods: The in-vivo assessments of analgesic activity involved the hot plate test, acetic acid-induced writhing test, and formalin-induced licking test. The anti-inflammatory efficacy was assessed through the human RBC membrane stabilization assay (HRBC), protein denaturation assay, and xylene-induced ear edema methods. Antioxidant potential was implemented by the DPPH scavenging method.Results: The SIF-ME consistently displayed significant anti-nociceptive activity in a dose-dependent pattern (p < 0.05). The maximum analgesic activity was found in the highest dose (200 mg/kg; p < 0.001) in a hot plate, acetic acid-induced writhing test 43.47%, and in formalin-induced licking test in both early phase (43.3%; p < 0.01) and late phase (61.84%; p < 0.001%). The extract provided optimal protection against hemolysis (83.41% decrease) at 1000 μg/mL and significantly inhibited protein denaturation (67.34– 26.05%) at doses of 1000– 62.5 μg/mL. At 200 mg/kg, the extract showed dose-dependent and substantial inhibition (54.07%; p < 0.01) of xylene-induced ear edema. The in-vitro DPPH (IC50 = 469.5 μg/mL) results showed remarkable scavenging activity and concentration-dependent reducing power. The extract demonstrates no acute oral toxicity, as indicated by an LD50 value exceeding 1000 mg/kg body weight. Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS) analysis was performed which yielded sixty bioactive compounds. In-silico and molecular docking studies revealed favorable pharmacological properties, including good binding affinities and ADME/T profiles.Conclusion: These results support the medicinal use of the plant, which makes it a potential source of analgesic, anti-inflammatory, and antioxidant candidates.Keywords: natural products, medicinal plants, shirakiopsis indica, acute oral toxicity, analgesic, anti-inflammatory, antioxidant, GC-MS/MS, molecular docking

Junyi Li,1,2,&ast; Zugui Wu,3,&ast; Bin Lu,2,&ast; Congcong Li,1 Shuai Wang,1 Jiahao Zhang,1 Xingxing Shen,1 Ruian Xiang,1 Jiahao Chen,1 Tao Jiang,1 Chuanxi Zhao,1 Wengang Liu,1 Xuemeng Xu1 1Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Osteoarthropathy II, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang, People’s Republic of China; 3Department of Orthopedics and Traumatology, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemeng Xu; Wengang Liu, Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, No. 60 Hengfu Road, Guangzhou, 510030, People’s Republic of China, Email xuxuemeng@163.com; 914194079@qq.comPurpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults.Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed.Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030).Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.Keywords: knee osteoarthritis, quadriceps femoris, ultrasound, muscle tone, stiffness

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

Dan Li,1 Fang Lv,2 Chenyuan Ding,3 Zhaohan Zhuang,3 Shijun Wang1 1Department of Obstetrics & Gynecology, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China; 2Department of Medical Record Statistics, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China; 3Education Section, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of ChinaCorrespondence: Shijun Wang, Department of Obstetrics & Gynaecology, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-13601222289, Email wangshijun20158866@126.comPurpose: This case report aimed to summarize the risk factors, clinical characteristics, imaging changes, and maternal and fetal prognosis associated with Moyamoya disease in pregnant women and to explore effective management strategies and a comprehensive delivery plan.Case Presentation: The clinical data of four pregnant women who were diagnosed with Moyamoya disease and admitted to our hospital between January 2010 and January 2019 were retrospectively analyzed. Their diagnosis, treatment, delivery, and postpartum management during the pregnancy were analyzed. Among the four pregnant women, three were primipara and one was multipara. The age ranged from 27 to 41 years old. The gestational week of termination of pregnancy ranged between 8 and 39 weeks. During pregnancy, one case died in utero; one case was complicated with postpartum hemorrhage; one case was complicated with chronic hypertension, multiple cerebral artery stenosis and occlusion, bilateral middle cerebral artery occlusion, bilateral internal carotid artery occlusion, and Hashimoto’s thyroiditis. Under epidural anesthesia, two cases underwent a lower segment cesarean section; one case underwent artificial abortion; and one case underwent induced labor during late pregnancy. Two newborns survived.Conclusion: Moyamoya disease is a rare and serious complication of pregnancy. Pregnancy and childbirth may exacerbate the progression of this disease or induce cerebrovascular accidents, with a high mortality and disability rate, which seriously threatens the safety of mother and infant lives; however, with the close collaboration of a multidisciplinary team, it is possible to maximize a good pregnancy outcome.Keywords: pregnancy, cerebrovascular lesions, moyamoya disease

Xuebing Zhang,1 Lianjie Wang,1 Ge Wang,1 Jiayue Li,1 Yiming Mu,2 Shidong Wang,1 Xiaoran Li1 1Department of Endocrinology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 2Department of Endocrinology, First Medical Centre of Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Shidong Wang; Xiaoran Li, Email A2082@bucm.edu.cn; 466187309@qq.comBackground: Nonalcoholic fatty liver disease (NAFLD) has become a major global health burden, which increases the risk of extra-hepatic complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, NAFLD remains underappreciated and underdiagnosed. Our study aimed to explore the prevalence of NAFLD and the association between NAFLD and CVD events among adults aged 40 and older in Northern China.Methods: This study was conducted in the Shijingshan district of Beijing, China from November 2011 to August 2012. A total of 18891 subjects were recruited in the study. The information including demographical information, lifestyle, previous history of diabetes, hypertension, dyslipidemia, CVD, and liver disease were gathered. Data on physical examination, blood lipid profile, fasting blood glucose, and 2-hour blood glucose were recorded. Determination of MetS was according to T2DM guideline of Chinese Diabetes Society (2020 edition). The association between CVD and NAFLD was evaluated by multivariate logistic regression.Results: The prevalence of NAFLD was 15.2%. After adjustment for age, smoking status, alcohol intake, WC, hypertension, dyslipidemia and hyperglycemia, the odds ratios (ORs) of CVD in men were 1.622 (95%CI: 1.345– 1.957) and 1.990 (95%CI: 1.709– 2.316) in women with NAFLD, compared with the subjects without NAFLD.Conclusions: NAFLD is independently associated with increased risk of CVD development.Keywords: nonalcoholic fatty liver disease, metabolic syndrome, cardiovascular disease, middle-aged and elderly, Chinese

Huizhen Yue,1– 3 Xiaolong Xu,1– 3 Bing Peng,1– 3 Xuanyu Wang,1 Shengnan Zhang,1 Jinhao Tian,4 Shuo Wang,1 Maifen Song,1 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, People’s Republic of China; 4Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Backstreet, Dongcheng District, Beijing, People’s Republic of China, Email liuqingquan_2003@126.comPurpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris.Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model.Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50– 200 mg/L and 100– 400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection.Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.Keywords: Candida auris, multidrug resistance, CaoHuangGuiXiang formula, aggregative form, biofilm formation, antifungal efficiency

Liu Yang,1 Kaijie Gao,1 Weihua Gong,1 Ci Li,1 Nan Chen,1 Tiewei Li,1 Shan Wang,1 Jiajia Ni,2,3 Junmei Yang1 1Department of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, Henan, People’s Republic of China; 2Research and Development Center, Guangdong Meilikang Bio-Science Ltd, Foshan, Guangdong People’s Republic of China; 3Department of Detection and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Junmei Yang, Email yangjunmei7683@163.comPurpose: Although allergic diseases in children are on the rise, there has been no comprehensive investigation of the allergens affecting children with allergic diseases in central China. Therefore, we aimed to analyze the distribution of serum allergen species among children with allergic conditions in central China to inform the prevention, diagnosis, and treatment of childhood allergies.Patients and Methods: A total of 9213 children (5543 males with 2.88 ± 0.04 years old and 3670 females with 2.91 ± 0.05 years old) underwent allergen screening, and serum allergen-specific IgE (sIgE) antibodies were detected using an automated fluorescent enzyme immunoassay system.Results: Our findings revealed a total sIgE-positive rate (sIgE-PR) of 57.83%, with mixed food (42.10%), egg whites (30.83%), milk (28.97%), mixed dust mites (24.57%), and mixed molds (23.20%) being the most prevalent source of allergens. The sIgE-PR for common sources of allergens exhibited significant sex-based differences, with males having greater susceptibility than females (p< 0.05). Dust mites were the primary source of inhaled allergens, whereas egg white was the predominant source of food allergens. Sources of food allergens were most dominant among infants (0– 3 years old); sIgE-PRs for most source of food allergens decreased with age, whereas those for most source of inhaled allergens increased. The autumn sIgE-PRs for mixed molds, weed pollen combinations, and tree pollen combinations were significantly higher than those found in other seasons (p< 0.05).Conclusion: Our findings suggest that sources of allergens profiles in children with allergies vary across age groups and seasons. Understanding these patterns can improve the effective prevention of childhood allergies.Keywords: allergen, childhood allergies, IgE antibodies, source of food allergens, allergy prevention

Jing Ren,1,&ast; Jiahua Zhou,2,&ast; Qinhui Wang,1,&ast; Linna Liu,1 Wei Liu,3 Shan Wang,4 Yao Zheng,1 Li Luo,1 Qi Yang1 1Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Orthopedics, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Pharmacy, New York University Langone Hospital – Long Island, Mineola, NY, USA&ast;These authors contributed equally to this workCorrespondence: Qi Yang; Li Luo, Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China, Tel +86 15829673096, Fax +86 029-84777154, Email 376230719@qq.com; luolixueshu@163.comAbstract: Aseptic abscess (AA) syndrome is a rare inflammatory disorder often associated with inflammatory bowel disease (IBD). Cases of IBD-associated AA have been reported in Japan, India, and Canada, but rarely in China. Herein, we present the case of a Chinese patient with IBD-associated AAs and review the literature on AA with underlying IBD. We report the case of a 48-year-old male patient with multiple AAs on his left hand and lungs who was successfully treated with prednisone. He had undergone cutaneous abscess incision and drainage twice in the previous 2 years. The patient presented to our hospital with ulcerative colitis and pain in the dorsum of the left hand. Pus from his hand and blood cultures revealed sterile cutaneous abscesses. Chest computed tomography examination during hospitalization revealed a lung abscess. The AA was unresponsive to cefotiam or cefoperazone-sulbactam. The patient’s left hand and lung conditions did not improve until prednisone was administered. The patient was followed up as an outpatient for 3 months and recovered without any clinical symptoms. We retrieved 17 cases of IBD-associated AA from the literature. None of the patients showed evidence of infection and failed antibiotic treatment, and all improved with corticosteroid use. AA may be an extra-intestinal manifestation of IBD. Effective medications include corticosteroids and immunosuppressive agents. This case may increase the awareness of AA and aid in early identification.Keywords: aseptic abscess, inflammatory bowel disease, ulcerative colitis, extra-intestinal manifestation

Shanshan Wu,1,2,&ast; Shuren Wang,3,&ast; Yonghong Ding,2 Zongwang Zhang1,2 1Department of Anesthesiology, Liaocheng People’s Hospital, Shandong University, Liaocheng, People’s Republic of China; 2Department of Anesthesiology, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 3Department of Anesthesiology, Dongchangfu District Maternal and Child Health Hospital, Liaocheng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongwang Zhang, Department of Anesthesiology, Liaocheng People’s Hospital, Shandong University, Liaocheng, People’s Republic of China, Tel +86-13346256809, Email zwzhang68@sina.comObjective: Postoperative pain is a common complication in endoscopic submucosal dissection (ESD) patients. This study aimed to develop and validate predictive models for postoperative pain associated ESD.Methods: We retrospectively constructed a development cohort comprising 2162 patients who underwent ESD at our hospital between January 2015 and April 2022. The dataset was randomly divided into a training set (n = 1541) and a validation set (n = 621) in a 7:3 ratio. The bidirectional stepwise regression with Akaike’s information criterion (AIC) and multivariate logistic regression analysis were used to screen the predictors of post-ESD pain and construct three nomograms. We evaluated the model’s discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, Hosmer–Lemeshow (HL) goodness-of-fit test and decision curve analysis (DCA) in internal validation.Results: The proportion of patients developing postoperative pain in the training and testing data set was 25.6% and 28.5%, respectively. Three nomograms were constructed according to the final logistic regression models. The clinical prediction models for preoperative risks, preoperative and intraoperative risks, and perioperative risks consisted of seven, nine and six independent predictors, respectively, after bidirectional stepwise elimination. The models demonstrated the AUC of 0.794 (95% CI 0.768– 0.820), 0.823 (95% CI 0.799– 0.847) and 0.817 (95% CI 0.792– 0.842) in the training cohort and 0.702 (95% CI 0.655– 0.748), 0.705 (95% CI 0.659– 0.752) and 0.747 (95% CI 0.703– 0.790) in the validation cohort. The calibration plot, HL and DCA demonstrated the model’s favorable clinical applicability.Conclusion: We developed and validated three robust nomogram models, which might identify patients at risk of post-ESD pain and promising for clinical applications.Keywords: endoscopic submucosal dissection, postoperative pain, nomograms

Ming Wei,1 Xi Chen,1 Jun Liu,1 Tianmeng Li,1 Peng Wang,1 Shuai Wang,1 Jing Wang,2,3 Li Gu1 1Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jing Wang, Beijing Anding Hospital, Capital Medical University, 5 Ankang Hutong Road, Xicheng District, Beijing, 100088, People’s Republic of China, Email kycwangjing@mail.ccmu.edu.cn Li Gu, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Email didcm2006@mail.ccmu.edu.cnPurpose: Carbapenem-resistant Enterobacterales (CRE) infection is an urgent threat to human health. This study aimed to develop and validate a novel multiplex real-time PCR (multi-qPCR) assay for the detection of the blaKPC, blaNDM, blaIMP, blaOXA-48-like, and blaVIM genes in CRE isolates and clinical samples, as well as to compare it with three phenotypic methods.Methods: The reliability and limit of detection (LOD) of the multi-qPCR assay were evaluated. PCR and DNA sequencing were used as the reference methods to identify carbapenemase genes in CRE isolates and clinical samples. The accuracy of the multi-qPCR assay, modified carbapenem inactivation and EDTA-modified carbapenem inactivation method (mCIMandeCIM), carbapenemase inhibitor-based combined disk test (CDT), and colloidal gold-based immunochromatographic test was compared with the reference methods with 182 isolates of CRE. Furthermore, 112 clinical samples were collected to validate the efficacy of this multi-qPCR assay.Results: The standard deviations (CVs) of intra-assay and inter-assay of the multi-qPCR assay were ≤ 0.53% and ≤ 2.04% for detecting the five major carbapenemase genes, respectively; while the LOD ranged from 2× 102 copies/mL to 8× 102 copies/mL. PCR and DNA sequencing confirmed 168 out of 182 CRE isolates producing carbapenemase(s): KPC (n = 93), NDM (n = 46), IMP (n = 8), OXA-48-like (n = 14), VIM (n = 1), KPC&NDM (n = 5), and KPC&NDM&IMP (n = 1). The accuracy of mCIMandeCIM, CDT, Colloidal Gold, and the multi-qPCR assay was 96.2%, 89.6%, 100%, and 100% respectively for detecting carbapenemase(s) producers. Moreover, the sensitivity and specificity of the multi-qPCR assay were all 100% for the detection of each carbapenemase gene in clinical samples, compared with PCR and sequencing.Conclusion: For clinical isolate detection, the multi-qPCR assay is comparable to Colloidal Gold, and superior to mCIMandeCIM and CDT; while for clinical samples detection, it also shows excellent performance. Therefore, the multi-qPCR assay has great potential for clinical diagnosis.Keywords: carbapenem-resistant Enterobacterales, carbapenemases detection, multiplex real-time PCR assay, mCIM/eCIM, combined disk test, immunochromatographic test

Senlan Wang,1,2,&ast; Jifan Tan,1,2,&ast; Can Wang,1,2 Jia Huang,1,2 Canquan Zhou1,2 1Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Canquan Zhou; Jia Huang, Email zhoucanquan@mail.sysu.edu.cn; hjia@mail.sysu.edu.cnPurpose: It is well known that androgen excess impairs oocyte quality, endometrial receptivity and even embryo invasion to some extent. Free androgen index (FAI) is strongly recommended to evaluate active androgen. Previous studies have showed conflicting conclusions on the effect of hyperandrogenism on the pregnancy outcomes in patients with polycystic ovary syndrome (PCOS). This study aims to analyze the influence of hyperandrogenemia based on FAI on frozen embryo transfer (FET) outcomes in patients with PCOS.Patients and Methods: Patients diagnosed with PCOS who underwent their first FET between January 2017 and April 2022 were stratified into two cohorts using FAI, a highly recommended parameter: PCOS with hyperandrogenemia (n=73) and PCOS without hyperandrogenemia (n=255). Basic and infertility characteristics were analyzed using Student’s t-test or chi-square (χ 2) statistics. Logistic regression analysis was performed to verify whether FAI was helpful in predicting pregnancy outcomes in women with PCOS.Results: Body mass index (BMI), total gonadotropin (Gn), basal serum follicle-stimulating hormone (bFSH), basal serum testosterone (bT), sex hormone binding globulin (SHBG), and FAI were significantly different between the two groups. (P=0.005, P< 0.001, P< 0.001, P< 0.001, and P< 0.001, respectively). However, clinical pregnancies, abortions, and live births did not differ significantly. Further regression analyses showed that FAI was not related to clinical pregnancy, abortion, or live birth rates (adjusted odds ratio (OR)=0.978, 95% confidence interval (CI)=0.911– 1.050, P=0.539; adjusted OR=1.033, 95% CI=0.914– 1.168, P=0.604; and adjusted OR=0.976, 95% CI=0.911– 1.047, P=0.499, respectively).Conclusion: FAI was not associated with pregnancy outcomes in patients with PCOS; that is, it did not reflect any negative effects of hyperandrogenemia on pregnancy outcomes in patients with PCOS and was not an informative clinical parameter. Therefore, more attention should be paid to the factors that influence the accuracy of FAI in reflecting androgen levels in vivo, and further discussion is needed.Keywords: FAI, Hyperandrogenemia, PCOS, Pregnancy, FET

Yishan Duan,1,&ast; Jing Ren,2,&ast; Jing Wang,3,&ast; Suyan Wang,4 Rui Zhang,1 Huohuo Zhang,1 Jinrui Hu,1 Wen Deng,1 Weimin Li,1,3,4 Bojiang Chen1,3 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2The Integrated Care Management Center, West China Hospital of Sichuan University, Chengdu, Chengdu, Sichuan Province, 610041, People’s Republic of China; 3Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 4Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojiang Chen; Weimin Li, Email cjhcbj@outlook.com; weimin003@163.comPurpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown.Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness.Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246– 4.060), p = 1.000) and ICU admission (HR=0.436(0.093– 2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296– 1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221– 8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort.Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.Keywords: Coronavirus disease 2019, COVID-19, early antibiotics use, bacterial co-infections, clinical outcomes

Zhuoran Li,1,&ast; Yirui Zhai,1,&ast; Fan Wu,2,&ast; Dayong Cao,2,&ast; Feng Ye,3,&ast; Yan Song,4 Shulian Wang,1 Yueping Liu,1 Yongwen Song,1 Yuan Tang,1 Hao Jing,1 Hui Fang,1 Shunan Qi,1 Ningning Lu,1 Ye-Xiong Li,1 Jianxiong Wu,2 Bo Chen1 1State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 3Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 4Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Chen, State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87788280, Email chenboo@outlook.com Jianxiong Wu, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87781700, Email Dr_wujx@163.comPurpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.Patients and Methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30– 65 Gy for planning target volume and 40– 65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level > 1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588– 20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027– 0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.Keywords: liver cancer, immunotherapy, systemic therapy, radiation therapy

Demeng Xia,1,2,&ast; Qingqing Qian,1,&ast; Sheng Wang,3,&ast; Xiao Dong,4 Ying Liu5 1Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, People’s Republic of China; 2Department of Pharmacy, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, People’s Republic of China; 3Department of Traumatic Orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 4School of Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China; 5Institute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liu; Xiao Dong, Email liuchanger1984@163.com; dong-xiao@shu.edu.cnIntroduction: Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.Methods: Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments.Results: In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice.Conclusion: In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.Keywords: bone targeting, alendronate functionalized liposome, pomolic acid, osteoporosis therapy

Chao Meng,1 Ping Yang,2 Yanan Wang,3 Siyan Liu,3 Xueyan Wu,3 Shaolian Wang3 1Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Integrated Chinese and Western Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Shaolian Wang, Email 15318816221@sina.cnBackground: To investigate the prevalence of thyroid nodules among medical staff and health check-up population in a Level-A hospital (Primary-level hospital) in Jinan City and analyze its influencing factors.Methods: A total of 5812 cases from the two groups were screened. t-test and χ2 tests were used to analyze the differences in the prevalence of thyroid nodules. Multivariate Logistic regression analysis was used to explore the influencing factors.Results: The average age of medical staff was (36.20± 9.11) years old, and the total prevalence was 48.5%. The average age of the healthcare population was (57.89± 12.51) years old, and the total prevalence rate was 63.9%, with statistical significance between the two groups (P

Kang Zhao,1,&ast; Rui Mao,2,&ast; Wei Yi,3– 6 Zhengyun Ren,3– 6 Yanjun Liu,3– 5 Huawu Yang,3– 5 Senlin Wang,3– 6 Zhonghui Feng4– 6 1Section for Day Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, 610031, People’s Republic of China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3College of Medicine, Southwest Jiaotong University, Chengdu, People’s Republic of China; 4Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, Sichuan, People’s Republic of China; 5The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, 610031, People’s Republic of China; 6Medical Research Center, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhonghui Feng, Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, 610031, People’s Republic of China, Email fengzh.2008@tsinghua.org.cnAim/Introduction: Type 2 diabetes mellitus (T2DM) is one of the most frequent and widespread disease in the world.Obesity is the most significant predictor of T2DM, but the exact mechanism how obesity promotes T2DM remains unknown. Finding specific biomarkers to assist in diagnosing and treating patients with obese and T2DM is critical.Materials and Methods: We collected liver tissues from obesity patients with and without T2DM for proteomic sequencing and immunohistochemistry assay. Analysis Gene Ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG), and protein interaction network (PPI) were performed on the parameters and data derived from the Tandem Mass Tags(TMT)-based proteomics analysis of liver tissues. Transcriptome data were downloaded from the Gene Expression Omnibus(GEO)website and genes that are deferentially expressed in both transcriptome and proteome were selected.Results: We identified 140 deferentially expressed proteins from proteomic sequencing. Six biomarkers were deferentially expressed in both proteome and transcriptome with consistent changes in direction. The protein–protein interaction (PPI) analysis suggested CMPK1, the expression with greatest difference, was the core protein among the six biomarkers. Immunohistochemistry validated CMPK1 was upregulated significantly in the liver tissues of T2DM patients. The correlation analysis revealed that the expression of CMPK1 was significantly associated with key molecules in T2DM-related pathways at both protein and transcriptome levels.Conclusion and Novelty: Our study showed CMPK1 was upregulated in the liver of T2DM patients and provides a possible new target for screening and diagnosing T2DM in patients with obese and a novel theoretical basis for the pathophysiological mechanism of obesity-related metabolic diseases.Keywords: type 2 diabetes mellitus, obesity, CMPK1, proteomic, transcriptomic, immunohistochemistry

Zheng Zhang,1,&ast; Yan Li,1,&ast; Siyuan Wang,2 Jizhi Wang,1 Ying Huang,1 Xiaoping Wang,1 Huijuan Guo,1 Jiansong Zhou1 1Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Pingtang Compulsory Isolation Detoxification Institute in Hunan Province, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijuan Guo; Jiansong Zhou, Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, 410011, Email guohuijuan2023@csu.edu.cn; zhoujs2003@csu.edu.cnBackground: Correctional officers face widespread workplace violence and the resulting overwork that can profoundly damage their physical and mental health.Purpose: This study aims to investigate the mediating role of overwork in the relationship between workplace violence and the manifestation of physical and mental health issues among correctional officers.Methods: This study enlisted 472 eligible participants. Cross-sectional data were obtained using the Chinese version of the Workplace Violence Scale (WVS), while the physical and mental health of correctional officers was evaluated through relevant scales. Analysis involved descriptive statistics, correlation analyses, and tests for mediation models.Results: The study found significant correlations between workplace violence, overwork, and various mental health variables (depression, anxiety, stress, suicidal ideation, and insomnia), with correlations ranging from 0.135 to 0.822 (p < 0.01). Mediation analysis revealed that workplace violence directly impacts correctional officers’ physical and mental health (p < 0.001) and also has an indirect effect through overwork (p < 0.023). These findings underscore the substantial impact of workplace violence on the health of correctional officers, both directly and indirectly.Conclusion: Workplace violence and overwork significantly contribute to the physical and mental health challenges faced by correctional officers. Overwork acts as a mediator in the relationship between workplace violence and these health issues. The study suggests addressing workplace violence and mental health issues among correctional officers by increasing their numbers, improving the work environment, and implementing enhanced welfare policies.Keywords: correctional officers, workplace violence, overwork, physical and mental health

Zhengmei Li,1 Shiai Wang,2 Xunli Yin,2 Dong Tao,2 Xuebing Wang,2 Junli Zhang3 1School of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, People’s Republic of China; 2Department of Cardiovascular Medicine, The Seventh People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China; 3Department of Emergency Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of ChinaCorrespondence: Junli Zhang, Email tyfyzjl@163.comBackground: Myocardial infarction (MI) is a chronic cardiovascular disease. This study aims to discern potentially angiogenesis- and epithelial mesenchymal transition (EMT)-related genes as biomarkers for MI diagnosis through bioinformatics.Methods: All datasets and angiogenesis- and EMT-related genes were collected from the public database. The differentially expressed genes (DEGs) of MI and MI-related genes were acquired. DEGs, MI-related genes, and angiogenesis- and EMT-related genes were intersected to obtain hub genes. Functional enrichment, immune microenvironment, and transcription factors (TFs)-hub genes regulatory network analysis were performed. The diagnostic markers and models were developed and validated. Drug prediction and molecular docking were performed. Finally, diagnostic markers expressions were validated using RT-qPCR.Results: A total of 224 angiogenesis- and EMT-related genes, 2,897 DEGs, 1,217 MI-related genes, and 9 hub genes were acquired. The immune infiltration levels of plasma cells, T cells CD4 memory activated, monocytes, macrophages M0, mast cells resting, and neutrophils were higher in patients with MI. LRPAP1, COLGALT1, QSOX1, THBD, VCAN, PLOD1, and PLAUR as the diagnostic markers were identified and used to construct diagnostic models, which can distinguish MI from controls well. Then, 9 drugs were screened, and the binding energies ranged from − 7.08 to − 5.21 kcal/mol. RT-qPCR results showed that the expression of LRPAP1, PLAUR, and PLOD1 was significantly increased in the MI group.Conclusion: The 7 diagnostic markers may play potential roles in MI and could contribute to improved future diagnostics.Keywords: myocardial infarction, angiogenesis, epithelial mesenchymal transition, diagnostic markers

Yanmeng Sun,1,2,&ast; Zheng Li,1,2,&ast; Yanfang Li,3 Chunyan Zhang,1,2 Mengyuan Wang,1,2 Wenwen Yu,1,2 Guohua Liu,2,3 Shifu Wang1,2 1Department of Microbiology Laboratory, Children’s Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Microbiology Laboratory, Shandong Provincial Clinical Research Center for Children’s Health and Disease, Jinan, Shandong, People’s Republic of China; 3Department of Neonatology, Children’s Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shifu Wang, Email wshfu709@163.comAbstract: Anaerobic bacterial meningitis is a serious infection of the central nervous system (CNS) that leads to severe neurological complications, resulting in high levels of disability and mortality worldwide. However, accurately diagnosing and isolating the responsible pathogens remains challenging due to the difficulty in culturing anaerobic bacteria, as they require harsh anaerobic culture conditions. Anaerobic bacteria have rarely been reported in meningitis, especially in children. This report details the first infant with anaerobic meningitis caused by Prevotella bivia. Additionally, we present a case of infant anaerobic meningitis caused by P. bivia, detected using metagenomics next-generation sequencing (mNGS). Our clinical experience highlights the importance of early identification of Prevotella spp. through mNGS and anaerobic culture, the effectiveness of antimicrobial medications, and the timely implementation of carefully planned precision therapeutic regimens. Furthermore, we have conducted a comprehensive review of 10 cases of Prevotella spp. infection, summarized their clinical and laboratory examination characteristics, and identified their commonalities.Keywords: Prevotella bivia, anaerobic meningitis, infant

Shengfeng Wang,1,&ast; Ruxue Fang,1,&ast; Lei Huang,1,&ast; Liping Zhou,1,2 Haibo Liu,3 Meiling Cai,4 Abubakar Sha’aban,5 Chunxiang Yu,1 Mohammed Ahmed Akkaif3 1Rehabilitation Department of Chinese Medicine, The Fourth People’s Hospital of Kunshan, Kunshan City, Jiangsu Province, People’s Republic of China; 2Department of Community Health, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Pulau Pinang, Malaysia; 3Department of Cardiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Obstetrics and Gynecology, Qingpu Branch, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Health and Care Research Wales Evidence Centre, Cardiff University, Heath Park, Cardiff, UK&ast;These authors contributed equally to this workCorrespondence: Mohammed Ahmed Akkaif, Department of Cardiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email akkaif@fudan.edu.cn Chunxiang Yu, Rehabilitation Department of Chinese medicine, The Fourth People’s Hospital of Kunshan, Kunshan City, Jiangsu Province, People’s Republic of China, Email yuchunxiang868@gmail.comAbstract: Cardiovascular diseases (CVDs) are increasingly prevalent in clinical settings. With the continuous improvement of people’s living standards, the gradual acceleration of the pace of life, and the deterioration of the living environment in recent years, the incidence of CVDs is increasing annually. The prevalence of CVDs among individuals aged 50 and above is notably elevated, posing a significant risk to patients’ well-being and lives. At this juncture, numerous clinical treatment choices are available for managing CVDs, with traditional Chinese medicine (TCM) therapy standing out as a practical, safe, and reliable option. Over the recent years, there has been growing acknowledgement among both medical professionals and patients. With the expanding integration of TCM in the treatment of various clinical conditions, the use of TCM in managing CVDs has gained significant attention within the medical community, potentially emerging as an efficacious approach for addressing cardiovascular diseases. This article conducts a comprehensive review of the TCM approach, particularly acupuncture, as a supplementary treatment for CVDs, highlighting its ability to effectively lower blood pressure, decrease coronary artery events, mitigate arrhythmias, and enhance cardiac function when used alongside conventional medication. The review underscores the promise of acupuncture in enhancing cardiovascular health, although variations in research methodologies necessitate standardized applications.Keywords: cardiovascular diseases, traditional Chinese medicine, acupuncture, clinical treatment

Kaiyue Zhang, Chunnan Li, Peitong Wu, Xiaochen Gao, Xueqin Feng, Jiaming Shen, Nanxi Zhang, Xuesheng Hu, Shuo Wang, Hui Zhang, Jingwei Lv, Jiaming Sun Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jiaming Sun; Jingwei Lv, Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Nanguan District, Changchun, 130117, People’s Republic of China, Tel +0431-86763809, Fax + 8676 3968, Email Sun_jiaming2000@163.com; jingwei-lv@hotmail.comPurpose: Zhixiao Tang (ZXT), a traditional Chinese compound prescription, has been used clinically to treat pneumonia in China. However, the underlying mechanism of ZXT treatment in pneumonia is still unclear. The present study aimed to reveal the potential mechanism of ZXT in pneumonia using a strategy combining metabolomics and network pharmacology.Methods: Initially, the chemical compositions were identified by UPLC-QE-Orbitrap-MS, while the prediction of potential signal pathways was performed through network pharmacology. To assess the anti-inflammatory properties of ZXT in the context of pneumonia, models of 16HBE cells induced by LPS and zebrafish induced by CuSO4 were established to measure levels of inflammatory markers and apoptosis. Subsequently, the differential changes of endogenous metabolites in cells caused by ZXT were examined using metabolomics technology, and the molecular docking analysis of key targets was carried out using Autodock Vina software. Ultimately, the validation of the primary pathways and targets was conducted through quantitative RT-PCR and Western blot techniques.Results: A total of 75 compounds were identified through UPLC-QE-Orbitrap-MS analyses. Network pharmacological analysis shows that it plays an anti-inflammatory role in C-type lectin receptor signaling pathway. After ZXT intervention, the inflammatory factors and apoptosis in cells were significantly reduced. Metabonomics analysis showed that 18 metabolites changed significantly. Four key genes were identified, which exhibited partial compatibility with the findings of network pharmacology. Molecular docking analysis confirmed the substantial affinity of the primary targets for ZXT. Furthermore, ZXT exerted a suppressive effect on neutrophil migration, down-regulated the expression of pro-inflammatory cytokine genes, and inhibited the up-regulation of the Dectin-1/SYK/NF-κB signaling pathway. In vivo cell experiments also yielded consistent experimental outcomes.Conclusion: This study enhances comprehension of the pharmacological mechanism underlying ZXT’s efficacy in pneumonia treatment, thereby establishing a scholarly basis for future research and clinical utilization of ZXT in pneumonia management. Keywords: Zhixiao Tang, pneumonia, network pharmacology, integrated metabolomics, 16HBE, Zebrafish

Yun Liu,1,&ast; Meirong Li,2,&ast; Yan Liu,3 Yu Wan,1 Bo Yang,1 Dan Li,4 Shaohua Wang1 1Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Department of Pathology, Deyang People’s Hospital, Deyang, Sichuan Province, 618099, People’s Republic of China; 3Department of Pathology, Chengdu Women and Children’s Central Hospital, Chengdu, Sichuan Province, 610073, People’s Republic of China; 4Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Wang, Department of Pathology, the Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Email wangshaohua20006@163.comBackground/Aims: There are currently few reports describing the liquid-based cytological characteristics of small cell neuroendocrine carcinoma of the cervix. This study aimed to retrospectively analyze these features to reduce missed or misdiagnosis.Methods: A total of 11 patients with histologically diagnosed small cell carcinoma of the cervix from three hospitals between 2017 and 2023 were included in this study. The cytological morphology of small cell carcinoma of the cervix and causes of missed or misdiagnosis were analyzed and summarized through a review of clinical data, liquid-based cytology, histology, immunohistochemistry, and human papillomaviruses (HPV) test results.Results: In this study, the positivity rate of preliminary cytological screening was 63.6% (7/11); however, no cases were accurately diagnosed as small cell carcinoma of the cervix. A total of 36.4% (4/11) of small cell carcinoma of the cervix cases were cytologically negative; retrospective cytology found that two of these were false negatives. The main cytological features of small cell carcinoma of the cervix were summarized. Most of the liquid-based cytology smear cells were dense, and almost all cases showed clustered and scattered cytoplasm-scanty tumor cells. The tumor cells were all deeply stained and relatively consistent small cells. Most cases showed typical nuclear molding, chromatin stippling, and no obvious nucleoli. Mild nuclear smears, nuclear fragments, and mitotic figures were seen in most cases.Conclusion: Liquid-based cytology has a high rate of missed diagnosis and misdiagnosis in small cell carcinoma of the cervix. This study confirms that reviewing cytology results can effectively reduce this proportion and that increasing understanding of small cell carcinoma of the cervix morphology is conducive to improving the cytology-based diagnosis rate.Keywords: cervical cytology, small cell carcinoma, cervical cancer, diagnostic rate, neuroendocrine

Shuqi Wang,1,2 Boying Jia,1,2 Sifan Niu,2,3 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Internal Medicine, North China University of Science and Technology, Tangshan, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: To explore the correlation between hemoglobin, albumin, lymphocyte count, platelet count (HALP) score and type 2 diabetic retinopathy (DR).Methods: The study was conducted on 674 patients with type 2 diabetes (T2DM). According to the results of the fundus examination, they were divided into non-diabetic retinopathy group (NDR, n=388) and diabetic retinopathy group (DR, n=286). Collected patients baseline data, calculated HALP score, analyzed the correlation between HALP score and DR.Results: In all patients, male patients and female patients, the HALP score of the DR group was lower than that of the NDR group (P< 0.001), and the HALP score was negatively correlated with the incidence of DR (P< 0.05). HALP score was independent risk factors for DR, regardless of gender. In male patients, HALP score and DR had a linear relationship, but in female patients, HALP score and DR showed a nonlinear relationship, and HALP score was more sensitive to the onset of DR in male patients. The combined diagnostic model of HALP score, course of disease, SBP and BUN was used to diagnose DR, and it was found that the diagnostic value was the highest among male patients, with AUC of 0.761, sensitivity of 58.3% and specificity of 80.3%.Conclusion: HALP score was an independent risk factor for DR, attention should be paid to monitoring HALP score, especially in male T2DM patients. The accuracy of HALP score, disease course, SBP and BUN combined model diagnosis of DR was high, which can become a biological indicator for early screening of DR.Keywords: HALP score, type 2 diabetes, diabetic retinopathy

Xinyue Yi,1,2,&ast; Pengyuan Leng,1,&ast; Supeng Wang,2 Liangle Liu,1 Bingju Xie1 1The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangle Liu; Bingju Xie, Email liuliangle@wmu.edu.cn; xiebingju@wmu.edu.cnAbstract: Osteoarthritis (OA) is the most common degenerative joint disease, affecting more than 595 million people worldwide. Nanomaterials possess superior physicochemical properties and can influence pathological processes due to their unique structural features, such as size, surface interface, and photoelectromagnetic thermal effects. Unlike traditional OA treatments, which suffer from short half-life, low stability, poor bioavailability, and high systemic toxicity, nanotherapeutic strategies for OA offer longer half-life, enhanced targeting, improved bioavailability, and reduced systemic toxicity. These advantages effectively address the limitations of traditional therapies. This review aims to inspire researchers to develop more multifunctional nanomaterials and promote their practical application in OA treatment. Keywords: nanostructures, osteoarthritis, drug delivery systems, nanomedicine, precision medicine

Song Wang,1,&ast; Xiang Zhang,1,&ast; Bo Qu,2,&ast; Kunhai Yang,1 Yongrong Hu,1 Hao Liu,2 Juntao Hong,2 Hao Niu,3 Hongsheng Yang2 1School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthopaedics, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 3Computer Science of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Niu, Computer Science of Sichuan University, Chengdu, Sichuan, People’s Republic of China, Email 13438368112@139.com Hongsheng Yang, Department of Orthopaedics, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China, Email hongsheng228@163.comPurpose: This study aims to develop a novel MRI-based paravertebral muscle quality (PVMQ) score for assessing muscle quality and to investigate its correlation with the degree of fat infiltration (DFF) and the vertebral bone quality (VBQ) score of paravertebral muscles. Additionally, the study compares the effectiveness of the PVMQ score and the VBQ score in assessing muscle quality and bone quality.Methods: PVMQ scores were derived from the ratio of paravertebral muscle signal intensity (SI) to L3 cerebrospinal fluid SI on T2-weighted MRI. Image J software assessed paravertebral muscle cross-sectional area (CSA) and DFF. Spearman rank correlation analyses explored associations between PVMQ, VBQ scores, DFF, and T-scores in both genders. Receiver operating characteristic (ROC) curves compared PVMQ and VBQ scores’ effectiveness in distinguishing osteopenia/osteoporosis and high paraspinal muscle DFF.Results: In this study of 144 patients (94 females), PVMQ scores were significantly higher in osteoporosis and osteopenia groups compared to normals, with variations observed between genders (P < 0.05). PVMQ showed stronger positive correlation with VBQ scores and DFF in females than males (0.584 vs 0.445, 0.579 vs 0.528; P < 0.01). ROC analysis favored PVMQ over VBQ for low muscle mass in both genders (AUC = 0.767 vs 0.718, 0.793 vs 0.718). VBQ was better for bone mass in males (0.737/0.865 vs 0.691/0.858), whereas PVMQ excelled for females (0.808/0.764 vs 0.721/0.718).Conclusion: The novel PVMQ score provides a reliable assessment of paravertebral muscle quality and shows a strong correlation with VBQ scores and DFF, particularly in females. It outperforms VBQ scores in evaluating muscle mass and offers valuable insights for assessing bone mass in females. These findings underscore the potential of the PVMQ score as a dual-purpose tool for evaluating both muscle and bone health, informing future research and clinical practice.Keywords: muscle quality, osteoporosis, magnetic resonance imaging, dual-energy X-ray absorptiometry, vertebral bone quality score, osteosarcopenia

Bailong Hou,1,&ast; Ying Zhou,2,&ast; Wei Wang,1 Weifeng Shen,1 Qinlong Yu,1 Minjie Mao,1 Siheng Wang,1 Wenxiu Ai,3 Fangyou Yu,2,3 Pingyang Shao1 1Department of Clinical Laboratory Medicine, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200000, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pingyang Shao, Department of Clinical Laboratory Medicine, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of China, Email spy202001@163.com Fangyou Yu, Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200000, People’s Republic of China, Email wzjxyfy@163.comIntroduction: This study aimed to investigate the emergence and characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains that demonstrate resistance to multiple antibiotics, including aminoglycosides and tigecycline, in a Chinese hospital.Methods: A group of ten CRKP strains were collected from the nine patients in a Chinese hospital. Antimicrobial Susceptibility Testing (AST) and phenotypic inhibition assays precisely assess bacterial antibiotic resistance. Real-time quantitative PCR (RT-qPCR) was used to analyze the mRNA levels of efflux pump genes (acrA/acrB and oqxA/oqxB) and the regulatory gene (ramA). The core-genome tree and PFGE patterns were analyzed to assess the clonal and horizontal transfer expansion of the strains. Whole-genome sequencing was performed on a clinical isolate of K. pneumoniae named Kpn20 to identify key resistance genes and antimicrobial resistance islands (ARI).Results: The CRKP strains showed high resistance to carbapenems, aminoglycosides (CLSI, 2024), and tigecycline (EUCAST, 2024). The mRNA expression levels of efflux pump genes and regulatory genes were detected by RT-qPCR. All 10 isolates had significant differences compared to the control group of ATCC13883. The core-genome tree and PFGE patterns revealed five clusters, indicating clonal and horizontal transfer expansion. Three key resistance genes (blaoxa-232, blaCTX-M-15, and rmtF) were observed in the K. pneumoniae clinical isolate Kpn20. Mobile antibiotic resistance islands were identified containing blaCTX-M-15 and rmtF, with multiple insertion sequences and transposons present. The coexistence of blaoxa-232 and rmtF in a high-risk K. pneumoniae strain was reported. Conjugation assay was utilized to investigate the transferability of blaoxa-232-encoding plasmids horizontally.Conclusion: The study highlights the emergence of ST15-KL112 high-risk CRKP strains with multidrug resistance, including to aminoglycosides and tigecycline. The presence of mobile ARI and clonal and horizontal transfer expansion of strains indicate the threat of transmission of these strains. Future research is needed to assess the prevalence of such isolates and develop effective control measures.Keywords: blaOXA-232, rmtF, Klebsiella pneumoniae, carbapenemase, plasmid

Siyuan Wang,1,&ast; Beiyao Gao,1,&ast; Minghui Shi,2– 6 Shiwei Qumu,2– 5 Fen Dong,2– 5,7 Peijian Wang,1 Ting Yang,2– 5 Shan Jiang1 1Department of Rehabilitation Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2National Center for Respiratory Medicine, Beijing, People’s Republic of China; 3National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 4Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 6Capital Medical University, Beijing, People’s Republic of China; 7Department of Clinical Research and Data management, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shan Jiang; Ting Yang, China-Japan Friendship Hospital, 2 Yinghuayuan East St. Hepingli, Chaoyang District, Beijing, 100029, People’s Republic of China, Email landjiang@126.com; dryangting@qq.comObjective: Given the established impact of exercise in reducing arterial stiffness and the potential for intermittent hypoxia to induce its elevation, this study aims to understand how oxygen desaturation during exercise affects arterial stiffness in individuals with COPD.Methods: We enrolled patients with stable COPD from China-Japan Friendship Hospital from November 2022 to June 2023. The 6-minute walk test (6-MWT) was performed with continuous blood oxygen saturation (SpO2) monitoring in these patients. The patients were classified into three groups: non-exercise induced desaturation (EID), mild-EID and severe-EID, according to the changes in SpO2 during the 6-MWT. The Cardio-Ankle Vascular Index (CAVI) and the change in CAVI (ΔCAVI, calculated as CAVI before 6MWT minus CAVI after the 6MWT) were measured before and immediately after the 6MWT to assess the acute effects of exercise on arterial stiffness. GOLD Stage, pulmonary function, and other functional outcomes were also measured in this study.Results: A total of 37 patients with stable COPD underwent evaluation for changes in CAVI (ΔCAVI) before and after the 6-MWT. Stratification based on revealed three subgroups: non-EID (n=12), mild-EID (n=15), and severe-EID (n=10). The ΔCAVI values was − 0.53 (− 0.95 to − 0.31) in non-EID group, − 0.20 (− 1.45 to 0.50) in mild-EID group, 0.6 (0.08 to 0.73) in severe-EID group. Parametric tests indicated significant differences in ΔCAVI among EID groups (p = 0.005). Pairwise comparisons demonstrated significant distinctions between mild-EID and severe-EID groups, as well as between non-EID and severe-EID groups (p = 0.048 and p = 0.003, respectively). Multivariable analysis, adjusting for age, sex, GOLD stage, diffusion capacity, and blood pressure, identified severe-EID as an independent factor associated with ΔCAVI (B = 1.118, p = 0.038).Conclusion: Patients with COPD and severe-EID may experience worsening arterial stiffness even during short periods of exercise.Keywords: COPD, arterial stiffness, exercise-induced oxygen desaturation, rehabilitation

Yingzi He,&ast; Jingjing Wang,&ast; Jianan Wang, Ruojun Qiu, Shuo Wang, Ting Jin, Hong Li, Fenping Zheng Department of Endocrinology, the Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fenping Zheng, Department of Endocrinology, the Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of China, Email 3407004@zju.edu.cnObjective: This study assessed possible associations among physical activity (PA), sitting time (ST), metabolic syndrome (MetS), and the individual components thereof. We analyzed the entire study sample and subpopulations stratified by visceral fat area (VFA). We hypothesized that individuals with elevated VFA might respond differently to modifiers of metabolic health, including PA and ST.Methods: This cross-sectional study, conducted between March and May 2010, enrolled 957 adults with abdominal magnetic resonance imaging (MRI) aged 40– 65 years living in the urban communities in Hangzhou, China. PA and ST were recorded using the standard International Physical Activity Questionnaire (IPAQ) and categorized into three levels. The ethnicity-specific cutoff for central obesity was VFA ≥ 80 cm2 on MRI according to Chinese population-based research. Multiple logistic regression models were used to analyze the associations between PA, ST, MetS and its components.Results: In the total subject population, participants reporting high level of PA were at a lower risk of MetS (OR = 0.46, 95% CI: 0.25, 0.86) than those declaring low PA. In the subgroup population with VFA ≥ 80 cm2 (ie, with central obesity), moderate-to-high PA levels were associated with a lower risk of MetS (p for trend < 0.05) and a lower risk of decreased high-density lipoprotein cholesterol (HDL-C) concentrations (p for trend < 0.05). In addition, ST > 3 h/day was a risk factor for both MetS (p for trend < 0.05) and hypertriglyceridemia (p for trend < 0.05) in the total subject population. While in the central obesity subgroup, ST > 3 h/day was found a stronger risk factor.Conclusion: Our study suggests that moderate-to-high levels of PA may have a role in prevention of MetS, and ST > 3 h/day was associated with a higher risk of MetS, particularly in individuals with central obesity.Keywords: metabolic syndrome, physical activity, sitting time, central obesity, visceral fat area

Yan Zhang,1,&ast; Senlu Wang,1,&ast; Xinqi Wang,2 Nianqiang Liu,2 Le Wang,2 Xiaomin Wang,1 Zhichao Liang,1 Junan Wang,1 Abulikemu Aili,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Center for Disease Control and Prevention of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingqin Cao, Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi, 830011, People’s Republic of China, Tel +86-13319912419, Email 573596229@qq.comObjective: To analyze the effectiveness of the “Xinjiang Model” for tuberculosis prevention and control in Kashgar Prefecture, Xinjiang, and to explore the determinants of the policy implementation effect.Methods: The registration data of pulmonary tuberculosis (PTB) patients in Kashgar Prefecture from 2012 to 2021 were collected to describe the temporal trend of registered incidence. A questionnaire survey was conducted among PTB patients registered and treated in the tuberculosis management information system in Zepu and Shache Counties from January 2022 to July 2023 to collect and analyze “Xinjiang model” determinants of effectiveness.Results: The PTB registered incidence in Kashgar Prefecture showed a significant increasing trend from 2012 to 2018 (APC=18.7%) and a significant decreasing trend from 2018– 2021 (APC=− 28.8%). Among the Kashgar Prefecture, compared with average registered incidence in 2012– 2017, registered incidence in 2021 in Shufu, Maigaiti, and Zepu Counties had a greater decline rate of 58.68%, 57.16%, and 54.02%, respectively, while the registered incidence in 2021 in Shache County increased by 6.32%. According to the comprehensive analysis of the factors affecting the effect of policy implementation, the proportion of PTB patients in Zepu County whose health status has now significantly improved compared with that before treatment was significantly greater than that in Shache County (P< 0.05); patients in Shache County were significantly less aware than those in Zepu County of how to take tuberculosis drugs, precautions, adverse reactions, and regular reviews during treatment; the factors that accounted for the greater proportion of heavy treatment burden in both Shache and Zepu Counties were discomfort caused by taking or injecting drugs, accounting for 12.8% and 8.7%, respectively.Conclusion: The “Xinjiang model” can effectively control the epidemic situation of tuberculosis in Kashgar, and the knowledge of tuberculosis treatment, adverse reactions to tuberculosis drugs, and treatment costs were the determinants of the effectiveness of policy implementation.Keywords: pulmonary tuberculosis, implementation effect, registered incidence, determinants, Xinjiang

Shiyu Wang,1– 4 Wei Qin,1– 4 Tingting Cheng,1– 4 Cong Zeng,1– 4 Xu Chen,1– 4 Yajing Xu1– 4 1Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Changsha, Hunan, People’s Republic of China; 3Hunan Hematologic Neoplasms Clinical Medical Research Center, Changsha, Hunan, People’s Republic of China; 4National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Soochow, Jiangsu, People’s Republic of ChinaCorrespondence: Yajing Xu, Department of Hematology, Xiangya Hospital, Central South University, &num;87 Xiangya Road, Changsha, Hunan, People’s Republic of China, Email xyyajingxu@csu.edu.cnPurpose: Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The tumour suppressor p53 plays a pivotal role in preventing aGVHD development. However, whether P53 pathway which contains p53 family members and other related genes participates in aGVHD development remains an unsolved question.Patients and Methods: Transcriptomic data was obtained from Gene Expression Omnibus (GEO) database. Gene set enrichment analysis was applied to determine the enrichment degree of signaling pathways. CIBERSORT and ssGSVA were used to evaluate immune cell compositions. Univariate and multivariate logistic regression analysis were performed to examine the independent diagnostic variables. qRT-PCR was utilized to validate the genes expression levels in our cohort.Results: A total number of 102 patients (42 aGVHD patients vs 60 non-aGVHD patients) were obtained after integrating two datasets in GEO database (GSE73809 and GSE4624). P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways. A risk model for aGVHD built by four genes (DDIT3, FBXW7, TPRKB and TOB1) in P53 pathway, exhibiting high differentiate and predictive value. DDIT3 and FBXW7 mRNA expression levels significantly decreased in peripheral blood mononuclear cells (PBMCs) from aGVHD patients compared with non-aGVHD group in our patient cohort, consisting with bioinformatics analysis.Conclusion: P53 pathway plays a potential role in impeding T cell activation through suppressing its related signaling pathways, thereby preventing aGVHD development. P53 pathway may emerge as a promising therapeutic target in aGVHD treatment.Keywords: allogeneic hematopoietic stem cell transplantation, aGVHD, P53 pathway, T cells, activation

Siyu Fan,1,&ast; Yu Zhao,1,&ast; Shiyu Wang,1,&ast; Na Zhang,1,&ast; Zhi Li,1,&ast; Hongyuan Liu,1 Yaodi Wei,1 Yunhui Yu,1 Yifeng Gu,2 Qun Wei,3 Weijuan Ye,4 Ninghan Feng,5 Fengping Liu1 1Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Surgical Oncology, Institute of Clinical Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Lishui Maternal and Child Health center, Lishui, Zhejiang, People’s Republic of China; 5Department of Urology, Jiangnan University Medical Center, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ninghan Feng, Department of Urology, Jiangnan University Medical Center, Wuxi, Jiangsu, 214002, People’s Republic of China, Email n.feng@njmu.edu.cn Fengping Liu, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China, Email liulaoshiyc@jiangnan.edu.cnAim: This study aims to explore the psychological reactions of medical students during the pandemic.Design: A qualitative study.Methods: A purposive sampling technique was employed, and a qualitative approach was adopted. Semi-structured questionnaires were utilized, and online interviews were conducted. Forty medical students were selected as participants for the interviews. The interview data were analyzed using Colaizzi’s seven-step analysis method.Results: The study identified five themes related to the psychological reactions of medical students during the pandemic. Firstly, COVID-19’s influence on medical careers was characterized by increased interest and determination in pursuing medical professions, heightened admiration for frontline workers, reinforced commitment to a medical career due to the pandemic, and recognition of the significance of medical education. Secondly, challenges and concerns in medical career pursuit were identified, including negative sentiments towards medical careers during COVID-19 and hesitations and concerns about entering the medical field amidst the pandemic. Thirdly, the impact on mental well-being encompassed diverse anxieties expressed by participants regarding control, transmission, treatment, and intentional spreading of the virus. Participants experienced an emotional progression from calmness to fear and anxiety, with heightened anxiety when relatives or acquaintances contracted COVID-19. Academic delays also contributed to anxiety among medical students. Fourthly, changes in behaviors and mindset were observed, including altered behaviors and mindset in response to the pandemic, as well as increased attention to personal hygiene and disease prevention measures. Lastly, expectations of medical students from government, public, and parents were explored.Conclusion: Understanding the psychological reactions of medical students during public health emergencies is crucial for their well-being and professional development. The findings have implications for medical education and the development of strategies to enhance the psychological well-being of medical students during similar crises.Keywords: COVID-19, medical students, psychological reactions, pandemic, mental health

Xundi Bao,1 Shuo Liang,1 Jun Li,1 Qian Ye,1 Dandan Wu,1 Shu Wang,2 Yue Li,1 Yunsheng Ding,1 Jie Liu3 1Clinical Laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 2Department of Science and Education, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 3Tuberculosis Control Institute, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of ChinaCorrespondence: Xundi Bao, Clinical laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), No. 397, Jixi Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86-13866774716, Email baoxundi@163.comObjective: To preliminarily assess the prevalence and control effect of tuberculosis and drug-resistant tuberculosis (TB) in Anhui province, and analyze the trends in the changing drug resistance spectrum of Mycobacterium tuberculosis (Mtb) isolated in Anhui province from 2016 to 2022.Methods: From 2016 to 2022, a total of 2336 culture-positive tuberculosis strains were collected from four drug resistance monitoring sites. Patient demographic information was collected and drug susceptibility testing was conducted.Results: Among the 2336 Mycobacterium tuberculosis complex strains, 1788 (76.54%) were from male patients and 548 (23.46%) were from female patients. The majority were of Han ethnicity, from rural areas, and employed in agriculture, with 12.54% (285/2273) having diabetes. A total of 1893 (81.04%) strains were sensitive to all six anti-TB drugs tested, and 443 (18.96%) strains were resistant to at least one or more anti-TB drugs. The drug resistance rate for patients undergoing initial treatment was 16.80% (348/2071), and 35.85% (95/265) for those receiving retreatment. Among the six anti-TB drugs, the resistance rates from highest to lowest were: INH (10.55%, 236/2336), SM (8.18%, 183/2336), OFX (6.53%, 146/2336), RFP (5.95%, 133/2336), EMB (2.37%, 53/2336), KM (1.97%, 44/2336). Significant differences were observed in MDR strains across different ages, types, with or without diabetes, and geographical sources (χ 2=14.895,76.534,6.032,5.109, all P< 0.05).Conclusion: The tuberculosis prevention and control measures have controlled the drug resistance rate of Mycobacterium tuberculosis to a certain extent. However, there are still statistical differences in drug resistance rates among TB patients with different categories, age groups, regions, and diabetic diseases. Early detection and prompt treatment of patients with drug-resistant TB remain critical to controlling the spread of this disease.Keywords: tuberculosis, mycobacterium, drug resistance, surveillance, population distribution, characteristic analysis

Haiping Xie,1,&ast; Xuexin Zhong,1,&ast; Junlin Chen,2 Shuang Wang,1 Yuefang Huang,2 Niansheng Yang1 1Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Pediatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Niansheng Yang, Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, 510080, People’s Republic of China, Tel +86-20-87755766 ext 8150, Email yangnsh@mail.sysu.edu.cnBackground: Interstitial lung disease (ILD), characterized by pulmonary fibrosis (PF), represents the end-stage of various ILDs. The immune system plays an important role in the pathogenesis of PF. V-domain immunoglobulin suppressor of T-cell activation (VISTA) is an immune checkpoint with immune suppressive functions. However, its specific role in the development of PF and the underlying mechanisms remain to be elucidated.Methods: We assessed the expression of VISTA in CD4 T cells from patients with connective tissue disease-related interstitial lung disease (CTD-ILD). Spleen cells from wild-type (WT) or Vsir−/− mice were isolated and induced for cell differentiation in vitro. Additionally, primary lung fibroblasts were isolated and treated with interleukin-17A (IL-17A). Mice were challenged with bleomycin (BLM) following VISTA blockade or Vsir knockout. Moreover, WT or Vsir−/− CD4 T cells were transferred into Rag1−/− mice, which were then challenged with BLM.Results: VISTA expression was decreased in CD4 T cells from patients with CTD-ILD. Vsir deficiency augmented T-helper 17 (Th17) cell differentiation in vitro. Furthermore, IL-17A enhanced the production of inflammatory cytokines, as well as the differentiation and migration of lung fibroblasts. Both VISTA blockade and knockout of Vsir increased the percentage of IL-17A-producing Th17 cells and promoted BLM-induced PF. In addition, mice receiving Vsir−/− CD4 T cells exhibited a higher percentage of Th17 cells and more severe PF compared to those receiving WT CD4 T cells.Conclusion: These findings demonstrate the significant role of VISTA in modulating the development of PF by controlling Th17 cell differentiation. These insights suggest that targeting VISTA could be a promising therapeutic strategy for PF. Keywords: VISTA, lung fibrosis, Th17 cells, IL-17A, fibroblast

Hongyuan Liu,1,&ast; Yaodi Wei,1,&ast; Zhenyi Xu,2,&ast; Hao Lin,2,&ast; Yu Zhao,1 Shiyu Wang,1 Fengbao Gao,1 Ninghan Feng,2 Alan J Wolfe,3 Fengping Liu1 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Urology, Affiliated Wuxi No. 2 Hospital, Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA&ast;These authors contributed equally to this workCorrespondence: Alan J Wolfe, Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA, Email awolfe@luc.edu Fengping Liu, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China, Email liulaoshiyc@jiangnan.edu.cnPurpose: Patients with recurrent urinary tract infections face complex management challenges. Fecal microbiota transplantation is a superior treatment for chronic infectious diseases, but limited patient knowledge affects treatment decisions. This study aims to identify factors associated with hesitancy towards fecal microbiota transplantation among patients with recurrent urinary tract infections, to help physicians and nurses in providing accurate and useful information to patients.Patients and Methods: A descriptive qualitative approach was employed, utilizing semi-structured interviews conducted with patients experiencing recurrent urinary tract infections who expressed hesitancy towards fecal microbiota transplantation. The interviews took place between September 2021 and December 2022. Thematic analysis was conducted on the semi-structured interviews to identify perceived facilitators and barriers associated with fecal microbiota transplantation.Results: The analysis included interviews with thirty adult female patients with recurrent urinary tract infections. Four facilitators influencing patients’ decision-making regarding fecal microbiota transplantation were identified: (1) the motivating role of hope and expectations for active patient participation; (2) the influence of healthcare providers, as well as family members and friends on patients’ decisions to pursue fecal microbiota transplantation; (3) the patients’ perception of fecal microbiota transplantation as a low-risk treatment option; and (4) the dedication to the advancement of medical treatments. In contrast, two primary barriers to accepting fecal microbiota transplantation were identified: (1) that conventional treatment controls disease activity, while fecal microbiota transplantation effects remain uncertain; and (2) that safety concerns surrounding fecal microbiota transplantation.Conclusion: Comprehensive information about fecal microbiota transplantation, including donor selection, sample processing, the procedure, and potential discomfort, is essential for patients and families to make informed treatment decisions.Registration: CHiCTR2100048970.Keywords: barriers, decision making, facilitators, fecal microbiota transplantation, qualitative study, recurrent urinary tract infections

Fengyao Liu,1,2,&ast; Haochen Wang,2,3,&ast; Bingqing Bai,2,4 Han Yin,5 Yuting Liu,2 Yu Wang,2 Quanjun Liu,2 Shuxia Wang,6 Huan Ma,3 Qingshan Geng1,2,5 1School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 2Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 5Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 6Department of Nuclear Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huan Ma, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106 Zhongshan Er Road, Guangzhou, People’s Republic of China, Fax +8620-83827812, Email mahuandoctor@163.com Qingshan Geng, Department of Cardiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), 1080 Cuizhu Road, Luohu District, Shenzhen, Guangdong, Fax +0755-25533018, Email gengqsh@163.netPurpose: Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited.Patients and Methods: We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI.Results: There is higher REI (7.8 vs 2.6, P=0.019), ODI (4.7 vs 9.2, P=0.028) and percentage of OSA (67.74% vs 33.33%, P=0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, P = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (β=1.226, OR = 3.408 (1.200– 9.681), P = 0.021).Conclusion: Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.Keywords: obstructive sleep apnea, mental stress induced myocardial ischemia, angina with no obstructive coronary artery disease, myocardial perfusion imaging

Ming Tang,1,2,&ast; Siyuan Wang,1,2,&ast; Yiwen Wang,1 Fanyi Zeng,1 Mianpeng Chen,1 Xindong Chang,1 Mingfei He,1 Qingqing Fang,1 Shiwu Yin1 1Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei City, Anhui Province, People’s Republic of China; 2The Fifth Clinical College of Medicine, Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiwu Yin, Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, 574 Changjiang East Road, Yaohai District, Hefei City, Anhui Province, 230011, People’s Republic of China, Email yinshiwu@126.comPurpose: Previous studies highlight paraspinal muscles’ significance in spinal stability. This study aims to assess paraspinal muscle predictiveness for postoperative recurrent lumbar disc herniation (PRLDH) after lumbar disc herniation patients undergo percutaneous endoscopic transforaminal discectomy (PETD).Patients and Methods: Retrospectively collected data from 232 patients undergoing PETD treatment at our institution between January 2020 and January 2023, randomly allocated into training (60%) and validation (40%) groups. Utilizing Lasso regression and multivariable logistic regression, independent risk factors were identified in the training set to construct a Nomogram model. Internal validation employed Enhanced Bootstrap, with Area Under the ROC Curve (AUC) assessing accuracy. Calibration was evaluated through calibration curves and the Hosmer-Lemeshow goodness-of-fit test. Decision curve analysis (DCA) and clinical impact curve (CIC) were employed for clinical utility analysis.Results: Diabetes, Modic changes, and ipsilesional multifidus muscle skeletal muscle index (SMI) were independent predictive factors for PRLDH following PETD (P< 0.05). Developed Nomogram model based on selected predictors, uploaded to a web page. AUC for training: 0.921 (95% CI 0.872– 0.970), validation: 0.900 (95% CI 0.828– 0.972), respectively. The Hosmer-Lemeshow test yielded χ2=5.638/6.259, P=0.688/0.618, and calibration curves exhibited good fit between observed and predicted values. DCA and CIC demonstrate clinical net benefit for both models at risk thresholds of 0.02– 1.00 and 0.02– 0.80.Conclusion: The Nomogram predictive model developed based on paraspinal muscle parameters in this study demonstrates excellent predictive capability and aids in personalized risk assessment for PRLDH following PETD.Keywords: lumbar disc herniation, percutaneous endoscopic transforaminal discectomy, postoperative recurrent lumbar disc herniation, predictive model

Abdullah Al Mamun,1,2 Chuxiao Shao,1 Peiwu Geng,1 Shuanghu Wang,1 Jian Xiao1– 3 1Central Laboratory of The Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 2Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Jian Xiao, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Email xfxj2000@126.com Shuanghu Wang, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Email wangshuanghu@lsu.edu.cnAbstract: Pyroptosis is a pro-inflammatory form of cell death resulting from the activation of gasdermins (GSDMs) pore-forming proteins and the release of several pro-inflammatory factors. However, inflammasomes are the intracellular protein complexes that cleave gasdermin D (GSDMD), leading to the formation of robust cell membrane pores and the initiation of pyroptosis. Inflammasome activation and gasdermin-mediated membrane pore formation are the important intrinsic processes in the classical pyroptotic signaling pathway. Overactivation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome triggers pyroptosis and amplifies inflammation. Current evidence suggests that the overactivation of inflammasomes and pyroptosis may further induce the progression of cancers, nerve injury, inflammatory disorders and metabolic dysfunctions. Current evidence also indicates that pyroptosis-dependent cell death accelerates the progression of diabetes and its frequent consequences including diabetic peripheral neuropathy (DPN). Pyroptosis-mediated inflammatory reaction further exacerbates DPN-mediated CNS injury. Accumulating evidence shows that several molecular signaling mechanisms trigger pyroptosis in insulin-producing cells, further leading to the development of DPN. Numerous studies have suggested that certain natural compounds or drugs may possess promising pharmacological properties by modulating inflammasomes and pyroptosis, thereby offering potential preventive and practical therapeutic approaches for the treatment and management of DPN. This review elaborates on the underlying molecular mechanisms of pyroptosis and explores possible therapeutic strategies for regulating pyroptosis-regulated cell death in the pharmacological treatment of DPN. Keywords: Diabetes mellitus, Diabetic peripheral neuropathy, Inflammation, Pyroptosis, NLRP3, Caspase-1, GSDMD, IL-1β and IL-18

Jingwen Xu,1,2 Yue Zhang,1,2 Xiaolin Yao,1 Sijuan Wang,1,2 Kaiqiang Lv,1,2 Guangwen Luo,1,2 Jiaqi Wang,1,2 Guoliang Li1 1School of Food Science and Engineering, School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi’an, 710021, People’s Republic of China; 2Xi’an Key Laboratory of Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Xi’an, 710021, People’s Republic of ChinaCorrespondence: Guoliang Li, Email 61254368@163.comIntroduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging.Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release.Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1.Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res. Keywords: trans-resveratrol, seleno-alginate, synergistic antioxidant, mucoadhesion, intestinal targeted delivery

Xulin Liu,1,&ast; Zhancheng Qiu,2,&ast; Elijah Ndhlovu,1,&ast; Yunyan Wan,3 Huapeng Sun,4 Shuai Wang,5 Yugang Cao,6 Peng Zhu1 1Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Taihe Hospital, Shiyan City, Hubei Province, People’s Republic of China; 4Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People’s Republic of China; 5Department of Hepatobiliary Surgery, Jingzhou Central Hospital, Jingzhou, People’s Republic of China; 6Department of Hepatobiliary and Pancreatic Surgery, Huangshi Central Hospital of Edong Healthcare Group, Huangshi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Zhu, Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, Tel +86 13907170712, Email zhupeng@tjh.tjmu.edu.cnPurpose: Early recurrence (ER) is associated with poor prognosis in hepatocellular carcinoma (HCC). In this study, we developed and externally validated a nomogram based on the hemoglobin, albumin, lymphocytes, and platelets (HALP) score to predict ER for patients with BCLC stage 0/A HCC who underwent radical liver resection.Patients and Methods: A total of 808 BCLC stage 0/A HCC patients from six hospitals were included in this study, and they were assigned to a training cohort (n = 500) and an external validation cohort (n = 308). We used univariate and multivariate Cox regression analysis to identify the independent risk factors for disease-free survival (DFS). We also established and externally validated a nomogram based on these risk predictors. The nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), the calibration curve, decision curve analysis (DCA), and Kaplan‒Meier analysis.Results: Multivariate COX regression showed that HBV DNA ≥ 10,000 IU/mL (P < 0.001), HALP score ≤ 38.20 (P < 0.001), tumor size (P = 0.003), clinically significant portal hypertension (P = 0.001), Edmondson-Steiner grade (III–IV) (P = 0.007), satellite nodules (P < 0.001), and MVI (P = 0.001) were independent risk factors for post-operative tumor recurrence. The AUC of our nomogram for predicting the 2-year and 5-year DFS was 0.756 and 0.750, respectively, in the training cohort and 0.764 and 0.705, respectively, in the external validation cohort. We divided the patients into low-, intermediate- and high-risk groups according to the risk score calculated by the nomogram. There were statistically significant differences in the DFS and overall survival (OS) among the three groups of patients (P < 0.001).Conclusion: We developed and externally validated a new nomogram, which is accurate and can predict ER in BCLC stage 0/A HCC patients after curative liver resection.Keywords: early recurrence, hepatocellular carcinoma, HALP score, nomogram, Barcelona Clinic of Liver Cancer staging system, disease-free survival

Yongzhi Xu,1,2,&ast; Yuanping Hao,2,&ast; Muhammad Arif,3 Xiaodong Xing,4 Xuyang Deng,1 Danyang Wang,1 Yang Meng,2 Shuai Wang,1 Mohamed Sayed Hasanin,5 Wanchun Wang,2 Qihui Zhou3,6 1School of Stomatology, Qingdao University, Qingdao, People’s Republic of China; 2Department of Stomatology, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 3Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 4School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 5Cellulose and Paper Department, National Research Centre, Dokki, Cairo, Egypt; 6Hubei Key Laboratory of Biomass Fibers and Eco-Dyeing & Finishing, Wuhan Textile University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wanchun Wang; Qihui Zhou, Email kqwwch@126.com; qihuizhou@uor.edu.cnIntroduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed.Methods: Here, &epsiv;-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms.Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 μg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo.Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs. Keywords: carbon quantum dots, Enterococcus faecalis, bacterial biofilm, persistent endodontic infections

Bo Wang,1,2 Jiquan Shen,2 Changjian Zhou,2 Xinggao Wang,2 Shuanghu Wang,3 Ruixing Hou1 1Department of Orthopaedics, Suzhou Ruihua Orthopedic Hospital Affiliated Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 2Department of Orthopaedics, the Sixth Affiliated Hospital of Wenzhou Medical University, the People’s Hospital of Lishui, Lishui, Zhejiang, 323000, People’s Republic of China; 3Central Laboratory of the Sixth Affiliated Hospital of Wenzhou Medical University, the People’s Hospital of Lishui, Lishui, Zhejiang, 323000, People’s Republic of ChinaCorrespondence: Shuanghu Wang, Central Laboratory of the Sixth Affiliated Hospital of Wenzhou Medical University, the People’s Hospital of Lishui, Lishui, Zhejiang, 323000, People’s Republic of China, Email wangshuanghu@lsu.edu.cn Ruixing Hou, Department of Orthopaedics, Suzhou Ruihua Orthopedic Hospital Affiliated Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China, Email hrx2020@suda.edu.cnBackground: Rheumatoid Arthritis (RA) involves prolonged inflammation of the synovium, damaging joints and causing stiffness and deformity. Celastrol (Cel), derived from the Chinese herbal medicine Tripterygium wilfordii Hook F, offers immunosuppressive effects for RA treatment but is limited by poor solubility and bioavailability.Purpose: In this study, long-circulating Cel-loaded liposomes (Cel-LPs) were used to increase the pharmacokinetics of Cel, thereby improving drug delivery and efficacy for the treatment of RA.Methods: Cel-LPs were prepared and administered orally and intravenously to compare the elimination half-life of drugs and bioavailability of Cel. Cel-LPs were prepared using the lipid thin-layer-hydration-extrusion method. Human rheumatoid arthritis synovial (MH7A) cells were used to investigate the compatibility of Cel-LPs. The pharmacokinetic studies were performed on male Sprague-Dawley (SD) rats.Results: The Cel-LPs had an average size of 72.20 ± 27.99 nm, a PDI of 0.267, a zeta potential of − 31.60 ± 6.81 mV, 78.77 ± 5.69% drug entrapment efficiency and sustained release (5.83 ± 0.42% drug loading). The cytotoxicity test showed that liposomes had excellent biocompatibility and the fluorescence microscope diagram indicated that liposome entrapment increased intracellular accumulation of Rhodamine B by MH7A cells. Furthermore, the results exhibited that Cel-LPs improved the pharmacokinetics of Cel by increasing the elimination half-life (t1/2) to 11.71 hr, mean residence time (MRT(0-∞)) to 7.98 hr and apparent volume of distribution (Vz/F) to 44.63 L/kg in rats, compared to the Cel solution.Conclusion: In this study, liposomes were demonstrated to be effective in optimizing the delivery of Cel, enabling the formulation of Cel-LPs with prolonged blood circulation and sustained release characteristics. This formulation enhanced the intravenous solubility and bioavailability of Cel, developing a foundation for its clinical application in RA and providing insights on poorly soluble drug management.Keywords: celastrol, rheumatoid arthritis, liposomes, oral and intravenous delivery, pharmacokinetic

Shuqi Wang,1,2 Haina Gao,3 Mengmeng Zhang,1,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Internal Medicine, The Second Hospital of Shijiazhuang, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: To explore the relationship between vitamin D (VitD) deficiency and the apolipoprotein B/apolipoprotein A1 (apo B/A1) in type 2 diabetes mellitus (T2DM) patients.Methods: This was a retrospective study that lasted 2 years and 6 months, collecting information and laboratory data from 784 patients with T2DM. Patients were divided into VitD deficiency group (n = 433) and non-VitD deficiency group (n = 351) based on VitD levels. Calculated apo B/A1 ratio, and patients were further divided into high-apo B/A1 group (n = 392) and low-apo B/A1 group (n = 392) based on the median of the apo B/A1. All data were analyzed using Prism 8.0.1 and R version 4.3.1 software.Results: Apo B/A1 levels of T2DM patients combined with VitD deficiency was significantly higher than that of non-VitD deficiency patients, and the VitD levels of patients with high apo B/A1 was significantly lower than that patients with low apo B/A1 (all P< 0.001). Spearman correlation analysis showed that VitD levels were negatively correlated with apo B/A1 (r=-0.238, P< 0.001). Multiple linear regression analysis revealed after adjusting other factors, VitD levels were significantly negatively associated with apo B/A1 (β=-0.123, P=0.001). Binary logistic regression analysis showed apoB/A1 was an independent risk factor for VitD deficiency in T2DM patients. Restrictive cubic spline indicated a significant linear relationship between apoB/A1 and VitD deficiency (P general trend < 0.0001, P nonlinear = 0.0896), after stratification of gender, the results showed that apo B/A1 was more susceptible to VitD deficiency in female patients. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve, sensitivity and specificity of the apo B/A1 for VitD deficiency were 0.654, 66.3% and 59.8%, respectively.Conclusion: The apo B/A1 was significantly negatively associated with VitD levels and an independent risk factor for VitD deficiency in patients with T2DM.Keywords: type 2 diabetes mellitus, vitamin D deficiency, apolipoprotein B/apolipoprotein A1

Shenjiao Wang,1,2,&ast; Xin Zou,3– 5,&ast; Jianguang Fu,1 Fei Deng,1 Huiyan Yu,1 Huan Fan,1 Qigang Dai,1 Qingxiang Shang,5 Ke Xu,1 Changjun Bao1,5 1Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People’s Republic of China; 2Ili Kazakh Autonomous Prefecture Center for Disease Control and Prevention, Ili, Xinjiang, People’s Republic of China; 3Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Viral Infectious Diseases, Chongqing, People’s Republic of China; 5School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Xu; Changjun Bao, Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), No. 172, Jiangsu Road, Gulou District, Nanjing, Jiangsu Province, 210009, People’s Republic of China, Tel +86-18915999237, +86-18118996911, Email xuke923@163.com; bao2000_cn@163.comBackground: Human adenovirus (HAdV) is common pathogens that cause various respiratory diseases. The genetic diversity of viruses caused by recombination is considered to be the main source of emerging outbreaks. The aim of this study is to explore the evolutionary relationship and recombination events of HAdV genome in respiratory tract infections in Jiangsu Province.Methods: Whole-genome sequencing (WGS) technology was used to sequence 66 patients with HAdV infection (37 patients with influenza-like illness (ILI) and 29 hospitalized patients with pneumonia) from Jiangsu Province. Epidemiological analysis was performed on hospitalized pneumonia and ILI patients infected with HAdV. Subsequently, phylogenetic, recombination, and nucleotide and amino acid identity analyses were performed.Results: Epidemiological analysis of patients undergoing WGS showed that 75.7% of ILI patients were infected with the HAdVB strain and 69.0% of hospitalized pneumonia patients were infected with the HAdVC strain. Moreover, the hospitalized pneumonia and ILI patients infected with HAdV were different in region and time. The strains of HAdVB3 and HAdVB7 genotypes were mainly infected in 2015 and 2017, and the strains of HAdVC1 and HAdVC2 genotypes were mainly infected in 2020. The results of histogram analysis showed that the HAdV strain mainly infected children under 5 years old. In addition, 36 novel recombinant strains were identified. The discovery of these recombinant strains may contribute to understanding the epidemiology of HAdV and research on related vaccines. Furthermore, the percentage of nucleotide and amino acid identities revealed a high level of genetic conservation within isolates from HAdVB3, HAdVB7, HAdVC1, HAdVC2 and HAdVC5 genotypes.Conclusion: The WGS analysis reveals the evolutionary relationships and recombination events of HAdV strains in Jiangsu Province, which is helpful to deepen the understanding of HAdV epidemiology and evolution. In addition, it provides a basis for the formulation of public health strategies in Jiangsu Province.Keywords: human adenovirus, whole genome sequencing, phylogenetic analysis, recombination

Yun Ren,&ast; Xiaona Luo,&ast; Haiyan Tong, Simei Wang, Jinbin Yan, Longlong Lin, Yucai Chen Department of Neurology, Shanghai Children’s Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yucai Chen, Email chenyc@shchildren.com.cnBackground: The IQ motif and Sec7 domain ArfGEF 2 (IQSEC2), an X-linked gene that encodes the BRAG1 protein, is a guanine nucleotide exchange factor for the ADP ribosylation factor (ARF) protein family in the small guanosine triphosphate (GTP) binding protein. Mutations in this gene result in disorders such as intellectual disability (ID) and epilepsy. In this study, we analyze the clinical features of two patients with IQSEC2-mutation-related disease and discuss their possible pathogenesis.Methods: The two patients were diagnosed with ID and epilepsy. Genetic testing was performed using whole-exome sequencing, and the three-dimensional protein structure was analyzed. UCSC Genome Browser was used to analyze the conservation of IQSEC2 in different species. We compared IQSEC2 expression in the proband families with that in a control group, as well as the expression of the postsynaptic identity protein 95 (PSD-95), synapse-associated protein 97 (SAP97), ADP ribosylation factor 6 (ARF-6), and insulin receptor substrate 53kDa (IRSP53) genes interacting with IQSEC2.Results: We identified two semi-zygote mutations located in conserved positions in different species: an unreported de novo mutation, C.3576C>A (p. Tyr1192&ast;), and a known mutation, c.2983C>T (p. Arg995Trp). IQSEC2 mutations resulted in significant changes in the predicted three-dimensional protein structure, while its expression in the two probands was significantly lower than that in the age-matched control group, and IQSEC2 expression in proband 1 was lower than that in his family members. The expression levels of PSD-95, ARF-6, and SAP97, IRSP 53, which interact with IQSEC2, were also significantly different from those in the family members and age-matched healthy children.Conclusion: The clinical phenotype resulting from IQSEC2 mutations can be explained by the significant decrease in its expression, loss of function of the mutant protein, and change in the expression of related genes. Our results provide novel insights into the molecular phenotype conferred by the IQSEC2 variants.Keywords: IQSEC2, expression level, intellectual disability, infantile spasm, related genes