Search

Chuanchuan Dong, Fei Hu, Zhen Ma, Xinkai Ma, Lulu Zhang, Yupeng Li, Xianglin Du, Liting Feng, Rujie Huo, Yanqing Xing, Peiqi Li, Yanting Dong, Erjing Cheng, Xinrui Tian,&ast; Min Huang&ast; The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinrui Tian, Email tianxr@126.com; Min Huang, Email 147652857@qq.comBackground: The lifting of the regional blockade in early December 2022 in Shanxi Province, China, caused an epidemic of Coronavirus disease 2019 (COVID-19). And the high allergy season from July to September each year.Purpose: To investigate the effect of the COVID-19 epidemic on the respiratory sensitivity status of the population, to provide a scientific and effective basis for the prevention, diagnosis, condition assessment, and treatment of allergic respiratory diseases.Methods: We collected 500 outpatient cases from Shanxi Medical University Second Hospital during the period from July to September 2022 and 500 cases during the period from July to September 2023 and divided them into the pre-COVID-19 epidemic group (the 2022 group) and the post-COVID-19 epidemic group (the 2023 group). We conducted statistical analysis on these patients’ general conditions, pulmonary function test results, laboratory parameters, and fractional exhaled nitric oxide.Results: Compared with 2022, the number of smokers decreased in 2023 (p = 0.007), while the incidence of respiratory allergic diseases such as bronchial asthma and allergic rhinitis increased (p < 0.05). In 2023, the results of pulmonary function tests showed that the positive rate of bronchial provocation/dilatation tests increased (p < 0.001), and the decline in FEV1 during provocation tests became more significant (p < 0.001). At the same time, laboratory results indicated that the count of eosinophils and the level of immunoglobulin E (IgE) in peripheral blood rose (p < 0.001), suggesting that the respiratory sensitivity of the population after COVID-19 infection might have increased.Conclusion: Research results from Shanxi Province, China, indicate that the COVID-19 epidemic leads to increased respiratory sensitization and the incidence of respiratory allergic diseases. This suggests that we should pay attention to the changes in immune status and respiratory sensitivity among the population after COVID-19 infection, to accurately and timely assess and intervene in patients’ conditions.Keywords: COVID-19, airway hyper responsiveness, lung function, IgE

Yunan Ling,&ast; Xiaqi Miao,&ast; Xiang Zhou,&ast; Jingjing Ma, Zhiguang Lin, Qing Li, Mengxue Zhang, Yan Ma, Bobin Chen Department of Hematology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bobin Chen, Department of Hematology, Huashan Hospital, Fudan University, 12 Urumuqi Road (Middle), Shanghai, 200040, People’s Republic of China, Email bbchen@fudan.edu.cnPurpose: Current prognostic scoring systems for newly diagnosed primary central nervous system lymphoma (PCNSL), such as IELSG prognostic score and MSKCC prognostic score, are widely used but have limitations in clinical practice. This study aimed to develop a novel prognostic model based on real clinical data and compare it with existing systems.Patients and Methods: A total of 288 patients newly diagnosed with PCNSL were recruited. Patients were randomly allocated to the development and validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were used to identify the risk factors for overall survival (OS) and construct a nomogram. Additionally, Kaplan-Meier survival curves were plotted to show the stratification ability of the risk groups.Results: Eastern Cooperative Oncology Group performance status (ECOG-PS), albumin, and two inflammatory biomarkers D-Dimer, and neutrophil-to-lymphocyte ratio (NLR)—were independent predictors of inferior OS. The prognostic model demonstrated concordance Index (C-index) of 0.731 and 0.679 in the development and validation cohorts, respectively. In terms of the time dependent area under the curve (AUC) values for OS, the development cohort exhibited values of 0.765, 0.762, and 0.812 for 1-year, 3-year, and 5-year OS, respectively. The corresponding AUC values in the validation cohort were 0.711, 0.731, and 0.840, respectively. The calibration curves showed excellent concordance. The novel prognostic model also provided superior risk stratification for patients with PCNSL compared with existing scoring systems.Conclusion: This study presents a novel prognostic model for predicting the OS of patients with newly diagnosed PCNSL. The model accurately and effectively stratifies the prognosis of patients with PCNSL and offers valuable clinical guidance for decision making.Keywords: PCNSL, prognostic model, risk stratification, NLR, albumin, D-Dimer

Di Shen,1,&ast; Xintian Cai,2,&ast; Junli Hu,2 Shuaiwei Song,1 Qing Zhu,2 Huimin Ma,2 Yingying Zhang,2 Rui Ma,2 Pan Zhou,2 Wenbo Yang,2 Jing Hong,2 Delian Zhang,2 Nanfang Li2 1Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Hypertension Research Laboratory, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, NHC Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region “Hypertension Research Laboratory”, Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, No. 91 Tianchi Road, Urumuqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8564818, Email lnanfang2016@sina.comObjective: Hypertension development and progression are largely influenced by inflammation, which plays a critical role by activating the immune system and causing damage to the vascular endothelium. Metabolic dysfunction-associated fatty liver disease (MAFLD) is also associated with chronic low-grade inflammation, which drives disease progression via metabolic imbalances and adipose tissue dysfunction. This study investigates the relationship between inflammatory indices and MAFLD in hypertensive patients and assesses the predictive accuracy of these indices for MAFLD.Methods: We performed a cross-sectional analysis involving 34,303 hypertensive patients from a Chinese hospital-based registry. The diagnosis of MAFLD was established using metabolic dysfunction criteria alongside evidence of hepatic steatosis confirmed through imaging. Complete blood counts were used to calculate inflammatory indices, including the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI). To assess the relationship between inflammatory indices and MAFLD, multivariable logistic regression was performed with adjustments for potential confounders. The diagnostic performance of these indices was analyzed using receiver operating characteristic (ROC) curves and area under the curve (AUC) calculations.Results: Patients with MAFLD exhibited significantly elevated levels of all inflammatory indices compared to those without. After multivariable adjustment, each standard deviation increase in AISI, SIRI, and SII was associated with a 74%, 62%, and 58% increased odds of MAFLD, respectively. The AUC for AISI was 0.659, indicating moderate diagnostic accuracy. The AUCs for SIRI and SII were 0.626 and 0.619, respectively, while NLR, PLR, and MLR had lower AUCs of 0.593, 0.558, and 0.589, respectively.Conclusion: In hypertensive patients, inflammatory indices, especially AISI, show a strong association with MAFLD, indicating their potential utility in risk stratification within clinical settings. Further research is needed to evaluate the effectiveness of these markers in the management of MAFLD. Keywords: metabolic-dysfunction-associated fatty liver disease, inflammatory indices, hypertension, diagnostic accuracy

Jiaqi Wang, Yujing Jiang, Yamin Yuan, Xin Ma, Tongqin Li, YaTing Lv, Jing Zhang, Liao Chen, Jinquan Zhou, Yanfei Meng, Bei Zhang, Xiaorong Dong, Li Ma Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Li Ma, Email ery_mali@lzu.edu.cnAim: Sepsis is a potentially fatal condition characterized by organ failure resulting from an abnormal host response to infection, often leading to liver and kidney damage. Timely recognition and intervention of these dysfunctions have the potential to significantly reduce sepsis mortality rates. Recent studies have emphasized the critical role of serum exosomes and their miRNA content in mediating sepsis-induced organ dysfunction. The objective of this study is to elucidate the mechanism underlying the impact of miR-122-5p on sepsis-associated liver and kidney injury using inhibitors for miR-122-5p as well as GW4869, an inhibitor targeting exosome release.Materials and Methods: Exosomes were isolated from serum samples of septic rats, sepsis patients, and control groups, while liver and kidney tissues were collected for subsequent analysis. The levels of miR-122-5p, inflammation indices, and organ damage were assessed using PCR, ELISA, and pathological identification techniques. Immunohistochemistry and Western blotting methods were employed to investigate the activation of inflammatory pathways. Furthermore, big data analysis was utilized to screen potential targets of miR-122-5p in vivo.Key Findings: Serum exosomal levels of miR-122-5p were significantly elevated in septic patients as well as in LPS-induced septic rats. Inhibition of miR-122-5p reduced serum pro-inflammatory factors and ameliorated liver and kidney damage in septic rats. Mechanistically, miR-122-5p upregulated TAK1, downregulated SIRT1, and facilitated NF-κB activation.Conclusion: Serum exosomal miR-122-5p promotes inflammation and induces liver/kidney injury in LPS-induced septic rats by modulating the TAK1/SIRT1/NF-κB pathway, highlighting potential therapeutic targets for sepsis management.Keywords: sepsis, exosome, miR-122-5p, NF-κB signaling pathway, sepsis-related liver and kidney injury

Ning Yan,1,&ast; Peng Wu,1,2,&ast; Baozhen Zhu,2,3 Ali Ma,2 Xin Wang,2 Xinrui Hai,2 Xueping Ma,1 Hao Jiang,4 Shaobin Yang1 1Heart Centre & Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2The First Clinical College of Ningxia Medical University, Yinchuan, People’s Republic of China; 3Department of Intervention, Tong Xin City People’s Hospital, Yinchuan, People’s Republic of China; 4Department of Cardiology, Yinchuan Hospital of Traditional Chinese Medicine, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Jiang, Department of Cardiology, Yinchuan Hospital of Traditional Chinese Medicine, Yinchuan, 750004, People’s Republic of China, Tel +18295496850, Email 18295496850@163.com Shaobin Yang, Heart Centre & Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +8613895625229, Email youngshb@126.comBackground: The relationship between mitral regurgitation (MR) and long-term outcomes in Chinese patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remains scarce. This study aimed to elucidate the connection between MR and long-term clinical outcomes following AMI treated with PCI.Methods: In this retrospective study 6940 patients who were diagnosed with AMI were consecutively enrolled from General Hospital of Ningxia Medical University (2014– 2019). The included AMI patients were divided into no MR, mild MR and moderate/serve MR according to MR occurred. All patients were clinically followed for 3-year to collect major adverse cardiac and cerebrovascular events (MACCEs), comprising all-cause death, nonfatal myocardial infarction (MI), rehospitalization for angina, rehospitalization for heart failure (RHF), and stroke. Cox regression models were employed to analyze the association between MR and 3-year clinical outcomes after adjusting for various confounding factors.Results: Among the 6940 patients, 2871 (41.35%) exhibited no MR, 3681 (53.04%) had mild MR, and 388 (5.59%) had moderate/severe MR. The cumulative 3-year incidence of MACCEs was 19.21% overall, with rates of 15.26%, 20.37%, and 37.37% in the no MR, mild MR, and moderate/severe MR groups, respectively (log-rank p < 0.001). Kaplan–Meier survival curves of MR with all-cause death and RHF were also plotted (log-rank p < 0.001). After controlling confounding variables completely, we found that moderate/severe MR compared to none MR was found to be significantly associated with 3-year MACCEs [hazard ratio (HR) = 1.83; 95% confidence interval (CI) = 1.21– 2.77; p = 0.0042], all-cause mortality (HR = 3.11; 95% CI = 1.75– 5.50; p=0.001) and RHF (HR = 1.69; 95% CI = 1.09– 2.62; p= 0.019) through Cox proportional hazards regression models.Conclusion: MR significantly predicted 3-year clinical outcomes in AMI patients undergoing PCI, highlighting the need for physicians to prioritize MR assessment in clinical practice.Keywords: mitral regurgitation, acute myocardial infarction, percutaneous coronary intervention, major adverse cardiac and cerebrovascular events

Hui Liu,1,&ast; Siyun Liu,1,&ast; Pengsheng Ma,1 Long Ma,1 Yuxin Liu,1 Fang Zhao,2 Ru Zhou1,3,4 1School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 3NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 4Ningxia Characteristic Traditional Chinese Medicine Modernization Engineering Technology Research Center, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ru Zhou, School of Pharmacy, Ningxia Medical University, Xingqing, Ningxia, Yinchuan, 750004, People’s Republic of China, Email zhou-ru926@163.com Fang Zhao, General Hospital of Ningxia Medical University, Xingqing, Ningxia, Yinchuan, 750004, People’s Republic of China, Email ysj119zf@163.comObjective: This study focuses on the development and evaluation of nanostructured lipid carriers (NLCs) loaded with aloperine as a potential therapeutic approach for the treatment of pulmonary arterial hypertension.Methods: The NLCs were designed to enhance the solubility, stability, and bioavailability of aloperine, a compound with vasodilatory and anti-inflammatory properties. Through a series of experiments including single-factor experimentation, transmission electron microscopy, high-performance liquid chromatography, in vivo pharmacokinetics, and tissue distribution studies, we assessed the physicochemical properties, drug release profiles, and in vitro and in vivo performance of this novel nanocarrier.Results: The prepared aloperine-loaded NLCs exhibited a milky white and translucent suspension appearance, presenting a quasi-spherical shape under a transmission electron microscope, with an average particle size of (509.48± 30.04) nm and an entrapment efficiency of (64.18± 1.14)%. The drug release profile demonstrated good sustained-release characteristics in vitro, and the formulation remained stable for up to 15 days when stored at 4°C. Compared to the aloperine solution group, the t1/2, AUC(0→t), AUC(0→∞), MRT(0→t), and clearance rate of the aloperine-loaded NLCs were 2.3, 2.96, 3.06, 3.03, and 0.22 times higher, respectively. This indicates that formulating aloperine into NLCs can prolong its circulation time in the body. Furthermore, the concentrations of aloperine in the lungs of the NLCs group were 1.79, 3.78, and 2.30 times higher than those in the solution group at three time points (0.25 h, 1.5 h, 4 h), suggesting that NLCs can increase the accumulation of aloperine in the lungs.Conclusion: Our findings suggest that NLCs loaded with aloperine could offer a promising strategy for the treatment of pulmonary arterial hypertension.Keywords: aloperine, nanostructured lipid carrier, aerosol inhalation, pharmacokinetics

Abstract Background This study sought to investigate the prevalence, correlates, and network structure of the manifested symptoms in gambling disorder (GD) among methamphetamine (MA) use disorder (MUD) patients in China. Methods We interviewed 1069 patients using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA), Chinese version. Besides MA and other substance use disorders, GD was also ascertained by SSADDA. Other psychiatric diagnoses were ascertained, including major depressive episodes (MDEs), antisocial personality disorder, suicide and self-harm, and environmental factors, including childhood experiences. Results Of 1069 participants, 711 met the DSM-5 diagnostic criteria for MUD. Among the 711 participants with MUD, 52.3% met DSM-5 diagnostic criteria for GD. We found that alcohol use together with MA, childhood violent experiences, MDEs, severe MUD, and gambling duration significantly differed between MUD participants with and without GD. In the GD-MUD network, the central symptoms were gambling preoccupation (GD1), giving up important activities (MUD6), financial trouble (GD9), and MA tolerance (MUD5). MA tolerance (MUD5) also served as a bridge symptom across the network, exhibiting substantial associations with gambling preoccupation (GD1). Conclusion GD is prevalent among individuals in treatment for MUD in China. Network analysis suggests that gambling preoccupation and MA tolerance represent central features, and that MA tolerance serves as a bridge across GD and MUD.

Tianqi Zhang,1 Xin Yu,1 Xiaolu Yang,1 Yilun Li,1 Xiaolong Li,2 Li Ma1 1Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Breast Surgery, The Fourth Hospital of Shijiazhuang, Shijiazhuang, People’s Republic of ChinaCorrespondence: Li Ma, Email 47500562@hebmu.edu.cnBackground: We have previously found that S100 calcium-binding protein A7 (S100A7) is strongly associated with chemoresistance in breast cancer (BC). In this study, we investigated whether S100A7 can be used to predict the efficacy of neoadjuvant chemotherapy (NAC) and assessed its relationship with clinicopathological characteristics in BC.Methods: We retrospectively analyzed the clinicopathological data of patients with BC who underwent NAC at the Fourth Hospital of Hebei Medical University between January 2021 and December 2021. The t-test, Wilcoxon test, and chi-square test were used to compare clinicopathological characteristics between the NAC-sensitive and NAC-insensitive groups and assess the relationship between S100A7 expression and clinicopathological characteristics. Binomial logistic regression analysis was used to identify the predictors of NAC efficacy. A prediction model was constructed and visualized using a nomogram for clinical prediction of NAC efficacy.Results: A total of 76 patients with BC who underwent NAC were included in this study; of these patients, 49 were sensitive to NAC, whereas 27 were insensitive to NAC. Statistically significant differences were observed in age, menstrual status, histological grade, T stage, Ki67, and S100A7 expression between the NAC-sensitive and NAC-insensitive groups. Regression analysis showed that age, histological grade, Ki67, subtype, menstrual status, TILs and S100A7 expression were predictors of NAC efficacy. However, only histological grade III (OR, 25.613; 95% CI, 1.254– 523.077; P = 0.035), Ki67 (OR, 9.781; 95% CI, 2.022– 47.317; P = 0.005), TILs (OR, 1.227; 95% CI, 1.064– 1.415; P = 0.005), and S100A7 expression (OR, 0.042; 95% CI, 0.010– 0.174; P< 0.001) were independent predictors. Therefore, we constructed a model incorporating these four characteristics and visualised the model in a nomogram to predict NAC efficacy in clinical settings, with a model prediction accuracy of 0.927.Conclusion: S100A7 may serve as a predictor of NAC efficacy in patients with BC.Keywords: neoadjuvant chemotherapy, breast cancer, S100A7, predictor

Mier Li,1,&ast; Yuncheng Bai,2,&ast; Yanjun Wang,1,&ast; Haoran Xing,1 Yingying Zhang,1 Wenjing Ding,1 Hong Ye,3 Li Ma,1 Weiwei Wang,4 Tianhao Bao1,5 1Department of Science and Education, The Affiliated Mental Health Center of Kunming Medical University, Yunnan Mental Hospital, Kunming, Yunnan Province, 650032, People’s Republic of China; 2Department of Orthopedic Surgery, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, 650032, People’s Republic of China; 3Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China; 4Department of Geriatrics, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China; 5The Second People’s Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe Hani and Yi Autonomous Prefecture, Yunnan Province, 661400, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiwei Wang, Department of Geriatrics, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China, Email doctor_b@whu.edu.cn Tianhao Bao, Department of Science and Education, The Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China, Email baotianhao@kmmu.edu.cnAbstract: Currently, the treatment of schizophrenia remains primarily pharmacological, with approximately 30% of patients diagnosed with treatment-resistant schizophrenia (TRS). Clozapine continues to be the first choice treatment for this subgroup of patients. As the preferred treatment, clozapine offers clear advantages in efficacy; however, its complex and troublesome adverse effects pose significant challenges for psychiatrists. Common side effects include granulocytopenia, intestinal obstruction, myocarditis, cardiomyopathy, constipation, and seizures. The first two complications are easier to manage due to the availability of laboratory monitoring, and improved management strategies are now in place in clinical practice. In recent years, clozapine-induced myocarditis (CIM) has gained considerable attention because of its potentially severe outcomes. However, the mechanism behind its lethality remains unclear, and there is no widely accepted consensus or treatment guideline, which complicates the implementation of targeted prevention in clinical practice. This review aims to summarize the clinical manifestations of CIM, explore the underlying mechanisms, and discuss recent advances in monitoring, diagnosis, and treatment, with the goal of offering constructive recommendations for future clinical management.Keywords: clozapine, myocarditis, mechanism, clinical features, monitoring

Zhiqiang Xie,1 Jianmin Chang,2 Lin Ma,3 Chunping Shen,3 Li Zhang,4 Qian An,5 Hua Wang,6 Xia Dou,7 Yue Zheng,8 Congxiu Ye,8 Ying Gao9 1Department of Dermatology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Key Discipline of Pediatrics, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children‘s Health, Beijing, People’s Republic of China; 4Department of Dermatology, The First Hospital of China Medical University; NHC Key Laboratory of Immunodermatology; National and Local Joint Engineering Research Center of Immunodermatological Theranostics, Shenyang, People’s Republic of China; 5Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 6Department of Dermatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 7Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 8Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 9Department of Dermatology, Capital Institute of Pediatrics, Beijing, People’s Republic of ChinaCorrespondence: Zhiqiang Xie, Peking University Third Hospital, Beijing, People’s Republic of China, Email xiezq66@163.comIntroduction: Atopic dermatitis (AD) is a common inflammatory skin disorder that affects both children and adults, characterized by pruritus and scaly, dry eczematous lesions. This study aimed to gather knowledge on the actual use and effectiveness of Pimecrolimus (PIM) in Chinese patients with mild-to-moderate AD affecting sensitive skin areas in routine clinical practice.Methods: This multicentre and non-interventional study included 130 subjects from China, divided into two age groups (2– 12 years and ≥ 12 years). The primary endpoint was the change in SCORAD index, in AD areas from inclusion to the end of the PIM treatment period.Results: The primary efficacy analysis showed a significant reduction in the SCORAD index from baseline to the end of the PIM treatment period (p < 0.0001). The mean change in SCORAD index (SD) from baseline at visit 2 and visit 3 was − 15.4 (10.50) and − 18.6 (11.57), respectively. The mean Investigator’s Global Assessment (IGA) score decreased from 2.3 at baseline to 0.7 at the end of the study, while the mean itching score decreased from 4.7 at baseline to 0.9 at the end of the study. The mean duration of PIM use was 38.3 days, with similar durations for patients above and below 12 years. There was progressive improvement in the quality of life of the patients with PIM treatment. The median time to first flare was 100 days and no adverse drug reactions or significant adverse events were reported during the study.Discussion: This study provides robust real-world evidence that PIM 1% cream is effective for the treatment of mild-to-moderate AD in Chinese patients, particularly in sensitive skin areas and paediatric population. PIM also offers a TCS-sparing approach, making it a valuable option for managing mild-to-moderate AD.Keywords: atopic dermatitis, pimecrolimus, China, SCORAD index, non-interventional study

Cui Ma,&ast; Ren-Zhen Zhang,&ast; Hong-Yu Lu, Ting-Ting Dou, Li Li, Xing-Ke Yan School of Acupuncture-Moxibustion and Tuina, Gansu University of Traditional Chinese Medicine, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing-Ke Yan, Acupuncture and moxibustion and Massage College of Gansu University of Traditional Chinese Medicine, 35 Dingxi East Road, Lanzhou, People’s Republic of China, Email yanxingke@126.comPurpose: Observing the effects and roles of acupuncture on the morphology and neural coding damage of central amygdala (CeA) neurons in chronic inflammatory pain with depression (CIPD) mice and exploring the central nervous mechanism of acupuncture intervention in CIPD.Methods: A CIPD model was established by injecting Complete Freund’s Adjuvant (CFA) into the left hind foot. Using paw withdrawal latency (PWLs), forced swimming, and open field tests, 40 mice with successfully replicated models were selected and randomly divided into a model group, acupuncture group, and sham acupuncture group, with 12 mice in each group. After treatment, Nissl staining was used to observe the morphology of CeA neurons and the number of Nissl bodies. In vivo multi-channel recordings measured the spontaneous firing frequency, waveform amplitude, inter-spike interval (ISI), and power spectral density (PSD) of CeA neurons.Results: The PWLs in the model and sham acupuncture groups were shortened, the activity time and distance in the central region were reduced, and the forced swimming immobility time increased. The arrangement of CeA neurons is sparse, neurons are damaged, and the number of Nissl bodies is reduced; CeA neurons exhibit abnormal changes in spatiotemporal patterns, with a decrease in spontaneous discharge frequency, discharge amplitude, PSD, and an increase in ISI. The acupuncture group showed prolonged PWLs, increased activity time and distance in the central region, and decreased immobility during forced swimming. The loss of CeA neurons decreased, the cells were arranged neatly, the nucleoli were evident, and the number of Nissl bodies increased. The damage to CeA neural coding was significantly improved, with increased spontaneous discharge frequency, discharge amplitude, PSD, and shortened ISI.Conclusion: Acupuncture may alleviate pain and depressive-like behaviors in CIPD mice and reduce neuronal damage, possibly through mechanisms related to improving the spatiotemporal characteristics of neural coding impairments in the CeA brain region.Keywords: acupuncture, chronic inflammatory pain with depression, central amygdala, neural coding

Zhishou Meng,1 Dongqin He,1– 3 Honggang Wang,1– 3 Lijuan Ma,1 Le Guan,1 Yongning Ai,1 Jianxin Yang,1 Ruxing Liu1– 3 1Department of Pain Management, Second Hospital of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Department of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 3Department of Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Second Hospital of Shanxi Medical University, Taiyuan, 030001, People’s Republic of ChinaCorrespondence: Ruxing Liu, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, Shanxi Province, People’s Republic of China, Email liuruxing0924@163.comObjective: The purpose of this study was to conduct a bibliometric analysis of the literature on stem cell therapy for osteoarthritis (OA) to visualize recent developments, identify hot spots, and determine trends in the field.Background: OA is a chronic disease that affects the joints and their surrounding tissues, leading to progressive damage to the articular cartilage and ultimately to the subchondral bone and the surrounding synovial structures. OA is a disabling disease with an increasing incidence and prevalence in the general population. Modulation of immunity and inflammation and improvement of cell survival and differentiation through multidirectional differentiation of stem cells is a potential strategy for the treatment of OA.Methods: We searched for publications on “stem cell therapy for osteoarthritis” in the Web of Science (WOS) core collection database from 1998– 2024 and summarized the results, including year of publication, country, institution, author, and collaborative network generated using VOSviewer and Citespace. In addition, research trends were identified. Finally, we summarized the hot topics and identified future research trends.Results: This study ultimately included 2341 valid papers, with a trend toward a gradual increase in the number of publications over time. The country, institution, author, and journal with the highest number of publications and citations were China, the University of California system, Sekiya I, and Osteoarthritis and Cartilage, respectively. High-frequency keyword clusters included cell therapy, stem cells, tissue engineering, and extracellular vesicles.Conclusion: Through visualization and analysis, we elucidated the trends and research hotspots in the field over the past five years. The analysis revealed that stem cell transplantation and exosome therapy for OA may be the focus of future research. This study lays the foundation for future research and clinical work on stem cell therapy in this field.Keywords: osteoarthritis, stem cell, tissue engineering, exosome, extracellular vesicles, bibliometric analysis, VOSviewer, citespace

With the improvement of the digitization degree of the aircraft，a large amount of multi-source and heterogeneous data will be generated throughout the full life-cycle of an aircraft，which plays a crucial role in ensuring its safety. This article reviews common types of data sources within the aircraft's life-cycle，including initial airworthiness design data，operational reliability data，operational maintenance data，and onboard equipment data. By combining the data characteristics of different data source types，the article introduces measures for the fusion application of multi-source heterogeneous data and provides a detailed analysis of the four stages that data fusion technology has undergone. On this basis，the fault diagnosis method of fusion data is introduced. Compared with the fault diagnosis analysis of traditional single data source，it is concluded that the fusion application of multi-source heterogeneous data can analyze the fault causes more accurately，and play a role in assisting troubleshooting and maintainability design，which is the development trend of data application technology in aircraft fault diagnosis.

The low-carbon transformation of data centers is highly significant for achieving carbon peaking and carbon neutrality. This study compared and analyzed the overall situation of data centers in China. Three variables—energy efficiency improvement rate, proportion of non-fossil energy—and negative emission technology intensity were introduced based on the CO2 emission and intensity targets of China in key years, and the total CO2 emissions of the data centers were projected via scenario analysis. The results demonstrated that the power consumption of the data centers increased gradually; the carbon emissions first increased and then decreased, and the power usage effectiveness (PUE) of the data centers decreased gradually. The carbon peak time of the three scenarios is 2030, and the expected times to achieve carbon neutrality are 2059, 2057, and 2055 in the three scenarios. In light of the goal to achieve carbon neutrality by 2060, the data center industry should further improve the energy efficiency utilization rate, increase the proportion of non-fossil energy, strengthen the technological innovation of carbon capture and storage, and enhance the level of carbon sinks.

Circulating water is used as the working medium in water-based chillers. Salt ions, such as calcium in circulating water, may precipitate during long-term operation, resulting in the attenuation of heat transfer performance. The application of small-diameter tubes in heat exchangers may lead to more prominent fouling problems. This study developed an accelerated fouling method to evaluate water fouling risk. The most typical operating conditions for water-based chillers were selected as the experimental conditions. The test samples included small diameter (5 mm) smooth tubes, with 7 mm smooth tubes selected for the control experiment. The experimental conditions include a circulating water inlet temperature of 60 ℃, a flow rate of 1 m/s, a foulant mass concentration of 800 mg/L, and a test time of 0-400 h. The results revealed that the total fouling mass was 39.5% higher and required fouling time was 17.6% shorter when comparing the 5 mm and 7 mm smooth tubes; the small diameter tubes had a larger total fouling mass and higher fouling rate. The heat transfer coefficients of the 5 mm and 7 mm tubes after fouling decreased by 12.5% and 9.7%, respectively, and the pressure drops increased by 50.6% and 10.4%, respectively, demonstrating a more severe heat transfer performance deterioration of small diameter tubes after fouling. The microscopic observation results of the fouling layer morphology demonstrated that the fouling layer in 5 mm tubes is a form of compact lamellar scaling, which is more difficult to remove compared with the 7 mm tube; therefore, the fouling risk should be considered when promoting the application of small diameter tubes in chillers.

The charging and discharging demand of electric vehicles is closely related to the load balance of the power grid. In order to effectively alleviate the load pressure caused by the disorderly connection of large-scale electric vehicle (EV) to the power system during the peak period of electric vehicle charging and discharging, a research on electric vehicle charging and discharging scheduling based on comprehensive energy grid load balance is proposed. In vehicle-to-grid (V2G) mode, the architecture and requirements of EV charging and discharging scenarios are analyzed. The upper layer takes the minimum peak valley difference as the objective function, and the lower layer takes the minimum charging cost as the objective function. The corresponding constraints are set and a dual layer scheduling model is established for electric vehicle charging and discharging. Innovatively using the roulette wheel selection algorithm combined with the crisscross optimization algorithm (CSO) to solve the dual layer scheduling model of electric vehicle charging and discharging, and obtain the optimal electric vehicle charging and discharging scheduling scheme. The experimental results show that the proposed method can effectively reduce the peak-valley difference and scheduling time consuming, and obtain more satisfactory scheduling scheme.

Abstract Background Early diagnosis of biliary atresia (BA) is crucial for improving patient outcomes, yet remains a significant global challenge. This challenge may be ameliorated through the application of artificial intelligence (AI). Despite the promise of AI in medical diagnostics, its application to multimodal BA data has not yet achieved substantial breakthroughs. This study aims to leverage diverse data sources and formats to develop an intelligent diagnostic system for BA. Methods We constructed the largest known multimodal BA dataset, comprising ultrasound images, clinical data, and laboratory results. Using this dataset, we developed a novel deep learning model and simplified it using easily obtainable data, eliminating the need for blood samples. The models were externally validated in a prospective study. We compared the performance of our model with human experts of varying expertise levels and evaluated the AI system’s potential to enhance its diagnostic accuracy. Results The retrospective study included 1579 participants. The multimodal model achieved an AUC of 0.9870 on the internal test set, outperforming human experts. The simplified model yielded an AUC of 0.9799. In the prospective study’s external test set of 171 cases, the multimodal model achieved an AUC of 0.9740, comparable to that of a radiologist with over 10 years of experience (AUC = 0.9766). For less experienced radiologists, the AI-assisted diagnostic AUC improved from 0.6667 to 0.9006. Conclusions This AI-based screening application effectively facilitates early diagnosis of BA and serves as a valuable reference for addressing common challenges in rare diseases. The model’s high accuracy and its ability to enhance the diagnostic performance of human experts underscore its potential for significant clinical impact.

Abstract Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To refine the genetic map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 46 that have not been previously reported. These include susceptibility variants at loci in which the therapeutic targets IL17RA and AHR are encoded, and deleterious coding variants supporting potential new drug targets (including in STAP2, CPVL and POU2F3). We conducted a transcriptome-wide association study to identify regulatory effects of psoriasis susceptibility variants and cross-referenced these against single cell expression profiles in psoriasis-affected skin, highlighting roles for the transcriptional regulation of haematopoietic cell development and epigenetic modulation of interferon signalling in psoriasis pathobiology.

Shuwen Lu,1 Haoyu Li,2,3 Xirui Yang,1 Chao Ma,4 Xian Li5 1Department of Ophthalmology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 2Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, People’s Republic of China; 4Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5School of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UKCorrespondence: Shuwen Lu, Department of Ophthalmology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, 450052, People’s Republic of China, Email lushuwen9900@163.com Haoyu Li, Hunan Clinical Research Centre of Ophthalmic Disease, No. 139, Renmin Road Central, Changsha, 410011, People’s Republic of China, Email med.dr.lihy@gmail.comBackground: Ocular trauma is a visually and economically devastating cause of visual loss. This study investigated the prevalence and clinical characteristics of ocular trauma in central and northern China, and assessed prognostic factors.Methods: Cases of ocular trauma that underwent surgical treatment in a tertiary hospital in China between January 1, 2012, and December 31, 2023, were reviewed. All patient data were collected, including demographic information, type of injury, cause of injury, overall condition, number of surgeries, structural damage, surgical complications, and initial and final visual acuity (VA). We constructed three models to explore the prognostic factors of final VA: linear regression, regression tree, and random forest.Results: Over 12 years, 1019 patients (1019 eyes) with ocular trauma underwent surgery, of which 836 were open globe injuries. Patients were predominantly male (80.8%), with an average age of 31.1 years. The most at-risk age group was 41– 50 years old. Farmers (33.3%) and students (20.9%) were the most common occupations. The most frequent complication was vitreous hemorrhage (95.7%). Most patients required three surgeries (42.2%). During vitrectomy, proliferative vitreoretinopathy and elevated intraocular pressure were observed in 735 patients (72.1%). The final VA ranged from 0 to 3.00 logMAR with a mean of 1.10± 0.43 logMAR. Among the three models, the random forest performed the best. Ocular structural damage and surgical complications, along with the number of surgeries, were important factors affecting the visual prognosis.Conclusion: Individuals at high risk should be given extra care, as traumatic and surgical complications are the main prognostic factors.Keywords: eye injuries, visual acuity, prognosis, predictive learning models

Xuntao He,1,&ast; Shibin Chen,2,&ast; Quyi Zhang,1 Shu He,2 Lin Yang,1 Jun Ma1 1School of Public Health, Chongqing Medical University, Chongqing, 401331, People’s Republic of China; 2Chenjiaqiao Hospital, Chongqing, 401331, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Ma, School of Public Health, Chongqing Medical University, No. 61 University Town Middle Road, Shapingba District, Chongqing, 401331, People’s Republic of China, Tel +86-13983086198, Email majun@cqmu.edu.cnBackground: Research highlights poor mental health among healthcare workers, but limited attention has been given to the mental health literacy and professional psychological help-seeking attitudes of primary healthcare workers.This study investigates the relationship between primary healthcare workers’ mental health literacy and their attitudes toward professional psychological help-seeking. It also explores the chain mediating roles of social support and mental illness stigma in this relationship.Methods: We conducted the study among primary healthcare workers in Shapingba District, Chongqing, China. The study utilized demographic questionnaires, the Multiple Mental Health Literacy Scale, Social Support Rating Scale, Perceived Devaluation-Discrimination Scale, and Attitudes Toward Seeking Professional Psychological Help Scale. We applied Pearson correlation, multiple linear regression, and structural equation modeling (SEM) for data analysis.Results: Correlation analysis revealed positive associations between mental health literacy and help-seeking attitudes, while stigma negatively impacted these attitudes. The regression analysis demonstrated that mental health literacy, social support, and mental illness stigma significantly influenced attitudes toward professional psychological help-seeking, with the adjusted R square being 0.402. Specifically, social support and stigma acted as partial mediators in the relationship between mental health literacy and help-seeking attitudes. SEM confirmed a significant chain mediation effect, with social support and stigma jointly mediating the link between mental health literacy and help-seeking attitudes, explaining 27.46% of the variance.Conclusion: This study underscores the critical role of mental health literacy, social support, and mental illness stigma in shaping primary healthcare workers’ attitudes toward professional psychological help-seeking. Strengthening these factors can enhance their mental health outcomes and encourage more proactive help-seeking behavior. Implementing targeted interventions in training programs to reduce stigma and promote social support could improve help-seeking behaviors and overall mental health within healthcare settings.Keywords: primary healthcare worker, mental health, social support, mental illness stigma, professional psychological help-seeking attitudes

Wanting Xu,1– 3 Xiaolin Jieda,1– 3 Yue Wu,1– 3 Fengling Du,1– 3 Lu Ma,1– 3 Lijuan Luo,1– 3 Dong Liu,1– 3 Ling Guo,3 Jing Liu,3 Wenbin Dong1– 3 1Division of Neonatology, Department of Pediatrics, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Sichuan Clinical Research Center for Birth Defects, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of ChinaCorrespondence: Wenbin Dong, Division of neonatology, Department of Pediatrics, the Affiliated Hospital of Southwest Medical University; Department of Perinatology, The Affiliated Hospital of Southwest Medical University; Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, People’s Republic of China, Email dongwenbin2000@163.comPurpose: Exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) hold great potential for treating bronchopulmonary dysplasia (BPD); however, safety concerns and effects of intranasal administration remain unexplored. This study aimed to explore the safety of hUC-MSCs and Exos and to investigate the efficacy and bio-distribution of repeated intranasal Exos administration in neonatal BPD models.Methods: Characteristics of hUC-MSCs and Exos were analyzed. A subcutaneous tumor formation assay using a single dose of hUC-MSCs or Exos was conducted in Crl:NU-Foxn1nu mice. Vital signs, biochemical indices, pathological alterations, and 18F-FDG microPET/CT analysis were examined. Pulmonary pathology, three-dimensional reconstructions, ultrastructural structures, in vivo and ex vivo bio-distribution imaging analyses, enzyme-linked immunoassay assays, and reverse transcription-quantitative polymerase chain reaction analyses of lung tissues were all documented following intranasal Exos administration.Results: Characteristics of hUC-MSCs and Exos satisfied specifications. Crl:NU-Foxn1nu mice did not exhibit overt toxicity or carcinogenicity following a single dose of hUC-MSCs or Exos after 60 days of observation. Repeated intranasal Exos administration effectively alleviated pathological injuries, restored pulmonary ventilation in three-dimensional reconstruction, and recovered endothelial cell layer integrity in ultrastructural analysis. Exos steadily accumulated in lung tissues from postnatal day 1 to 14. Exos also interrupted the epithelial–mesenchymal transition and inflammation reactions in BPD models.Conclusion: As a nanoscale, non-cellular therapy, intranasal administration of Exos was an effective, noninvasive treatment for BPD. This approach was free from toxic, tumorigenic risks and repaired alveolar damage while interrupting epithelial–mesenchymal transition and inflammation in neonatal mice with BPD.Plain language summary: This study aimed to address the safety concerns surrounding hUC-MSCs and Exos and to investigate, for the first time, the bio-distribution and efficacy of repeated intranasal administration of Exos in a neonatal BPD model. Repeated intranasal Exos administration significantly ameliorated pulmonary pathological injuries and predominantly accumulated in the lungs, as demonstrated by fluorescence tracking from the first day after birth. Furthermore, Exos reduced epithelial–mesenchymal transition and inflammatory cytokines in BPD models. These findings suggest that intranasal administration of Exos is a safe, effective, and noninvasive approach to treat BPD without toxic or tumorigenic risks. Intranasal exos as a nanoscalic, non-cellular therapy has a significant potential for the treatment of BPD, although further examinations are necessary to fully clarify their mechanisms and long-term effects. Keywords: BPD, Exos, intranasal administration, safety, efficacy, bio-distribution analysis

Yixuan Wu,1 Jiaxin Han,1 Yawen Cheng,1 Meng Wei,1 Fude Liu,1 Chen Chen,1 Ying Tan,1 Wenlong Ma,1 Jia Yu,1 Jianfeng Han,1 Guogang Luo,1,2 Kang Huo1,2 1Department of Neurology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Center for Brain Science, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaCorrespondence: Kang Huo; Guogang Luo, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi, People’s Republic of China, Tel +8615202971941 ; +8613991974085, Email huokang@xjtufh.edu.cn; lguogang@163.comBackground: Some acute ischemic stroke (AIS) patients due to large-vessel occlusion, who underwent endovascular thrombectomy (EVT), continue to experience unfavorable outcomes. Furthermore, the impact of internal carotid artery (ICA) tortuosity remains uncertain. This study aimed to determine the value of ICA tortuosity and clinical features in predicting 3-month unfavorable outcome and early neurological deterioration (END) after EVT in AIS patients through nomograms.Methods: A total of 313 AIS patients treated with EVT at the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed and randomized into two cohorts: training cohort (n=219) and validation cohort (n=94). After the selection of relevant features, nomograms for predicting the 3-month unfavorable outcome (mRS > 2) and END (an increase in NIHSS score of ≥ 4 within 24 hours) were established. The predictive accuracy of the nomograms was evaluated using ROC curves, calibration plots, and decision curve analysis (DCA).Results: Among 313 patients, ICA tortuosity was observed in 19.50% (extracranial) and 21.10% (cavernous) of patients. Furthermore, 53.30% of patients experienced a 3-month unfavorable outcome, while END occurred in 15.70%. The independent predictors for the 3-month unfavorable outcome included age, NIHSS score, puncture-to-recanalization time, eTICI score, and blood glucose. The addition of two tortuosity features (extracranial and cavernous ICA tortuosity) resulted in a significant improvement in model differentiation. The nomogram that included ICA tortuosity achieved an AUC of 0.826 and 0.803 in the training and validation cohorts. ASPECT score, occlusion site, number of retriever passes, and blood glucose were identified as factors associated with END. The AUC was 0.770 and 0.772 in the training and validation cohorts. However, the incorporation of ICA tortuosity did not significantly enhance the model for predicting END.Conclusion: ICA tortuosity characteristics significantly improve the discrimination of the nomogram model in predicting the 3-month unfavorable outcome. This can be used as guidance in clinical decision-making.Keywords: nomogram, internal carotid artery tortuosity, endovascular thrombectomy, acute ischemic stroke, early neurological deterioration, 3-month unfavorable outcome

Baolan Ji,1,&ast; Shuwei Shi,1,2,&ast; Hongyan Zhao,1,2 Xuan Ma,1,2 Jie Sheng,1,2 Bo Ban,3 Guanqi Gao1 1Department of Endocrinology, Linyi People’s Hospital, Linyi, Shandong, 276034, People’s Republic of China; 2School of Clinical Medicine, Shandong second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 3Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanqi Gao, Department of Endocrinology, Linyi People’s Hospital, North Side of the Intersection of Wohushan Road and Wuhan Road in Lanshan District, Linyi, Shandong, 276034, People’s Republic of China, Email guanqi_gao@yeah.net Bo Ban, Department of Endocrinology, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272029, People’s Republic of China, Email banbo2011@163.comAim: Diabetes is an independent risk factor for thyroid nodules (TNs), however, the influencing factors of TNs have not been fully clarified under the condition of diabetes. Previous studies have shown a connection between pituitary-thyroid hormone (TH) functions and TNs in different populations. However, the potential link in euthyroid patients with diabetes is unclear. We aimed to explore the correlates of TNs in euthyroid type 2 diabetes (T2D) patients.Methods: This cross-sectional study included 1965 euthyroid adults with T2D. Clinical and biochemical data, including TH and relevant covariates were collected. TNs were evaluated using ultrasound. Univariate and multivariate logistic regression analyses were performed to identify factors associated with TNs, with analyses stratified by sex.Results: The overall prevalence of TNs was 51.9%. The prevalence of TNs was higher in females. Stratified by sex, the results from univariate and further logistic regression analyses showed that free triiodothyronine (FT3) (OR: 1.381; 95% CI: 1.066– 1.790) and thyroid-stimulating hormone index (TSHI) (OR: 0.740; 95% CI: 0.584– 0.937) were independently correlated with TNs only in females, while no TH-related indicators entered the regression model in males.Conclusion: The relationship between TH and related indices with TNs exhibited sex differences. Specifically, FT3 and TSHI were independently associated with TNs in females. These findings underscore the importance of evaluating TH and related indices for early monitoring and management of TNs, particularly in euthyroid female T2D patients.Keywords: pituitary-thyroid hormone, type 2 diabetes, thyroid nodules, correlates

Jun Ma,1,&ast; Li Wang,1,&ast; Xubin Zheng,2 Haiyan Cui,1 Wei Sha1– 3 1Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyan Cui; Wei Sha, Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +861861687019 ; +8613671758200, Email cuihaiyan23@163.com; shfksw@tongji.edu.cnPurpose: New economic, rapid, and efficient diagnostic methods are desirable for the control of tuberculosis. This study aimed to evaluate the performance of a dual-gene qPCR melting curve assay (DGPMC) in detecting tuberculosis among patients with suspected pulmonary tuberculosis.Patients and Methods: The DGPMC assay based on rpoB and IS6110 gene sequences has been established for detection of Mycobacterium tuberculosis. A prospective study was conducted among adult patients with suspected pulmonary tuberculosis from June 2021 to September 2023 at Shanghai Pulmonary Hospital, China. All patients received symptom assessment, high-resolution chest CT scan, and bronchoscopy. Bronchoalveolar lavage fluid was collected for mycobacterial culture and acid-fast staining, GeneXpert MTB/RIF, and DGPMC assay. The diagnostic performance of DGPMC assay was evaluated against the composite reference standard.Results: Overall, 240 patients were included in this trial, including 80 (33.3%) asymptomatic patients. Clinical diagnosis of tuberculosis was confirmed in 191 (79.6%) patients and 49 (20.4%) patients were confirmed without tuberculosis. The overall sensitivity of the DGPMC assay was 55.0% (95% CI: 47.6– 62.1%), and the corresponding specificity was 85.7% (95% CI: 72.1– 93.6%) in the diagnosis of tuberculosis. The sensitivity of DGPMC assay was higher than that of GeneXpert test (55.0% vs 47.1%, P = 0.038). The Youden index and weighted Youden index of the DGPMC assay were 40.7% and 28.4%, respectively. Subgroup analyses demonstrated that the sensitivity was 32.4% (95% CI: 22.3– 44.4%) in the individuals with negative results for both culture and GeneXpert test. The DGPMC assay performed significantly better than the melting curves based on rpoB gene or IS6110 gene alone (P = 0.0000; P = 0.0020).Conclusion: The DGPMC assay is an alternative tool favorable for the detection of tuberculosis in patients with suspected pulmonary tuberculosis, especially in the patients with low bacterial load.Keywords: pulmonary tuberculosis, polymerase chain reaction, melting curve, diagnostic performance

Cheng Ma,1,&ast; Bo-Ching Chen,2,&ast; Mei-Yen Chen3 1Department of Physical Education, University of Shanghai for Science and Technology, Shanghai 200093, People’s Republic of China; 2Undergraduate Program of Sports Coaching, CTBC Business School, Tainan 709301, Taiwan; 3Graduate Institute of Sport, Leisure and Hospitality Management, National Taiwan Normal University, Taipei 106308, Taiwan&ast;These authors contributed equally to this workCorrespondence: Mei-Yen Chen, Email meiyen686@gmail.comPurpose: To explore the impact and mechanism of weight status on the disordered eating behavior of university students, this study conducted a moderated chain mediation model based on the Escape Theory and the Strength Model of Self-Control.Methods: This was a cross-sectional online study conducted at a university in Shanghai. The questionnaire was distributed via communication tools such as WeChat from March 6 to 15, 2022, receiving 2618 valid responses. The moderated chain mediation model was empirically examined with 10,000 Bootstrap samples using AMOS software.Results: (1) Weight status can indirectly predict disordered eating behavior through the mediating effect of body dissatisfaction (β = 0.24, 95% CI: 0.22– 0.26, p < 0.001); (2) Body dissatisfaction and negative affect play a chain mediation role in the positive impact of weight status on disordered eating behavior (β = 0.01, 95% CI: 0.01– 0.02, p < 0.001); (3) Physical activity moderates the positive impact of negative affect on disordered eating behavior (Diff = − 0.11, t = 2.20, p < 0.05) and further plays a moderating role in the chain mediation model (Diff = − 0.01, t = 2.30, p < 0.05). Specifically, the higher the level of physical activity among university students, the weaker the impact of negative affect on disordered eating behavior, and the weaker the chain mediation effect; (4) The level of physical activity moderates the relationship between weight status, body dissatisfaction, and disordered eating, suggesting that the higher the level of physical activity, the stronger the mediating role of body dissatisfaction between weight status and abnormal eating (Diff = 0.12, t = 2.74, p < 0.05).Conclusion: These findings revealed the pathways through which weight status affects the eating behavior of university students and how physical activity might weaken or strengthen this impact. This research supplements prior studies and offers insight into health promotion for university students.Keywords: body shape, body dissatisfaction, disordered eating behavior, university students, physical activity level

Xiaoqiang Wang,1 Zhixin Jiang,1 Xiubin Ma2 1Tianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, People’s Republic of China; 2Qingdao Eye Hospital, Shandong First Medical University, Qingdao, People’s Republic of ChinaCorrespondence: Xiubin Ma, Shandong Eye Institute, Shandong First Medical University, Qingdao, 266071, People’s Republic of China, Tel +86-532-85876380, Email maxiubin2005@126.com Zhixin Jiang, Tianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, 300020, People’s Republic of China, Email zhixin.jiang@outlook.comPurpose: To evaluate the clinical effects of direct cyclopexy in the treatment of traumatic cyclodialysis cleft.Methods: This is a retrospective case study. Patients with traumatic cyclodialysis cleft, who were treated with direct cyclopexy and had complete medical records at Tianjin Eye Hospital between February 2021 and August 2022 were selected. The detailed characteristics of the 23 patients were analyzed. Preoperative and postoperative visual acuity, intraocular pressure (IOP), and the extent of ciliary detachment were recorded. All patients were followed up for six months.Results: 19 of the 23 patients who underwent single direct cyclopexy, the other 4 patients with severe posterior segment damage underwent direct cyclopexy combined with vitrectomy, suprachoroidal drainage, etc. After surgery, 22 of the 23 patients successfully reset the ciliary body, including four patients who underwent combined operations, which showed a statistically significant difference (P < 0.01). The mean preoperative IOP was 6.48 ± 1.62 mmHg and it has a different degree of rebound in 21 cases reaching 13.29 ± 2.11 mmHg on 6 months after operation, including 6 cases of transient high intraocular pressure (> 21 mmHg) (P < 0.01). Best corrected visual acuity was increased from preoperatively 0.60 ± 0.21 logMAR to 0.38 ± 0.26 log MAR postoperatively, in which the vision > 0.3 logMAR reached 65.2% (P < 0.01).Conclusion: Direct cyclopexy with or without vitrectomy is an effective method for treating traumatic ciliary body detachment.Keywords: cyclodialysis cleft, trauma, direct cyclopexy, intraocular pressure

Ruoyu Zhao,1 Lei Ma,2 Joan Li,3 Sen Liu,1 Dalong Yang,2 Guobin Liu,1 Sidong Yang4 1Department of Orthopedic Surgery, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Spine Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Medical School, Faculty of Medicine, the University of Queensland, Brisbane, Queensland, Australia; 4Department of Orthopedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Sidong Yang, Department of Orthopedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, People’s Republic of China, Email sidongyang@hebmu.edu.cn Guobin Liu, Department of Orthopedic Surgery, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China, Email liuguobin@hebmu.edu.cnPurpose: This study aimed to investigate the protective effect of adipose tissue-derived exosomes (AT-Exo) on rat nucleus pulposus cells (NPCs).Methods: Ultracentrifugation was used to extract exosomes from rat adipose tissue. Transmission electron microscopy (TEM), Western blot, and nanoparticle tracking analysis (NTA) were used to characterize the exosomes. Tert-butyl hydrogen peroxide (TBHP) was used to induce apoptosis of rat NPCs. Cell viability was determined by CCK-8 assay. AT-Exo was administered to investigate its effect on rat NPCs using Western blot and immunofluorescence staining.Results: AT-Exo was successfully extracted and characterized by NTA, TEM, and Western blots. Uptake assay showed that AT-Exo can be taken up by the NPCs. TBHP (60 μM) resulted in decreased cell viability and increased apoptosis of NPCs. Interestingly, AT-Exo protected NPCs against TBHP, indicated by increased cell viability, decreased apoptosis, upregulated Aggrecan and type II collagen deposition, and downregulated matrix metalloproteinase 3/13.Conclusion: In summary, rat adipose tissue-derived exosomes can increase the levels of Aggrecan, type II collagen, and Bcl2, and decrease the levels of matrix metalloproteinase 3/13, cleaved caspase3, and Bax. Therefore, rat adipose tissue-derived exosomes can maintain metabolic balance of extracellular matrix and protect against apoptosis in rat nucleus pulposus cells.Keywords: exosome, adipose, intervertebral disc degeneration, nucleus pulposus, extracellular matrix

Weiwei Jing, Yushan Ma, Yantong Wan, Hao Li Department of Anesthesiology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Hao Li, Department of Anesthesiology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, 610041, People’s Republic of China, Tel/Fax +86 028 85503753, Email lihao0510@163.comBackground: Post-dural puncture headache (PDPH) is the most common and troublesome complication following iatrogenic puncture of the dura. This study aims to evaluate the efficacy and safety of intrathecal or epidural saline injection to prevent PDPH.Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library, supplemented by a manual search of reference lists of related articles. Studies were eligible if they compared intrathecal or epidural injection or continuous saline infusion with no intervention in patients with accidental or intentional dural puncture. Trials reporting PDPH outcomes were considered eligible. The type of surgeries and patient populations were not restricted. Risk ratios (RRs) with 95% confidence intervals (CI) were calculated for the risk estimate of dichotomous outcomes. The funnel plot, Egger, and Begg tests were performed to assess the publication bias.Results: We identified 13 studies involving 1589 patients, revealing a high publication bias. Normal saline injection reduced the incidence of PDPH (RR=0.57, 95% CI: 0.43 to 0.74, P< 0.0001, I2=66%, P-heterogeneity=0.0004) and the requirement for an epidural blood patch (RR=0.37, 95% CI: 0.25 to 0.54, P< 0.00001, I2=29%, P-heterogeneity=0.23).Conclusion: Saline administration after dural puncture appears to be a promising option for preventing PDPH. However, heterogeneity among the studies and publication bias with positive results limits the available evidence. Therefore, further large-scale randomized controlled trials are needed to confirm our findings.Register: CRD42022342509.Keywords: dural puncture, saline, post-dural puncture headache, meta-analysis

Jing Zhang,&ast; Yue Chen,&ast; Duanni Xu, Shaoyin Ma, Yichuan Gan, Yuwu Luo Guangzhou Dermatology Hospital, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Chen; Yuwu Luo, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, People’s Republic of China, Email cheny767@mail3.sysu.edu.cn; lyw202407@163.comAbstract: Acute generalized exanthematous pustulosis (AGEP) is a rare, painful, and pruritic drug-induced rash characterized by sterile pustules on an erythematous base, followed by desquamation. While commonly induced by antibiotics, cases associated with antineoplastic drugs have become more frequent in recent years. Here, we report a 76-year-old Chinese male with lung large-cell neuroendocrine carcinoma who developed erythema and pustules on his left lower leg, which spread to the trunk and limbs after the fourth cycle of immunotherapy and chemotherapy. Despite initial treatments with antihistamines, antibiotics, and systemic glucocorticoids, the patient’s condition worsened with the development of extensive pustules and fever. Histopathological and laboratory findings confirmed AGEP, with elevated IL-17 levels. Following the discontinuation of immunotherapy and administration of the anti-IL-17 monoclonal antibody ixekizumab, the patient showed rapid improvement within 5 days, marked by a significant reduction in pustules and normalization of body temperature. This case underscores the role of IL-17 in AGEP’s pathogenesis and suggests that IL-17 inhibitors such as ixekizumab may provide an effective treatment option for severe, refractory cases.Keywords: acute generalized exanthematous pustulosis (AGEP), skin adverse reactions, immunotherapy, ixekizumab

Abstract This study aimed to quantify the age-specific risk and burden of fall-related mortality attributable to ambient temperature among older adults in China. Using data in 2759 counties/districts during 2005–2022, we found that both high and low temperatures significantly increased the risk of fall-related mortality, with a notably higher risk associated with high temperatures, particularly among the oldest old and people in Southern China. Projections indicate that the fall-related mortality burden associated with temperature will increase in the future, primarily affecting the oldest old, and the increase is mainly driven by climate change. These findings highlight the need for effective adaptation strategies to reduce the impact of temperature on fall-related mortality among older adults, particularly facing double challenges of climate change and population aging.

Abstract Introduction Greater occipital neuralgia is the syndrome of pain and abnormal sensation in its distribution area caused by anatomical nerve entrapment. Patients with greater occipital neuralgia experience not only limited head and neck movement, but also posterior occipital pain. However, treatment options are restricted and usually linked to adverse reaction. Case presentation A 33-year-old ethnic Han woman received structure-based medical acupuncture therapy for greater occipital neuralgia. On the basis of clinical examination, visual analogue scale, and six-point behavioral scale, the patient had rear occipital pain the whole day and felt enormous pressure and was uncomfortable. Visual analogue scale score and six-point behavioral scale score were 9 and 4, respectively. After 4 weeks of structure-based medical acupuncture therapy, the patient reported that the symptoms of pain and stress were greatly improved without any discomfort. Conclusion Structure-based medical acupuncture could greatly alleviate clinical symptoms in patients with greater occipital neuralgia. Moreover, structure-based medical acupuncture is a safe, accurate, and efficient complementary and alternative treatment.

Jianyun Sheng,1 Jieshi Wang,1 Tengda Ma,1 Peina He2 1General Surgery Department, The First People’s Hospital of Pingdingshan, Pingdingshan, Henan Province, 467000, People’s Republic of China; 2Pingdingshan University, Pingdingshan, Henan Province, 467000, People’s Republic of ChinaCorrespondence: Peina He, Pingdingshan University, South Section of Future Road, Urban and Rural Integration Demonstration Zone, Pingdingshan, Henan Province, 467000, People’s Republic of China, Tel +86-03753383293, Email Hepeina3823@163.comObjective: This research investigated the relationship between serum macrophage inhibitory cytokine-1 (MIC-1), vascular endothelial growth factor (VEGF), and transforming growth factor-β 1 (TGF-β 1) levels and clinicopathologic features, lymph node metastasis (LNM), and prognosis of gastric cancer (GC) patients.Methods: The GC group (GC patients, 198 cases)) and healthy group (healthy people, 100 cases) were established. The relationship between serum MIC-1, VEGF, TGF-β 1, and clinical and pathological features in GC patients was analyzed. GC patients were divided into a metastasis group (77 patients) and a non-metastasis group (121 patients) based on whether they had LNM. The factors influencing LNM in GC patients were identified. The predictive value of serum MIC-1, VEGF, and TGF-β 1 for LNM in GC patients and the relationship between serum MIC-1, VEGF, TGF-β 1 levels and prognosis were analyzed.Results: MIC-1, VEGF, and TGF-β 1 were higher in GC. Serum MIC-1, VEGF, and TGF-β 1 levels were higher in GC patients with tumor diameter ≥ 3 cm, T stage of T3 and T4, low/moderate differentiation, and LNM. Multivariate Logistic regression analysis showed that TNM stage, tumor differentiation, and serum MIC-1, VEGF, and TGF-β 1 levels were risk factors for LNM in GC patients. The ROC results indicated that the combination of serum MIC-1, VEGF, and TGF-β 1 had the highest AUC for predicting LNM in GV patients. The median survival time of patients with low serum MIC-1, VEGF, and TGF-β 1 was higher than that of patients with high serum MIC-1, VEGF, and TGF-β 1 (26.13 months vs 19.24 months, 27.06 months vs 20.18 months, and 24.20 months vs 20.08 months).Conclusion: The changes of serum MIC-1, VEGF and TGF-β 1 levels are related to the clinicopathological characteristics of GC patients, and the elevated levels of these indices are independent risk factors affecting LNM and prognosis of GC patients.Keywords: gastric cancer, macrophage inhibitory cytokine-1, vascular endothelial growth factor, transforming growth factor-β 1, lymph node metastasis, clinicopathological characteristics, prognosis

Yuting Liu,1 Yanting Liang,1 Huan Ma,2 Hengyuan Gao,3,4 Xinzhou Zhang1,5 1Department of Nephrology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Thyroid Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Department of Thyroid and Breast Surgery,Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 5Shenzhen Key Laboratory of Kidney Diseases, The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of ChinaCorrespondence: Hengyuan Gao, Email geland136@163.com Xinzhou Zhang, Email xinzhouzhang1946@163.comObjective: The American Heart Association has recently emphasized the significance of the cardiovascular-kidney-metabolic (CKM) syndrome. However, the cumulative impact of these factors on cardiorespiratory fitness remains inadequately characterized. This study aimed to examine the responses observed during cardiopulmonary exercise testing (CPET) of CKM syndrome patients and explore the potential correlation between cardiorespiratory fitness and hemoglobin concentration in this cohort.Design: Cross-sectional study.Methods: We retrospectively collected medical data of 8206 patients who underwent CPET from 2012– 2022. Among the 878 individuals enrolled, 12 were healthy controls, 809 had isolated CVD, and 57 were in CKM stage 4. After propensity score matching, 112 patients were included in the matched cohort analysis, with 56 each in the CVD and CKM groups. CPET responses were compared between the groups using propensity matched analysis. Additionally, simple mediation models were employed to investigate the potential mediating role of hemoglobin concentration in the association between CKM syndrome and peak VO2.Results: After propensity score-matching, CKM stage 4 was associated with diminished cardiorespiratory fitness compared to the other two groups. This included diminished exercise capacity, reflected by shorter exercise time, lower maximum workload (and its percent predicted value), and reduced peak VO2 (including its percent predicted value and peak VO2/kg). Additionally, cardiac autonomic function was impaired, as evidenced by decreased heart rate recovery (HRR) and a reduced slope of HR recovery (all p< 0.05). Mediation model regression analysis indicated a significant and direct detrimental effect of CKM syndrome on peak VO2 (β = − 228.502; P = 0.003), and a significant indirect partial effect of hemoglobin concentration on the direct effect (β = − 335.718; P < 0.001), with the percentage mediated through hemoglobin concentration of 46.9%.Conclusion: Individuals with CKM syndrome demonstrate compromised responses to CPET manifested by diminished exercise capacity and cardiac autonomic function. While diminished peak oxygen uptake can be partly explained by hemoglobin concentration as we found, further research is necessary to understand other underlying mechanisms.Keywords: cardiovascular-kidney-metabolic, cardiovascular disease, diabetes, chronic kidney disease, cardiorespiratory fitness, Cardiopulmonary Exercise Testing

Lidi Ma,1,2,&ast; Shuting Liao,1,2,&ast; Xiaolan Zhang,3,&ast; Fan Zhou,1,2,&ast; Zhijun Geng,1,2,&ast; Jing Hu,3 Yunfei Zhang,4 Cheng Zhang,1,2 Tiebao Meng,1,2 Shutong Wang,5 Chuanmiao Xie1,2 1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China; 3Shukun Technology Co., Ltd, Beijing, People’s Republic of China; 4Central Research Institute, United Imaging Healthcare, Shanghai, People’s Republic of China; 5Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanmiao Xie, Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email xchuanm@sysucc.org.cn Shutong Wang, Center of Hepato-Pancreato-Biliary Surgery, Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China, Email wangsht23@mail.sysu.edu.cnObjective: To explore the value of intravoxel incoherent motion (IVIM) sequences in predicting intra-tumoral tertiary lymphoid structures (TLSs).Materials and Methods: This prospective study pre-operatively enrolled hepatocellular carcinoma (HCC) patients who underwent magnetic resonance imaging including IVIM sequences, between January 2019 and April 2021. Intra-tumoral TLSs presence was assessed on pathological slide images. Clinical and radiological characteristics were collected. IVIM quantitative parameters and radiomics features were obtained based on the whole delineated tumor volume. By using feature selection techniques, 22 radiomics features, clinical-radiological features (lymphocyte count and satellite nodules), and IVIM parameters (apparent diffusion coefficient (ADC_90Percentile), perfusion fraction (f_Maximum)) were selected. The logistic regression algorithm was used to construct the prediction model based on the combination of these features. The diagnostic performance was assessed using the area under the receiver operating characteristic (AUC). The recurrence-free survival (RFS) was evaluated with Kaplan–Meier curves.Results: A total of 168 patients were divided into training (n=128) and testing (n=40) cohorts (mean age: 56.83± 14.43 years; 149 [88.69%] males; 130 TLSs+). In testing cohort, the model combining multimodal features demonstrated a good performance (AUC: 0.86) and significantly outperformed models based on single-modality features. The model based on radiomics features (AUC: 0.80) had better performance than other features, including IVIM parameter maps (ADC_90Percentile and f_Maximum, AUC: 0.72) and clinical-radiological characteristics (satellite nodules and lymphocyte counts, AUC: 0.59). TLSs+ patients had higher RFS than TSLs- patients (all p < 0.05).Conclusion: The nomogram based on the proposed model can be used as a pre-operative predictive biomarker of TLSs.Critical Relevance Statement: The nomogram incorporating IVIM sequences may serve as a pre-operative predictive biomarker of intra-tumoral tertiary lymphoid structure (TLS) status.Keywords: intravoxel incoherent motion, tertiary lymphatic structures, hepatocellular carcinoma, radiomics, recurrence-free survival

Shunxing Wang,1,2,&ast; Shuxin Yao,1,&ast; Peng Xiao,3,&ast; Lei Shang,4 Chao Xu,1,4,&ast; Jianbing Ma1,&ast; 1Department of Knee Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Xi’an Medical University, Xi ‘An, People’s Republic of China; 3Department of Orthopedics (International Ward), Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 4Department of Health Statistics, Faculty of Preventive Medicine, the Air Force Military Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianbing Ma, Department of Knee Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, No. 555 E.Youyi Road, Xi’an, 710061, People’s Republic of China, Email drmajianbing@163.comPurpose: Research on the Minimum Clinically Important Difference (MCID) of the Brief Pain Inventory (BPI) following Total Knee Arthroplasty (TKA) is limited. This study addresses this gap by determining the MCID of the BPI for patients undergoing primary TKA.Patients and Methods: This study was designed to quantitatively determine the MCID of the BPI for patients undergoing primary TKA. A prospective cohort of 288 patients was evaluated, with the BPI administered both preoperatively and at a one-year follow-up. The MCID was calculated using two primary approaches: the anchor-based method, considered the gold standard, and the distribution-based method. Additionally, this study explored various calculation approaches within the distribution-based framework, benchmarking them against the anchor-based method. The distribution-based methods included calculations based on Standard Deviation (SD), Effect Size (ES), Standardized Response Mean (SRM), and Standard Error of Measurement (SEM). All statistical calculations were performed using established formulas.Results: The anchor-based method determined the MCID for BPI pain severity to be 3.9 points, the pain interference dimension to be 5.8 points, and the total score to be 9.7 points. Comparisons with the gold standard highlighted the 0.65ES, 1.96SEM, and 0.5SRM methods as the most suitable approaches for distribution-based MCID estimation.Conclusion: The MCID for BPI in TKA patients was established using both anchor-based and distribution-based methods. When anchor-based determination is impractical, the distribution-based methods— 0.65ES, 1.96SEM, and 0.5SRM—are recommended for MCID calculation.Plain Language Summary: Understanding whether a treatment makes a meaningful difference to patients is crucial. This study focuses on determining the Minimum Clinically Important Difference (MCID) of the Brief Pain Inventory (BPI) for individuals undergoing Total Knee Arthroplasty (TKA). The MCID helps identify the smallest improvement in pain that patients perceive as beneficial and significant enough to influence their care. By analyzing BPI scores before and one year after surgery, the study used two methods: anchor-based (considered the gold standard) and distribution-based approaches. Various calculation techniques within the distribution-based method were compared to the anchor-based method. The results showed that when the anchor-based method is not feasible, specific distribution-based methods, such as 0.65ES, 1.96SEM, and 0.5SRM, can reliably estimate the MCID. These findings provide clinicians with clear benchmarks for interpreting pain outcomes, ensuring a patient-centered approach to post-TKA care.Keywords: brief pain inventory, total knee arthroplasty, minimal clinically important difference, patient-related outcome, quality of life

Xueyuan Chen,1,&ast; Tingting Liu,1,&ast; Silang Mo,1,&ast; Yuwen Yang,1 Xiang Chen,1 Shaodong Hong,1 Ting Zhou,1 Gang Chen,1 Yaxiong Zhang,1 Yuxiang Ma,2 Yuanzheng Ma,1 Li Zhang,1 Yuanyuan Zhao1 1Medical Oncology Department, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Clinical Research, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Zhang; Yuanyuan Zhao, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, People’s Republic of China, Email zhangli@sysucc.org.cn; zhaoyy@sysucc.org.cnPurpose: This study aimed to investigate the prognostic value of inflammation markers for advanced pulmonary lymphoepithelioma-like carcinoma (PLELC) and develop an effective prognostic model based on inflammation markers to predict the overall survival (OS) of this population.Methods: Cox regression analysis was performed on 18 clinical and inflammation features, and a nomogram was created to predict overall survival (OS). The nomogram was evaluated by the concordance index (C-index), the time-dependent area under the receiver operating (ROC) curves (AUCs), calibration curves, and Decision Curve Analysis (DCA).Results: This study included a training cohort (n = 177) and a validation cohort (n = 77). The following variables were found to be independent prognostic factors for OS and used in the nomogram: Hepatitis B virus surface antigen status, gender, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein-to-albumin ratio (CAR). The C-indexes of the nomogram in the training and validation cohort were 0.740 (95% CI: 0.706– 0.747) and 0.733 (95% CI: 0.678– 0.788), respectively. Furthermore, time-dependent AUCs and well-fitted calibration curves showed good discriminative ability in both cohorts. Additionally, among the subset of EBV DNA data (n = 111), both ROC curve and DCA curve analysis demonstrated that the nomogram plus EBV DNA provided superior predictive performance compared to EBV DNA or the nomogram alone. Patients who received chemoimmunotherapy as the first-line treatment had better OS (not reached vs 44.4 months, P = 0.015) than those with chemotherapy alone and those who received immunotherapy at any line had better OS than those who never received it (not reached vs 31.0 months, P < 0.001).Conclusion: This study established and validated a prognostic nomogram model for patients with advanced PLELC. Combining the nomogram with EBV DNA more effectively predicted the prognosis of patients than the nomogram alone. Immunotherapy was found to be a critical treatment option for PLELC.Keywords: pulmonary lymphoepithelioma-like carcinoma, overall survival, inflammation markers, nomogram

Yaohui Ma, Hang Gong, Long Cheng, Dekui Zhang Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of ChinaCorrespondence: Dekui Zhang, Email zhangdk8616@126.comAbstract: Macrophages, as a crucial component of the body’s immune system, play a vital role in the onset, progression, and outcome of diseases. Discoidin domain receptors (DDRs), important members of the novel receptor tyrosine kinase superfamily, exhibit unique functions in macrophage physiology. Through interactions with the extracellular matrix, DDRs activate signaling pathways such as p38 MAPK and NF-κB, regulating macrophage adhesion, migration, and secretory functions, thereby influencing their behavior in diseases. Recent studies have indicated a direct correlation between DDRs and the progression of various diseases, including inflammation, cancer, and fibrosis. However, there remain numerous knowledge gaps regarding the specific mechanisms by which DDRs function in macrophage-mediated diseases. This article provides an in-depth summary of the regulatory mechanisms of DDRs on macrophages, detailing their modulatory roles in various diseases through macrophages and their underlying mechanisms. The aim is to offer new insights into biomedical therapies targeting DDRs and the development of novel drugs.Keywords: DDR1, DDR2, macrophages, disease

Wei Zhang,1– 3 Ruirui Ma,2 Xiubin Tao,2 Aiping Wang1 1The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 3Key Laboratory of Public Health Social Governance, Philosophy and Social Sciences of Anhui Province, Hefei, People’s Republic of ChinaCorrespondence: Aiping Wang, The First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, Liaoning Province, People’s Republic of China, Email apwang@cmu.edu.cnPurpose: Stroke can cause long-term disability in elderly individuals, and improving the functional ability of patients is vital. This study sought to determine the facilitators and barriers to functional ability in elderly stroke patients from the perspective of healthy aging and to provide a theoretical basis for precise interventions.Patients and Methods: This study was conducted between December 2023 and January 2024. Eleven patients and eight medical staff from a tertiary hospital were selected for semi-structured interviews using purposive sampling. The interview data were analyzed using thematic analysis.Results: A total of 19 interviewees participated, including 11 patients and eight medical staff members. Among the patients, four had hemorrhagic stroke and seven had ischemic stroke; ages ranged from 60 to 77 years. Among the medical staff, five had bachelor’s degrees and three had master’s degrees; ages ranged from 30 to 47 years. Five major themes were identified, including 16 sub-themes. Key themes included: medical service factors, health belief factors, patient factors, family factors, and social/environmental factors.Conclusion: The core elements for improving the functional ability of patients are establishing a service model of multidisciplinary teamwork; guaranteeing the continuity of in-hospital and home rehabilitation; enriching the form and content of health education to improve patient knowledge of the disease; providing psychological support to alleviate patients’ negative emotions; and establishing of effective social safeguards and support systems.Key Points: Functional ability is a key indicator of the health status of elderly patients with stroke based on the principles of healthy aging.Multidisciplinary teamwork model and positive health beliefs can promote patients’ functional abilities. Disease symptoms, negative psychological emotions, and insufficient family and social support may be detrimental to functional abilities.This article provides suggestions of measures for practitioners to undertake to improve patient functional abilities in response to facilitators and barriers.Keywords: facilitators, barriers, functional ability, elderly, stroke, qualitative

Xinwen Li,1,&ast; Lin Cao,1,&ast; Jianmin Li,2,&ast; Zhengyang Li,1 Hongyu Ma,3 Shifeng Cheng,1 Hongyi Xu,1 Yang Zhao1,2 1Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 2Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 3Image Center, Cangzhou Integrated Traditional and Western Medicine Hospital, Cangzhou, 061000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Zhao, Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China, Email yang.zhao@tmu.edu.cnBackground: Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with no clinical cure. Excessive production of reactive oxygen species (ROS) at the inflammatory sites leads to the onset and progression of IBD. And the current non-invasive imaging methods are not ideal for the diagnosis and monitoring of IBD.Methods: Herein, we developed inulin (IN)-coated cerium oxide nanoparticles (CeO2@IN NPs) for treatment and monitoring of IBD guided by computed tomography (CT). The physicochemical properties, ROS scavenging ability and CT imaging capabilities of CeO2@IN were investigated in vitro. Moreover, the therapeutic and targeted inflammation imaging effects of CeO2@IN were validated in dextran sulfate sodium (DSS)-induced colitis model.Results: CeO2@IN with catalase (CAT) and superoxide dismutase (SOD) capabilities effectively scavenged ROS, thus protecting the cells against oxidative stress. In colitis model mice, orally administered CeO2@IN successfully traversed the gastrointestinal tract to reach the colon under the protection of IN, and effectively reduced intestinal inflammation, thereby maintaining the intestinal epithelial integrity. Notably, CeO2@IN performed better than conventional CT contrast agents for gastrointestinal tract imaging, particularly in detecting the inflamed areas in the colon. In addition, CeO2@IN exhibited excellent biocompatibility in vitro and in vivo.Conclusion: The study provided a novel integrated diagnostic and therapeutic tool for the treatment and monitoring of IBD, presenting great potential as a clinical application for IBD.Keywords: inflammatory bowel disease, ceria, nanozyme, antioxidation, CT imaging

Didi Yan,1 Xinyue Ma,1 Yixin Hu,1 Guogang Zhang,1 Beibei Hu,1 Bo Xiang,2 Xiaokun Cheng,1,3 Yongshuai Jing,1 Xi Chen1,4 1College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People’s Republic of China; 2Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3New Drug Research & Development Co., Ltd., North China Pharmaceutical Group Corporation, Shijiazhuang, 050015, People’s Republic of China; 4Hebei Research Center of Pharmaceutical and Chemical Engineering, Shijiazhuang, 050018, People’s Republic of ChinaCorrespondence: Xi Chen, College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Road, Shijiazhuang, 050018, People’s Republic of China, Tel +86-15203319951, Email chenxi0310@163.comBackground: Paclitaxel-induced blood system disorders and peripheral neuropathy impede the progress of new formulations in clinical trials.Purpose of Study: To mitigate these adverse effects by developing and validating a prodrug strategy that encapsulates a glucose-paclitaxel conjugate within nanomicelles.Material and Methods: Succinic anhydride was used as a bridge to couple C2’-paclitaxel with methyl 2’-glucopyranose and prepare a glucose-paclitaxel conjugate. Nanomicelles were prepared via solid-phase dispersion, and dynamic light scattering was used to determine their average diameter and the polydispersity index. High-performance liquid chromatography (HPLC) was employed to evaluate drug-loading capacity and encapsulation efficiency. Pharmacokinetic studies and in vivo toxicity assays were performed in Sprague-Dawley (SD) rats.Results: The nanomicellar product exhibited a spherical shape with a particle size distribution between 20– 60 nm, a PDI of 0.26 ± 0.01, and an encapsulation efficiency of 95.59 ± 1.73%. The pharmacokinetic profile of glucose-paclitaxel nanomicelles in SD rats was markedly different from that of the paclitaxel solution group. Notably, the plasma drug concentration of glucose-paclitaxel nanomicelles was significantly higher than the paclitaxel solution 15 minutes post-administration, with a Vz at only 40% of that of the paclitaxel solution, while the AUC0-∞ was five times greater than that of the paclitaxel solution. Ultimately, glucose-paclitaxel nanomicelles effectively alleviated blood system disorders and peripheral neuropathy in SD rats.Conclusion: The encapsulation of glucose-paclitaxel conjugates within nanomicelles presents a viable solution to the dose-limiting toxicities associated with paclitaxel, offering new perspectives on safety for the development of paclitaxel-based therapeutics.Keywords: glucose-paclitaxel conjugate, nanomicelles, pharmacokinetics, toxicity of paclitaxel

Guomin Gao,1 Jiayun Liu,1 Rui Sun,1 Xuankai Liu,1 Dan Meng,2 Weiyuan Ma1 1Department of Dermatology, Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Dermatology, Heze Municipal Hospital, Heze, Shandong, People’s Republic of ChinaCorrespondence: Dan Meng; Weiyuan Ma, Email 1056348654@qq.com; fymaweiyuan@sdsmu.edu.cnAbstract: Dermatosis neglecta (DN) is a rare condition, often linked to psychosomatic disorders, with an unclear etiology. Chilblain lupus erythematosus (CHLE) constitutes a rare variant of cutaneous lupus erythematosus, frequently mistaken for idiopathic chilblain due to its chilblain-like lesions. To date, no instances of concurrent DN and CHLE occurring at the site of a skin flap or graft have been documented. Herein, we present a case that the occurrence of DN and CHLE developed on a skin flap at once. The simultaneous occurrence of DN and CHLE on a skin flap is exceptionally rare. Clinicians must exercise heightened vigilance due to the common misdiagnosis of CHLE. Various skin disorders can manifest on skin flaps and grafts post-transplantation. Thus, clinicians must remain vigilant for both recurrence and metastasis during post-operative monitoring, while also attending to patients’ mental well-being and the condition of skin flaps.Keywords: dermatosis neglecta, skin flap, basal cell carcinoma, chilblain lupus erythematosus

Yexian Zhao,&ast; Yunlei Ma,&ast; Limei Geng, Jia Nie, Xiangyan Yu, Zenglu Kang, Yun Liu, Yinghao Su Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei University of Traditional Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinghao Su, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei University of Traditional Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China, Email syh197812@163.comBackground: Chronic Obstructive Pulmonary Disease (COPD) significantly impacts morbidity and mortality globally. While established risk factors like smoking and occupational exposures are well-documented, patients’ beliefs—especially those from the miasma theory attributing disease to “bad air” in cultures like China—may also significantly influence health outcomes.Methods: This case-control study was conducted at Hospital of Hebei University of Traditional Chinese, involving 500 individuals diagnosed with COPD and 500 matched control participants. Each participant completed questionnaires that gathered information on demographic details, clinical history, and beliefs about the causes of COPD. Clinical data were collected, including spirometry tests to assess lung function, the COPD Assessment Test (CAT) to evaluate symptom burden, and the St. George’s Respiratory Questionnaire (SGRQ) to measure health-related quality of life.Results: The study found that 81% of COPD patients endorsed high miasma beliefs, compared to 28% of controls (p < 0.01). Those with strong beliefs reported significantly worse symptoms (mean CAT score: 23 vs 14, p < 0.001) and poorer quality of life (mean SGRQ score: 48 vs 39, p < 0.001) compared to low-belief individuals. Higher levels of anxiety and depression were also observed in patients with strong miasma beliefs. Laboratory biomarkers such as neutrophils, RDW width, and CRP were also elevated in the high-belief group compared to the low-belief group.Conclusion: The findings suggest that adherence to miasma theory beliefs is associated with adverse health outcomes in COPD patients. Addressing these beliefs through targeted education may enhance patient engagement and adherence to evidence-based treatments, ultimately improving health outcomes.Keywords: miasma mentality, chronic obstructive pulmonary disease, COPD, quality of life beliefs, treatment adherence

Peng Cui,&ast; Tao Cheng,&ast; Huichun Yan, Dong Xu, Guohua Ren, Shangmin Ma Rheumatology Immunology Department, Zibo First Hospital, Zibo, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Cui, Email chyi011@163.comObjective: This retrospective cohort study investigated the value of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in the diagnosis and treatment of rheumatoid arthritis complicated with interstitial lung disease (RA-ILD).Methods: A total of 163 patients with newly diagnosed rheumatoid arthritis (RA) were enrolled, with 122 patients in the RA group and 41 patients in the RA-ILD group. The mean age of the RA group was 63.84 ± 8.53 years, with a male-to-female ratio of 14:47. The RA-ILD group had a mean age of 66.29 ± 12.72 years, with a male-to-female ratio of 13:28. During the 2-year follow-up period, 10 patients in the RA group developed interstitial lung disease (ILD).Results: NLR and PLR were significantly higher in RA-ILD group than in RA group (p < 0.05). The optimal critical values of NLR and PLR for the diagnosis of RA-ILD were 3.15 and 152.62, the area under ROC curve was 0.615 and 0.61, the sensitivity was 72%, 62%, and the specificity was 54% and 64%. NLR and PLR were significantly increased after ILD during follow-up in RA patients but decreased after ILD in the predicted percentage of vital capacity (VC%), forced vital capacity (FVC%), forced expiratory volume in the first second (FEV1%) and carbon monoxide dispersion (DLcoSB%) (p < 0.05). Moreover, NLR and PLR decreased after treatment. While VC%, FVC%, FEV1%, and DLcoSB% increased after treatment (p < 0.05). NLR was negatively correlated with FVC% and DLcoSB% both before and after treatment. PLR was also significantly negatively correlated with FVC% and DLcoSB% before and after treatment (p < 0.05).Conclusion: When NLR and PLR increase, we should be alert to the possibility of RA complicated with ILD, which can be used as an evaluation index of the treatment effect of RA-ILD.Keywords: neutrophils, lymphocyte, platelets, the ratio, rheumatoid arthritis, interstitial lung disease

Jia Shang,1,2 Zehao Zhang,1 Shifang Ma,1 Hailong Peng,1 Lan Hou,1,3 Fan Yang,1 Pei Wang1,3 1Department of Neurology, Baoding No 1 Central Hospital, Baoding, People’s Republic of China; 2Graduate School of Hebei Medical University, Shijiazhuang,People’s Republic of China; 3Department of Neurology, Key Laboratory of Neurological Diseases, Baoding, People’s Republic of ChinaCorrespondence: Pei Wang, Department of Neurology, Baoding No 1 Central Hospital, Baoding Great Wall North Street No. 320, Baoding, Hebei Province, 071000, People’s Republic of China, Email w_z_h_01@163.comPurpose: Early neurological deterioration (END) frequently complicates acute ischemic stroke (AIS), worsening prognosis, particularly in patients with type 2 diabetes mellitus (T2DM), where hyperglycemia accelerates atherosclerosis, increasing both stroke risk and subsequent END. This study aimed to identify predictors of END in minor stroke patients with T2DM and develop a nomogram integrating these factors with intracranial atherosclerosis (ICAS) scores, evaluating its performance against various machine learning (ML) models.Methods: We retrospectively analyzed clinical data from 473 minor stroke patients with T2DM treated at our hospital between January 2021 and December 2023. Utilizing LASSO and multivariate logistic regression, we identified characteristic predictors. The cohort was randomly allocated into training (n = 331) and validation (n = 142) groups. Six ML algorithms—SVM, LR, RF, CART, KNN, and Naive Bayes—were assessed, and nomograms were used to visualize the predictive model’s performance, evaluated via Area Under the Curve (AUC), calibration plot, and Decision Curve Analysis (DCA).Results: The ICAS score has been recognized as a pivotal determinant of END, alongside four other significant factors: NIHSS score, low-density lipoprotein cholesterol (LDL-C) levels, presence of branch atheromatous disease (BAD), and stenosis of the responsible vessel ≥ 50%. The model demonstrated robust predictive capabilities, achieving strong performance in training (AUC = 0.795) and validation (AUC = 0.799) sets. This advanced ML model, which integrates biochemical and imaging indicators, enables accurate risk assessment for END in minor stroke patients with T2DM.Conclusion: By integrating the ICAS score with the NIHSS score, LDL-C levels, presence of BAD, and stenosis of responsible vessels ≥ 50%, we developed a clinical model for predicting END in patients with minor stroke and T2DM. This model provides critical decision support for clinicians, facilitating early identification of high-risk patients, personalized treatment, and improved outcomes.Keywords: early neurological deterioration, prediction model, type 2 diabetes mellitus, machine learning, nomograms

Yong Cai, Yijun Ma, Chao Tang, Wei Li, Xuan Lv, Zhijie Xie, Jun Wang Department of Neurosurgery, First People’s Hospital of Linping District, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jun Wang, Department of Neurosurgery, The First People’s Hospital of Linping District, Hangzhou, Zhejiang, People’s Republic of China, Email wangjun57188@163.comBackground: Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is involved in secondary brain injury after acute intracerebral hemorrhage (ICH). The objective of this study was to determine its ability to predict early neurological deterioration (END) and 3-month neurological outcome after ICH.Methods: In this prospective cohort study, serum NLRP3 levels were measured in 128 patients with sICH and 100 healthy controls. National institute of health stroke scale (NIHSS) scores and hematoma volumes were recorded. Post-ICH END and 3-month poor outcome (modified Rankin Scale (mRS) scores of 3– 6) were documented. The results were assessed using multivariate analysis.Results: Serum NLRP3 levels in sICH patients increased significantly as compared to controls (P< 0.001). Serum NLRP3 levels were independently correlated with hematoma volumes (β=0.046; 95% confidence interval (CI), 0.020– 0.072; P=0.001) and NIHSS scores (β=0.071; 95% CI, 0.004– 0.139; P=0.039), independently forecasted END (OR=1.268; 95% CI, 0.892– 1.801; P=0.036) and poor prognosis at post-ICH 3 months (OR=1.448; 95% CI, 1.006– 2.085; P=0.046), and were predictive of them with areas under receiver operating characteristic curve at 0.788 (95% CI, 0.706– 0.855) and 0.805 (95% CI, 0.725– 0.870) separately. Serum NLRP3 levels, along with the two independent predictors, that are NIHSS scores and hematoma volumes, are combined to establish prediction models of END and poor prognosis. The models worked well by applying a series of statistical methods.Conclusion: Increased serum NLRP3 levels after ICH are independently associated with bleeding severity, END and adverse outcomes of patients, meaning that serum NLRP3 may be a potential prognostic biomarker of sICH.Keywords: intracerebral hemorrhage, disease severity, early neurological deterioration, outcome, NLRP3

Xin Ma,1,2,&ast; Jing Yuan,1,&ast; Lihong Tang,1,&ast; Xue Chen,1,&ast; Yan Zhou,3 Ningna Wang,1 Hong Sun1 1Department of Clinical Laboratory, Urumqi Friendship Hospital, Urumqi City, Xinjiang Uygur Autonomous Region, People’s Republic of China; 2School of Basic Medicine, Xinjiang Medical University, Urumqi City, Xinjiang Uygur Autonomous Region, People’s Republic of China; 3The second Medical College, Xinjiang Medical University, Laboratory Class, Karamay City, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Sun, Urumqi Friendship Hospital, Tianshan District, Urumqi City, Xinjiang Uygur Autonomous Region, 830049, People’s Republic of China, Tel +86-13899816208, Email 632598426@qq.comPurpose: To explore the association of the Systemic Inflammatory Response Index (SIRI) and Systemic Inflammatory Immunity Index (SII) with extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) and its resistance prediction.Methods: A total of 425 patients with K. pneumoniae infections were included in the study. Data on general clinical characteristics and relevant laboratory indicators were collected. The patients were divided into ESBL-producing and non-ESBL-producing groups based on the presence of ESBLs. Logistic regression analysis was used to analyze the risk factors associated with ESBL-producing K. pneumoniae. The receiver operating characteristic (ROC) curve was employed to assess the predictive efficacy of SIRI and SII for ESBL-producing K. pneumoniae and its resistance to antibiotics.Results: SIRI and SII levels in the ESBL-producing group were significantly higher than those in the non-ESBL-producing group. Logistic regression analysis showed that the odds ratios for SIRI and SII were 1.092 and 1.158, respectively, with 95% confidence intervals of 1.001– 1.115 and 1.015– 1.204, respectively. The critical values for predicting ESBL-producing K. pneumoniae were 1.067 for SIRI and 579.68 for SII, with area under the curve (AUC) values of 0.725 and 0.723, respectively. The AUC values for predicting resistance of ESBL-producing K. pneumoniae to piperacillin (PIP), amoxicillin/clavulanate (AMC), and cefazolin (CZO) were 0.614, 0.657, and 0.648 for SIRI, and 0.675, 0.613, and 0.625 for SII, respectively.Conclusion: SIRI and SII are significantly associated with the risk of ESBL-producing K. pneumoniae and can be used to predict a patient’s risk of infection with this organism. Additionally, SIRI and SII accurately predict the resistance of ESBL-producing K. pneumoniae to PIP, AMC, and CZO antibiotics.Keywords: systemic inflammation response index, systemic inflammatory immune index, extended-spectrum β-lactamase, Klebsiella pneumoniae, prediction of drug resistance

Yuzi Jin,1,&ast; Joshua S Fleishman,2,&ast; Yudong Ma,3 Xiaoqing Jing,4 Qin Guo,1 Weiguang Shang,1 Hongquan Wang5 1Department of Pediatrics, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110020, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, 11439, USA; 3Department of Critical Care Medicine, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110020, People’s Republic of China; 4Department of Pediatrics, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China; 5Department of Geriatrics, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuzi Jin, Department of Pediatrics, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110020, People’s Republic of China, Email Jinyz@cdmc.edu.cnAbstract: Cardiac or myocardial dysfunction induced by sepsis, known as sepsis-induced cardiomyopathy or sepsis-induced myocardial injury (SIMI), is a common complication of sepsis and is associated with poor outcomes. However, the pathogenesis and molecular mechanisms underlying SIMI remain poorly understood, requiring further investigations. Emerging evidence has shown that NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes contribute to SIMI. Compounds that inhibit NLRP3-associated pyroptosis may exert therapeutic effects against SIMI. In this review, we first outlined the principal elements of the NLRP3 signaling cascade and summarized the recent studies highlighting how NLRP3 activation contributes to the pathogenesis of SIMI. We outlined selective small-molecule modulators that function as NLRP3 inhibitors and delineated their mechanisms of action to attenuate SIMI. Finally, we discuss the major limitations of the current therapeutic paradigm and propose possible strategies to overcome them. This review highlights the pharmacological inhibition of SIMI as a promising therapeutic strategy.Keywords: sepsis, sepsis-induced myocardial injury, NLRP3, pyroptosis, bioactive compounds

Lan Li,1,2 Yue Li,2,3 Shuang Qin,2 Jing Zeng,2 Wanxia Ma,2 Dong Wei2 1Medical Examination Center, Chengdu Second People’s Hospital, Chengdu, 610017, People’s Republic of China; 2Department of Endocrinology and Metabolism, Diabetic Foot Care Center, Chengdu Second People’s Hospital, Chengdu, 610017, People’s Republic of China; 3Department of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, People’s Republic of ChinaCorrespondence: Dong Wei, Department of Endocrinology and Metabolism, Diabetic Foot Care Center, The Chengdu Second People’s Hospital, Chengdu, Sichuan, 610017, People’s Republic of China, Tel/Fax +86 02867830801, Email weidong314@126.comBackground: Diabetic foot ulcer (DFU) inpatients admitted with non-ulcer complaints constitute a neglected group that might suffer from more non-standard treatments. This study intends to describe their clinical characteristics, and clarify the problems existing in the DFU management process.Methods: In this retrospective study, admission complaints were determined by combining the final diagnosis and clinical documentation, and were categorized as: ulcer-related or non-ulcer complaints.Results: A total of 264 DFU inpatients were included in the final analysis, of which, 80 (30.3%) were admitted with non-ulcer complaints. A total of 82.5% of the DFU inpatients with non-ulcer complaints were admitted to departments without DF specialists. IWGDF/IDSA grade, cerebrovascular diseases, chronic kidney disease, infection in other parts, glycosylated hemoglobin A1c and the source of hospitalization expenses were the independent influencing factors for admission with non-ulcer complaints (all P < 0.05). Before admission, only 11.3% of the patients with non-ulcer complaints had ever been treated by a DF specialist and/or in a clinical setting with DF specialists. After admission, 25.0% of the DFU inpatients with non-ulcer complaints did not receive any local wound care, and only 7.6% of the patients admitted to the departments without DF specialists obtained a referral.Conclusion: Approximately one-third of inpatients with DFU are admitted with non-ulcer complaints and most of them are admitted to departments without DF specialists. Inpatients with non-ulcer complaints have milder wounds but more severe and greater comorbidities and worse organ function. These patients do not receive standardized management for DFU either before or after admission. Targeted measures are needed to improve this situation.Keywords: diabetic foot ulcer, admission complaint, non-ulcer, non-specialist

Tao Yan,1,2 Qiuyan Wang,2 Chengcheng Ma,2 Xuan Teng,2 Zhen Gong,2 Wenwen Chu,2 Qiang Zhou,2 Zhou Liu1 1Department of Clinical Laboratory Center, Anhui Chest Hospital, Hefei, 230031, People’s Republic of China; 2Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Zhou Liu, Department of Clinical Laboratory Center, Anhui Chest Hospital, Hefei, People’s Republic of China, Email liuzhou0112@ahmu.edu.cnPurpose: Klebsiella pneumoniae is a globally prevalent pathogen responsible for severe hospital- and community-acquired infections, and presents significant challenges for clinical management. Current therapeutic strategies are no longer able to meet the clinical needs; therefore, there is an urgent need to develop novel therapeutic strategies. This study aimed to evaluate the efficacy of phage therapy in treating bacterial infections.Methods: Isolated phage vB_Kpn_HF0522 and phage morphology were observed using transmission electron microscopy. Analysis of vB_Kpn_HF0522 characteristics, including optimal multiplicity of infection (MOI), one-step growth curve, host range, stability in different environments, and adsorption capacity. The phage genomic sequence was analyzed to explore evolutionary relationships. The effect of phage vB_Kpn_HF0522 on biofilms was assessed using crystal violet staining assay. The Galleria mellonella (G. mellonella) infection model and mouse infection models were established to evaluate the practical application potential of the phage and the fitness cost of phage-resistant bacteria.Results: Phage was isolated from hospital sewage for experimental studies. Genome analysis revealed that vB_Kpn_HF0522 is a double-stranded linear DNA virus. Biological characterization demonstrated that this phage specifically targets serotype K1 K. pneumoniae with an optimal multiplicity of infection (MOI) of 0.01, effectively disrupting biofilms and inhibiting bacterial growth. The bacterial growth rate remained largely unchanged after the phage resistance mutation, but mice infected with the mutant strain showed significantly higher survival rates than those infected with the wild-type strain. vB_Kpn_HF0522 increased the survival rate of infected G. mellonella from 12.5% to 75%, inhibited incisional surgical site infections and alleviated inflammatory response in mice.Conclusion: These findings indicate that vB_Kpn_HF0522 has significant potential for treating specific bacterial infections, and may serve as an antimicrobial agent for research and clinical anti-infective therapy.Keywords: phage vB_Kpn_HF0522, phage therapy, Klebsiella pneumoniae, phage resistance, incisional surgical site infection, biofilm