Search

Qin Zhang,1,&ast; Jian Liu,2,&ast; Ruize Zhang,3 Changfen Wang,4 Yanyan Song,5 Xi Wang,2 Fanling Zeng6 1Department of Cardiology, Xi Chang People’s Hospital, Xi Chang, Sichuan Province, 615000, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Dougherty Valley High School, San Ramon, CA, 94582, USA; 4Department of Cardiology, People’s Hospital of Qianxinan Prefecture, Guizhou Province, People’s Republic of China; 5Department of Endocrinology, Chongqing Jianshe Hospital, Chongqing, People’s Republic of China; 6Health Management Ctr, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Wang; Fanling Zeng, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email 201884@cqmu.edu.cn; zengfanling@hospital.cqmu.edu.cnObjective: To evaluate the predictive value of the triglyceride-glucose waist circumference index (TyG-WC) for hyperuricemia (HUA) risk in the hypertensive population.Methods: This prospective cohort study involved 831 hypertensive patients with normal uric acid levels, who underwent continuous health examinations for five years. Participants were categorized into four groups based on baseline TyG-WC quartiles, and the incidence of hyperuricemia was monitored in each group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for HUA incidence were calculated using Cox proportional hazards regression analysis. The predictive ability of various TyG indices for HUA was evaluated using receiver operating characteristic curves.Results: After five years of follow-up, 117 participants developed HUA. The cumulative incidence of HUA was significantly higher in the highest TyG-WC quartile (Q4) compared to the lowest quartile (Q1). The TyG-WC index demonstrated the highest predictive value, with an area under the curve of 0.685 (95% CI: 0.635– 0.734) compared to other obesity-related TyG indices. After adjusting for confounding factors, per standard deviation increase in the TyG-WC index was associated with a 1.28-fold higher risk of developing HUA (95% CI: 1.04– 1.56, P < 0.001).Conclusion: The TyG-WC index is a robust independent predictor of HUA risk in the hypertensive population. It provides a practical, reliable, and cost-effective tool for the early identification of high-risk individuals in this population.Keywords: hypertension, hyperuricemia, TyG-WC index, insulin resistance, obesity

Mingmei Yang,1,2 Huiying Wang,1 Ruzhi Zhang1 1Department of Dermatology, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 2Department of Dermatology, Affiliated Changzhou Children’s Hospital of Nantong University, Changzhou, Jiangsu Province, 213003, People’s Republic of ChinaCorrespondence: Ruzhi Zhang, Email zhangruzhi628@163.comBackground: Vitiligo is an autoimmune disorder characterized by pigment loss, and current treatment options remain inadequate.Objective: This study aims to identify oxidative stress-related biomarkers and hub genes associated with vitiligo diagnosis through genomic analysis and to examine the role of immune cell infiltration in the pathogenesis of vitiligo.Methods: The mRNA expression profile dataset GSE75819 was retrieved from the GEO database. Differential expression of oxidative stress-related genes in vitiligo was analyzed using R software. Protein-protein interaction (PPI) analysis, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted on the differentially expressed genes (DEGs). Immune cell infiltration between vitiligo and normal control groups was assessed using the CIBERSORT algorithm. Additionally, two machine learning algorithms were employed to identify hub genes, perform enrichment analyses, and evaluate their correlation with immune infiltration.Results: A total of 415 Oxidative Stress-DEGs were identified in vitiligo, including 317 up-regulated and 98 down-regulated genes. PPI analysis highlighted the significance of certain ribosomal protein genes. KEGG enrichment analysis suggested an association between vitiligo and various neurodegenerative conditions, particularly through pathways such as oxidative phosphorylation and ribosome biogenesis. GO enrichment analysis indicated that the hub genes were significantly enriched in mitochondrial-related activities. Significant differences in immune infiltration patterns were observed between vitiligo patients and normal controls. Machine learning algorithms identified oxidative stress-related key genes associated with vitiligo, notably the DCT gene, whose expression was strongly linked to the activity of specific immune cell subsets and melanin biosynthetic pathways.Conclusion: Oxidative stress-related DEGs, ribosomal proteins, immune infiltration, and hub genes related to melanin biosynthesis, particularly DCT, are closely associated with the pathogenesis of vitiligo. These findings enhance our understanding of vitiligo and may aid in identifying therapeutic targets for the disease. Keywords: vitiligo, oxidative stress, DEGs, hub gene, DCT, immune infiltration

Wenyue Zhou,1 Haoxuan Cheng,1 Miaomiao Li,1 Ruian Zhang,1 Zhiren Li,1 Guangyong Sun,2 Dong Zhang,2 Xinjuan Liu,1 Yanxiang Pei1 1Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, 100024, People’s Republic of ChinaCorrespondence: Xinjuan Liu; Yanxiang Pei, Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email liuxinjuan@mail.ccmu.edu.cn; peiyanxiang1972@126.comPurpose: This study evaluates and compares the eradication rates of Helicobacter pylori (H. pylori) achieved through susceptibility-guided therapy (SGT) based on resistance genotyping and empirical therapy (ET).Patients and Methods: A retrospective study was conducted at Beijing Chaoyang Hospital (2021– 2023) on patients with H. pylori infection receiving initial eradication therapy. Resistance genotypes for clarithromycin and levofloxacin were identified using fluorescent PCR of gastric biopsy samples. Patients underwent a 14-day bismuth-containing quadruple therapy (BQT) and were evaluated via the C13 urea breath test (UBT). Based on genotyping or clinical judgment, 550 patients were assigned to SGT (n = 125) or ET (n = 425). The SGT group received personalized treatment based on genotype testing results, avoiding the use of antibiotics to which the bacteria were resistant. The ET group received the standard bismuth-containing quadruple therapy (BQT). Additionally, 29 ET patients underwent follow-up genotypic testing and eradication rates were analyzed retrospectively.Results: SGT achieved higher eradication rates than ET (ITT: 94.4% vs 86.1%, P = 0.012; PP: 95.2% vs 87.6%, P = 0.016). In levofloxacin-resistant strains, SGT showed significantly higher eradication rates in the PP analysis (95.7% vs 50.0%, P = 0.049).Conclusion: SGT exhibited remarkably superior eradication rates, notably in levofloxacin-resistant strains, proposing a compelling alternative for the treatment of H. pylori, particularly in instances of antimicrobial resistance.Keywords: Helicobacter pylori infection, susceptibility-guided therapy, bismuth-containing quadruple regimen, propensity score matching

Rongyi Zhang,1,&ast; Shi Chen,2,&ast; Liuhu Han,1,3 Bingbing Xu,1 Yuyu Guo,1 Likui Wang1 1Department of Pain Medicine, the First Affiliated Hospital of AnHui Medical University, HeFei, People’s Republic of China; 2Department of Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, ShenZhen, People’s Republic of China; 3Anhui Medical University, HeFei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Likui Wang, Department of Pain Medicine, the First Affiliated Hospital of AnHui Medical University, Shushan District, Hefei City, Anhui Province, People’s Republic of China, Tel +86 13705690702, Email wlk9560@163.comIntroduction: Coblation nucleoplasty is a minimally invasive procedure developed for the treatment of symptomatic disc herniation.Methods: We evaluated 118 cases of cervical and lumbar intervertebral discs treated with coblation nucleoplasty. The clinical results were assessed using the visual analogue scale (VAS), modified MacNab criteria, and efficacy. Complications and the re-surgery rate were also evaluated. The procedure was carried out under CT guidance, and the patients were followed up for 1 day, 1 month, 6 months, and 5 years postoperative.Results: At the 5-year follow-up, the VAS score in the cervical and lumbar groups significantly decreased from 6.20 to 2.43 and 6.11 to 3.29, respectively. While MacNab scores were indistinguishable at the 6-month follow-up, they differed significantly between the cervical (58.2%) and lumbar (34.9%) groups at the 5-year follow-up. At the 5-year follow-up, 6 patients in the cervical group and 11 in the lumbar group underwent conventional operation. The efficacy of coblation nucleoplasty at the 5-year follow-up was higher in cervical group (81.82%) compared with lumbar group (61.90%).Conclusion: The results of this study suggest that coblation nucleoplasty is a safe and effective treatment option for patients with cervical and lumbar disc herniation. The long-term benefits of this procedure were more pronounced in patients with cervical disc herniation.Clinical Trial Registration: The trial was registered on ClinicalTrials.gov (ChiCTR2400089145).Keywords: coblation nucleoplasty, lumbar disc herniation, cervical disc herniation, pain

Xiaolong Cao,1,2,&ast; Xinyue Li,1,3,&ast; Zexuan Song,4 Ping He,5 Ruiqing Zhang,1,3 Chong Teng,6 Qian Sun,2 Xue Wang,2 Bing Zhao,3 Zhiguo Zhang,7 Yanlin Zhao3 1National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 2Outpatient Department, Beijing Changping Institute for Tuberculosis Prevention and Treatment, Beijing, 102200, People’s Republic of China; 3National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 4Department of Clinical Laboratory, Children’s Hospital, Capital Institute of Pediatrics, Beijing, 100020, People’s Republic of China; 5Center for Infection Biology, School of Medicine, Tsinghua University, Beijing, 100084, People’s Republic of China; 6Tuberculosis Prevention and Control Department, Beijing Dongcheng District Center for Disease Control and Prevention, Beijing, 100050, People’s Republic of China; 7Hospital Management Office, Beijing Changping Mental Health Care Hospital, Beijing, 102202, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiguo Zhang, Beijing Changping Mental Health Care Hospital, Changping District, Beijing, 102202, People’s Republic of China, Email zhgzh8689@126.com Yanlin Zhao, National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Changping District, Beijing, 102206, People’s Republic of China, Email zhaoyl@chinacdc.cnBackground: College students are a crucial link in curbing the epidemic. The aim of this study is to analyze the genetic diversity and drug resistance of Mycobacterium tuberculosis strains in college students with tuberculosis in Beijing, revealing the lineage structure and transmission patterns specific to this group.Methods: This study used the hospital’s electronic management system to screen for tuberculosis among college students in Changping District, Beijing, from January 2004 to December 2023. Socio-demographic and clinical data were collected, and whole-genome sequencing was performed on culture-positive isolates. Isolates with a genetic distance of less than 12 SNPs were grouped into the same genomic cluster. The TB Profiler software predicted drug resistance mutations, and categorical data were analyzed using Chi-square or Fisher’s exact tests.Results: Among the 1436 college students with tuberculosis, a total of 153 isolates successfully underwent whole-genome sequencing. The results showed that about one-third (49/153) of the isolates carried one or more drug resistance genes, with more than half (26/49) associated with first-line anti-tuberculosis drugs. However, encouragingly, the incidence of drug-resistant tuberculosis showed a significant downward trend, with statistical significance (p< 0.05). Lineage 2 (86.3%, 132/153) was the predominant genotype, with the Beijing genotype (90.1%, 120/153) being the most common, while the isolation of Lineage 3 in a student from Xinjiang. Sixteen college student isolates clustered, and all of which were Beijing genotype. Transmission within the same campus showed characteristics of short clustering time.Conclusion: The drug resistance rate among college students is relatively high, however it shows a declining trend. School tuberculosis infections could stem not only from within-campus transmission but also necessitate consideration of spatial and cross-regional spread possibilities.Keywords: Mycobacterium tuberculosis, whole genome sequencing, lineage, transmission, drug resistance, college students

Zhenrui Zhao,1 Xiaofei Feng,1 Yuhao Zhao,1 Zhengdong Song,1 Ruihao Zhang,1 Kui Zhang,1 Yixiang He,1 Guoliang Chen,1 Jing Zhang,2 Wenji Wang3 1Department of Orthopedics, The First Clinical Medical College of Lanzhou University, Lanzhou, People’s Republic of China; 2Department of Orthopedics, Anlu People’s Hospital, Anlu, People’s Republic of China; 3Department of Orthopedics, the First Hospital of Lanzhou University, Lanzhou, People’s Republic of ChinaCorrespondence: Wenji Wang, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China, Tel +8613893221698, Email wwjldyy@163.comBackground: Given the risks associated with autologous bone transplantation and the limitations of allogeneic bone transplantation, scaffolds in bone tissue engineering that incorporate bioactive peptides are highly recommended. Teriparatide (TPTD) plays a significant role in bone defect repair, although achieving controlled release of TPTD within a bone tissue engineering scaffold remains challenging. This work reports a new approach for treatment of teriparatide using a water-in-oil-in-water (w/o/w) microspheres be equipped on gelatin (GEL)/Poly lactic-glycolic acid (PLGA)/attapulgite (ATP) scaffold.Methods: In this study, TPTD microspheres were prepared by the water-in-oil-in-water (w/o/w) double emulsion technique and GEL/PLGA/ATP composite scaffolds with different setups were prepared by salt leaching method. Both microspheres and scaffolds underwent physicochemical characterization. Mouse bone mesenchymal stem cells (BMSCs) were co-cultured with extracts from the microspheres and scaffolds to evaluate cell proliferation and osteogenesis. Four weeks post-implantation, the effectiveness of the scaffolds containing microspheres for repairing skull defects in mice was assessed.Results: Both TPTD microspheres and the GEL/PLGA/ATP scaffold significantly enhanced the proliferation and osteogenic differentiation of BMSCs. Markers of osteoblast activity, including COL1, RUNX2, OCN, and OPN, were markedly up-regulated. Further, micro-CT, histological, and immunohistochemical analyses revealed extensive new bone formation on the scaffold.Conclusion: The GEL/PLGA/ATP composite scaffold, equipped with TPTD microspheres, demonstrates significant potential for use in bone tissue engineering, providing an effective option for bone regeneration and repair in clinical applications. Keywords: teriparatide, microsphere, gelatin, PLGA, attapulgite, bone tissue engineering, bone defect, bone regeneration

Liqiu Chen,1,2,&ast; Ran Zhang,1,2,&ast; Jing Xiao,1,2,&ast; Ying Liang,1,2 Zhen Lan,3 Yingao Fan,2 Xi Yu,2 Shengnan Xia,2– 5 Haiyan Yang,2– 5 Xinyu Bao,2– 5 Hailan Meng,1– 6 Yun Xu,1– 6 Linjie Yu,1– 6 Xiaolei Zhu1– 6 1Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 2Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of China; 3Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 4State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, 210008, People’s Republic of China; 5Jiangsu Provincial Key Discipline of Neurology, Nanjing, 210008, People’s Republic of China; 6Nanjing Neurology Medical Center, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linjie Yu; Xiaolei Zhu, Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China, Email yulinjie126@126.com; zhuquelee@126.comObjective: To explore the neuroprotective effect of Eugenol Acetate (EA) on post-stroke neuroinflammation and investigate the underlying mechanisms.Methods: For in vitro experiments, primary microglia were pre-incubated with EA for 2 hours, followed by lipopolysaccharide (LPS) stimulation for 24 hours or Oxygen-Glucose Deprivation (OGD) treatment for 4 hours. Real-time quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to examine the expression levels of inflammatory cytokines in primary microglia. The activation of NF-κB signaling pathway was evaluated by immunofluorescence staining and Western blot. For in vivo experiments, middle cerebral artery occlusion (MCAO) was constructed to mimic ischemic brain injury on 8-week-old male C57BL/6J mice. The mice were continuously injected intraperitoneally with EA or vehicle after MCAO. Neurobehavioral tests and TTC staining were conducted to estimate the neurological deficits and infarct area. Moreover, the white matter integrity after MCAO was observed via immunofluorescence staining.Results: EA significantly reduced the expression of pro-inflammatory cytokines in LPS or OGD treated primary microglia, and inhibited LPS-induced activation of the NF-κB signaling pathway. In addition, EA alleviated ischemic brain injury and improved neuromotor function of MCAO mice. Furthermore, long-term neurological deficits and white matter integrity were improved by EA treatment after MCAO.Conclusion: EA alleviated ischemic injury and restored white matter integrity in MCAO mice, which might be associated with the inhibition of NF-κB signaling pathway in microglia. Therefore, EA might be a promising candidate for the treatment of ischemic stroke.Keywords: Eugenol Acetate, Ischemic Stroke, Neuroinflammation, NF-κB Signaling Pathway

Yuer Li,1 Shaobo Ge,1 Jin Liu,1 Rui Li,1 Rui Zhang,1 Juan Wang,2 Jianli Pan,3 Qiuhong Zhang,1 Jie Zhang,1 Ming Zhang1 1Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Ultrasound, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Special Need, Xi’an Children’s Hospital, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Ming Zhang, Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 West Fifth Road, Xi’an, Shaanxi, 710004, People’s Republic of China, Email zhangmingdr@163.comBackground: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and systemic inflammation. The peripheral blood (neutrophil + monocyte)/lymphocyte ratio (NMLR) can predict the clinical outcomes of several inflammatory diseases. However, its prognostic value in COPD remains unknown.Methods: This retrospective study included 870 patients with COPD due to acute exacerbation, and the 5-year all-cause mortality of these patients was recorded. The Kaplan-Meier method was used to compare the mortality risk of these patients according to their NMLR value. Multivariable COX hazard regression and restricted cubic spline model were used to assess the relationship between the NMLR and 5-year all-cause mortality of patients with COPD.Results: The NMLR values of non-surviving patients with COPD were significantly increased compared to the survivors [3.88 (2.53– 7.17) vs 2.95 (2.08– 4.89), P=0.000]. The area under the NMLR receiver operating characteristic curve for predicting the 5-year all-cause mortality of COPD patients was 0.63. Kaplan-Meier survival curves showed that the 5-year all-cause mortality of COPD patients was significantly increased when the admission peripheral blood NMLR was ≥ 5.90 (27.3% vs 12.4%, P=0.000). The COX regression model showed that NMLR was an independent predictor of 5-year all-cause mortality in COPD patients (hazard ratio=1.84, 95% confidence interval: 1.28– 2.64, P=0.001). Moreover, the restricted cubic spline model showed a non-linear relationship between NMLR and COPD death risk (Pnon-linear < 0.05).Conclusion: The admission peripheral blood NMLR is a significant predictor of 5-year all-cause mortality in patients with COPD, and high NMLR values may indicate a poor clinical prognosis.Keywords: chronic obstructive pulmonary disease, neutrophil, monocyte, lymphocyte, inflammation, prognosis

Rong Zhang,&ast; Wenjuan Zhang,&ast; Qiuhua Zhang,&ast; Lijun Wang, Fengzhu Yang, Wenlong Sun, Zhengbao Xu, Chao Wang, Xinhua Song, Meng Wang School of Life Science and Medicine, Shandong University of Technology, Zibo, 255000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meng Wang, Email wm902012@163.comPurpose: This study aimed to synthesize curcumin-modified selenium (Cur/Se) nanoparticles via a simple and green method for tumour treatment and explore their effects on the gut microbiota.Methods: Curcumin was applied as a reducing and capping agent for the construction of Cur/Se nanoparticles with Tween 80 as a stabilizer. The drug release behaviour and DPPH and ABTS radical scavenging activities of the Cur/Se nanoparticles were detected. MTT and CCK8 assays were used to evaluate the cytotoxicity against HeLa and S180 tumour cells. The cellular distribution, uptake and reactive oxygen species (ROS) levels were detected. In vivo anti-S180 tumour activity was studied by oral administration. 16S rRNA Illumina high-throughput sequencing technology was used to analyse the gut microbiota in ileocecal faeces.Results: Nanoparticles with good water dispersibility and a size of 6.86 nm were obtained. The characteristic peaks of curcumin were observed in the UV and FTIR spectra of the Cur/Se nanoparticles. Curcumin release from the Cur/Se nanoparticles occurred in a pH-dependent and sustained manner at 48 h. The Cur/Se nanoparticles presented significantly higher DPPH and ABTS radical scavenging rates than the same concentration of free curcumin. At 48 h, the Cur/Se nanoparticles showed higher cytotoxicity against HeLa and S180 tumour cells. The results of the cellular uptake experiments revealed that the Cur/Se nanoparticles significantly delivered more curcumin into the HeLa tumour cells and induced greater ROS production. In vivo, the Cur/Se nanoparticles significantly inhibited S180 tumours, with a 54.33% tumour inhibitory rate. Cur and Cur/Se nanoparticles significantly reduced the relative abundances of Rikenellaceae_RC9_gut_group, Enterorhabdus and Bilophila and increased the relative abundance of Lachnospiraceae_UCG-006. Moreover, Cur/Se nanoparticle treatment significantly improved the relative abundance of Limosilactobacillus compared with that in the curcumin group.Conclusion: Cur/Se nanoparticles could increase the bioactivity of curcumin and improve cancer therapy by regulating the gut microbiota.Keywords: curcumin, nanodelivery system, chemotherapy, ROS, gut microbiota

Ruo Zhang, Yang Jiao, Yuchao Wu, Lijing Yan, Chunhong Zhang, Jing Xu On behalf of the China National Diabetic Chronic Complications Study GroupDepartment of Endocrinology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Yang Jiao; Jing Xu, Department of Endocrinology, The Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi Province, 710004, People’s Republic of China, Tel +86 15029930210; +86 18092746638, Fax +862986320305, Email jyjoan@126.com; xujingjdefy85@163.comPurpose: This study aimed to explore the association of globulin and albumin-to-globulin ratio (AGR) with diabetic kidney disease (DKD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Methods: This study used data from the China National Diabetic Chronic Complications Study in Shaanxi Province. From April to May 2019, T2DM patients at disease surveillance sites in Shaanxi Province were investigated using a stratified multi-stage sampling method. The participants completed questionnaire surveys, anthropometric and blood pressure measurements, laboratory tests, and fundus photograph examinations. Multivariate Logistic regression and restricted cubic spline model were used to analyze the association of globulin and AGR with DKD and DR, and subgroup analysis was performed according to age, sex, and diabetes duration to test the stability of the results.Results: A total of 1494 T2DM patients were enrolled in this study, including 495 patients with DKD (33.1%) and 341 patients with DR (22.8%). After adjusting for all covariates, globulin and AGR were linearly associated with DKD. For every 1g/L increase in globulin level, the risk of DKD increased by 7% (OR=1.07, 95% CI=1.04, 1.10). For every 1 unit increase in AGR, the risk of DKD was reduced by 55% (OR=0.45, 95% CI=0.28, 0.72). Subgroup analysis showed that the association between globulin and DKD was consistent across all subgroups, and the association between AGR and DKD was consistent across subgroups of age and diabetes duration; however, only in males, higher AGR was associated with a reduced risk of DKD. No association was found between globulin and AGR with DR.Conclusion: Globulin is an independent risk factor and AGR is an independent protective factor for DKD. Screening for DKD should be performed in T2DM patients with high globulin and low AGR levels, especially in men.Keywords: globulin, albumin-to-globulin ratio, diabetic kidney disease, diabetic retinopathy

Jinrong Liu,&ast; Jin Qi,&ast; Jiadi Li,&ast; Tong Zhang, Jianing Ren, Zheyuan Zhang, Xiao Ning, Ran Zhang, Xiaoming Liu, Bing Li, Xiuping Wu Shanxi Medical University School and Hospital of Stomatology; Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, Shanxi, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Li; Xiuping Wu, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email libing-1975@163.com; wxp1666@sxmu.edu.cnPurpose: During fixed orthodontic treatment, oral hygiene is difficult to ensure and can easily lead to an imbalance in the oral micro-ecological balance. In this study, based on the adhesive properties of polydopamine (PDA) and the good antimicrobial and remineralization properties of carboxymethyl chitosan (CMC) and xylitol (Xy), new nanocomposites with both antimicrobial and remineralization capabilities were prepared to coat on orthodontic brackets.Methods: Composite carbon dots (CDs) were synthesized using carboxymethyl chitosan and xylitol, we characterized them and the antimicrobial properties of the CMC-Xy-CDs were investigated by co-cultivation with S. mutans in vitro and in vivo. The composite coating was then adhered to the brackets. After the characterization measurements, antibacterial properties against S. mutans and the ability to promote remineralization of isolated teeth were investigated.Results: Biological studies demonstrated that L929 cells co-cultured with CMC-Xy-CDs did not observe significant cytotoxicity and CMC-Xy-CDs have good biocompatibility. In the adhesive action of PDA, various characterizations have proved that CDs are modified on the brackets surface. In the antibacterial experiment, CMC-Xy-CDs and the adhesive coating on the brackets were found to have better antibacterial performance than the control group, with an antibacterial rate of up to 80%. In the animal experiment, the results of CMC-Xy-CDs promoting the healing of S. mutans infection wound models showed that there was a significant difference at 7d (P < 0.001), indicating that the experimental group had good antibacterial effects. The SEM of teeth after CMC-Xy-CDs promoted remineralization showed that the structure of the tooth surface became dense and some precipitation appeared, and the surface hardness measurement was significantly increased (p< 0.0001).Conclusion: Our study revealed that new nanocomposites with both antimicrobial and remineralization capabilities coated on orthodontic brackets provide a good basis for future clinical applications.Keywords: carbon dots, coating, antibacterial, remineralization, orthodontic brackets

Mengqi Wang,1,&ast; Shuting Lan,2,&ast; Mingjun Song,3 Rongrong Zhang,2 Wenqi Zhang,2 Xiaomei Sun,2 Gang Liu2 1College of Life Science and Oceanography, Weifang University, Weifang, Shandong, People’s Republic of China; 2Key Laboratory of Medical Cell Biology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 3College of Chemical Engineering and Environmental Chemistry, Weifang University, Weifang, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengqi Wang; Gang Liu, Email wangmengqi@tju.edu.cn; 20190043@immu.edu.cnIntroduction: The anti-cancer properties of zinc oxide-doped carbon dots (CDs/ZnO) in inhibiting triple-negative breast cancer (TNBC) progression merit more investigation.Methods: With citric acid as the carbon source, urea applied as the nitrogen source, and zinc oxide (ZnO) used as a reactive dopant, CDs/ZnO were synthesized by microwave heating in the current study, followed by the characterization and biocompatibility assessments. Subsequently, the anti-cancer capabilities of CDs/ZnO against TNBC progression were evaluated by various biochemical and molecular techniques, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, metabolome, and transcriptome assays of MDA-MB-231 cells. Additionally, the in vivo anti-cancer potentials of CDs/ZnO against TNBC progression were analyzed using TNBC xenograft mouse models.Results: The biocompatibility of CDs/ZnO was supported by the non-significant changes in the pathological and physiological parameters in the CDs/ZnO treated mice, alongside a non-cytotoxic effect of CDs/ZnO on the proliferation of normal cells. Notably, the CDs/ZnO treatments effectively decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells. Furthermore, the CDs/ZnO treatments induced cell cycle arrest, apoptosis, redox imbalance, metabolome disturbances, and transcriptomic alterations of MDA-MB-231 cells by regulating the MAPK signaling pathway. Additionally, the CDs/ZnO treatments markedly suppressed the in vivo tumor growth in the TNBC xenograft mouse models.Conclusion: In this study, we synthesized CDs/ZnO via microwave heating, using citric acid as the carbon source, urea as the nitrogen source, and ZnO as a reactive dopant. We confirmed the biosafety and potent anti-cancer efficacy of CDs/ZnO in inhibiting TNBC progression by disrupting malignant cell behaviors through modulation of the MAPK signaling pathway.Keywords: zinc, carbon dots, triple-negative breast cancer, MAPK signaling pathway

Ying Chen,1 Jiahua Pan,2 Yan Zhong,3 Bin Wu,1 Mengxia Yan,4 Ruiyun Zhang2 1Clinical Research Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200000, People’s Republic of China; 2Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200000, People’s Republic of China; 3China Association for Promotion of Health Science and Technology, Beijing, 100000, People’s Republic of China; 4Department of Pharmacy, Ningbo Hangzhou Bay Hospital, Ningbo, 315000, People’s Republic of ChinaCorrespondence: Ruiyun Zhang, Email 19610@renji.comObjective: Prostate Cancer can be treated with various formulations of Gonadotropin-Releasing Hormone Agonists (GnRHa), but cost analyses of these treatments in China are lacking. This study aims to evaluate the differences in cost and resource utilization between various formulations of GnRHa for Prostate Cancer by conducting a resource utilization assessment and cost minimization analysis.Methods: From the perspective of society and medical healthcare, this study used the cost minimization model to generate cost and resource estimates for GnRHa drug acquisition and administration for “Current practice” and for a “Base case” scenario. In the “Base case” scenario, all of the patients who were receiving 1-monthly or 3-monthly GnRHa therapy in “Current practice” switched to a 6-monthly formulation triptorelin. Cost/Resource estimates were calculated per patient per administration and scaled to annualized population levels. Deterministic sensitivity analysis was conducted to explore the uncertainty of the model variables and applied assumptions.Results: From a societal perspective, if all 1-monthly and 3-monthly formulations of GnRHa were switched to a 6-monthly formulation triptorelin, it is conservatively estimated that the annual societal cost could be reduced by ¥ 13,382,951.13, with an average annual cost savings of ¥ 46.53 per patient. Additionally, the 6-monthly formulation could save 3,608,973.91 hours annually, translating to an average time savings of 12.55 hours per patient, reducing treatment time by 78%. From a healthcare system perspective, if the introduction of the 6-monthly formulation of GnRHa is delayed, it would lead to an annual increase of ¥ 94 million in medical costs, and require an additional 64,445.96 working days for doctors and nurses. Deterministic sensitivity analysis demonstrated the model’s robustness, showing the 6-monthly GnRHa remains cost-effective across various parameter changes, with drug price being the most influential factor.Conclusion: Compared to current 1-monthly and 3-monthly formulations, the 6-monthly GnRHa can reduce the total burden associated with prostate cancer treatment.Keywords: triptorelin, prostate cancer, cost-minimization, budget impact

Hong Zeng,1,2,&ast; Xitong Geng,2,&ast; Hao Wan,3,&ast; Xiaoyu Qu,2 Shengwei Tang,2 Ruiyu Zhang,3 Minqin Zhou,2 Zichuan Yu,2 Jingying Pan,3 Hao Zheng,2 Yanting Zhu,2 Shuhan Huang,2 Da Huang1 1Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 3First College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, 1 minde Road, Nanchang, Jiangxi Province, 330000, People’s Republic of China, Email danmo0904@163.comBackground: The ubiquitin-proteasome system (UPS) is vital for protein quality control and its dysregulation is linked to diseases, including cancer. Targeting the UPS is becoming a promising approach in cancer therapy. However, the role of UPS modulation in thyroid carcinoma (THCA) remains to be fully elucidated.Methods: Initially, we utilized data from The Cancer Genome Atlas (TCGA) database to employ weighted gene co-expression network analysis (WGCNA) with LASSO regression to develop a prognostic model for core UPS genes implicated in THCA. Subsequently, we stratified the THCA training set into two distinct subtypes based on ubiquitin-proteasome system prognostic model score (UPS-PMS) characteristics. Key genes within the model were then subjected to functional analysis, immunotherapy evaluation, and drug sensitivity studies.Results: We delineated a prognostic model of the UPS comprising six genes, which we subsequently demonstrated was capable of forecasting patient prognosis. Moreover, our findings indicated a substantial correlation between UPS-PMS and immune microenvironmental factors, notably a negative correlation with myeloid immune cells and a potential influence on the Th1 to Th2 cells ratio. Especially, we observed a significant association between high UPS-PMS and an immunosuppressive microenvironment. Then, we elucidated the biological distinctions among various THCA sample subtypes, highlighting that the cluster_1 subtype is associated with an unfavorable prognosis. Of note, KCNA1 was identified as a pivotal prognostic gene within the UPS-PMS framework. We constructed a three-tiered regulatory network centered on KCNA1-related competing endogenous RNA (ceRNA). Furthermore, our results suggested that KCNA1 has potential as a target for immunotherapeutic strategies. Concurrently, drug sensitivity analyses demonstrated that high KCNA1 expression promoted gemcitabine resistance in patients, while KCNA1 knockdown increased sensitivity to gemcitabine.Conclusion: In conclusion, we developed a novel UPS-based prognostic model for THCA, identified key gene KCNA1, and assessed immunotherapy and drug sensitivity, revealing new therapeutic targets.Keywords: ubiquitin-proteasome system, thyroid carcinoma, prognostic model, immune microenvironment, drug sensitivity

Lina Wang,1 Jiang Liu,1 Yafang Guo,1 Meiling Zhao,1 Bozheng Zhang,2 Junyan Zhang,3 Ruijuan Zhang1 1Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pediatrics, College of Arts and Sciences, Emory University, Atlanta, GA, USA; 3Department of Clinical Epidemiology and Evidence-Based Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Ruijuan Zhang; Junyan Zhang, Email 13593169668@163.com; richard.zhang@both-win.netPurpose: To investigate the outcomes and risk factors for patients with hematologic malignancies (HM) following late-stage SARS-CoV-2 infection.Background: Patients with HM such as lymphoproliferative malignancies (including acute lymphoblastic leukemia and multiple myeloma) and myeloproliferative malignancies (including acute myeloid leukemia, myeloproliferative neoplasm, and myelodysplastic syndrome) are at increased risk of severe illness and high mortality from COVID-19. This study examines the impact of SARS-CoV-2 infection severity on HM prognosis during the late phase of COVID-19, using data from 203 patients at Shanxi Bethune Hospital.Methods: This is a retrospective cohort study. Data was collected from hospitalized HM patients at a single center from December 1, 2023, to December 31, 2023. The primary outcome was overall survival (OS). Multivariable Cox regression was used to identify risk factors.Results: This analysis includes data from 203 hospitalized patients with HM aged 36 to 67 years (median, 58 years). SARS-CoV-2 infection was observed in 42.86% (87/203) of the patients, among whom severe/critical cases accounted for 14.29% (29/203). Multivariable Cox regression shows active disease (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.00– 4.64, p = 0.049), hematopoietic stem cell transplantation (HSCT) (HR 4.06, 95% CI 1.02– 16.12, p = 0.047), and targeted therapy (HR 2.60, 95% CI 1.23– 5.50, p = 0.012) were associated with a higher incidence of progression. In contrast, individuals whose platelets count ≥ 50× 109/L at baseline (HR = 0.36, 95% CI 0.17– 0.78, p = 0.009) and ferritin levels less than 500 μg/L (HR = 0.54, 95% CI 0.34– 0.86, p = 0.010) were associated with a lower incidence of progression. Active status (HR 7.06, 95% CI 2.10– 23.76, p = 0.002), HSCT (HR 7.17, 95% CI 1.10– 46.63, p = 0.039), and severe/critical SARS-CoV-2 infection in HM patients (HR 11.98, 95% CI 2.57– 55.82, p = 0.002) were associated with higher incidences of all cause of mortality. While a higher platelet level (≥ 50× 109/L) was linked to a lower mortality (HR 0.16, 95% CI 0.05– 0.49, p = 0.002).Conclusion: In the late stage of the COVID-19 pandemic, active disease status, recent HSCT, and severe/critical SARS-CoV-2 infection significantly increased the risks of disease progression and mortality in HM patients. Higher baseline platelet counts were associated with improved outcomes.Keywords: late stage of COVID-19, hematologic malignancies, progression-free survival, overall survival

Runcong Zhang,1,2,&ast; Jing Fan,1,2,&ast; Lu Han,3,4,&ast; Juehui Mao,4,5 Liang Sun,1,2 Yuetian Yu,2,6,7 Weibin Fan,1,2 Jiao Xie,2,8 Bin Lin,1,2,7 Nengming Lin1,2,9 1Department of Pharmacy, Changxing People’s Hospital, Changxing, People’s Republic of China; 2Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou, Changxing, People’s Republic of China; 3School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 6Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 7Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou, People’s Republic of China; 8Department of Pharmacy, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 9Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Lin, Department of Pharmacy, Changxing People’s Hospital, Changxing, 313100, People’s Republic of China, Tel/Fax +86-572-6267652, Email lb_wzmc@126.com Nengming Lin, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, 310006, People’s Republic of China, Tel/Fax +86-572- 56007905, Email lnm1013@zju.edu.cnPurpose: Nirmatrelvir/ritonavir (N/R) is the first drug to receive emergency authorization for the treatment of COVID-19 infection. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of potential covariates and explore dosing regimen.Patients and Methods: Sparse data of serum concentrations of N/R were obtained from 129 patients with COVID-19 infection receiving oral 300/100 mg N/R twice daily for 5 days. Plasma samples were assayed using ultra-high-performance liquid chromatography–tandem mass spectrometry. The PopPK model was developed using a nonlinear mixed effects approach utilizing the NONMEM 7.4 software. Monte Carlo simulation was conducted to optimize the dosage regimen.Results: A one-compartment model with first-order absorption and first-order elimination provided the best fit for the data. Allometric scaling of parameters on creatinine clearance (CrCl) and body weight were identified as covariates that significantly influenced exposure-efficacy after oral administration of nirmatrelvir. Monte Carlo simulation using the final model generated concentration-time profiles for virtual patients (1,000 per group) with varying renal functions and body weight. Furthermore, we developed a web-based dashboard to visualize the dynamic changes in nirmatrelvir concentration and provide individualized dosage regimens.Conclusion: This study showed that dosing regimen optimization of nirmatrelvir should be based on CrCl and body weight. Moreover, a web-based dashboard has been developed to facilitate individualized pharmacotherapy.Keywords: population pharmacokinetics, nirmatrelvir, COVID-19, simulations, dosing regimen

Hong Chen,&ast; Xie Wang,&ast; Nian Peng, Yue Pu, Hao Ye, Yu Gui, Rui Zhang, Juan Zhang Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Zhang, Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, People’s Republic of China, Email zhangdoumi2019@163.comBackground: Wilson’s disease (WD) is a hereditary disorder characterized by an abnormality in copper metabolism. Liver fibrosis, and potentially cirrhosis, induced by copper accumulation are critical factors in the pathogenesis of WD. CircRNAs exhibit high stability and play crucial roles in numerous biological processes.Methods: RNA-seq technology was employed to conduct transcriptome sequencing of the liver from 12 homozygous (TX) mice in the model group (NL group) and 12 wild-type (WT) mice in the control group (N group). Differentially expressed circular RNAs (DE-circRNAs) were identified, and following GO and KEGG analysis, a competitive endogenous RNA (ceRNA) regulatory network was constructed. The identified DE-circRNAs were then randomly validated using RT-qPCR.Results: Utilizing RNA sequencing (RNA-seq), the study identified 54 DE-circRNAs in TX-j mice with WD-induced liver fibrosis model, among which 19 were up-regulated and 35 were down-regulated. GO analysis revealed multiple biological processes, including single-organism process, cellular process, and metabolic process. Further pathway identification using KEGG implicated several pathways, including the HIF-1, PI3K-Akt, AMPK, FoxO, signaling pathway regulating pluripotency of stem cells, phospholipase D, mTOR, Ras, cGMP-PKG, and MAPK signaling pathway, among others. A ceRNA regulatory network was constructed with 20 circRNAs, 7 miRNAs, and 75 mRNAs as crucial core components. Additionally, RT-qPCR validation was performed on randomly selected DE-circRNAs, yielding consistent results (P< 0.05).Conclusion: The findings provide a significant molecular biology foundation for understanding the pathogenesis of liver fibrosis in WD and offer new insights for exploring potential diagnostic and therapeutic targets.Keywords: circRNA, circRNA-miRNA-mRNA, ceRNA, Wilson’s disease, liver fibrosis

Wenqin Liu,1 Shuyan Qian,1 Yihan Hu,2 Ruo Zhang3 1DSA Center, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 3Nurse Practitioner, Nursing Department, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Ruo Zhang, Email zr2005zr@163.comBackground: Coronary heart disease (CHD) is a significant public health concern affecting an increasing number of young and middle-aged adults. Effective self-management is essential to promote the recovery and quality of life of patients with CHD after percutaneous coronary intervention (PCI), and is closely related to health literacy. However, little is known about the underlying mechanisms of this association.Objective: This study aimed to investigate the mediating effects of social support and self-efficacy in the relationship between health literacy and self-management behaviors among young and middle-aged patients with CHD after PCI.Methods: A cross-sectional study was conducted among 360 CHD patients aged 18– 59 who after PCI within 1 to 3 months. The data were collected from September 2022 to July 2023 in a tertiary hospital in China. The questionnaires were utilized to gather data on demographic characteristics, social support, self-efficacy, health literacy, and self-management behaviors. The serial mediation model was examined via bootstrapping techniques using SPSS PROCESS v.4.3 macros (Model 6).Results: Participants health literacy was associated with self-management behaviors both directly (β=0.334, P< 0.001) and indirectly through social support (β=0.149, P< 0.001) and self-efficacy (β=0.095, P< 0.001). Social support and self-efficacy serially mediated the association between health literacy and self-management behaviors (β=0.226, P< 0.001), with the total indirect effects accounting for 44.3%, these three mediating paths account for 24.8%, 15.8%, and 3.7% of the overall effect, respectively.Conclusion: Health literacy influences self-management behaviors that the study’s findings suggest were significant. Social support and self-efficacy act as mediators in the relationship between health literacy and self-management behaviors. Our findings provide helpful guidance for the future development of targeted and effective psychosocial interventions to enhance CHD patients’ self-management, ultimately improving prognosis and quality of life.Keywords: young and middle-age, health literacy, self-management behaviors, social support, self-efficacy, serial mediation

Qing Gao,1,&ast; Shang Gao,2,3,&ast; Haiyang Li,1,&ast; Zuoguan Chen,2 Ran Zhang,2 Yongjun Li,2 Hongjia Zhang1 1Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Vascular Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongjun Li; Hongjia Zhang, Email liyongjun4679@bjhmoh.cn; zhanghongjia722@ccmu.edu.cnIntroduction: Takayasu arteritis (TAK) is an autoimmune disease affecting the aorta and its branches. Despite anti-inflammatory treatments, some patients require surgical vascular reconstruction due to rapid disease progression. The mechanisms behind persistent inflammation are unclear due to a lack of arterial samples. This study explores ferroptosis in TAK using high-throughput and single-cell transcriptomics.Methods: Transcriptomic data were collected from 8 TAK patients (2 for single cell RNA-seq and 6 for bulk RNA-seq) and 8 renal transplant donors, with single-cell data from 3 public carotid artery samples for control. Bioinformatic analysis was performed to identify ferroptosis-related genes in inflamed arteries.Results: We identified 1526 differentially expressed genes and 46 ferroptosis-related genes, with 6 genes including PTGS2 and HIF1A as hub genes. Single-cell analysis of 27,828 cells revealed increased M1-like macrophages, with PTGS2 highly expressed in these cells. Enrichment analysis indicated NF-κB signal pathway involvement.Conclusion: PTGS2 is a core ferroptosis-related gene in TAK vascular inflammation, highly expressed in M1-like macrophages, potentially upregulated via the IL1B-NF-κB pathway.Keywords: Takayasu arteritis, single-cell RNA sequencing, bulk RNA sequencing, ferroptosis, PTGS2

Zhiyuan You,1 Jialin Zhang,1 Yifeng Xu,1 Junhong Lu,1 Renling Zhang,2 Zhujing Zhu,3 Yiqin Wang,1 Yiming Hao1 1Shanghai Key Laboratory of Health Identification and Assessment/Laboratory of TCM Four Diagnostic Information, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Gastroenterology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Rheumatology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Yiming Hao, Email hymjj888@163.comObjective: This study aimed to establish a model for identifying chronic gastritis with the traditional Chinese medicine damp phlegm pattern by examining metabolite changes in the tongue coating of patients. It also explored the role of metabolic pathways in the pathogenesis of this condition.Methods: This cross-sectional study involved 300 patients diagnosed with chronic gastritis. Of these, 200 patients exhibited the damp phlegm pattern, while 100 did not. Metabolomic methods employing GC-TOF-MS and UHPLC-QE-MS were utilized to identify various metabolites in the tongue coating of patients. An identification model for chronic gastritis with the damp phlegm pattern was created based on ROC curves derived from differential biomarkers. Additionally, 50 samples not included in model construction were collected for external validation.Results: Comparison of the damp phlegm pattern group with the non-damp phlegm pattern group revealed a total of 116 differential metabolites. Among these, lipids and lipid-like compounds were most abundant, comprising 27 types, which included four lipid metabolites related to sphingomyelin metabolism. The ROC model, which included phenol, 2.6-diaminoheptanedioic acid, and N-hexadecanoyl pyrrolidine, demonstrated the highest accuracy, with accuracy, sensitivity, and specificity metrics of 94.0%, 91.0%, and 87.0%, respectively. Furthermore, external validation using tongue coating metabolites from 50 patients revealed accuracy, sensitivity, and specificity in the validation set of 93.9%, 90.6%, and 83.3%, respectively.Conclusion: Differential metabolites between patients with the damp phlegm pattern and those without are primarily lipids and lipid-like compounds. N-hexadecanoyl pyrrolidine, phenol, and 2.6-diaminoheptanedioic acid may serve as potential biomarkers for chronic gastritis characterized by the damp phlegm pattern.Keywords: chronic gastritis, damp phlegm pattern, tongue coating, metabolomics, biomarkers

Ran Li,1,2,&ast; Yanwei Li,1,2,&ast; Zijian Song,1,2 Yixuan Gu,1,2 Xiaofeng Jiao,1,2 Chaoqiong Wan,1,2 Tiantian Liu,1,2 Rongrong Zhang,1,2 Ruifang Gao,1,2 Xiangyu Wang1,2 1Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ran Li; Xiangyu Wang, Email lraner@163.com; wangxiangyu76@163.comPurpose: Chemotherapy is one of the most commonly used treatments for oral squamous cell carcinoma (OSCC), but its use is limited by drug resistance and severe systemic toxicity. To eliminate these side effects and improve anti-tumor efficacy, several therapeutic approaches have been developed for use with chemotherapy. In this study, we developed a graphene-based lipid modulation nanoplatform (NSD) that carries SB-204990, a small molecule inhibitor specific for ATP citrate lyase (ACLY), and doxorubicin (DOX), a chemotherapeutic agent, and the trio enables synergistic treatment of OSCC with lipid starvation, chemotherapy, and photothermal therapy.Methods: We first determined whether ACLY expression was upregulated in OSCC, and then assessed the growth inhibitory effects of SB-204990 on SCC-15 cells and changes in lipid (acetyl coenzyme A, free fatty acids, and cholesterol) levels. We characterized NSD and then evaluated the stability, photothermal properties, drug loading, and release ability of NSD. Finally, the therapeutic effects of NSD on OSCC were investigated by in vitro and in vivo experiments, and the changes in lipid levels in OSCC tissues after ACLY inhibition were further evaluated.Results: The results showed that ACLY was highly expressed in OSCC, and ACLY inhibition produced reproductive suppression and decreased lipid levels in SCC-15 cells. The NSD nanoplatform possessed good stability, photothermal properties, high drug loading capacity and controlled release. In addition, the triple therapy achieved satisfactory anticancer effects in both in vivo and in vitro assays, and the inhibition rate of tumors was as high as 99.4% in the NSD+Laser treatment group.Conclusion: The changes in tumor cell lipid levels and cell proliferation arrest induced by ACLY inhibition suggest that ACLY may be a promising target for lipid starvation therapy and resistance to chemoresistance, and its inhibitors are expected to become new anticancer drugs. The NSD nanocarrier system enables synergistic treatment with lipid starvation, chemotherapy, and photothermal therapy, which represents an innovative approach to combating tumors. Keywords: starvation therapy, ACLY, nanotechnology, chemotherapy resistance, OSCC

Ruixue Zhang,1 Hui Xu,1 Xiaoxue Zhang,1 Hui Xiong,2 Fei Tang,3 Liping Lv,3 Xiangdong Mu,4 Wei Tian,5 Yueguang Cheng,6 JianRong Lu,6 Xiuhong Nie,7 Yang Guo,8 Yingying Liu,9 Zhi Zhang,10 Lianjun Lin1 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Emergency, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Interventional Pulmonology, Anhui Province Chest Hospital, Hefei, People’s Republic of China; 4Department of Respiratory, Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 5Department of Geriatrics, Jishuitan Hospital, Beijing, People’s Republic of China; 6Department of Emergency, Jingmei Group General Hospital, Beijing, People’s Republic of China; 7Department of Respiratory, Xuanwu Hospital, Beijing, People’s Republic of China; 8Department of Endoscopic Diagnosis &treatment, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 9CapitalBio Technology Co., Ltd, Beijing, People’s Republic of China; 10Bio Biological Group Co., Ltd, Beijing, People’s Republic of ChinaCorrespondence: Lianjun Lin, Department of Geriatrics, Peking University First Hospital, No. 8 Xishiku Avenue, Beijing, 100034, People’s Republic of China, Email 06474@pkufh.comPurpose: The detection of pathogenic microorganisms plays a significant role in the diagnosis and management of pneumonia that are responsible for a substantial number of deaths worldwide. However, conventional microbiological tests (CMT) have low accuracy and are time-consuming. In this study, we aim to evaluate the clinical value of Chips for Complicated Infection Detection (CCID) in detecting pneumonia pathogens.Patients and Methods: This study was conducted at nine hospitals in China from January 2021 to September 2022. Respiratory samples from adult pneumonia patients were collected from each patient. CMT and CCID were performed in parallel to identify the pathogens.Results: A total of 245 patients were included, with 73% being elderly. CCID identified pathogenic microbes in 78.0% of patients and conventional microbiological tests (CMT) in 57.1% of the patients (p< 0.001). The overall positive and negative percent agreements between CCID and CMT for pathogen detection were 90.07% and 38.46%, respectively. 38.8% of patients were diagnosed with mixed infections with at least two pathogens by CCID. Bacterial infections identified by CCID accounted for 60.0% of 245 patients, with the top 3 being Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecium, respectively. K. pneumoniae was the most common pathogen in elderly patients, with a significantly higher prevalence compared to non-elderly patients (p = 0.0011). Among the 197 patients who had used antibiotics before sample collection, the positive rate of CCID was significantly higher than that of CMT (p < 0.001).Conclusion: This study indicates that compared to CMT, this novel chip has significant advantages in detecting pathogens in pneumonia patients, especially in the elderly.Keywords: pneumonia, elderly, pathogens, chip, LAMP

Hao Peng,1,2,&ast; Jixue Li,1,&ast; Xiaoru Zhou,1 Zhewen Nong,1 Ruiying Zhang,1 Pei Lu,1 Shasha Ye,1 Liping Lei,3 Chuang Qin,2 Jiangfa Li1,4,5 1Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Liuzhou People’s Hospital, Liuzhou, 545001, People’s Republic of China; 3Department of Geriatric Medicine, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, People’s Republic of China; 5Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuang Qin, Department of Hepatobiliary and Pancreatic Surgery, Liuzhou People’s Hospital, No. 8, Wenchang Road, Central District, Liuzhou, 545001, People’s Republic of China, Email 382944957@qq.com Jiangfa Li, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, No. 15, Lequn Road, Xiufen District, Guilin, Guangxi, 541001, People’s Republic of China, Email 247546160@qq.comObjective: To explore a more effective and practical comprehensive index for differentiating benign from malignant obstructive jaundice by analyzing the clinical data of patients with benign obstructive jaundice (BJ) group and malignant obstructive jaundice (MJ) group.Methods: A retrospective analysis was conducted on the clinical data of 339 patients with obstructive jaundice. The cases were divided into two data sets: training cohort and validation cohort. The cases were divided into two groups: malignant and benign obstructive jaundice group. Logistic regression analysis was used to build a prediction model for judging the nature of obstructive jaundice, and the prediction model was verified using the validation cohort.Results: Multivariate analysis revealed that CEA, TBIL, and NLR were independent factors in malignant obstructive jaundice. A comprehensive index for differentiating benign from malignant obstructive jaundice was established based on these indicators. The sensitivity, specificity, and receiver operating characteristic curve of this model for differentiating benign from malignant obstructive jaundice were 79.57%, 93.26%, and 0.920, respectively.Conclusion: The prediction model based on the comprehensive index of CEA, TBIL, and NLR has a higher accuracy in differentiating malignant obstructive jaundice.Keywords: obstructive jaundice, comprehensive index, differentiation diagnosis

Rui Zhang,1,&ast; Yongjian Mai,1,&ast; Huijing Ye,2,&ast; Xiufen Lian,2 Huasheng Yang,2 Yanling Zhu,1 Xiaoliang Gan1 1Department of Anesthesiology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, People’s Republic of China; 2Department of Orbital Diseases and Ocular Oncology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoliang Gan; Yanling Zhu, Email ganxl@mail.sysu.edu.cn; zhuyling8@mail.sysu.edu.cnBackground and Objectives: Opioid-minimizing strategies are making their appearance in enhanced recovery after surgery. This study is aimed to explore the potential advantages of opioid-free analgesia (OFA) compared to opioid-sparing analgesia (OSA) in patients undergoing orbital fracture reconstruction.Methods: In this prospective, single-center, randomized controlled study, we randomly recruited 122 patients undergoing orbital fracture reconstruction under general anesthesia. Patients received total intravenous anesthesia with a flexible laryngeal mask airway, and multimodal analgesia with either OSA or OFA methods. The OSA group (n = 61) received low doses of fentanyl and nonsteroidal anti-inflammatory drugs (NSAIDs), and the OFA group (n = 61) received medial canthus peribulbar block (MCPB) combined with NSAIDs. The primary outcomes consisted of area-under-the-curve (AUC) of the numerical rating scale (NRS) pain score, and the incidence of postoperative nausea and vomiting (PONV) through the first 24h.Results: Compared to the OSA group, the OFA group demonstrated non-inferiority in postoperative analgesia through the first 24 postoperative hours (difference of the medians, − 6; 95% confidence interval [CI], − 12 to 6), but failed to meet the non-inferiority criterion in the incidence of PONV (difference ratio, 3%; 95% CI, − 7% to 14%). The Quality of Recovery-40 questionnaire (QoR-40) scores on postoperative day 1 was significantly higher in group OFA compared to group OSA (188 [178 to 196] vs 181 [169 to 191], respectively; P = 0.005).Conclusion: In orbital fracture reconstruction, both OFA and OSA strategies provide effective postoperative pain relief, but OFA using MCPB combined NSAIDs enhances the quality of early postoperative recovery.Registered: Chinese Clinical Trial Registry ChiCTR1900028088.Keywords: peribulbar block, opioid-free, opioid-sparing, analgesia, orbital fracture reconstruction

Ou Yang,1 Yuhuan Teng,1 Ruoxi Zhang,2 Jie Qu1 1Department of Cadre Ward, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Department of Cardiology, Harbin Yinghua Hospital, Harbin, Heilongjiang, 150199, People’s Republic of ChinaCorrespondence: Jie Qu; Ruoxi Zhang, Email qj610714@jlu.edu.cn; ruoxizhang8@qq.comIntroduction: Polymer-free sirolimus-eluting stent (PF-SES) possess multiple properties improving targeted drug elution and in-stent reendothelialization without the presence of polymers. The long-term clinical performance comparison between PF-SES and the latest generation polymer-coated sirolimus-eluting stents (SES), particularly regarding intravascular imaging assessment and in the type 2 diabetes mellitus (DM) population, remains unexplored.Methods: We conducted a retrospective study involving 2646 diabetes patients meeting coronary artery disease (CAD) criteria underwent coronary stents in the real-world. All patients were divided into the PF-SES group and the SES group. Optical coherence tomography (OCT) was used to evaluate the imaging characteristics of in-stent reendothelialization. Patient information between the two groups was systematically compared in hospital and at 5-year follow-up.Results: In terms of basic characteristics, the proportion of current smoker and stable angina patients in the PF-SES group was significantly higher than that in the SES group. The PF-SES group exhibited significantly higher rate of left anterior descending (LAD) lesion and more stents per patients compared to the SES group. The value of minimum lumen area (MLA), neointimal area (NA) and neointimal thickness (NT) were higher in the PF-SES group. Additionally, the occurrence rates of heterogeneous, lipid layer, intimal tears, thrombi, and micro-vessels were notably lower in the PF-SES group compared to the SES group. A higher all-cause mortality was observed in the SES cohort.Discussion: PF-SES could effectively improve in-stent reendothelialization in patients with type 2 DM, with positive effects on survival rate and may, therefore, be considered as an alternative treatment option for improving clinical long-term outcomes.Keywords: Polymer-free, polymer-coated, Nano Plus stent, drug-eluting stents, type 2 diabetes mellitus, optical coherence tomography

Yujia Huang,1,2,&ast; Yinan Li,2,&ast; Tong Su,3 Hao Wang,2 Shuyu Xu,2 Jingzhou Xu,2 Siqi Zheng,4 Jing Du,2 Yajing Wang,2 Ruike Zhang,2 Yao Meng,2 Xin Guo,2 Lei Xiao,2 Yunxiang Tang3 1Psychology Department, The Second Naval Hospital of Southern Theater Command, Sanya, People’s Republic of China; 2Department of Medical Psychology, Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 3Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 4Department of Psychology, TongJi University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Xiao; Yunxiang Tang, Email xiaolei0237@163.com; tangyun7633@sina.comObjective: To investigate the effects of sleep quality, sleep deprivation, and napping on facial emotion recognition (FER) accuracy and speed.Methods: This research included a cross-sectional study (102 qualified participants) and a randomized controlled study (26 in the napping group and 24 in the control group). The stimuli for the FER task were obtained from the Chinese Facial Affective Picture System (CFAPS). Four facial expressions (fearful, disgusted, sad, and angry) were used. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale, and Self-Rating Depression Scale were used to measure participants’ sleep quality and psychological conditions. In Study 1, FER ability was compared between good and poor sleepers. In Study 2, all participants were sleep-deprived for one night, and completed the FER task before and after sleep deprivation. After different interventions (ie, napping for one hour, or walking around for ten minutes), the participants completed the third FER task.Results: Study 1: Poor sleepers were able to recognize sad expressions more accurately compared with good sleepers. Study 2: 30-h sleep deprivation had no significant effect on the accuracy (ACC). Napping after sleep deprivation improved the FER ACC of upper-face expressions and marginally significantly improved the FER ACC of disgusted expressions.Conclusion: Better sleep quality was linked to lower FER accuracy, particularly in recognizing sad expressions, while no significant differences in recognition speed were observed. Additionally, 30 hours of sleep deprivation did not affect FER accuracy, but napping after sleep deprivation improved accuracy for upper-face and marginally for disgusted expressions.Keywords: facial emotion recognition, sleep quality, facial features, facial emotion, sleep deprivation, sleep loss

Yijia Guo,1– 3,&ast; Ruyun Zhang,4,&ast; Xinling Gan,5 Erli Wang,6 Shuihua Lu,7 Hui Jiang,3 Hongfei Duan,8 Zhengzhou Yuan,9 Weimin Li,2,3,10 Yong Liu1 1Department of Neurology, Chengdu Medical College, The First Affiliated Hospital, Chengdu, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Radiology, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 7National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 8Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 9Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 10National Tuberculosis Clinical Laboratory of China, Beijing Key Laboratory in Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this work as first authorsCorrespondence: Yong Liu, Chengdu Medical College, The First Affiliated Hospital, No. 278, Middle Section, Baoguang Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Email 410578100@qq.comBackground: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.Keywords: tuberculous meningitis, systemic inflammation, neurological outcome

Huabin Wang,1– 4 Rui Zhang,1,3,4 Jing Xu,1,3,4 Min Zhang,1,3,4 Xueyun Ren,1,3,4 Yuhui Wu5 1Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People’s Republic of China; 2Postdoctoral Mobile Station, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Jining Key Laboratory for Prevention and Treatment of Severe Infection in Children, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China; 4Shandong Provincial Key Medical and Health Discipline of Pediatric Internal Medicine, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China; 5Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xueyun Ren; Yuhui Wu, Email renxueyun2006@163.com; wyuhoo@163.comObjective: Identifying high-risk children with poor prognoses during the early stages of sepsis and providing timely and appropriate interventions are imperative. The objective of this study was to develop a prognostic prediction model for pediatric sepsis utilizing the neutrophil to lymphocyte and platelet ratio (NLPR).Methods: A multivariable logistic regression analysis was conducted to investigate the association between the NLPR and in-hospital mortality among septic children upon admission. To minimize the potential confounding factors that could introduce bias, a propensity score matching analysis was employed. Subsequently, a nomogram prediction model was developed to assess the risk of in-hospital mortality in septic children, incorporating the NLPR as a key factor. The performance of this prediction model was then evaluated.Results: A total of 230 septic children were enrolled in the study. Multivariate logistic regression analysis revealed that the NLPR was an independent risk factor for in-hospital mortality, with an odds ratio of 8.31 (95% CI 3.69– 18.68). The finding remained consistent after propensity score matching analysis. A nomogram prediction model was developed that incorporates the NLPR, arterial blood lactate level, and Pediatric Critical Illness Score (PCIS). Among the various models, this nomogram exhibited the highest area under the curve (AUC) value of 0.831. The calibration curve demonstrated good agreement between the predicted and observed outcomes. Decision curve analysis indicated that the prediction model outperformed the PCIS. Internal validation of the model yielded an AUC value of 0.824 and a kappa value of 0.420, indicating its reliability and accuracy.Conclusion: The NLPR serves as an independent risk factor for in-hospital mortality among septic children. The nomogram prognostic prediction model could effectively guide clinicians in accurately predicting the prognosis of septic children, thus enabling timely and effective treatment interventions.Keywords: pediatric sepsis, NLPR, prognosis, clinical prediction model

Junshuang Guo,1,2 Ruike Zhang,1 Ruirui Dong,1 Fan Yang,1 Yating Wang,1 Wang Miao1 1Neuro-Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Department of Immunology, School of Basic Medical Science, Central South University, Changsha City, Hunan Province, People’s Republic of ChinaCorrespondence: Wang Miao, Neuro-Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450000, People’s Republic of China, Email miaowang7211@126.comBackground: Machine learning (ML) is increasingly used in medical predictive modeling, but there are no studies applying ML to predict prognosis in Guillain-Barré syndrome (GBS).Materials and Methods: The medical records of 223 patients with GBS were analyzed to construct predictive models that affect patient prognosis. Least Absolute Shrinkage and Selection Operator (LASSO) was used to filter the variables. Decision Trees (DT), Random Forest (RF), Extreme Gradient Boosting (XGBoost), k-nearest Neighbour (KNN), Naive Bayes (NB), Neural Network (NN). Light Gradient Boosting Machine (LGBM) and Logistic Regression (LR) were used to construct predictive models. Clinical data from 55 GBS patients were used to validate the model. SHapley additive explanation (SHAP) analysis was used to explain the model. Single sample gene set enrichment analysis (ssGSEA) was used for immune cell infiltration analysis.Results: The AUCs (area under the curves) of the 8 ML algorithms including DT, RF, XGBoost, KNN, NB, NN, LGBM and LR were as follows: 0.75, 0.896 0.874, 0.666, 0.742, 0.765, 0.869 and 0.744. The accuracy of XGBoost (0.852) was the highest, followed by LGBM (0.803) and RF (0.758), with F1 index of 0.832, 0.794, and 0.667, respectively. The results of the validation set data analysis showed AUCs of 0.839, 0.919, and 0.733 for RF, XGBoost, and LGBM, respectively. SHAP analysis showed that the SHAP values of blood neutrophil/lymphocyte ratio (NLR), age, mechanical ventilation, hyporeflexia and abnormal glossopharyngeal vagus nerve were 0.821, 0.645, 0.517, 0.401 and 0.109, respectively.Conclusion: The combination of NLR, age, mechanical ventilation, hyporeflexia and abnormal glossopharyngeal vagus used to predict short-term prognosis in patients with GBS has a good predictive value.Keywords: Guillain-Barré syndrome, machine learning, prognosis, SHAP

Ran Zhang,1,2 Ya-Jie Lei,1,2 Sheng-Yue Wen,1,2 Jian Pang,1,2 Yue-Long Cao,1,2 Min Zhang,1,2 Hong-Sheng Zhan,1,2 Xun Lin,3 Bo Chen1,2 1Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Orthopedics and Traumatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Bo Chen; Xun Lin, Tel +86-21-20256519, Email cbm818@shutcm.edu.cn; linxund@163.comPurpose: To prove more accurately that Chinese herbal bath therapy may be a safe, effective, simple alternative treatment modality for knee OA, we designed a randomized, double-blind, placebo-controlled trial to explore the effectiveness of SSBD for the relief of pain, daily activities, and quality of life in patients with knee OA.Patients and Methods: A single-center, 52-week, randomized controlled trial of SSBD versus placebo is being performed. A total of 200 patients with symptomatic knee OA will be randomly allocated to the SSBD treatment or placebo intervention group for 4 weeks. The two groups of patients are allowed to steam and bathe their knees once every other day, using one packet of SSBD each time, for 30 minutes, 3 times a week, for a total of 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at 4 weeks is the primary outcome measure, and the secondary outcomes include WOMAC stiffness and function scores, the Lysholm knee scale score, quality of life, the Brief Pain Inventory score, the Patient’s Global Impressions of Improvement Scale score and the Clinical Global Impressions of Severity scale score. The safety of the herbal medications will also be evaluated.Conclusion: We will discuss whether SSBD has greater advantages in terms of efficacy, safety, and patient overall perception than does placebo control in middle-aged and elderly patients with knee OA. The findings may provide new and valuable information about the efficacy and safety of Chinese herbal bath therapy in the treatment of knee osteoarthritis.Keywords: balneotherapy, traditional Chinese medicine, complementary and integrative medicine, randomized placebo-controlled trial, knee osteoarthritis

Juncai Lv,1,&ast; Weiwei Yan,1,&ast; Ran Zhang,1 Xi Chen,1,2 Ziyuan Ren,1,2 Dawei Chen,1 Jinming Yu1 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Cheeloo College of Medicine, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinming Yu; Dawei Chen, Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China, Tel +86-531-8798-4777, Fax +86-531-8798-4079, Email sdyujinming@163.com; dave0505@yeah.netPurpose: There exists a dearth of research concerning non-small cell lung cancer (NSCLC) patients experiencing overall progressive disease concomitant with shrinking lesions after immunotherapy. This is a special type of mixed response. We aim to evaluate the clinical characteristics and treatment options of these patients during immunotherapy.Patients and Methods: We categorized patients into two groups: Progressive Disease with Mixed Responses (PDMR) (n = 31) and Progressive Disease with None Mixed Responses (PDNMR) (n = 144), depending on whether at least one target lesion had shrunk by ≥ 30% at the point of overall progression. Computed tomography scans and magnetic resonance imaging were utilized to evaluate the clinicopathological significance of these patients, and a multivariate analysis was conducted to scrutinize the clinical characteristics and prognosis-influencing factors in these patients.Results: Patients in the PDMR group had worse staging and a greater proportion of previous radiotherapy. The median overall survival (mOS 22 vs 36.4 months; P = 0.019) and median progression-free survival (mPFS 5.83 vs 9.03 months; P = 0.031) of the PDMR group were shorter than PDNMR group. Longer subsequent OS with continued immunotherapy after PDMR compared with patients who do not continue with immunization after PDMR (mOS 23.9 vs 6.5 months; P = 0.024).Conclusion: PDMR was primarily observed in stage IV patients and previously irradiated patients. OS and PFS were inferior in patients with PDMR compared to patients with PDNMR. The continuation of immunotherapy in PDMR patients could extend their survival.Keywords: non-small cell lung cancer, immunotherapy, mixed response, progression

Xin Guo,1,&ast; Ying Xu,1,&ast; Yao Meng,1,2,&ast; Hao Lian,1,&ast; Jingwen He,1 Ruike Zhang,1 Jingzhou Xu,1 Hao Wang,1 Shuyu Xu,1 Wenpeng Cai,1 Lei Xiao,1 Tong Su,3 Yunxiang Tang3 1Department of Medical Psychology, Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Diving and Hyperbaric Medical Research, Naval Special Medical Center, Naval Medical University, Shanghai, People’s Republic of China; 3Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunxiang Tang, Email tangyun7633@sina.comBackground: Napping deprivation in habitual nappers leads to cognitive impairment. The ameliorative effect of acute aerobic exercise has been demonstrated for this post-cognitive impairment. However, it is still unclear which intensity of aerobic exercise is the most effective and how long this improvement can be sustained.Methods: Fifty-eight healthy adults with a chronic napping habit were randomly assigned to four intervention groups after undergoing nap deprivation: a sedentary control group, a low-intensity exercise group (50– 59% maximum heart rate, HRmax), a moderate-intensity exercise group (60– 69% HRmax), and a high-intensity exercise group (70– 79% HRmax). Working memory (N-back task), vigilance (Psychomotor Vigilance Task, PVT), and response inhibitory capacity (Go/NoGo task) were measured.Results: Regression analyses showed a quadratic trend between exercise intensity and working memory reaction time and accuracy (F =3.297– 5.769, p < 0.05, R2 =10.7– 18.9%). The effects of exercise were optimal at low-intensity. There was a significant quadratic trend between exercise intensity and PVT lapse (F =4.314, p =0.042, R² =7.2%). The effect of exercise increased with higher intensity. Prolonged observation found that the effect of low-intensity exercise on working memory was maintained for 2 hours.Conclusion: The effect of low-intensity exercise might be underestimated. Low-intensity exercise significantly improved working memory performance, and the effects could be maintained throughout the afternoon. In contrast, the effects of high-intensity exercise were unlikely to be maintained and might even have negative effects. Future researchers can broaden the categories of participants to enhance the external validity and collect diverse physiological indicators to explore related physiological mechanisms.Keywords: exercise intensity, executive function, habitual nappers, nap deprivation, working memory

Fanlingzi Shen,1,2,&ast; Yu Song,3,&ast; Yan Qiang,1,&ast; Xiangjin Gao,1 Siyuan Li,2 Rui Zhang,1 Zhongzhi Gao,1 Bin Li,1 Wencheng Jiang,4 Ruiping Wang1,2 1Clinical Research Center, Shanghai Skin Diseases Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wencheng Jiang, Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, Medical School, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Email drjiangwencheng@163.com Ruiping Wang, Clinical Research & Innovation Transformation Center, Shanghai Skin Diseases Hospital, Medical School, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Email w19830901@126.comPurpose: Tobacco smoking and alcohol drinking are positively associated with psoriasis prevalence and disease severity. Researches focusing on the influence of smoking and drinking on the treatment efficacy of psoriasis are still limited, especially their interaction effect. This study aims to explore the interactive effects of smoking and drinking on the treatment efficacy in psoriasis patients.Patients and Methods: From 2021 to 2022, we recruited 560 patients with psoriasis from Shanghai Skin Diseases Hospital. Demographic and clinical features as well as treatment efficacy were collected through questionnaire interview and physical examination during patient’s hospital visit at week 0, week 4 and week 8. Logistic regression model was used to explore the influence of smoking and drinking on the treatment efficacy in psoriasis patients, and multiplicative and additive interaction models were used to verify the interaction effect of smoking and drinking on the treatment efficacy.Results: The prevalence of smoking and drinking among psoriasis patients was respectively 43.8% and 25.4%, and 19.6% of them with both smoking and drinking. Logistic regression analysis showed that patients with smoking (OR=7.78, 95% CI: 5.26~11.49) and drinking (OR=5.21, 95% CI: 3.29~8.27) had higher risk of experiencing the failure to achieve PASI75 at week 8, even with the adjustment of confounders. Moreover, multiplicative as well as additive model showed that tobacco smoking interacted with alcohol drinking which influenced the treatment efficacy more severely (OR=12.74, 95% CI: 7.16~22.67). The proportion of PASI75 achievement in female patients (OR=19.54) and patients with methotrexate (OR=28.31) and biologics (OR=21.61) were more likely being affected by smoking and drinking.Conclusion: Tobacco smoking and alcohol drinking could increase the failure of PASI75 achievement in patients with psoriasis, individually and interactively. We recommend that dermatologists should educate patients to pay attention to the negative effects of smoking and drinking, encourage them to quit, and thus improve the treatment efficacy.Keywords: psoriasis, tobacco smoking, alcohol drinking, interaction, additive model, multiplicative model

Mengyue Sun,1 Yuanyuan Liu,2 Shan Tang,2 Yiming Li,2 Ridong Zhang,2 Li Mao2 1Department of Geratology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of China; 2Department of Endocrinology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of ChinaCorrespondence: Li Mao, Email maoli_mail@126.comAim: This study investigated differences in gut flora between osteoporosis (OP) patients and healthy individuals using 16S rDNA sequencing. The correlation between differential flora abundance and bone mineral density (BMD) was analyzed, and key flora and potential mechanisms associated with OP were explored.Methods: Forty-three OP patients and twenty-four healthy volunteers were recruited. Gender, age, height, weight, and BMD data were collected. DNA from fecal samples was extracted for 16S rDNA sequencing. The Kruskal–Wallis test assessed differences in gut flora composition, while LEfSe analysis identified significant flora. Spearman correlation analysis examined the relationship between differential flora and BMD, and PICRUSt predicted pathways involved in OP.Results: Significant differences in microbial composition were found between the two groups. Klebsiella, Escherichia-Shigella, and Akkermansia were biomarkers in OP patients, with Faecalibacterium in the healthy group. Akkermansia abundance negatively correlated with lumbar BMD, while Klebsiella and Escherichia-Shigella negatively correlated with femoral neck and hip BMD. Faecalibacterium showed a positive correlation with BMD. Functional predictions indicated differences in metabolism-related pathways between the groups.Conclusion: Gut flora differed significantly between OP patients and healthy individuals. Akkermansia, Klebsiella, and Escherichia-Shigella could serve as diagnostic biomarkers for OP, highlighting the potential of gut flora in OP diagnosis and treatment.Keywords: osteoporosis, intestinal flora, 16S rDNA

Jiangpei Shi,1,&ast; Rongguang Zhang,1,&ast; Yu Wang,1 Yingwei Sun,1 Xiaoyan Gu,1 Yu An,1 Xinyu Chai,1 Xiaoyu Wang,2 Zhi Wang,1 Yaqi Lyu,1 Teng Guo,1 Nianping Feng,1 Ying Liu1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nianping Feng; Ying Liu, Email npfeng@shutcm.edu.cn; debbyly@shutcm.edu.cnBackground: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging.Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb–nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum–Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid–polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC–Orbitrap–MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated.Results: The HNS reduced particle–mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer’s patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-β 1, which altered the TME in 4T1 tumor-bearing mice.Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.Keywords: herb–nanoparticle hybrid system, intestinal biological barrier, tumor microenvironment, breast cancer lung metastasis

Li Lin,1,* Zeyu Huang,2,* Bangsheng Xi,3,* Xiaoming Qin,1 Kongchao Yang,1 Ruzhi Zhang1 1Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 2Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Wannan Medical college, Wuhu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruzhi Zhang, Email zhangruzhi628@163.comAbstract: Cutaneous squamous cell carcinoma (SCC) is a common non-melanoma skin cancer (NMSC). Although most cutaneous SCC in people with lighter skin pigmentation as a result of sun damage, patients with underlying conditions such as skin ulcers and chronic inflammation-including conditions such as lupus vulgaris (LV) and chronic discoid lupus erythematosus—are also predisposed to developing SCC. Here we report a case of secondary SCC diagnosed in a 54-year-old patient with 20 years of lupus vulgaris without prior formal systemic treatment, a rarity in clinical practice. Two months ago, the patient developed papules on the right cheek that ulcerated and discharged purulent fluid. Laboratory tests revealed a positive TSPOT result and histopathological examination confirmed granulomatous lesions, supporting the diagnosis of SLE. However, a tissue biopsy unexpectedly revealed a moderately differentiated SCC of the keratinizing type. In this case, we performed surgical excision of the lesion followed by cosmetic closure and adjuvant photodynamic therapy (PDT). Concurrently, the patient underwent systemic anti-tuberculosis treatment. At 6 months post-treatment, no tumour recurrence was observed and the rash associated with lupus erythematosus had also resolved. The patient was satisfied with the treatment outcome.Keywords: lupus vulgaris, squamous cell carcinoma, surgical excision, photodynamic therapy

Zhongbiao Nie,1 Cuilv Liang,2 Zhihong Li,1 Xinqiang Han,3 Ran Zhang4 1Department of Pharmacy, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China; 2Department of Pharmacy, Second Affiliated Hospital, Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 3Department of General, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China; 4Department of Nephrology, Affiliated Hospital of Shanxi University of Chinese Medicine, Taiyuan, 030024, People’s Republic of ChinaCorrespondence: Ran Zhang, Department of Nephrology, Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, Taiyuan, 030024, People’s Republic of China, Tel +86-13633516515, Email 115462888@qq.comPurpose: This study comprehensively describes and evaluates the correlation between gabapentinoids and all types of delirium.Methods: We used AERSMine to select all adverse reaction data from 2004 Q1 to the 2022 Q4 in the FDA Adverse Event Reporting System (FAERS) database, and delirium events reported by gabapentinoids drugs were included in this study. Collected and analyzed the clinical details of these reports. We have developed four models. Among the four models, reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to evaluate the potential association between and delirium. We undertook a subgroup analysis for the age and sex cohorts.Results: A total of 2950 reports of gabapentinoids-related delirium was collected. Excluding cases with a history of delirium (Model 2), opioid drugs (Model 3), and other adverse events related to gabapentinoids drugs (Model 4), pain cases with gabapentin drugs as the main suspected drug were selected. In model 1, the reporting rates of delirium at the delirium and delirium tremens levels were higher in the gabapentinoids group than in the non-gabapentinoids group (ROR 1.09(1.05,1.13); ROR 1.54(1.16,2.04)). In model 2.3 the delira and the delirium level were higher in the gabapentinoids group (ROR 1.42(1.29,1.56), ROR 1.44(1.31,1.59); ROR 1.43(1.30,1.58), ROR 1.46(1.33,1.61)). There is no difference in delirium levels in Model 4. Delirium levels were higher in the gabapentinoids group than in the non-gabapentinoids group in ≥ 65 years old. The delirium and deliria levels were higher in the male group than in the female group.Conclusion: The delirium adverse reactions of the gabapentinoids group were significantly higher than those of non-gabapentinoids group in the first three models. However, with the removal of confounding factors, there was no significant difference in this type of adverse reaction in Model 4. In elderly and male patients, the incidence of delirium with gabapentinoids was significantly increased.Keywords: gabapentinoids, delirium, adverse reactions, FAERS, pharmacovigilance

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

Yuxia Fang,1 Yilu Zhao,2 Lei Qin,1 Ziyue Song,1 Ruzhi Zhang1 1Department of Dermatology and STD, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Ruzhi Zhang, Department of Dermatology and STD, The Second Affiliated Hospital of Wannan Medical College, 10 Kangfu Road, Wuhu, Anhui, 241001, People’s Republic of China, Tel +8618761161826, Email zhangruzhi628@163.comBackground: Intramuscular (IM) injection of penicillin G Benzathine (PGB) is widely recognized as the primary treatment for patients at all stages of syphilis. However, the discomfort and induration associated with PGB injections are often a challenge for patients. While lidocaine is already known to reduce injection pain and is standard practice in some countries, the added value of combining lidocaine with the z-track technique has not been thoroughly investigated. This study aims to observe the use of combining lidocaine with the Z-track technique in the treatment of syphilis, and to explore less painful methods of administering IM PGB for the treatment of syphilis in adult patients.Methods: 32 syphilis patients requiring penicillin treatment were injected with 1.2 million units of penicillin on both sides of the buttocks. The left side was injected using the traditional method with 0.9% saline as the solvent (control Group), while the right side was injected using a “z” injection method with 0.2% lidocaine as the solvent (experimental Group). The success rate of the single injection, the intensity and duration of the post-injection pain and the induration reaction were observed and recorded.Results: There was no statistically significant difference in single injection success rate and immediate post injection pain score between the two sides (P> 0.05). However, the right side had a lower pain score at 30 minutes post injection and fewer induration reactions, showing a statistically significant difference between the two sides (P< 0.05). Chi-squared analysis showed that age, gender and BMI had no significant effect on pain scores 30 minutes after injection in either the control or intervention groups. (P> 0.05).Conclusion: The lidocaine + Z-track penicillin method can reduce delayed pain and induration reactions in patients with syphilis, and provides an additional approach to improving patient comfort beyond the standard use of lidocaine alone. This method merits clinical promotion.Keywords: syphilis, penicillin G benzathine, PGB, intramuscular injection

Yawen Mo,1,&ast; Wenjuan Zhang,1,&ast; Xiangcheng Tang,1 Rui Zhang,2 Yinghuan Wang,1 Lingling Zheng3 1Department of Strabismus and Amblyopia, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China; 2Department of Anesthesia, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China; 3Department of Nursing Administration, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingling Zheng, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 7 Jinsui Road, Guangzhou, People’s Republic of China, Email zhenglingling@gzzoc.comPurpose: Strabismus surgery is most commonly performed on children under general anesthesia. However, few studies have focused on the postoperative discomfort in children after strabismus surgery. This study aimed to evaluate postoperative discomfort and the associated risk factors in children who underwent strabismus surgery under general anesthesia.Patients and Methods: A single-center prospective observational study including 300 children who underwent strabismus surgery after general anesthesia was conducted. Patients’ characteristics, preoperative anxiety, surgical and anesthesia data, discomfort within 24 hours after postanesthesia care unit were recorded. The primary outcome was the incidence of postoperative discomfort.Results: Approximately 51.33% of the children complained of at least one of the following types of postoperative discomfort: postoperative nausea and vomiting (PONV) (23.00%), headache (4.33%), dizziness (20.33%) and emergence agitation (EA) (5.33%). Multivariate analysis indicated that history of motion sickness (P< 0.001, odds ratio [OR]=3.72), and surgery in the dominant eye (P=0.010, OR=2.00) were independent predictors of postoperative discomfort; age was an independent predictor of EA (P< 0.001, OR=0.36); prism diopter≥ 40 was an independent predictor of headache (P=0.005, OR=5.53); age (P=0.020, OR=1.12) and history of motion sickness (P=0.001, OR=2.80) were independent predictors of dizziness; history of motion sickness (P=0.001, OR=2.63) and surgery of inferior oblique anterior transposition (IOAT) (P=0.004, OR=3.10) were independent predictors of PONV.Conclusion: The most frequent postoperative symptoms in children after undergoing strabismus surgery under general anesthesia are PONV, dizziness, EA, and headache. Younger age, larger angle of strabismus, history of motion sickness, surgery on the dominant eye, and surgery of IOAT may be additional risk factors for postoperative discomfort.Keywords: strabismus surgery, discomfort, postoperative nausea, vomiting, general anesthesia

Rongrong Zhang,1,&ast; Wenjun Xu,1,&ast; Hongquan Wei,1,&ast; Boshi Li,1 Yaoxing Wang,1 Xueqing He,1 Jun Cao,1 Xinyu He,1 Mingxiang Xu,1,2 Wenjie Lu,1 Youzhi Xu1 1College of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Center for Scientific Research, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youzhi Xu; Wenjie Lu, Email xuyouzhi@ahmu.edu.cn; wenjie63136@163.comPurpose: Currently, there is still no clear treatment for polycystic ovary syndrome (PCOS). YJKL has better therapeutic effects and lower toxic side effects for PCOS type infertility. This study aims to clarify the potential mechanism of YJKL Decoction in the treatment of PCOS based on network pharmacology and experiments verification.Patients and Methods: Network pharmacology and experimental validation approach were used to investigate the bioactive ingredients, critical targets and potential mechanisms of YJKL Decoction against PCOS. Firstly, we use network pharmacology methods to collect core targets, and then validate their effects on diseases through experiments.Results: Five core targets were screened, Threonine kinase 1 (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Albumin (ALB) and Vascular endothelial growthfactor A (VEGFA). KEGG analysis showed that YJKL treatment for PCOS mainly include AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway and HIF-1 signaling pathway. The molecular docking results showed that compounds have higher affinity with targets. Finally, experimental results had shown that YJKL Decoction had an better therapeutic effects in the treatment of PCOS.Conclusion: Based on a systematic network pharmacology approach and experimental verification, our results comprehensively illustrated the active ingredients, potential targets, and molecular mechanism of YJKL for application to PCOS and helps to illustrate mechanism of action on a comprehensive level.Keywords: traditional Chinese Medicine, YJKL, polycystic ovary syndrome, PCOS, molecular docking, experimental validation

Yucheng Hu,1 Rong Zhang,2 Junjie Li,1 Huan Wang,3 Meiya Wang,3 Qiuyi Ren,1 Yueqi Fang,1 Li Tian1 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Chengdu university of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li Tian, Hospital of Chengdu university of Traditional Chinese Medicine, No. 41, 12 Qiaolu, Qingyang District, Chengdu, Sichuan, People’s Republic of China, Email 18980880129@qq.comhaAbstract: Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.Keywords: allergic rhinitis, microbiota dysbiosis, nasal microbiome, short-chain fatty acids, immunomodulation

Fengxing Huang,1,2,&ast; Youwei Wang,1,2,&ast; Yu Shao,1,2,&ast; Runan Zhang,1,2 Mengting Li,1,2 Lan Liu,1,2,&ast; Qiu Zhao1,2,&ast; 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan Liu; Qiu Zhao, Email lliugi@whu.edu.cn; qiuzhao@whu.edu.cnIntroduction: Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored.Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework.Results: We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk.Discussion: Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations. Keywords: CRC, macrophages, metabolic classification, tumor immunity, prognosis model

Wenze Han,1,2 Ran Zhang,1,2 Shuzhi Liu,1,2 Tong Zhang,1,2 Xuemin Yao,1,2 Yuxin Cao,1,2 Jiadi Li,1,2 Xiaoming Liu,1,2 Bing Li1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Xiaoming Liu; Bing Li, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email lxming0912@163.com; libing1975vip@163.comAbstract: Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry.Keywords: whiskers, dentistry, growth mechanism, biomaterials

Xiaoqing Ma,&ast; Ruoying Zhang,&ast; Xinjun Cai, Yuying Lang, Huaichong Wang, Jinmeng Li Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinmeng Li, Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Email jinmeng608@163.comAbstract: As a new generation of oxazolidinone antibacterial drugs, contezolid has been shown to have comparable or even stronger activity than linezolid and has a low risk of adverse reactions such as bone marrow suppression toxicity. However, there are currently very few clinical reports and pharmacokinetic data of contezolid on the anti-tuberculosis therapy. Therefore, we report a case study of the pharmacokinetic study of contezolid in elderly patients with renal insufficiency and tuberculosis. The patient’s condition improved after receiving an anti-tuberculosis regimen containing contezolid, with significant absorption of pleural effusion and lung plaques and nodules reduced. During the treatment, the patients’ platelet and white blood cell levels fluctuated within normal ranges, but hemoglobin levels significantly decreased and did not recover after discontinuation of contezolid. The trough concentration of contezolid and the concentration at 2, 4, 6, and 10 h after administration were 1.27μg/mL, 3.88μg/mL, 6.32μg/mL, 8.99μg/mL, and 3.14μg/mL, respectively. The plasma concentrations of bedaquiline and cycloserine during the treatment were also monitored. This study demonstrated the efficacy and safety of contezolid in the treatment of multidrug-resistant tuberculosis and analyzed its pharmacokinetic changes in elderly patients with renal insufficiency, providing a reference for the clinical use of contezolid.Keywords: contezolid, tuberculosis, plasma concentration, efficacy, safety

Ruijie Zhang,1,&ast; Xinran Dong,2,&ast; Lu Zhang,1,&ast; Xinao Lin,1 Xuefeng Wang,1 Yan Xu,3 Chuyan Wu,4 Feng Jiang,1 Jimei Wang1 1Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Center for Molecular Medicine, Children’s Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of Neurology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jimei Wang; Feng Jiang, Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China, Email wjm821920@163.com; dxyjiang@163.comBackground: Neonatal sleep is pivotal for their growth and development, yet manual interpretation of raw images is time-consuming and labor-intensive. Quantitative Electroencephalography (QEEG) presents significant advantages in terms of objectivity and convenience for investigating neonatal sleep patterns. However, research on the sleep patterns of healthy neonates remains scarce. This study aims to identify QEEG markers that distinguish between different neonatal sleep cycles and analyze QEEG alterations across various sleep stages in relation to postmenstrual age.Methods: From September 2023 to February 2024, full-term neonates admitted to the neonatology department at the Obstetrics and Gynecology Hospital of Fudan University were enrolled in this study. Electroencephalographic (EEG) recordings were obtained from neonates aged 37– 42 weeks, within 1– 7 days post-birth. The ROC curve was employed to evaluate QEEG features related to amplitude, range EEG (rEEG), spectral density, and connectivity across different sleep stages. Furthermore, regression analyses were performed to investigate the association between these QEEG characteristics and postmenstrual age.Results: The alpha frequency band’s spectral_diff_F3 emerged as the most potent discriminator between active sleep (AS) and quiet sleep (QS). In distinguishing AS from wakefulness (W), the theta frequency’s spectral_diff_C4 was the most effective, whereas the delta frequency’s spectral_diff_P4 excelled in differentiating QS from W. During AS and QS phases, there was a notable increase in entropy within the delta frequency band across all monitored brain regions and in the spectral relative power within the theta frequency band, correlating with postmenstrual age (PMA).Conclusion: Spectral difference showcases the highest discriminative capability across awake and various sleep states. The observed patterns of neonatal QEEG alterations in relation to PMA are consistent with the maturation of neonatal sleep, offering insights into the prediction and evaluation of brain development outcomes.Keywords: quantitative EEG, neonates, sleep, postmenstrual age

Yunyan Zheng,1,&ast; Weiwei Shi,1,2,&ast; Huiying Wang,1 Ruzhi Zhang3 1Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Department of Dermatology, Affiliated Hospital 2 of Nantong University, Nantong, People’s Republic of China; 3Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruzhi Zhang, Department of Dermatology, The Second Affiliated Hospital of Wannan Medical College, 10 Kangfu Road, Wuhu, 241000, People’s Republic of China, Email zhangruzhi628@163.comPurpose: This study aimed to improve the understanding of sporotrichosis by analyzing the epidemiological characteristics, clinical manifestations, mycological features, and pathological characteristics of the disease in eastern China.Methods: Clinical data of 49 patients diagnosed with cutaneous sporotrichosis in dermatology clinics over a 20-year period were collected and analyzed retrospectively. The analysis included patient demographics, occupations, clinical types, lesion sites, misdiagnosis rates, laboratory investigations, treatment and outcomes.Results: The study included 22 male and 27 female patients, with a mean age of 52.4 years. Farmers (42.86%) and manual workers (28.57%) had a higher risk of infection. The most common clinical types were lymphocutaneous (30.61%) and fixed (69.39%), predominantly affecting the face and upper limbs. Misdiagnosis as other infectious skin diseases occurred in 35 patients (71.43%). Fungal culture and histopathological examination were important diagnostic tools. Treatment with oral itraconazole for three months led to relief and regression of the skin lesions in most patients, although a few experienced recurrences.Conclusion: Cutaneous sporotrichosis mainly affects individuals working in agriculture and manual labour, with lymphocutaneous and fixed types being the predominant clinical manifestations. The high misdiagnosis rate emphasizes the importance of early recognition, accurate diagnosis and standardized treatment for the prognosis and cure of sporotrichosis. Fungal culture and histopathological examination are essential for diagnosis, and oral itraconazole is an effective treatment option.Keywords: sporotrichosis, cutaneous form, clinical analysis, epidemiology, misdiagnosis

Xinyu Dai,1,&ast; Rui Zhang,2,&ast; Nan Deng,1 Le Tang,3 Bangshu Zhao1 1Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangshu Zhao, Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel +8615823079815, Email Bangshuzhao@hospital.cqmu.edu.cnAbstract: The prevalence of severe mental disorders has been rising annually. Electroconvulsive therapy (ECT) is considered a valuable treatment option in psychiatry for conditions such as schizophrenia and medication-resistant depression, especially when other treatments have proven insufficient. ECT rapidly improves patients’ mood, alleviates symptoms, and demonstrates significant therapeutic effects. Currently, the form of ECT used in clinical practice is modified electroconvulsive therapy (mECT), which is administered under general anesthesia. Accumulative evidence has confirmed that different anesthetic drugs, anesthetic-ECT time interval, anesthetic depth, and airway management can impact the outcomes of ECT. Therefore, this review aims to summarize the current impact of anesthesia factors on ECT, providing reference for clinical anesthesia during ECT procedures.Keywords: mental disorders, ECT, anesthesia factors

Junjie Cheng,1,&ast; Yuan Yuan,1,&ast; Jinmeng Li,1 Ruoying Zhang,1 Xudong Fan,1 Zhirou Xu,2 Huirong Lin,3 Xinjun Cai,1 Mingfeng Zheng4 1Department of Pharmacy, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China; 2Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, People’s Republic of China; 3Department of Pharmacy, Taizhou Cancer Hospital, Taizhou, People’s Republic of China; 4Department of Orthopaedics, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingfeng Zheng; Xinjun Cai, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Email zmfyxz3@163.com; zjtcmcxj@zcmu.edu.cnPurpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity.Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis.Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728.Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.Keywords: linezolid, therapeutic drug monitoring, influencing factors, hematological toxicity

Yuan Zhuang,1,2 Ru Zhang,3,4 Miaomiao Li,3,4 Yaru Zou,1 Shui Jiang,1 Yanan Zhang,1 Shiguo Liu,3,4 Bo Yu1 1Dermatological Department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China; 2dermatological department, Women and Children’s hospital, Qingdao University, Qingdao, People’s Republic of China; 3Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Yu, Dermatological department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China, Email yubo@qduhospital.cn Shiguo Liu, Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email liushiguo@qdu.edu.cnIntroduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.Keywords: EDA, X-linked hypohidrotic ectodermal dysplasia, gene mutation