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Lei Tan,1,2,* Han She,1,2,* Yi Wang,1,2,* Yuanlin Du,1 Jun Zhang,1 Yunxia Du,1 Yinyu Wu,1 Wei Chen,1 Bingqiang Huang,1 Duanyang Long,1 Xiaoyong Peng,2 Qinghui Li,2 Qingxiang Mao,1 Tao Li,2 Yi Hu1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Li; Yi Hu, Email lt200132@163.com; huyi921@sina.comBackground: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer’s (AR) and Lactate Ringer’s solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear.Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury.Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats’ survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity.Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.Keywords: myocardial injury, hemorrhagic shock, mitochondria, ferroptosis

Jie Cheng,1,* Ya Liu,2,* Guangli Zhang,3 Liping Tan,1 Zhengxiu Luo3 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Big Data Engineering Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of China; 3Department of Respiratory Medicine, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Big Data Engineering Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengxiu Luo, Email luozhengxiu816@hospital.cqmu.edu.cnObjective: Mycoplasma pneumoniae (MP) is highly resistant to macrolides in China. However, macrolides still exhibit clinical effectiveness in some macrolide-resistant patients. We tend to explore azithromycin effectiveness in Mycoplasma pneumoniae pneumonia (MPP) children with A2063/2064G mutation.Methods: This retrospective observational cohort study was conducted at the Children’s Hospital of the Chongqing Medical University. Children with macrolide-resistant mutations (A2063/2064G) diagnosed as MPP were retrospectively enrolled. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate and identify independent risk factors for treatment failure (progress to refractory Mycoplasma pneumoniae pneumonia [RMPP]) in macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) children with the A2063/2064G mutation.Results: One hundred fifty-five children were retrospectively enrolled. More than 20% (36/155, 23.23%) of patients experienced defervescence within 3 days of azithromycin treatment. RMPP was diagnosed in 54 patients (54/155, 34.84%) and the incidence of RMPP during hospitalization was 22.72 per 1000 person-days. Logistic regression analysis showed that lactate dehydrogenase (LDH) ≥ 399 (U/L) was an independent risk factor for RMPP (odds ratio [OR] 4.66, 95% confidence interval [CI] 1.31– 17.10, P=0.017). During the year followed, RMPP patients had a significantly higher incidence of bronchiolitis obliterans and bronchiectasis than non-RMPP patients (16.67% vs 1.98%, P=0.001; 9.26% vs 0.00%, P=0.005, respectively).Conclusion: Azithromycin was effective in children with MPP with the A2063/2064G mutation. For MUMPP children with A2063/2064G mutation, children with LDH ≥ 399 (U/L) had significant higher risk for progression to RMPP, and should consider to be treated with alternative antibiotics (eg tetracyclines, and fluoroquinolones).Keywords: azithromycin effectiveness, A2063/2064G mutation, mycoplasma pneumoniae pneumonia, children

Zhaowei Huang,1,2,* Changming Chen,3,* Linlin Tan,4 Yi Ling,3 Wukai Ma,3 Jinan Zhang1,2 1Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 3Department of Rheumatology & Immunology, The Second Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, Guizhou, People’s Republic of China; 4Department of Internal Medicine, Jinshazhou Hospital Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinan Zhang, Email zhangjinan@hotmail.comBackground: Rheumatoid arthritis (RA) is a common autoimmune disease with the main symptoms being joint swelling and pain. In severe cases, joint deformity or even complete loss of function occurs. Technetium methylene diphosphonate (99Tc-MDP) is widely used for RA treatment in China, but there are no studies on the effects of 99Tc-MDP on intestinal flora.Objective: To explore the effects of 99Tc-MDP treatment on the composition and function of the intestinal flora and to provide new information on the mechanism of 99Tc-MDP in RA treatment.Methods: Stool samples from RA patients before and after 99Tc-MDP treatment were collected to form two groups (Before and After). Total genomic DNA of the samples was extracted for 16S rRNA gene sequencing. The altered composition of the intestinal flora, the key target bacteria regulated by 99Tc-MDP, and the pathways of action of 99 Tc-MDP were analyzed by bioinformatics.Results: A total of 64 fresh stool samples were collected from 32 RA patients. Compared to the Before group, the After group showed increased Bacteroidetes abundance and decreased Firmicutes abundance. At the genus level, Prevotella increased whereas Escherichia decreased. Both α and β diversity analyses showed that 99Tc-MDP treatment did not affect gut microbial diversity in RA patients. LEfSe analyses and random forest analyses showed Bacteroidetes, Prevotella, Enterococcus, Escherichia and Ruminococcaceae were the main 99Tc-MDP regulating bacteria. Functional enrichment analysis revealed that the functional differences in gut flora of the two groups centered on Metabolism and Genetic Information Processing.Conclusion: This study revealed differences in the composition of the gut microbiota in RA patients before and after 99Tc-MDP treatment. The therapeutic effect of 99Tc MDP is mainly achieved through Bacteroidetes, Prevotella, and Enterococcus. Regulating metabolism and genetic information processing of gut flora may be the mechanism of 99Tc-MDP in treating RA.Keywords: rheumatoid arthritis, 99Tc-MDP, gut microbiota, 16S rRNA, bioinformatics

Lingfang Tan,1 Xuefeng Yang,2 Jianxin Zhang,3 Kebing Zhou1,2 1The Nanhua Affiliated Hospital, Department of Respiratory Physicians, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 2The Nanhua Affiliated Hospital, Department of General Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3The Nanhua Affiliated Hospital, Department of Cardiothoracic Surgeon, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of ChinaCorrespondence: Kebing Zhou, Tel +86-17397392536, Email zhoukebing9999@163.comBackground: Airway remodeling is a significant pathological characteristic of chronic obstructive pulmonary disease (COPD). In recent years, hypoxia-inducible factor 1-α (HIF-1α), a member of the hypoxia-inducible factor protein family, has gained attention. However, the potential correlation between HIF-1α and COPD airway remodeling remains unclear.Objective: This study explored the expression patterns of HIF-1α in patients with COPD and its association with airway remodelling. This investigation aims to furnish novel insights for the clinical identification of prospective therapeutic targets for ameliorating COPD-related airway remodelling.Patients and Methods: A total of 88 subjects were included, consisting of 28 controls and 60 COPD patients. Various staining methods were employed to observe the pathological changes in airway tissues. Immunohistochemistry was utilized to detect the expression of HIF-1α and MMP9 (matrix metalloproteinase 9) in airway tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration in serum of HIF-1α and MMP9. Computed tomography (CT) airway parameters were measured in all participants to assess airway remodeling. The relationship between serum HIF-1α and MMP9 concentrations and airway parameters was analyzed.Results: Staining of airway structures in COPD patients revealed significant pathological changes associated with airway remodelling, including mixed cilia and subepithelial fibrosis. The expression of HIF-1α and MMP9 was significantly higher in both human airway tissue and serum compared to controls. Chest CT scans exhibited typical imaging features of airway remodeling and increased airway parameters.Conclusion: The findings suggest a correlation between increased HIF-1α expression and COPD airway remodelling. This study provides novel evidence that HIF-1α may be a potential biomarker for airway remodelling in COPD patients.Keywords: hypoxia-inducible factor 1-α, chronic obstructive pulmonary disease, matrix metalloproteinase 9, airway remodelling

Liang Tan,1,&ast; Feilong Wang,1,&ast; Yi Huang,2 Chuhua Fu,3 Haijun Zhang,4 Jianfei Feng,5 Yincai Xu,6 Xinzhen Ye,7 Rongrui Tang,8 Yinglian Chen,9 Liansheng Mou,10 Ronghao Li,11 Jingyu Chen,1 Jishu Xian1 1Department of Neurosurgery, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, The Ninth People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 3Department of Neurosurgery, Xiangyang No.1 People’s Hospital, University of Medicine, Xiangyang, Hubei, People’s Republic of China; 4Department of Neurosurgery, Kaifeng Central Hospital, Kaifeng, Henan, People’s Republic of China; 5Department of Encephalopathy, Beibei Traditional Chinese Medical Hospital, Chongqing, People’s Republic of China; 6Department of Neurosurgery, Zheng Coal General Hospital, Zhengzhou, Henan Province, People’s Republic of China; 7Department of Neurosurgery, Songshan General Hospital, Chongqing, People’s Republic of China; 8Department of Neurosurgery, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 9Zhuhai Brainlightning Research Institute, Zhuhai City, Guangdong, People’s Republic of China; 10Department of Neurosurgery, Liangping District People’s Hospital, Chongqing, People’s Republic of China; 11Department of Basic Medicine, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyu Chen; Jishu Xian, Email Cjy1_2001@Hotmail.com; 1370321419@qq.comPurpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs.Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes.Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p> 0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1– 12) vs 4(1– 8), p< 0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p< 0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death.Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients.Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.Keywords: SARS-CoV-2, intensive care unit, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury

Jie Cheng,1 Ya Liu,2 Shaojun Li,1 Kaibin Pu,1 Lin Yang,1 Liping Tan1 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of ChinaCorrespondence: Liping Tan, Tel +86-23-63630194, Email tanlp0825@hotmail.comObjective: Third-generation cephalosporin-resistant (3GC-R) bloodstream infection (BSI) is associated with poor prognosis. We investigated the incidence of and risk factors for 3GC-R Escherichia coli (E. coli) BSI in children.Methods: Patients with E. coli BSIs who were hospitalized at the Children’s Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for 3GC-R BSI.Results: Two hundred fifty-two children with E. coli BSIs were enrolled. The mortality rate was 11.51% (29/252). The infection rate of 3GC-R E. coli was 48.81% (123/252), and the incidence of E. coli BSI during hospitalization was 18.58 per 1000 person-days. Approximately half (47.22%, 119/252) of the children were infected with extended-spectrum beta-lactamases (ESBLs) produced by E. coli. More than one-third (37.30%, 94/252) of the children were unnecessarily administrated carbapenems. According to our logistic regression analysis, a history of carbapenem administration, an elevated Pediatric Sequential Organ Failure Assessment (pSOFA) score ≥ 2, and antimicrobial agent administration before blood culture were independently associated with 3GC-R BSI (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.08– 3.94, P=0.029; OR 2.00, 95% CI 1.10– 3.71, P=0.025, OR 1.86, 95% CI 1.02– 3.42, P=0.044, respectively).Conclusion: In this study, the incidence of 3GC-R E. coli BSI among children was retrospectively evaluated. Patients with a history of carbapenem administration, an elevated pSOFA score ≥ 2 and who were administrated antimicrobial agents before blood culture had an increased risk of 3GC-R E. coli BSI.Keywords: third-generation cephalosporin-resistant, inappropriate use of carbapenems, Escherichia coli, bloodstream infection, children

Weiguo Wang, Qiuxaing Zhong, Ke Cheng, Lili Tan, Xincheng Huang Department of Clinical Laboratory, The First Hospital of Nanchang, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Xincheng Huang, Email Hxc1817281@163.comPurpose: This study aimed to investigate the molecular characteristics, antimicrobial resistance, and biofilm-forming ability of Staphylococcus aureus isolates from invasive infections.Methods: A total of 92 non-repetitive S. aureus isolates from invasive infections were analyzed by Multi-locus Sequence Typing (MLST), spa typing, and chromosomal cassette mec (SCCmec) typing. Antibiotic susceptibility testing was performed using the disk diffusion and agar dilution methods. Biofilm-forming ability was assessed using crystal violet assay. The presence and expression of biofilm-associated genes were examined using PCR and RT-qPCR.Results: Among the 55 Methicillin-resistant S. aureus (MRSA) and 41 Methicillin-sensitive S. aureus (MSSA) isolates, ST59 (43.6%) predominated in MRSA, while ST7 (39.0%) was most common in MSSA. As expected, MRSA exhibited higher antibiotic resistance rates compared to MSSA isolates. Biofilm formation assays revealed that the majority of isolates (88.5%) produced biofilms, with 26.0% classified as strong producers (OD570 ≥ 1.0) and 62.5% as weak producers (0.2 ≤ OD570< 1.0). MSSA exhibited a higher biofilm-forming ability than MRSA (P < 0.01), with variations across clones. Notably, ST7 isolates displayed greater biofilm-forming ability than other sequence types (ST59, ST5, and ST239). RT-qPCR results revealed that ST7 isolates exhibited higher expression levels of icaA compared to other sequence types.Conclusion: This study revealed significant molecular heterogeneity among invasive S. aureus isolates, with ST59 and ST7 as dominant clones. The strong biofilm-forming capacity of ST7 merits concern given its rising prevalence regionally. Continuous surveillance of emerging successful lineages is critical to help guide infection control strategies against invasive S. aureus infections.Keywords: Staphylococcus aureus, invasive infection, biofilm, ST7

Qianfei Liu,1,&ast; Liping Tan,2 Jianbo He,2 Ruiling Ning,2 Aiping Zeng,2,&ast; Yilin Chen1,&ast; 1Department of Pulmonary and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hu Bei, People’s Republic of China; 2Department of Respiratory Oncology, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aiping Zeng, No. 71 Hedi Road, Nanning City, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email zengaipingone@163.com Yilin Chen, No. 158 Wuyang Avenue, Enshi City, Hu Bei, 445000, People’s Republic of China, Email chenyl891128@163.comPurpose: This study examined the association between plasma D-dimer levels and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients treated with osimertinib.Methods: In this multicenter study, 88 patients with advanced non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) mutations and receiving osimertinib were enrolled. The target independent and dependent variables were the D-dimer levels before osimertinib treatment and OS time, respectively. The t-test or chi-square test was utilized to analyze the variances among various groups. The predictive significance of D-dimer for overall survival (OS) was assessed using Kaplan-Meier survival analysis and the Cox proportional hazard regression model.Results: The selected patients had an average age of 58.01± 10.72 years, with females comprising 54.55%. Based on their D-dimer levels, the patients were categorized into three groups: low-level (< 0.6 mg/L), middle-level (0.6 ~ 2 mg/L), and high-level (≥ 2 mg/L). After accounting for possible confounding variables, the Cox proportional hazard model showed that increased D-dimer levels were linked to a greater likelihood of death (HR 2.28, 95% CI = 1.09 ~ 4.76, p = 0.029). Importantly, there was a significant trend indicating that as D-dimer levels rose, the risk of mortality also increased (p for trend, HR 1.15, 95% CI = 1.03 ~ 1.28, p = 0.012). Consistently comparable outcomes were noted in the majority of subcategories. Patients with low-middle and high D dimer levels had a median OS of 28.6 and 17 months, respectively (p =0.014).Conclusion: In conclusion, elevated levels of D-dimer in the bloodstream were found to have a significant negative correlation with the overall survival (OS) of patients with EGFR-positive non-small cell lung cancer (NSCLC) who underwent treatment with osimertinib.Keywords: D-dimer, EGFR, NSCLC, osimertinib, prognosis

University human research ethics application procedures can be complicated and daunting, especially for international students unfamiliar with the process and the language. We conducted focus groups and interviews with four research higher degree and 21 Master's coursework international students at an Australian university to gain their views on the human ethics application process. We found the most important influences on their experience were: the time it took to do an application; support from supervisors, peers and others; their own language skills; and their lack of familiarity with research ethics procedures. To improve the experience of international students undertaking research involving human research ethics applications, we recommend universities provide guidance on institutional ethics review processes, concepts and terminology, with translations in a range of languages, together with guidance on how to conduct research ethically within and outside the students' own countries. We also recommend curricula be developed to further students' understanding of the importance of ethical research practice, and that these curricula be embedded in undergraduate and postgraduate degree programs and reflected in course learning outcomes.

Yinyi Chen,1 Chunlan Xiao,2 Yubin Liao,2 Liming Tan1 1Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, People’s Republic of ChinaCorrespondence: Liming Tan, Email ndefy84029@ncu.edu.cnObjective: The purpose of the research was to explore the possible risk factors for the development of hypocomplementemia (HC) in rheumatoid arthritis (RA) patients by analyzing their clinical and laboratory features.Methods: This retrospective research contained 501 RA patients, divided into RA patients with HC (n=78) and RA patients without HC (n=423). Demographic characteristics and laboratory test results of RA patients were collected and analyzed, such as age, sex, anti-mutated citrullinated vimentin antibody (Anti-MCV), serum complements (C3, C4), immunoglobulins (IgA, IgG, IgM), hemoglobin (Hb), platelets (PLT) and erythrocyte sedimentation rate (ESR), etc. Spearman correlation was served as assessing the correlations of the levels of serum C3 and C4 with each index. Receiver operating characteristic (ROC) curves were served as assessing the diagnostic efficacy of each index for RA patients with HC. Furthermore, risk factors for the occurrence of HC in RA patients were analyzed by employing binary logistic regression of single and multiple factors.Results: Compared RA patients with HC to without HC, the former were older and had a longer disease duration with increased levels of Anti-MCV, IgM and DAS28 and lower levels of Hb, PLT and ESR; Spearman correlation analysis verified the level of serum Anti-MCV was a negative correlation with C3 (r=− 0.156); the area under the ROC curve (AUC) of PLT in diagnosing RA patients with HC was the largest at 0.65 (95% CI: 0.60– 0.69); binary logistic regression analysis indicated that advanced age (> 66 years), long disease duration (> 62 months), high DAS28 value (> 6.13), the levels of Anti-MCV> 107.68IU/mL, IgM> 1.54g/L, ESR≤ 69.00mm/h, Hb≤ 99.00g/L and PLT≤ 305.00× 109/L were probable risk factors for the occurrence of HC in RA patients.Conclusion: Age and disease duration, DAS28, Anti-MCV, IgM, ESR, Hb, and PLT are closely related to the development of HC in RA patients. Timely monitoring of these indicators can help to evaluate disease activity of RA patients and further improve their prognosis.Keywords: rheumatoid arthritis, hypocomplementemia, risk factors, disease activity

Bo Li,1 Weiqing Wu,1 Aijun Liu,1 Lifeng Feng,1 Bin Li,1 Yong Mei,1 Li Tan,1 Chaoyang Zhang,2 Yangtao Tian1 1Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China; 2Department of Ultrasound Medicine, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of ChinaCorrespondence: Yangtao Tian, Department of Pancreatic Surgery, Shangluo Center Hospital, 37 Shangyang, Shangzhou, Shangluo, Shaanxi, 726000, People’s Republic of China, Email 928763821@qq.comBackground: Severe acute pancreatitis (SAP) can progress to lung and kidney dysfunction, and blood clotting within 48 hours of its onset, and is associated with a high mortality rate. The aim of this study was to establish a reliable diagnostic prediction model for the early stage of severe pancreatitis.Methods: The clinical data of patients diagnosed with acute pancreatitis from October 2017 to June 2022 at the Shangluo Central Hospital were collected. The risk factors were screened by least absolute shrinkage and selection operator (LASSO) regression analysis. A novel nomogram model was then established by multivariable logistic regression analysis.Results: The data of 436 patients with acute pancreatitis, 45 (10.3%) patients had progressed to SAP. Through univariate and LASSO regression analyses, the neutrophils (P < 0.001), albumin (P < 0.001), blood glucose (P < 0.001), serum calcium (P < 0.001), serum creatinine (P < 0.001), blood urea nitrogen (P < 0.001) and procalcitonin (P = 0.005) were identified as independent predictive factors for SAP. The nomogram built on the basis of these factors predicted SAP with sensitivity of 0.733, specificity of 0.9, positive predictive value of 0.458 and negative predictive value of 0.967. Furthermore, the concordance index of the nomogram reached 0.889 (95% CI, 0.837– 0.941), and the area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis was significantly higher than that of the APACHEII and ABISAP scoring systems. The established model was validated by plotting the clinical decision curve analysis (DCA) and clinical impact curve (CIC).Conclusion: We established a nomogram to predict the progression of early acute pancreatitis to SAP with high discrimination and accuracy.Keywords: acute pancreatitis, prediction model, risk factor, nomogram, decision curve analysis

Wang W, Zhong Q, Cheng K, Tan L, Huang X. Infect Drug Resist. 2023;16:7671–7681. Page 7671, Abstract, Methods section, first line, the text “A total of 92 non-repetitive” should read “A total of 96 non-repetitive”. The authors apologize for this error.

Xiufen Wang,1– 3 Ying Wang,1,2 Li Luo,3 Liuting Tan,4 Wenzhi Cai,1 Ling Chen,1 Wei Ren1 1Department of Nursing, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of the Third Pulmonary Disease, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 4Department of Endocrine, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Wei Ren; Ling Chen, Department of Nursing, Shenzhen Hospital, Southern Medical University, 1333 Xinhu Road, Baoan District, Shenzhen, Guangdong Province, 518101, People’s Republic of China, Tel +86-755-23360006, Fax +86-755-23323777, Email renwei196911@163.com; dangdang601@smu.edu.cnIntroduction: Diabetic neurogenic bladder is one of the common complications in patients with diabetic neuropathy. However, studies reporting the prevalence and associated factors of urinary tract infections (UTIs) in patients with diabetic neuropathy are rare. Therefore, the present study aimed to explore the prevalence and influencing factors of UTI in patients with diabetic neuropathy.Methods: A hospital-based cross-sectional study that recruited patients with diabetic neuropathy was conducted from January 2019 to December 2021. Collected data included patient demographic information (age, sex, education level, body mass index), clinical data (duration of diabetes, method of administration), and laboratory tests. Multivariable logistic regression models were used to identify the factors associated with UTI risk. The strength of association was expressed as the odds ratio (OR) and 95% confidence interval (95% CI).Results: A total of 579 patients were recruited (male, 68.2%; overall average age, 57.89 years). Using multivariate analysis with adjustment for confounding factors, female sex (odds ratio [OR]: 4.12; 95% CI: 2.24– 7.60; P < 0.001), hypodermic insulin injection (OR: 2.10; 95% CI: 1.02– 4.35; P = 0.045), chronic kidney disease (OR: 3.12; 95% CI: 1.11– 8.80; P = 0.032), history of UTI (OR = 45.92; 95% CI: 8.62– 244.76; P < 0.001), positive urinary nitrite (OR: 32.87; 95% CI: 7.37– 146.70; P < 0.001), and high residual urine volume (OR: 2.19, 95% CI: 1.17– 4.10; P = 0.014) were independent risk factors for UTI in patients with diabetic neuropathy. Compared with the patients aged < 45 years, UTI prevalence increased 2.91-fold in patients aged 45– 54 years (OR: 3.91; 95% CI: 1.02– 15.03; P = 0.047) and 3.87-fold in those aged ≥ 65 years (OR: 4.87; 95% CI: 1.23– 19.25; P = 0.024).Conclusion: The main findings of this study showed that older age, female sex, hypodermic insulin injection, CKD, history of UTI, and positive urinary nitrite were independent risk factors for UTI in patients with diabetic neuropathy. To minimize the occurrence and resulting disease burden of UTI, knowledge regarding UTI risk factors in patients with diabetic neuropathy is critical to designate interventions.Keywords: epidemiology, prevalence, urinary tract infection, diabetic neuropathy, risk factors

Guang Yang,1,2,&ast; Lishan Tan,1,&ast; Hua Yao,3 Zuying Xiong,1 Jun Wu,4,5 Xiaoyan Huang1 1Division of Renal Medicine, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518000, People’s Republic of China; 2Department of Life Sciences, Yuncheng University, Yuncheng, 044006, People’s Republic of China; 3Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical College, Guilin, 541004, People’s Republic of China; 4Department of Burn and Plastic Surgery, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China; 5Human Histology & Embryology Section, Department of Surgery, Dentistry, Pediatrics & Gynecology, University of Verona Medical School, Verona, Venetia, 37134, Italy&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Huang; Jun Wu, Email huangxiaoyan@pku.org.cn; junwupro@126.comAbstract: Burns are a seriously underestimated form of trauma that not only damage the skin system but also cause various complications, such as acute kidney injury (AKI). Recent clinical studies have shown that the proportion of chronic kidney diseases (CKD) in burn patients after discharge is significantly higher than that in the general population, but the mechanism behind this is controversial. The traditional view is that CKD is associated with hypoperfusion, AKI, sepsis, and drugs administered in the early stages of burns. However, recent studies have shown that burns can cause long-term immune dysfunction, which is a high-risk factor for CKD. This suggests that burns affect the kidneys more than previously recognized. In other words, severe burns are not only an acute injury but also a chronic disease. Neglecting to study long-term kidney function in burn patients also results in a lack of preventive and therapeutic methods being developed. Furthermore, stem cells and their exosomes have shown excellent comprehensive therapeutic properties in the prevention and treatment of CKD, making them increasingly the focus of research attention. Their engineering strategy further improved the therapeutic performance. This review will focus on the research advances in burns on the development of CKD, illustrating the possible mechanism of burn-induced CKD and introducing potential biological treatment options and their engineering strategies.Keywords: inflammation, acute kidney injury, chronic kidney diseases, stem cells, exosomes, sepsis, cytokine storm

Huan Liu,1,2,&ast; Zhiping Yu,3,&ast; Yueguang Liu,4 Mingzhen Li,1,2 Cheng Chen,1,2 Zhiyu Zhu,4 Fang Liu,4 Liming Tan2,3 1Department of Precision Medicine Center, The Second People’s Hospital of Huaihua, Huaihua, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Treatment of Huaihua, Huaihua, People’s Republic of China; 3School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Department of Clinicopathology Center, The Second People’s Hospital of Huaihua, Huaihua, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liming Tan, The Second People’s Hospital of Huaihua, Lulin Road, Huaihua, 418000, People’s Republic of China, Email tanliming1973@126.comPurpose: C-type lectin domain family 4 member M (CLEC4M) has been found to be involved in the occurrence and development of cancer, but its role in NSCLC remains to be fully explored. Our work aims to evaluate the diagnostic and prognostic value of CLEC4M in NSCLC and to investigate the underlying mechanisms of CLEC4M in the immune microenvironment of NSCLC.Methods: Integrating publicly accessible data and clinical tissue samples to verify the expression of CLEC4M in NSCLC. The diagnostic value of CLEC4M was determined by receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis, nomogram plot, univariate and multivariate Cox regression models were performed to evaluate the prognostic impact of CLEC4M on NSCLC patients. The correlation between CLEC4M and tumor immune infiltration was estimated using TIMER and UALCAN databases. Functional assessments including GO, KEGG pathway and GSEA analyses were implemented to illustrate the potential mechanisms of CLEC4M in NSCLC.Results: CLEC4M was significantly downregulated in NSCLC tissue, as confirmed by immunohistochemistry of clinical tissues. The high AUC value of ROC curves demonstrated the diagnostic accuracy of CLEC4M in NSCLC. Additionally, low CLEC4M expression was associated with poor survival in NSCLC patients. Furthermore, CLEC4M was found to be significantly associated with tumor immune infiltration, and CLEC4M may be involved in immune activation and proliferation inhibition through the functional assessment, suggesting that CLEC4M may be a therapeutic target for NSCLC patients.Conclusion: Our findings reveal CLEC4M is significantly downregulated in NSCLC tissues, and illustrate the diagnostic and prognostic value of CLEC4M in NSCLC, as well as its potential serve as an immune-related therapeutic target.Keywords: CLEC4M, non-small cell lung carcinoma, NSCLC, prognosis, diagnosis, tumor immune microenvironment

Ning-Ke Guo,1,2,&ast; Han She,1,&ast; Lei Tan,1 Yuan-Qun Zhou,1 Chun-Qiong Tang,1 Xiao-Yong Peng,1 Chun-Hua Ma,1 Tao Li,1 Liang-Ming Liu1 1State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 2The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Li; Liang-Ming Liu, Email lt200132@163.com; lmliu62@tmmu.edu.cnBackground: Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured.Methods: In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis.Results: The encapsulation rate of Nano PTL was 95± 1.5%, the drug loading rate was 11± 0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL.Conclusion: Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.Keywords: sepsis, nano PTL, intestinal permeability, 5-HTR2A, apoptosis

Bailong Hu,1,2,&ast; Mei Zhang,2,&ast; Zhen Wu,2,&ast; Xiaoyuan Zhang,2,&ast; Xiaohua Zou,1,2 Li Tan,1 Tao Song,1 Xingyu Li1 1Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 2College of Anesthesiology, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Zou, Email zouxiaohuazxh@163.comBackground: Remimazolam tosilate (RT) is a new ultrashort-acting γ-aminobutyric acid subtype A (GABAA) agonist, with the characteristics of rapid onset and offset, minimal cardiorespiratory depression. Currently, few studies have compared the effect of RT and etomidate on hemodynamics during anesthesia induction. Here, we aimed to compare the hemodynamic effects of different doses of RT and etomidate for anesthesia induction in patients undergoing cardiac surgeries.Methods: Patients were recruited from January to September 2022 in this single-center, prospective, randomized, double-blind trial. A total of 117 patients undergoing selective valve replacement surgery were randomly divided into low-dose RT (0.2 mg/kg) group (group LR), high-dose RT (0.3 mg/kg) group (group HR), or etomidate (1.5 mg/kg) group (group E), respectively. The primary outcome was hemodynamic fluctuations (mean arterial pressure fluctuation value [∆MAP]; heart rate fluctuation value [∆HR]) during anesthesia induction. Secondary outcomes included the incidence of adverse drug reactions (injection pain and myoclonus) and adverse cardiovascular events, vital signs at different time points and the cumulative doses of vasoactive drugs.Results: The hemodynamic fluctuations (∆MAP) in group LR and group E were significantly lower than that in group HR. In addition, the incidence of hypotension and the cumulative norepinephrine doses in group E and group LR were also significantly lower than that in group HR. Furthermore, the incidence of injection pain and myoclonus in group LR and group HR were less frequently recorded compared with group E. There were no significant differences in terms of ∆HR, tachycardia, hypertension, severe bradycardia, vital signs at different time points, lactic acid and blood glucose between both groups.Conclusion: Compared with etomidate, low-dose RT (0.2mg/kg) can not only provide stable hemodynamic parameters but also cause fewer adverse reactions when used for anesthesia induction in patients with cardiac disease.Keywords: remimazolam tosilate, etomidate, hemodynamics, cardiac surgery

Lingcan Tan,1 Hong Yu,1 Junyu Yan,2 Chunyuan Liu,3 Kun Xiao,4 Jin Yin,5 Yunxia Zuo,1 Tao Zhu,1 Xiaoqian Deng1 1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology, Karamay Hospital of Integrated Traditional Chinese and Western Medicine, Karamay, People’s Republic of China; 3Department of Anesthesiology, Chongqing Liangping District People’s Hospital, Chongqing, 405200, People’s Republic of China; 4School of Information and Software Engineering, University of Electronic Science and Technology of China, Chengdu, 610054, People’s Republic of China; 5West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Xiaoqian Deng, Department of Anesthesiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People’s Republic of China, Email d_xiaoqian@163.comPurpose: The National Remote Emergency System for Malignant Hyperthermia (MH-NRES) is an applet in China, designed to help anesthesiologists manage MH crisis. However, there is limited information about encountered difficulties in dealing with MH among Chinese anesthesiologists. The purpose of the study was to explore the current competency and encountered difficulties in the management of MH, as a key first step for assessing the potential user needs to develop the MH-NRES.Methods: The hospitals of different levels in different provinces across China were invited to participate in an online survey from November to December 2021. Anesthesiologists completed the online questionnaire containing four sections including demographic information, knowledge, competency, and continuing education about MH.Results: A total of 1357 valid questionnaires were completed from anesthesiologists, most respondents (66.7%, n = 905) correctly answered the MH trigger drugs included volatile anesthetics and succinylcholine. However, most respondents (77.0%, n = 1045) did not know that the recommended initial dose of domestic dantrolene. Up to 83.9% (n = 1138) stated that their hospitals did not store dantrolene for MH emergency. More than half of respondents thought that it would take more than one hour to obtain dantrolene in emergency. Less work experiences, lower levels of hospital and educations and professional titles were associated with lower competency scores in managing MH. Only 31.0% (n = 936) reported that their hospital had ever conducted MH continuing education curricula. Scenario simulation is the training method that most interests the participants (79.0%, n = 1072) but a whopping 46.9% (n = 637) never received simulation.Conclusion: The study indicated that difficulty in obtaining dantrolene, lack of competency in management of MH, difficulty in obtaining professional help, and poor teamwork were the main problems of most anesthesiologists in face of MH.Keywords: malignant hyperthermia, questionnaire, competency, dantrolene, education

Characterizing the temporal uncertainty in palaeoclimate records is crucial for analysing past climate change, correlating climate events between records, assessing climate periodicities, identifying potential triggers and evaluating climate model simulations. The first global compilation of speleothem isotope records by the SISAL (Speleothem Isotope Synthesis and Analysis) working group showed that age model uncertainties are not systematically reported in the published literature, and these are only available for a limited number of records (ca. 15 %, n = 107/691). To improve the usefulness of the SISAL database, we have (i) improved the database's spatio-temporal coverage and (ii) created new chronologies using seven different approaches for age- depth modelling. We have applied these alternative chronologies to the records from the first version of the SISAL database (SISALv1) and to new records compiled since the release of SISALv1. This paper documents the necessary changes in the structure of the SISAL database to accommodate the inclusion of the new age models and their uncertainties as well as the expansion of the database to include new records and the qualitycontrol measures applied. This paper also documents the age-depth model approaches used to calculate the new chronologies. The updated version of the SISAL database (SISALv2) contains isotopic data from 691 speleothem records from 294 cave sites and new age-depth models, including age-depth temporal uncertainties for 512 speleothems.