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Yixian Liu,1,2,* Xiaoyu Li,1,2,* Mengyu Zhang,1,2 Yuchun Men,1,2 Ying Wang,1,2 Xiaohong Zhu,1,2 Li Zheng1,2 1Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Clinical Trial Center, NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Zheng, Cancer Center, West China Hospital, Sichuan University, No. 5 Telecom Road, Wuhou District, Chengdu, 610041, People’s Republic of China, Email zhengli@wchscu.cnPurpose: HA121-28, a novel multi-targeting tyrosine kinase inhibitor, has dual efficacy against tumor growth and neovascularization. The objectives of this study were to assess the effect of high-fat and high-calorie food on the pharmacokinetic (PK) profile and safety of HA121-28 tablet in healthy subjects.Patients and Methods: A single-dose, randomized, open-label, two-period, crossover-designed phase I clinical trial was conducted. Subjects received 200 mg HA121-28 in the fasted state or with high-fat and high-calorie breakfast. The effects of high-fat and high-calorie food on the PK profile and safety of HA121-28 were evaluated by using noncompartmental analysis and whole-process safety assessment.Results: Twenty subjects were successfully completed the trial. The geometric mean ratios (GMRs) for the peak concentration in plasma (Cmax), area under the curve from zero to the time point (AUClast), and area under the curve from zero to infinite (AUCinf) postprandially versus fasted were 108.45% (98.51% – 119.40%), 105.23% (100.25% – 110.47%), and 104.14% (97.41% – 111.34%), respectively. The majority of reported adverse events were graded as either level 1 or 2 in severity and recovered spontaneously without any interventions.Conclusion: The exposure of HA121-28 was not significantly affected by the high‐fat and high-calorie food. The clinical application of HA121-28 tablet can be recommended for use in both fasted and postprandial states.Keywords: HA121-28, ##Food effects, pharmacokinetics, safety, tyrosine kinase inhibitor

Yu Ding,1 Yuxia Liu,2 Jianjian Yu,2 Chengsen Cai,2 Lina Fu,2 Jie Zhu,3 Shengzhen Yang,4 Yu Jiang,1 Jun Wang2 1The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Department of Pulmonary, Rizhao Hospital of Traditional Chinese Medicine, Rizhao, People’s Republic of ChinaCorrespondence: Jun Wang, Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China, Email jnwj660606@163.comPurpose: The C-reactive protein (CRP)–albumin–lymphocyte (CALLY) index is a newly developed biomarker that combines measurements of CRP, serum albumin, and lymphocyte count. This index provides a thorough assessment of a patient’s inflammation level, nutritional condition, and immunological function. The objective of this study is to examine the correlation between the CALLY index and all-cause mortality in COPD patients.Methods: We calculated the CALLY index using data from the National Health and Nutrition Examination Survey (NHANES) for the 2007– 2008 and 2009– 2010 cycles, extracted from the participants’ peripheral blood samples. The study utilized Kaplan-Meier curves, restricted cubic spline (RCS) curves, and Cox regression analysis to evaluate the relationship between the CALLY index and the risk of all-cause mortality in COPD patients. To assess the predictive accuracy of the CALLY index, we calculated the area under the receiver operating characteristic (ROC) curve (AUC).Results: The study included 1,048 participants and found a significant negative correlation between the CALLY index and all-cause mortality in patients with COPD. The CALLY index was a major predictor of survival in COPD patients [fully adjusted model: in the 3rd quartile, HR = 1.61, 95% CI: 1.02– 2.52, p = 0.039; in the 2nd quartile, HR = 2.11, 95% CI: 1.22– 3.65, p = 0.008; in the 1st quartile, HR = 3.12, 95% CI: 2.00– 4.85, p < 0.001]. The RCS curves demonstrated a non-linear association between the CALLY index and all-cause mortality in COPD patients. The areas under the curve (AUC) in predicting 5- and 10-year all-cause mortality were 0.693 and 0.656.Conclusion: The CALLY index has a strong relationship with all-cause mortality in patients with COPD in the US and could serve as a prognostic biomarker for these patients.Keywords: chronic obstructive pulmonary disease, the C-reactive protein–albumin–lymphocyte index, national health and nutrition examination survey, biomarker

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

Yu Liu,1 Yang Peng,2 Bimin Zhu,2 Zhihua Xia,1 Yonghua Yuan,3 Fujun Zhang4 1Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Pharmacy, Dianjiang County People’s Hospital, Chongqing, 408300, People’s Republic of China; 3College of Pharmacy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Fujun Zhang, Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email cnzfj@cqmu.edu.cnPurpose: To develop a training program on cancer pain management for pharmacists and to evaluate the effectiveness of the training.Methods: The program developed a well-structured curriculum and subsequent evaluation of training effectiveness, guided by the Kirkpatrick four-tier evaluation model, including reaction, learning, behavior, and results. The training approach incorporated mentoring, study groups, and problem-based learning to create an immersive and impactful learning experience.Results: Fifty-three pharmacists participated in the survey. The reaction evaluation results showed that the cumulative percentage of “satisfied” and “very satisfied” with each of the nine statements exceeded 85%. The findings from the learning level assessment revealed that the cumulative percentage of accurate responses to the 13 items on the Cancer Pain Management Questionnaire was 57.7% before training. This percentage rose to 64.2% following the training, showcasing a statistically significant improvement (p=0.014). The behavioral scoring results showed that 53 trainees scored an average of more than 15 points on all four behavioral benchmarks. The pass rate for the trainees was 86.8%. The percentages of trainees who scored proficient, good, and excellent were 18.9% (10/53), 50.9% (27/53), and 17.0% (9/53), respectively. The evaluation of the results showed that all the respondents were engaged in cancer pain management practices. Of these participants, 85.7% (42/49) were members of a multidisciplinary cancer pain management team, and 53.1% (26/49) performed a cancer pain consultation or attended an outpatient clinic.Conclusion: Study results suggested that the training program was effective in all dimensions defined by the Kirkpatrick model. This collective achievement indicates a substantial enhancement in the comprehension and proficiency of pharmacists regarding cancer pain management.Keywords: pharmacist, cancer pain management, continuing education, evaluation of training effectiveness, Kirkpatrick four-tier evaluation model

Huihui Zhou,1,&ast; Sifang Niu,1,2,&ast; Yangziye Guo,1,3 Yan Qin,1,3 Hao Sun,4 Fuqin Mu,5 Ximing Duan,5 Yi Zheng,5 Ying Zhang,6 Yan Liu,1 Ning Liu7 1School of Public Health, Jining Medical University, Jining, 270213, People’s Republic of China; 2School of Public Health and Management, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 3School of Public Health, Shandong First Medical University, Jinan, 250117, People’s Republic of China; 4School of Clinical Medicine, Jining Medical University, Jining, 270213, People’s Republic of China; 5School of Mental Health, Jining Medical University, Jining, 272013, People’s Republic of China; 6School of Public Health, University of Sydney, Sydney, NSW, 2006, Australia; 7School of Basic Medicine, Jining Medical University, Jining, 272067, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liu, School of Public Health, Jining Medical University, Jining, 272065, People’s Republic of China, Email hakunaly@163.com Ning Liu, Department of Graduate, Jining Medical University, Jining, 272065, People’s Republic of China, Email 631864@qq.comPurpose: Stressful life events are risk factors of depression. To explore whether the avoidant personality disorder (AVPD) features play a mediating role between stressful life events (SLEs) and depression among Chinese first-year university students.Methods: The cross-sectional study was conducted from April to October 2018. The participants were the freshmen selected from Jining Medical University and Weifang Medical University (n=7390) in Shandong Province in China. Depression was assessed by the Beck Depression Inventory-II, AVPD were measured by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5). The data were processed and analyzed by SPSS24.0 software, Pearson correlation analysis and PROCESS3.3 program intermediary analysis. The method of Bootstrap was adopted to determine whether the AVPD features act as mediating factors in the association between the NLEs and depression.Results: A total of 34.68% of the participants reported one to three AVPD features, and 18.15% reported four to seven AVPD features. AVPD features (r=0.384, P< 0.05) and the SLEs (r=0.309, P< 0.05) were positively related to the risk of depression, respectively. AVPD features play a partial mediating effect on the relationship between SLEs and depression (the effect value is 0.133, P < 0.01; 32.28% of the total effect).Limitation: There might be recall bias in this cross-sectional study.Conclusion: AVPD features are prevalent among Chinese university students. AVPD features displayed the mediation effect on depression related to stressful life events. Psychological interventions for depression in college students should focus not only on stress but on individual personality traits and cognitive mode. Care-givers, teachers, and health professionals should pay more attention to the early identification of the AVPD features among university students.Keywords: stressful life events, depression, avoidant personality disorder, mediator

Changrong Guan,1 Yonghua Liu,2 Riqiu Chen,1 Yingbiao Zhu3 1Department of Endocrinology, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 2Department of Hematology, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 3Department of Neurology, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of ChinaCorrespondence: Yingbiao Zhu, Department of Neurology, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Tel +86-18957097750, Email zybiao5107@163.comAbstract: Primary amyloidosis (AL type) is a systemic disease that can lead to structural and functional damage to organs and tissues such as the kidney, heart and liver with non-specific symptoms. Most of the affected patients develop thyroid infiltration and thus diffuse enlargement of the thyroid gland, while cases leading to hypothyroidism are exceedingly rare. Some researchers have analyzed thyroid function in newly diagnosed patients with AL amyloidosis, and found that the incidence of overt hypothyroidism is only 7%. In this case, we describe a 66-year-old female patient who visited the nephrology department due to lower limb edema for 2 months and numbness of the extremities for more than 2 years. Examination revealed massive proteinuria and hypoproteinemia, and a needle biopsy of the kidney revealed amyloid deposition. The patient was also found to have hypothyroidism and diffuse enlargement of the thyroid gland. We evaluated the etiology of thyroid disease from the pathogenesis of the disease after consulting an endocrinologist. The result of the thyroid fine needle puncture and pathological examination showed thyroid amyloidosis. The patient received levothyroxine sodium tablets as replacement therapy and received chemotherapy in the hematology department. At the same time, we monitored the improvement in thyroid function and reduction in thyroid volume.Keywords: thyroid amyloidosis, hypothyroidism, renal amyloidosis, nephrotic syndrome, macroalbuminuria

Linxia Wu,1– 3,&ast; Lei Chen,1– 3,&ast; Lijie Zhang,1,4,&ast; Yiming Liu,1,5,&ast; Die Ouyang,1 Wenlong Wu,5,6 Yu Lei,5,6 Ping Han,1 Huangxuan Zhao,1– 3 Chuansheng Zheng1– 3 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China; 2Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China; 3Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, Hubei Province, 430022, People’s Republic of China; 4Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, People’s Republic of China; 5Department of Interventional Radiology, Auto Valley Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430056, People’s Republic of China; 6Department of Interventional Radiology, Jinyinhu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430048, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuansheng Zheng; Huangxuan Zhao, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China, Email hqzcsxh@sina.com; zhao_huangxuan@sina.comPurpose: Type II diabetes mellitus (T2DM) has been found to increase the mortality of patients with hepatocellular carcinoma (HCC). Therefore, this study aimed to establish and validate a machine learning-based explainable prediction model of prognosis in patients with HCC and T2DM undergoing transarterial chemoembolization (TACE).Patients and Methods: The prediction model was developed using data from the derivation cohort comprising patients from three medical centers, followed by external validation utilizing patient data extracted from another center. Further, five predictive models were employed to establish prognosis models for 1-, 2-, and 3-year survival, respectively. Prediction performance was assessed by the receiver operating characteristic (ROC), calibration, and decision curve analysis curves. Lastly, the SHapley Additive exPlanations (SHAP) method was used to interpret the final ML model.Results: A total of 636 patients were included. Thirteen variables were selected for the model development. The final random survival forest (RSF) model exhibited excellent performance in the internal validation cohort, with areas under the ROC curve (AUCs) of 0.824, 0.853, and 0.810 in the 1-, 2-, and 3-year survival groups, respectively. This model also demonstrated remarkable discrimination in the external validation cohort, achieving AUCs of 0.862, 0.815, and 0.798 in the 1-, 2-, and 3-year survival groups, respectively. SHAP summary plots were also created to interpret the RSF model.Conclusion: An RSF model with good predictive performance was developed by incorporating simple parameters. This prognostic prediction model may assist physicians in early clinical intervention and improve prognosis outcomes in patients with HCC and comorbid T2DM after TACE.Keywords: hepatocellular carcinoma, type II diabetes mellitus, transarterial chemoembolization, overall survival, SHapley Additive exPlanations

Yi Liu,1– 4,&ast; Xiao Wang,1– 3,5,&ast; Ni Zhang,1– 4,&ast; Simin He,1– 4 Jianping Zhang,1– 4 Xiaoping Xu,1– 4 Shaoli Song1– 4 1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Center for Biomedical Imaging, Fudan University, Shanghai, 200032, People’s Republic of China; 4Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, 200032, People’s Republic of China; 5State Key Laboratory of Vaccines for Infectious Diseases, Xiang an Biomedicine Laboratory & Center for Molecular Imaging and Translational Medicine, School of Public Health, Shenzhen Research Institute of Xiamen University, Xiamen University, Xiamen, 361102, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoli Song; Xiaoping Xu, Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China, Email shaoli-song@163.com; xxp0012@ustc.eduPurpose: None of the antibody-drug conjugates (ADCs) targeting Claudin 18.2 (CLDN18.2) have received approval from regulatory authorities due to their limited clinical benefits. Leveraging the radiosensitizing ability of Deruxtecan (DXd) and the internal radiation therapy of 131I for tumors, we aimed to develop the first radio-antibody-drug conjugates (RADCs) for the treatment of gastric cancer.Methods: The CLDN18.2-specific antibody HLX58 was conjugated with the payload DXd through a cleavable maleimide glycynglycyn-phenylalanyn-glycyn (GGFG) peptide linker. HLX58-Der was labeled with 131I to produce RADC-131I-HLX58-Der. HLX58 was labeled with 125I for imaging CLDN18.2-positive tumors, providing a reference for RADC treatment in solid tumors. The antigen-binding properties and biodistribution of the RADC were studied both in vitro and in vivo. The cytotoxic effects of the RADC were evaluated in CLDN18.2-positive tumor cell lines and xenografts.Results: HLX58 was successfully conjugated with DXd using the cleavable maleimide GGFG peptide linker and labeled with 131I to produce RADC-131I-HLX58-Der. HLX58 was labeled with 125I for imaging CLDN18.2-positive tumors. Both 125I-HLX58 and 131I-HLX58-Der exhibited significant binding affinity for the CLDN18.2-positive cancer cell line. The cytotoxic effect of 131I-HLX58-Der was observed in the CLDN18.2-positive cell line, with an IC50 of 11.28 ng/mL. In terms of cytotoxicity, 131I-HLX58-Der exhibited greater activity compared to HLX58-Der. 125I-HLX58 and 131I-HLX58-Der demonstrated similar biodistribution profiles in CLDN18.2-positive tumor models, achieving 5.72 ± 0.41%ID/g (48 h) and 5.83 ± 0.41%ID/g (72 h) in the tumor tissues postinjection, respectively. The average tumor size in groups treated with 131I-HLX58-Der and HLX58-Der was reduced by factors of 12.15 and 4.80, respectively, compared to the control group. 131I-HLX58-Der demonstrated no toxic effects on hepatorenal function, routine blood tests, or major organs in mice when compared to the control group.Conclusion: These findings validate the potential of RADCs targeting CLDN18.2 in treating CLDN18.2-expressing solid tumors. Keywords: CLDN18.2, radio-antibody-drug conjugates, molecular imaging, precision medicine

Yunheng Liu,1,&ast; Longqing Si,1,&ast; Yuxuan Jiang,1,&ast; Shaojing Jiang,2 Xiaokang Zhang,1 Song Li,1 Jing Chen,1 Jinghui Hu2 1School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 2Yantai Engineering Research Center for Digital Technology of Stomatology, Characteristic Laboratories of Colleges and Universities in Shandong Province for Digital Stomatology, Institute of Stomatology, Binzhou Medical University, Yantai, 264003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Chen, School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, People’s Republic of China, Email chenjingbyyxy@163.com Jinghui Hu, Yantai Engineering Research Center for Digital Technology of Stomatology, Characteristic Laboratories of Colleges and Universities in Shandong Province for Digital Stomatology, Institute of Stomatology, Binzhou Medical University, Yantai, 264003, People’s Republic of China, Email bykfhjh@163.comAbstract: The metabolic activity of tumor cells leads to the acidification of the surrounding microenvironment, which provides new strategies for the application of nanotechnology in cancer therapy. Researchers have developed various types of pH-responsive nanomaterials based on the tumor acidic microenvironment. This review provides an in-depth discussion on the design mechanisms, drug-loading strategies, and application pathways of tumor acidic microenvironment-responsive nanodrug delivery systems. These materials trigger drug release upon reaching the tumor microenvironment, enhancing therapeutic targeting and reducing toxicity to healthy cells. pH-responsive nanomaterials include organic nanomaterials, inorganic nanomaterials, and composite nanomaterials. Additionally, this review outlines the drug-loading strategies, application prospects, and challenges of pH-responsive nanomaterials, aiming to promote the development and clinical translation of this field.Keywords: tumor microenvironment, pH response, nanocarriers, drug-loading strategies, drug delivery system

Qiuyue Zhang,1,&ast; Yingchao Liu,1,&ast; Chuntang Tong,2 Lina Zhang,3 Rongchen Li,1 Wenbin Guo,4 Jianliang Li5 1Department of Clinical Laboratory, The Second People’s Hospital of Liaocheng, Linqing, Shandong, 252600, People’s Republic of China; 2Department of Respiratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong, 252600, People’s Republic of China; 3Department of Scientific Research Management Division, The Second People’s Hospital of Liaocheng, Linqing, Shandong, 252600, People’s Republic of China; 4Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, Linqing, Shandong, 252600, People’s Republic of China; 5Department of Thoracic Surgery, The Second People’s Hospital of Liaocheng, Linqing, Shandong, 252600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianliang Li, Department of Thoracic Surgery The Second People’s Hospital of Liaocheng, 306 health Street, Linqing, Shandong, 252600, People’s Republic of China, Tel +86 15020622456, Email lijianliangl724@163.comObjective: This study aimed to investigate the levels of coagulation parameters in elderly patients with severe pneumonia and analyse their correlation with disease severity and prognosis.Methods: A retrospective study was conducted on 207 elderly patients (aged ≥ 60 years) with severe pneumonia admitted to our hospital between January 2022 and December 2023. Demographic data, clinical characteristics and coagulation parameters, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time and fibrinogen (FIB), were collected. Patients were divided into survivor and non-survivor groups based on 28-day mortality. The differences in coagulation parameters between groups and their correlation with disease severity and prognosis were analysed.Results: The 28-day mortality rate was 52.2%. Non-survivors had significantly higher PT, APTT and D-dimer levels and lower FIB levels than survivors (p < 0.05). Multivariate logistic regression analysis showed that elevated PT (odds ratio [OR] = 1.218, 95% confidence interval [CI]: 1.076– 1.379, p = 0.002) and D-dimer (OR = 1.109, 95% CI: 1.032– 1.192, p = 0.005) were independent risk factors for 28-day mortality. The combined model using PT and D-dimer showed the highest predictive value for 28-day mortality (area under the curve = 0.801, 95% CI: 0.739– 0.863, p < 0.001), with a sensitivity of 0.759 and specificity of 0.758.Conclusion: Coagulation dysfunction is common in elderly patients with severe pneumonia. Prothrombin time and D-dimer levels are closely associated with disease severity and can be valuable indicators for predicting prognosis in this population.Keywords: elderly, severe pneumonia, coagulation parameters, disease severity, prognosis

Hao-bo Chen,1,&ast; Ling Li,2,&ast; Yun-kai Sun,2 Yi Liu,2 Wei Chen,3 Peng Liu,1 Yan-Hui Liao,1,2 An Xie1 1Department of Radiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Changsha, Hunan, People’s Republic of China; 2Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3MR Research Collaboration Team, Siemens Healthineers Ltd., Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: An Xie, Department of Radiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), 61 Jiefang West Road, Changsha, Hunan, 410005, People’s Republic of China, Tel/Fax +86-0731-81866132, Email xiean@hunnu.edu.cn Yan-Hui Liao, Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, People’s Republic of China, Email liaoyanhui@zju.edu.cnBackground: COVID-19 has led to reports of fatigue and sleep problems. Brain function changes underlying sleep problems (SP) post-COVID-19 are unclear. Purpose: This study investigated SP-related brain functional connectivity (FC) alterations.Patients and methods: Fifty-five COVID-19 survivors with SP (COVID_SP) and 33 without SP (COVID_NSP), matched for demographics, completed PSQI and underwent rs-fMRI at baseline and 2-month follow-up. Correlations between FC and clinical data were analyzed by Pearson correlation analysis with Gaussian random field (GRF) correction. The repeated-measures analysis of variance (R-M ANOVA) was completed to explore the interaction with time.Results: At baseline, COVID_SP exhibited elevated FC: right precentral gyrus (PrG) with left lateral occipital cortex (LOcC)/right PrG, left inferior parietal lobule (IPL) with right superior frontal gyrus (SFG), left hippocampus with right inferior frontal gyrus (IFG). Higher FC between left hippocampus and right SFG correlated with PSQI scores. At 2-month follow-up, decreased FC implicated in emotion regulation, executive function, and memory; increased FC in semantics, attention, and auditory-visual processing. The changes in these regions are correlated with the scores of PSQI, GAD, and PHQ. The Repeated-Measures Analysis of Variance (R-M ANOVA) revealed a significant time interaction effect between sleep and various emotion scales. Moreover, the analysis of the functional connectivity between the right PrG and the right PrG as well as that between the left IPL and the right SFG also discovered a significant time interaction effect.Conclusion: This study provides insight into the changes in brain function associated with SP after COVID-19. These changes may partially explain the development of SP, and they also changed over time.Keywords: COVID-19, SP, rs-fMRI, FC

Shaoji Li,1,&ast; Hongjian Li,2,&ast; Baofang Wu,1,&ast; Rujun Pan,3 Yuqi Liu,4 Jiayin Wang,1 De Wei,3 Hongzhi Gao1 1Department of Neurosurgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 2School of Medical Imaging, North Sichuan Medical College, Nanchong, 634700, People’s Republic of China; 3Department of Neurosurgery, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 4Department of Intensive Care Unit, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: De Wei; Hongzhi Gao, Email weidele@fjmu.edu.cn; gaohongzhi@fjmu.edu.cnBackground: Post-traumatic cerebral infarction (PTCI) is a severe complication resulting from traumatic brain injury (TBI), which can lead to permanent neurological damage or death. The investigation of the factors associated with PTCI and the establishment of predictive models are crucial for clinical practice.Methods: We made a retrospective analysis of clinical data from 1484 TBI patients admitted to the Neurosurgery Department of a provincial hospital from January 2018 to December 2023. Predictive factors were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) and multivariable logistic regression analysis. Several machine learning (ML) classification models were developed and compared. The interpretations of the ML models’ predictions were provided by SHAP values.Results: Key predictors included age, bilateral brain contusions, platelet count, uric acid, glucose, traumatic subarachnoid hemorrhage, and surgical treatment. The logistic regression (LR) model outperformed other ML algorithms, demonstrating superior performance in the test set with an AUC of 0.821, accuracy of 0.845, Matthews correlation coefficient (MCC) of 0.264, area under the receiver operating characteristic curve (AUROC) of 0.711, precision of 0.56, and specificity of 0.971. It had stable performance in the ten-fold cross-validation.Conclusion: ML algorithms, integrating demographic and clinical factors, accurately predicted the risk of PTCI occurrence. Interpretations using the SHAP method offer guidance for personalized treatment of different patients, filling gaps between complex clinical data and actionable insights.Keywords: traumatic brain injury, post-traumatic cerebral infarction, retrospective study, machine learning, prediction model

Huiting Liu,&ast; Sai Yang,&ast; Hua Xian, Yinghui Liu, Yan Zhang, Yangxia Chen, Yingping Xu, Jun Liu, Bin Yang, Ying Luo Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Yang; Ying Luo, Department of Dermatology, Dermatology Hospital, Southern Medical University, No. 2 Lujing Road, Yuexiu District, Guangzhou, People’s Republic of China, Email yangbin1@smu.edu.cn; luoyingmab@yahoo.comBackground: Alopecia areata (AA) is a common autoimmune disease, causes sudden hair loss on the scalp, face, and sometimes other areas of the body. Previous studies have suggested more severe manifestations and higher recurrence rates in children than in adults. Moreover, pediatric AA patients with atopic predisposition often exhibit elevated IgE levels, early onset, and a poor prognosis.Purpose: This study aimed to investigate the impact of age and IgE levels on AA by conducting RNA sequencing on scalp samples from AA patients with atopic predisposition, age-matched healthy controls, and AA samples with varying IgE levels.Patients and Methods: We employed the single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm in conjunction with gene expression analysis to assess immune infiltration. Differential gene expression analysis was performed using the DESeq package in R. Immunohistochemical staining and qPCR was performed to validate these findings.Results: Our results revealed a more pronounced inflammatory immune infiltration in AA patients across all age groups compared to healthy controls. Pediatric AA was characterized by an upregulation of genes controlling inflammatory responses, such as the IFN-γ pathway and JAK-STAT cascade, contrasting to adult AA. Compared to age-matched healthy controls, pediatric AA patients exhibited a significant increase in the infiltration of B cell subtypes, mast cells, and regulatory T cells. Additionally, high IgE levels in AA patients led to the upregulation of IFN-γ pathway genes, compared to AA patients with normal IgE levels.Conclusion: In summary, the heightened immune and inflammatory responses, along with the more significant infiltration of immune cells in pediatric AA with atopic predisposition, may explain the increased clinical severity and recurrence rates. Dissecting these molecular mechanisms sheds some light on the contributions of age and IgE to the pathogenesis and progression of AA, revealing potential age-specific and allergy-related therapeutic targets.Keywords: alopecia areata, age, IgE, immune response, inflammatory response

Ruanjuan Zhan,1,&ast; Yanan Liu,1,2,&ast; Jun Wu,1,2 Yuxin Shen,1,2 Xinhao Xu,1,2 Guanyang Lin,1,2 Xiaocheng Chen1 1The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 2School of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanyang Lin; Xiaocheng Chen, Email 13867702133@163.com; cxcwzcn@139.comBackground: Givinostat, a potent histone deacetylase (HDAC) inhibitor, is promising for the treatment of relapsed leukemia and myeloma.Purpose: This study aimed to develop and verify a quick assay for the measurement of givinostat concentration using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) with eliglustat as the internal standard (IS), establishing a basic pharmacokinetic profile for its pre-clinical application and metabolic stability in vitro.Methods: Sample preparation was performed via protein precipitation using acetonitrile. The analyte (givinostat) and IS were gradient eluted on a Waters ACQUITY UPLC BEH C18 column (1.7 μm, 2.1 × 50 mm) with 0.1% formic acid (A) and acetonitrile (B) as the mobile-phase system. The multiple reaction monitoring (MRM) in positive ion mode was used to detect the mass transition pairs for givinostat and IS as follows: m/z 422.01→ 186.11 for givinostat, and m/z 405.40→ 84.10 for IS, respectively.Results: In the bioanalytical method, good linearity was observed between 2 and 4000 ng/mL (r2=0.998). The intra- and inter-day precisions (RSD%) were lower than 15%, with an accuracy (RE%) of 95.8%– 108.6%. The recovery exceeded 90%, and the matrix effect was within the range of 98.2%– 107.6%. Additionally, this method was successful in evaluating pharmacokinetics in rats after an oral dose of 10 mg/kg givinostat. Finally, in vitro results showed that givinostat had a slow intrinsic clearance (CLint) value of 14.92 μL/min/mg protein with a half-life (t1/2) value of 92.87 min.Conclusion: Givinostat was rapidly absorbed and cleared slowly in vivo, and it was confirmed by in vitro experiments. This study provides a potential reference for givinostat in clinical studies.Keywords: givinostat, UPLC-MS/MS, rat plasma, pharmacokinetic study, in vitro metabolic stability

Ying Liu,1,&ast; Hongmin Liu,1,2,&ast; Dongkun Sun,1,&ast; Yi Zheng,1 Gary Tse,1,3,4 Kangyin Chen,1 Jiuchun Qiu,1 Shouling Wu,2 Tong Liu1 1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 2Department of Cardiology, Kailuan General Hospital, Tangshan, 063001, People’s Republic of China; 3School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong, People’s Republic of China; 4Diabetes Research Unit, Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tong Liu, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, No. 23 Pingjiang Road, Hexi District, Tianjin, 300211, People’s Republic of China, Email liutong@tmu.edu.cn; liutongdoc@126.com Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, 063001, People’s Republic of China, Email drwusl@163.comBackground: Both renal function decline and systemic inflammation may synergistically increase the risk of atrial fibrillation (AF). This study investigates the association between estimated glomerular filtration rate (eGFR) and high-sensitivity C-reactive protein (hs-CRP) levels with the risk of new-onset AF in patients with diabetes mellitus.Methods: We included diabetic patients without AF who participated in physical exams in the Kailuan Study from 2006 to 2010. Participants were categorized into four groups based on baseline eGFR and hs-CRP levels: 1) high eGFR (≥ 60 mL/min/1.73m²) and low hs-CRP (< 3 mg/L) (n=6,915), 2) high eGFR and high hs-CRP (≥ 3 mg/L) (n=3,154), 3) low eGFR (< 60 mL/min/1.73m²) and low hs-CRP (n=4,638), 4) low eGFR and high hs-CRP (n=1,809). We employed multivariable Cox regression analysis to evaluate the relationships between eGFR, hs-CRP, and new-onset AF, adjusting for confounders including smoking status, alcohol consumption, blood pressure, fasting blood glucose (FBG), heart rate, lipid levels, body mass index (BMI), and medication usage. Competing risk analysis was also performed.Results: Among 16,516 patients, 222 developed new-onset AF over a mean follow-up of 12.6 years. After adjusting for confounders, elevated hs-CRP and reduced eGFR were significantly associated with higher risk of new-onset AF compared to the high eGFR/low hs-CRP group. These findings remained consistent after excluding AF cases within the first 2-year. No significant interaction between eGFR and hs-CRP was observed (P=0.227). Subgroup analysis revealed that the combination of eGFR and hs-CRP had predictive value primarily in males under 60 years of age, individuals with FBG < 9 mmol/L, hypertension, and those not on hypoglycemic medications.Conclusion: In diabetic patients, decreased eGFR and elevated hs-CRP were independently linked to an increased risk of new-onset AF, emphasizing the importance of monitoring these factors for early detection and prevention of AF.Keywords: estimated glomerular filtration rate, high-sensitivity C-reactive protein, atrial fibrillation, diabetes mellitus

JinHua Cui,1 YaMan Liu,2 Hua Fu,1 MiaoHang Cui,1 JiZhong Li,3 ZiYu Bai,1 Jian Li1 1Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical College, Chengde City, Hebei Province, People’s Republic of China; 2Department of Gynaecology, Affiliated Hospital of Chengde Medical College, Chengde City, Hebei Province, People’s Republic of China; 3Department of Operating Room, Affiliated Hospital of Chengde Medical College, Chengde City, Hebei Province, People’s Republic of ChinaCorrespondence: Jian Li, Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical College, Chengde City, Hebei Province, People’s Republic of China, Email lijian111008@126.comAim: To perform a comparative analysis of the clinical data of patients with and without recurrent pyogenic liver abscess and explore the influencing factors, clinical characteristics, and pathogenic bacteria associated with the recurrence of liver abscesses.Patients and Methods: A retrospective analysis was conducted on 436 recently diagnosed patients with pyogenic liver abscess admitted to the Affiliated Hospital of Chengde Medical College between June 2017 and June 2023. Patients with recurrence comprised the observation group, whereas those without recurrence comprised the control group.This analysis included the examination of clinical characteristics, pathogens, drug resistance patterns, and treatment modalities. Additionally, regression analysis was employed to investigate the factors influencing liver abscess recurrence.Results: Of 436 patients initially diagnosed with pyogenic liver abscess, 58 experienced recurrence. The proportion of Escherichia coli infection was 23.3% in the observation group and 10.3% in the control group, indicating a statistically significant difference. Multivariate analysis identified diabetes mellitus and cerebral infarction as significant risk factors for recurrent pyogenic liver abscess.Conclusion: In comparison with patients without recurrence, those who experienced recurrent pyogenic liver abscess following initial diagnosis exhibited a higher prevalence of E. coli as a pathogenic bacterium. In addition, a history of diabetes mellitus and cerebral infarction are high-risk factors for with pyogenic liver abscess recurrence for the first time.Keywords: pyogenic liver abscess, relapse, Klebsiella pneumoniae, Escherichia coli, diabetes mellitus

Tianwen Chen,1 Mingying Li,1 Yuchen Liu,2 Xiaoxia Zhang,1 Xiaoli Sun,1 Jie Li,1 Miao He,1 Zhenyuan Wang1 1Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China; 2Department of Hernia and Abdominal Wall Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of ChinaCorrespondence: Mingying Li, Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 5 Jingyuan Street, Shijingshan District, Beijing, 100043, People’s Republic of China, Tel +86 13581900676, Email mingyinglilmy@126.comObjective: To evaluate the clinical efficacy and safety of ultrasound-guided rectus sheath block (RSB) in laparoscopic umbilical hernia repair with intraperitoneal onlay mesh (IPOM).Methods: A total of 139 patients scheduled for laparoscopic umbilical hernia repair with IPOM were selected and randomly assigned to either the group receiving general anesthesia combined with bilateral rectus sheath block (Group GR, 71 patients) or the group receiving general anesthesia alone (Group G, 68 patients). We monitored the patients’ heart rate (HR) and mean arterial pressure (MAP) at four time points: before anesthesia induction (T1), at the start of surgery (T2), during mesh fixation (T3), and upon removal of the laryngeal mask (T4). Postoperative pain levels were evaluated using the Visual Analogue Scale (VAS) at 1 hour (T5), 6 hours (T6), and 12 hours (T7) after surgery while resting, as well as at 24 hours (T8) during activity. We also compared the number of times the patient-controlled intravenous analgesia (PCIA) pump was pressed and the use of additional analgesics within 24 hours post-surgery, along with recording any adverse reactions and complications associated with RSB.Results: At time points T2 and T3, the HR and MAP in Group GR were significantly lower than those in Group G (P < 0.05). Additionally, VAS scores at various postoperative intervals were lower in Group GR, with significant differences noted at T5, T7, and T8 (P < 0.05). Group GR also had significantly fewer presses on the analgesia pump within 24 hours post-surgery compared to Group G, while the incidence of adverse events was similar between the two groups.Conclusion: Ultrasound-guided RSB is a straightforward and safe technique for laparoscopic umbilical hernia repair with IPOM. It offers clear analgesic benefits and significantly reduces early postoperative pain.Keywords: analgesia, IPOM, rectus sheath block, ultrasound-guided, umbilical hernia

Yang Liu,1,2 Liang Kong,1,2 Yang Yu,1,2 Juan Zang,1,2 Lu Zhang,1,2 Rui-Bo Guo,1,2 Shu-Tong Li,1,2 Lan Cheng,1,2 Xue-Tao Li,1,2 You-Qiang Chen1,2 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China; 2Shenyang Key Laboratory of Chinese Medicine Targeted Delivery Key Laboratory, Shenyang, 110847, People’s Republic of ChinaCorrespondence: Xue-Tao Li; You-Qiang Chen, School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shengming 1 Road 77, Double D Port, Dalian, 116600, People’s Republic of China, Tel +86411 8589 0170, Fax +86411 8589 0128, Email lixuetao1979@163.com; 89427765@qq.comBackground: Ovarian cancer is difficult to detect in its early stages, and it has a high potential for invasion and metastasis, along with a high rate of recurrence. These factors contribute to the poor prognosis and reduced survival times for patients with this disease. The effectiveness of conventional chemoradiotherapy remains limited. Nano-particles, as a novel drug delivery system, have significant potential for improving therapeutic efficacy and overcoming these challenges.Methods: According to the high expression level of matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, MMP-2 responsive nano-particles (PVGLIG-MTX-D/T-NMs) containing docetaxel and triptolide were prepared by the thin-film dispersion method. The synergistic effect between docetaxel and triptolide was systematically investigated, the ratio of the two drugs was optimized, and the physicochemical properties of the nano-particles and their ability to inhibit ovarian cancer cell growth and metastasis were evaluated in vitro and in vivo.Results: PVGLIG-MTX-D/T-NMs enhanced the targeting, stability, and bioavailability of the drug, while reducing the dose and toxicity. In addition, by regulating the expression levels of E-Cadherin, N-Cadherin, matrix metalloproteinases (MMPs), hypoxia-inducible factor 1-alpha (HIF-1α), and vascular endothelial growth factor (VEGF), it exhibited an inhibitory effect on epithelial-mesenchymal transformation (EMT) and tumor cell angiogenesis, and effectively inhibited the invasion and metastasis of ovarian cancer cells.Conclusion: PVGLIG-MTX-D/T-NMs achieved passive targeting of tumor sites by enhancing permeability and retention (EPR) effects. Subsequently, the uptake of the drug by tumor cells was enhanced by MMP-2 responsiveness and the modification of methotrexate targeting ligands. By regulating the expression levels of invasion- and metastasis-related proteins in tumor tissues, the nano-particles affected the EMT process, inhibited tumor angiogenesis, and suppressed the malignant potential of invasion and metastasis in ovarian cancer. These findings provided a new direction for further exploration of tumor-targeted therapy.Keywords: nano-drug delivery system, tumor microenvironment, docetaxel, triptolide, epithelial mesenchymal transition, angiogenesis

Yang Liu,1 Shikang Hao,2 Hongyu Hao,3 Guona Zheng,1 Jie Bing,1 Lin Kang,1 Jia Li,4 Huanfen Zhao,1,&ast; Han Hao5,&ast; 1Department of Pathology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2The First Clinical Medical School, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Neurology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 4Outpatient Department, Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Center of Innovative Drug Research and Evaluation, Hebei Medical University, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han Hao; Huanfen Zhao, Email 18800790@hebmu.edu.cn; ZHAO552588@126.comBackground: Recent studies have shown necroptosis may play a role in the development of inflammation-associated pain. However, research on the correlation between necroptosis-related genes and neuropathic pain in the dorsal root ganglia (DRG) is limited. This study aims to identify a gene signature related to necroptosis in DRG that can predict neuropathic pain.Methods: The mRNA expression profiles associated with neuropathic pain (GSE24982 and GSE30691) were acquired from the Gene Expression Omnibus (GEO) database. The Least Absolute Shrinkage and Selection Operator (Lasso) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) regressions were performed in GSE24982 database to constructed the necroptosis-related diferentially expressed genes (NRDEGs) signature related to neuropathic pain. Nomogram, Receiver Operating Characteristic (ROC), GSE30691 database analysis and basic experiments were used to verify the accuracy of the signature. Go and KEGG analysis, interaction network and immune infiltration were used to analyze the biological function of the signature.Results: A predictive signature targeting rat DRG for neuropathic pain through a variety of methods to verify the accuracy was developed based on 3 NRDEGs (TLR4, CAPN2, RIPK3). Significantly enriched KEGG and GO pathways, drug target prediction and non-coding RNAs related to the signature holded promise for advancing our understanding of potential avenues for treatment and the mechanisms underlying neuropathic pain. Immune infiltration analysis revealed which types of immune cells related to the NRDEGs signature played an important role in the occurrence and development of neuropathic pain. Basic experiments provided crucial evidence that the 3 NRDEGs in DRG served as important regulators of neuropathic pain.Conclusion: The prediction signature based on 3 key NRDEGs showed promise in predicting the presence of neuropathic pain, which may open up new avenues for the development of novel therapies for neuropathic pain.Keywords: DRG, neuropathic pain, necroptosis, signature, prediction

Yuwei Jiang,1,&ast; Jiaoya Xu,1,2,&ast; Junyao Ding,1,&ast; Tao Liu,1 Yang Liu,1,3 Ping Huang,1 Qianlei Wang,1 Peiyong Zheng,1 Haiyan Song,1 Lili Yang1 1Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Gout, Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Teaching Experiment Center, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyan Song; Lili Yang, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, People’s Republic of China, Email songhy@126.com; yanglili76@126.comPurpose: Mitochondrial dysfunction mediated by c-Jun N-terminal kinase (JNK) plays an important role in lipotoxic liver injury in nonalcoholic steatohepatitis (NASH). This study aims to investigate the pharmacological mechanism of Jiangzhi Granule (JZG), a Chinese herbal formula against NASH, with a focus on its regulation of JNK signaling-mediated mitochondrial function.Methods: Hepatocytes were induced by palmitic acid (PA) for 24 h to establish an in vitro lipotoxic model, which was simultaneously treated with either JZG or vehicle control. Male C57BL/6J mice were fed a high-fat diet (HFD) for 22 weeks and then treated with JZG via gavage for additional 8 weeks. Lipotoxic injury in hepatocytes or mice liver tissues, as well as JNK signaling-related molecules, were further investigated.Results: JZG improved PA-induced lipid deposition, cell viability, apoptosis, and mitochondrial dysfunction in hepatocytes. In NASH mice, JZG reduced hepatosteatosis, and inflammatory infiltration, and improved mitochondrial morphology and quantity in liver tissues. Additionally, elevated phosphorylation ratio of non-receptor tyrosine kinase c-Src (Src) and reduced phosphorylation ratio of JNK and SH2-containing protein tyrosine phosphatase (SHP-1) were found in both hepatocytes and mice liver tissues treated with JZG versus those with the vehicle.Conclusion: Taken together, JZG could improve mitochondrial dysfunction and reduce lipotoxic liver injury in NASH in vivo and in vitro models. The inhibition of the JNK signaling pathway may contribute to the underlying mechanism of JZG in preventing and reversing NASH development. Keywords: nonalcoholic steatohepatitis, Jiangzhi Granule, c-Jun N-terminal kinase, mitochondrial dysfunction, lipotoxic injury

Han Li,1,&ast; Dongsheng Wei,2,&ast; Huimin Cao,2 Yelei Han,1 Luzhen Li,1 Yuting Liu,1 Jiajie Qi,1 Xinyue Wu,1 Zhe Zhang2,3 1The First School of Clinical Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 2Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 3Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhe Zhang, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33 Beiling Street, Shenyang, 110032, People’s Republic of China, Tel +86-18102459155, Email pedtrainzhzh7676@163.comPurpose: Myocardial infarction (MI) is a prevalent cardiovascular disorder affecting individuals worldwide. There is a need to identify more effective therapeutic agents to minimize cardiomyocyte damage and enhance cardioprotection. Ginkgo biloba extract is extensively used to treat neurological disorders and peripheral vascular diseases. The aim of this study was to determine the protective effects and mechanisms of ginkgetin on postinfarction cardiomyocytes through bioinformatics and experimental validation.Methods: Bioinformatics analysis was performed to predict the underlying biological mechanisms of ginkgetin in the treatment of MI. Next, we performed further validation through experiments. For in vivo studies, we used coronary ligation to construct an MI rat model. In vitro, oxygen and glucose deprivation (OGD) was performed to simulate ischemia in H9c2 cardiomyocytes.Results: Bioinformatics analysis revealed that the key targets of ginkgetin for MI treatment were MMP2, MMP9, and VEGFA. Immune infiltration analysis revealed that ginkgetin might be involved in immune regulation by acting on the TCR signaling pathway. The results of the GO enrichment analysis revealed that ginkgetin might protect the heart by acting on the cell membrane to alleviate the senescent apoptosis of cardiomyocytes after MI. In vivo studies revealed that ginkgetin ameliorated myocardial pathological damage and cardiac decompensation after MI. It also alleviated the inflammatory infiltration and senescent apoptosis of cardiomyocytes after MI. Additionally, ginkgetin can downregulate the activation signals of the TCR signaling pathway by dephosphorylating CD3 and CD28. In vitro studies revealed that ginkgetin attenuated elevated OGD-induced cytotoxicity, increased cell viability, and alleviated OGD-induced senescent apoptosis, thus protecting cardiomyocytes.Conclusion: Ginkgetin inhibits postinfarction myocardial fibrosis and cardiomyocyte hypertrophy, scavenges oxygen free radicals, decreases postinfarction limbic cell inflammatory infiltration, suppresses activation of the inflammatory-immune pathway, and delays postinfarction peripheral cells from undergoing senescent apoptosis, thus protecting the heart. Keywords: myocardial infarction, ginkgetin, senescence-associated secretory phenotype, immune infiltration, TCR signaling pathway

Keting Liu,1,2,&ast; Li Yang,1,&ast; Yang Liu,3 Yun Zhang,1 Juncheng Zhu,4 Haofeng Zhang,5 Zemin He6 1Department of Neurology, Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan Province, 610213, People’s Republic of China; 2Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 3Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, 610075, People’s Republic of China; 4Department of Radiology, Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan Province, 610213, People’s Republic of China; 5Department of Information, Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan Province, 610213, People’s Republic of China; 6Department of Thoracic Surgery, The First People’s Hospital of Shuangliu District (West China Airport Hospital of Sichuan University), Chendu, Sichuan Province, 610200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zemin He, Email 993092572@qq.comBackground: Systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are novel inflammatory markers based on neutrophil, platelet and lymphocyte counts. Atherosclerosis is a chronic inflammatory vascular disease. This study aimed to verify the predictive value of the clinical parameters such as systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) for the severity in Large Artery Atherosclerosis (LAA) stroke patients.Methods: The SII is defined as platelet × (neutrophil count/lymphocyte count), the NLR is defined as neutrophil count/lymphocyte count. Univariate logistic regression was used to analyze the association between SII and NLR and NIHSS score in patients with LAA stroke. Multiple logistic regression was used to analyze the risk factors for the severity of LAA stroke. We plotted receiver operating characteristic curves to determine the diagnostic role of SII and NLR in differentiating stroke disease severity.Results: We included 283 LAA stroke patients, the SII and NLR in the moderate-to-severe stroke group were significantly higher than the mild stroke group. Multiple logistic regression analysis showed that SII (OR 1.051 95% CI (1.035– 1.066), P < 0.001), NLR (OR 1.077,95% CI (1.032– 1.123), P < 0.001) were significantly associated with stroke severity. The SII values under the receiver operating characteristic curve (0.701, 95% CI (0.649– 0.791, P < 0.001, cut-off value 912.97) and NLR values under the receiver operating characteristic curve (0.604,5% CI (0.519– 0.689), P < 0.01, cut-off value 1.461), and SII values had high discrimination ability. Both SII and NLR had high diagnostic and predictive value for stroke severity, and SII was better than NLR.Conclusion: The higher SII and NLR, the more severity in LAA stroke patients. SII and NLR are independent risk factors for LAA stroke, and they can also effectively predict stroke severity; moreover, SII has a higher diagnostic efficacy than NLR. However, multicenter studies with large sample size are still needed to confirm this conclusion.Keywords: large-artery atherosclerosis stroke, systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, stroke severity, predictor

Cui He,1 Haidong Ma,2 Tingting Zhang,1 Yu Liu,1 Cuiying Zhang,3 Surong Deng1 1Department of Blood Transfusion of Yong-chuan Hospital, Chongqing Medical University, Chongqing, 402160, People’s Republic of China; 2Department of Pharmacy of Yong-chuan Hospital, Chongqing Medical University, Chongqing, 402160, People’s Republic of China; 3Department of Obstetrics and Gynaecology of Yong-chuan Hospital, Chongqing Medical University, Chongqing, 402160, People’s Republic of ChinaCorrespondence: Surong Deng, Email 172346252@qq.comPurpose: To study the platelet adhesion and aggregation behaviour of late pregnancy women under arterial shear rate using microfluidic chip technology and evaluate the risk of thrombosis in late pregnancy.Methods: We included pregnant women who were registered in the obstetrics department of our hospital between January 2021 and October 2022 and underwent regular prenatal examinations. Blood samples were collected at 32– 35 weeks of gestation for routine blood tests and progesterone, oestradiol, and platelet aggregation function. A microfluidic chip was used to construct an in vitro stenosis vascular model to explore the platelet reactivity at shear rates of 1000s-1, 1500s-1 and 4000s-1. Flow cytometry was used to analyse the effect of shear rate induction on the expression of platelet membrane surface fibrin receptor (PAC-1) and P-selectin (CD62P) in pregnant women.Results: Compared to the non-pregnant healthy control group, the white blood cell count increased and platelet count decreased significantly in late pregnant women (P < 0.05), and platelet reactivity to agonists increased under non-flow conditions (adhesion and aggregation rates, P < 0.05). Microfluidic chip technology showed that platelet aggregation in late pregnant women increased significantly (P < 0.05) in the shear-rate environment and was positively correlated with the shear rate. The degree of aggregation at 4000s− 1 was more evident, but the stability of platelet aggregates was low. Shear rate increased PAC-1 and CD62P expression.Conclusion: Microfluidic chip technology was used to analyse the platelet aggregation function under arterial shear rate combined with flow cytometry to detect platelet activation, which was consistent with the traditional non-flow conditions used to evaluate platelet function. However, microfluidic technology can simulate a more realistic in vivo shear rate environment, providing more effective clinical application data and a theoretical basis for the diagnosis and prevention of platelet dysfunction and thrombotic diseases during pregnancy.Keywords: microfluidic chip, late pregnancy, platelets, adhesion aggregation, thrombosis

Yufang Liu,1,&ast; Chunyan Li,2,&ast; Weiwei Deng2 1Department of Dermatology and Venereology, Fuyang People’s Hospital, Fuyang, Anhui, 236000, People’s Republic of China; 2Department of Dermatology and Venereology, Dermatology Hospital of Southern Medical University, Department of Dermatology, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiwei Deng, Email dengww@smu.edu.cnBackground: Signaling pathways play crucial roles in tumor cells. However, functional heterogeneity of signaling pathways in skin cutaneous melanoma (SKCM) has not been established.Methods: Based on a recent computational pipeline, pathway activities between SKCM and normal samples were identified.Results: The results showed that high activities in 12 pathways were associated with poor prognoses, while high activities in 17 pathways were associated with favorable prognoses. Interestingly, elevated metabolic pathway activity was unfavorable, whereas elevated immune activity was favorable for SKCM. Unfavorably elevated metabolic pathways strongly correlated with Wnt/beta-catenin signaling. Conversely, favorable pathways, such as glycosaminoglycan biosynthesis and keratan sulfate, were strongly correlated with anti-tumor pathways. Moreover, the activities of favorable pathways were strongly positively correlated with infiltrating CD8+ T cells, macrophages M1, immune score, and stromal score, all of which were favorable for SKCM.Conclusion: Taken together, our study provides insights into the characteristics of several pathways in SKCM.Keywords: skin cutaneous melanoma, pathway activity, immune infiltration, prognosis, bioinformatics, tumor microenvironment

Weizhou Qiao,1,&ast; Cuiping Zhu,2,&ast; Dan Huang,1 Yue Liu,1 Zengkai Wang,1 Tianjie Zhu,1 Qingyu Song,1 Xu Yang,1 Yueying Wang,1 Yushuang Wang1 1Department of Clinical Laboratory, Central Hospital of Dalian University of Technology, Dalian, 116033, People’s Republic of China; 2Blood Purification Center, Central Hospital of Dalian University of Technology, Dalian, 116033, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhou Qiao, Department of Clinical Laboratory, Central Hospital of Dalian University of Technology, No. 826, Southwest Road, Shahekou District, Dalian, Liaoning, 116033, People’s Republic of China, Email qiaoweizhou2024@163.comObjective: Juvenile dermatomyositis (JDM) is a complex autoimmune disease, and its pathogenesis remains poorly understood. Building upon previous research on the immunological and inflammatory aspects of JDM, this study aims to investigate the role of pyroptosis in the pathogenesis of JDM using a comprehensive bioinformatics approach.Methods: Two microarray datasets (GSE3307 and GSE11971) were obtained from the Gene Expression Omnibus database, and a list of 62 pyroptosis-related genes was compiled. Differential gene expression analysis and machine learning analysis were performed to identity the hub pyroptosis-related differentially expressed genes (PR-DEGs). Functional enrichment analysis, immune cell infiltration analysis, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) were performed to elucidate the potential roles of PR-DEGs in JDM pathogenesis.Results: A total of 2526 common DEGs were identified, among which 12 PR-DEGs were identified, with CASP1, IRF1, NOD2, and PYCARD identified as hub PR-DEGs. These genes were involved in cytokine production, inflammasome activity, necroptosis, NOD-like receptor signaling, and TNF signaling. Immune infiltration analysis showed increased pro-inflammatory immune cell infiltration in JDM patients, with PR-DEGs positively correlated with various immune cell types. GSVA and GSEA analyses demonstrated the involvement of PR-DEGs in multiple inflammation and immunity-related pathways, with the NOD-like receptor signaling pathway playing a central role.Conclusion: This study highlights the crucial role of pyroptosis in the pathogenesis of JDM, with the identified PR-DEGs potentially contributing to disease development and progression by regulating key inflammatory and immune-related pathways.Keywords: pyroptosis, JDM, immune infiltration analysis, machine learning, diagnostic

Zixiong Huang,1– 3 Yanying Liu,4,5 Yunshu Xiao,5 Hao Hu,1,2 Tao Xu1,2 1Department of Urology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 2Applied Lithotripsy Institute, Peking University, Beijing, 100044, People’s Republic of China; 3Department of Urology, Michigan Medicine, Ann Arbor, MI, 48109, USA; 4Department of Rheumatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 5Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaCorrespondence: Hao Hu; Tao Xu, Department of Urology, Peking University People’s Hospital, 11 Xizhimen South Street, Beijing, 100044, People’s Republic of China, Email huhao@bjmu.edu.cn; xutao@pkuph.edu.cnObjective: This study investigated the efficacy of comprehensive management and predictable inflammatory markers for idiopathic retroperitoneal fibrosis (iRPF)-related hydronephrosis outcomes.Methods: Patients with iRPF-related hydronephrosis underwent surgical (ureteral stent and/or nephrostomy tube placement) and medical (corticosteroid-based multiple immunosuppressants) management were classified according to stent-indwelling outcomes. Univariate analysis of clinical profiles was conducted to screen possible predictors of hydronephrosis remission.Results: In a series of 38 patients, 52.6% achieved hydronephrosis remission and stent/tube removal (stent-free group). The median indwelling time in the stent-free group (12 months) was significantly lower than that in the treatment-failure group (37 months, p< 0.05). Mean retroperitoneal mass diameters was significantly reduced (anteroposterior by 11.66 mm (95% CI 2.31– 21.01), transverse by 15.41 mm (95% CI 3.37– 27.46), suprainferior by 30.53 mm (95% CI 4.87– 56.19); p< 0.05) during the treatment course, in line with mean renal pelvis width (by 36.2%) and renal function parameters (serum creatinine by 16.9%, blood urea nitrogen by 12.9%). Renal function improved (36.9%) or remained stable (44.7%) in most patients, the mean estimated glomerular filtration rate increasing by 8.7% (from 55.4 mL/min/1.73 m2 to 60.2 mL/min/1.73 m2). At the initial diagnosis, median serum immunoglobulin IgG and CRP levels were significantly higher in the stent-free group than in the treatment-failure group (IgG 17.55 g/L vs. 13.50 g/L, CRP 19.60 mg/L vs. 3.15 mg/L; p< 0.05). Decline in serum IgG (− 5.80 g/L vs. − 2.30 g/L), CRP (− 18.93 mg/L vs. − 1.72 mg/L) and erythrocyte sedimentation rate (− 22.00 mm/h vs. − 1.50 mm/h) levels in the stent-free group surpassed those in the treatment-failure group (p< 0.05).Conclusion: Comprehensive management benefits iRPF patients with hydronephrosis by preserving renal function. The 24-month scale might guide stent/tube removal. Elevated inflammatory markers (IgG and CRP) at the initial iRPF diagnosis and IgG, CRP, and erythrocyte sedimentationrate (ESR) variations associated with hydronephrosis outcomes.Plain Language Summary: The 24-month scale might guide the decision of final removal.Elevated inflammatory markers (IgG and CRP) at initial iRPF diagnosis and IgG, CRP, and ESR decreasing during the treatment course could predict hydronephrosis remission and stent-free outcomes.Alternative treatments, such as immunosuppressants other than corticosteroids, rather than longer stent indwelling could be recommended for patients with minimal possibility of hydronephrosis remission.Keywords: idiopathic retroperitoneal fibrosis, hydronephrosis, ureteral stent, immunosuppressant medications, stent-free outcome

Ping Wang,&ast; Mengchao Wang,&ast; Zhe Xie,&ast; Zhongwen Zhi, Yuqian Wang, Fan Liu, Yufeng Liu, Liandong Zhao Department of Neurology, the Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufeng Liu; Liandong Zhao, Department of Neurology, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China, Email lyf996226@163.com; zld202109@163.comPurpose: Research suggests that insulin resistance (IR) is associated with acute ischemic stroke (AIS) and depression. The use of insulin-based IR assessments is complicated. Therefore, we explored the relationship between four non-insulin-based IR indices and post-stroke depression (PSD).Patients and Methods: A total of 638 consecutive AIS patients were enrolled in this prospective cohort study. Clinical data were collected to compute indices such as the triglyceride glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI), insulin resistance metabolic score (METS-IR), and triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C). One month post-stroke, neuropsychological assessments were conducted using the 17-item Hamilton Depression Scale. Binary logistic regression analysis was performed to explore the relationship between the four non-insulin-based IR indices and PSD.Results: Ultimately, 381 patients completed the 1-month follow-up, including 112 (29.4%) with PSD. The PSD group exhibited significantly higher levels of the four IR indices compared to the non-PSD group. Logistic regression analysis demonstrated that these indicators were independently associated with PSD occurrence, both before and after adjusting for potential confounders (all P < 0.001). Tertile analyses indicated that the highest tertile group had a greater risk of PSD occurrence than the lowest tertile group for four IR indicators, even after adjusting for potential confounders (all P < 0.05). Restricted cubic spline analysis revealed a linear dose-response relationship between the four IR indices and PSD. In the subgroup analysis, only the TyG index showed a significant interaction with diabetes (P for interaction = 0.014). The area under curve values for the TyG index, TyG-BMI, METS-IR, and TG/HDL-C were 0.700, 0.721, 0.711, and 0.690, respectively.Conclusion: High TyG index, TyG-BMI, METS-IR, and TG/HDL-C at baseline were independent risk factors for PSD in AIS. Each of these indicators exhibits predictive value for PSD occurrence, aiding in the early identification of high-risk groups.Keywords: acute ischemic stroke, post-stroke depression, insulin resistance, non-insulin-based insulin resistance indices

Yang Liu,1,2 Yunhui Zhou,3 Cong Liao,1,2 Hang Li,2 Xiaolan Zhang,4 Haigang Gong,5 Hong Pu1,2 1School of Medicine, University of Electronic Science and Technology, Sichuan, China; 2Department of Radiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, People’s Republic of China; 3Department of Radiology, Chengdu Pidu District People’s Hospital, Sichuan, People’s Republic of China; 4Shukun Technology Co., Ltd, Beijing, People’s Republic of China; 5School of Computer Science and Engineering, University of Electronic Science and Technology, Sichuan, People’s Republic of ChinaCorrespondence: Hong Pu, Department of Radiology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital; School of Medicine, University of Electronic Science and Technology, Chengdu, Sichuan Province, 610000, People’s Republic of China, Email ph196797@163.com Haigang Gong, School of Computer Science and Engineering, University of Electronic Science and Technology, Chengdu, Sichuan Province, 610000, People’s Republic of China, Email hggong@uestc.edu.cnObjective: This study aimed to investigate how dynamic contrast-enhanced CT imaging signs correlate with the differentiation grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to assess their predictive value for MVI when combined with clinical characteristics.Methods: We conducted a retrospective analysis of clinical data from 232 patients diagnosed with HCC at our hospital between 2021 and 2022. All patients underwent preoperative enhanced CT scans, laboratory tests, and postoperative pathological examinations. Among the 232 patients, 89 were identified as MVI-positive and 143 as MVI-negative. Regarding tumor differentiation, 56 patients were well-differentiated, 145 moderately, and 31 poorly. Multivariate logistic regression analysis was employed to establish a prediction model for variables showing significant differences. Additionally, the diagnostic performance of various indicators were evaluated using ROC analysis.Results: Among the qualitative data, significant differences (P< 0.05) were observed between the MVI-positive and MVI-negative groups in 5 items such as peritumoral enhancement. In terms of quantitative data, the MVI-positive group exhibited higher maximum tumor length, AST, ALT, AFP levels and the ALBI score (P< 0.05). Conversely, CT values in the arterial phase (AP), portal venous phase (PVP), and PT levels were lower in the MVI-positive group (P< 0.05). Multivariate Logistic regression analysis identified ALBI score, PT level, CT value in PVP, and tumor capsule as independent risk factors for MVI occurrence (AUC: 0.71, 0.58, 0.66, and 0.60). The combined diagnostic AUC value was 0.82 (95% CI: 0.76– 0.87). Significant differences were found among different differentiation grade groups in 10 items such as non-smooth tumor margin (P< 0.05).Conclusion: Preoperative dynamic contrast-enhanced CT examination in patients with HCC can be utilized to predict the presence of MVI. When combined with clinical characteristics, these imaging signs demonstrate good predictive performance for MVI status. Furthermore, this approach has significant implications for determining the differentiation grade of tumors.Keywords: hepatocellular carcinoma, microvascular invasion, computed tomography, differentiation grade

Yanyun Li,1 Changying Li,2 Junzi Fan,3 Yutong Liu,1 Yincong Xu,4 Guowei Pang1 1School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2School of Ophthalmology and optometry, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 4College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yincong Xu; Guowei Pang, Email onion521@sina.com; pgw@sdutcm.edu.cnBackground: Cancer immunotherapy is an advanced therapeutic approach that harnesses the body’s immune system to target and eliminate tumor cells. Traditional Chinese medicine (TCM), with a history rooted in centuries of clinical practice, plays a crucial role in enhancing immune responses, alleviating cancer-related symptoms, and reducing the risks of infections and complications in cancer patients.Methodology: This review systematically examines the current literature on TCM-based formulations in cancer immunotherapy. It explores the mechanisms by which TCM augments immune responses, particularly focusing on how these formulations influence both innate and adaptive immunity. Various TCM herbs and compounds, their active ingredients, and their application in cancer prevention and treatment were analyzed through an integrated review of preclinical studies, clinical trials, and molecular mechanistic investigations.Results: TCM formulations contribute to cancer therapy by modulating the body’s internal environment to improve immune defense. They enhance the immune system’s ability to detect and destroy cancer cells, promote apoptosis in tumor cells, inhibit tumor growth and metastasis, and augment the effectiveness of conventional cancer treatments. The review highlights specific TCM herbs and formulations that have demonstrated significant anti-cancer properties, including their ability to strengthen immune responses and provide synergistic effects with existing cancer therapies.Conclusion: TCM-derived formulations represent a promising addition to cancer immunotherapy. The mechanisms through which these formulations enhance anti-tumor immunity are multifaceted, involving modulation of immune cell activity, apoptosis induction, and suppression of tumor progression. As cancer immunotherapy evolves, the integration of TCM into conventional treatment regimens may offer enhanced therapeutic efficacy, reduced side effects, and improved overall outcomes for cancer patients. Further clinical research is needed to fully elucidate the therapeutic potential and safety of TCM-based immunotherapeutic strategies in cancer care.Keywords: traditional Chinese medicine, TCM, cancer, nanocarriers, immune ability, anti-tumor therapy, tumor microenvironment, drug delivery systems

Hao Cheng,1,&ast; Jiao Ma,1,&ast; Fengyu Zhao,2 Yiwei Liu,3 Jie Wu,4 Tao Wu,1 Hui Li,1 Boxiang Zhang,3 Hui Liu,5 Junke Fu,3 Haiqi He,3 Cailin Zhu,3 Hong Ren,3 Chengcheng Yang,2 Sida Qin3 1Department of Rehabilitation, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Radiation Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 5Biobank, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sida Qin, Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +86 15388666585, Email qinsida@xjtu.edu.cn Chengcheng Yang, Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +86 17629260656, Email ccyang@xjtufh.edu.cnObjective: This research sought to assess the predictive potential of the inflammation-immunity-nutrition score (IINS) and the high-sensitivity C-reactive protein-albumin-lymphocyte (CALLY) index in individuals with NSCLC post-surgery.Methods: The study enrolled 506 patients with NSCLC undergoing R0 resection at the First Affiliated Hospital of Xi’an Jiaotong University. The training cohort was analyzed utilizing X-tile software to identify the ideal threshold values for categorizing high-sensitivity C-reactive protein, albumin, lymphocyte count, and the CALLY index. The predictive significance of the IINS and CALLY index was evaluated through Kaplan–Meier survival curves and univariate and multivariate Cox regression analyses. Predictive capabilities of the IINS and CALLY index were compared utilizing receiver operating characteristic (ROC) curve analysis, time-dependent ROC curve analysis, and decision curve analysis (DCA). Internal validation was performed in the validation cohort and all data from both the training and validation cohorts using Kaplan–Meier curves and DCA.Results: Patients with lower IINS exhibited prolonged overall survival (OS), whereas those with lower CALLY had shorter OS. Multivariate analysis identified N stage, NSE, and IINS as independent prognostic factors for individuals with NSCLC. ROC analysis revealed that IINS provided superior prognostic performance to CALLY and other traditional indicators (CAR, PLR, and NLR). Time-dependent ROC analyses and DCA further confirmed the superior prognostic value of IINS over the CALLY index at 1, 2, and 3 years.Conclusion: This study reveals that both the IINS and CALLY index are effective in forecasting the prognosis of individuals with NSCLC following surgery, with the IINS demonstrating superior prognostic efficacy to the CALLY index.Keywords: NSCLC, prognosis, IINS, CALLY index

Jiamei Chen,1 Jin Wang,1 Ziwei Deng,2 Yongzhong Li,1 Yuni Liu,3 Jianliang Zhou4 1Department of Infectious Diseases, Hunan University of Medicine General Hospital, Huaihua, Hunan Province, People’s Republic of China; 2Department of Clinical Pharmacy Group, Hunan University of Medicine General Hospital, Huaihua, Hunan Province, People’s Republic of China; 3Department of Gastroenterology, Yiyang Third People’s Hospital, Yiyang, Hunan Province, People’s Republic of China; 4Department of Intensive Care Medicine, Hunan University of Medicine General Hospital, Huaihua, Hunan Province, People’s Republic of ChinaCorrespondence: Jianliang Zhou, Email 82125817@qq.comBackground: Our objective was to analyze the clinical and imaging features of Chlamydia psittaci pneumonia to enhance its diagnostic accuracy.Methods: We systematically reviewed the cases of Chlamydia psittaci diagnosed by next-generation sequencing at the Hunan University of Medicine General Hospital between March 2019 and June 2024, summarizing and analyzing their clinical characteristics and imaging features.Results: A total of 50 cases that met the inclusion criteria were ultimately included in the study analysis. The median age of the patients was 62.96± 11.08 years. Notably, 46 patients (92%) had potential exposure to birds or poultry. Forty-six patients (92%) temperature ≥ 39.0 °C, 37 patients (74%) had cough, 34 patients (68%) had moist rale, and 39 patients (78%) had a relatively slow pulse. Laboratory tests indicated that over 70% of patients exhibited elevated infection markers, accompanied by abnormalities in liver and renal function, electrolyte levels, and cardiac enzymes. Meanwhile, the patient’s white blood cell count was normal. Chest CT (Computed Tomography) frequently revealed flaky shadows (94%), thoracic effusions (68%), and thickened pleura (54%). Bronchoscopy revealed significant bronchial mucosal hyperemia, swelling (93.478%), and reduced secretion (56.522%). A total of 44 patients (88%) showed a gradual improvement over 12 days. Forty patients (80%) were treated with doxycycline. Fifty patients were classified into two groups according to whether severe pneumonia occurred after admission. WBC (white blood cell), N% (percentage of neutrophils), NLR (Neutrophil-to-lymphocyte ratio), PLR (platelet/lymphocyte ratio), SII (platelet&ast;Neutrophil/lymphocyte ratio), and PCT (procalcitonin) are indicators that suggest severe cases.Conclusion: The combination of the following indicators is expected to aid in diagnosis of Chlamydia psittaci pneumonia: opportunities to come into contact with birds or poultry, high fever, relatively slow pulse, and elevated infection indicators accompanied by organ injury. Treatment with doxycycline was effective and resulted in favorable prognosis.Keywords: Chlamydia psittaci, metagenomic next-generation sequencing, clinical features, treatment

Yi Shang,1 Lefan Yu,1 Hanqi Xing,1 Yue Chang,1 Ke Dong,1 Yao Xiao,1 Yuanqing Liu,1 Mengmeng Feng,1 Yiren Qin,2 Hui Dai1,3 1Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3Institute of Medical Imaging, Soochow University, Suzhou, 215006, People’s Republic of ChinaCorrespondence: Hui Dai, Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Email huizi198208@126.comObjective: Sleep disorders are common in Alzheimer’s disease (AD) patients and can impair the glymphatic system, leading to cognitive decline. This study aimed to investigate whether AD patients with sleep disorders exhibit worse glymphatic function and more severe cognitive impairment compared to those without sleep disorders and to explore the underlying molecular imaging mechanisms.Methods: This study included 40 AD patients with sleep disorders (ADSD), 39 cognitively matched AD patients without sleep disorders (ADNSD), and 25 healthy middle-aged and elderly controls (NC). Participants underwent functional magnetic resonance imaging (fMRI), and cognitive and sleep assessments. The ALPS (Along the Perivascular Space) index was calculated, followed by intergroup comparisons, correlation analyses, and mediation analyses. The diagnostic utility of the ALPS index was assessed using a receiver operating characteristic (ROC) curve.Results: The ALPS index was lower in the ADNSD and ADSD groups compared to the NC group. In the ADSD group, PSQI scores were negatively correlated with MMSE scores. The ALPS index was positively correlated with MMSE scores and negatively with PSQI scores. Mediation analyses indicated that the ALPS index partially mediated the effect of sleep disturbances on cognitive impairment (indirect effect = − 0.134; mediation effect = 30.505%). The area under the ROC curve (AUROC) for distinguishing ADSD from ADNSD was 0.86, with a cutoff ALPS index value 1.309.Conclusion: Sleep disorders worsen glymphatic function and cognitive impairment in AD patients. The ALPS index partially mediates the impact of sleep disorders on cognitive function and shows moderate accuracy in distinguishing between patients with ADSD and ADNSD.Keywords: Alzheimer’s disease, sleep disorders, glymphatic system, diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), mediation analysis

Yingying Du,1– 3,&ast; Yan Liu,4,&ast; Tong Liu,1 Fen Pan,5 Shikui Mu,2 Yunlou Zhu,2 Hanlu Gao,2 Xin Jing,2 Xing Wang,6 Yuhao Liu,2 Sheng Wang1– 3 1Intensive Care Medical Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 3Key Laboratory of Pathogen-Host Interaction, Ministry of Education, Shanghai, 200092, People’s Republic of China; 4Department of Clinical Microbiology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 5Department of Laboratory Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 200032, People’s Republic of China; 6Department of Laboratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhao Liu; Sheng Wang, Email lyh-7906@163.com; wangsheng@tongji.edu.cnObjective: This study aimed to evaluate the in vitro activity of omadacycline (OMC) and OMC-based combination therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: The broth microdilution assay assessed the in vitro susceptibility of CRKP to OMC. The checkerboard assay was performed to evaluate the activity of OMC combined with polymyxin B (PB), amikacin (AN), or meropenem (MEM) against KPC-producing (class A) CRKP strains, and OMC combined with PB, aztreonam (ATM), MEM, or AN against class B and class A plus class B CRKP strains. Synergistic effects of OMC and PB were further evaluated by time-kill assays in the KPC-producing CRKP strains.Results: Broth microdilution assays revealed a notable variation in susceptibility between KPC-producing and class B CRKP strains, with MIC50/90 of 32/32 mg/L and 0.5/8 mg/L, respectively. Although KPC-producing CRKP strains were resistant to OMC, a synergistic effect was observed in 37.5% of KPC-producing CRKP strains when OMC was combined with PB. In the nine KPC-producing CRKP strains, time-kill assays found that cell densities of six strains (66.7%) decreased by 3.61 ± 0.23 log10 CFU/mL compared to the initial inoculum after 2 hours of PB exposure. The cell densities further decreased by an average of 2.38 ± 0.23 log10 CFU/mL when the six strains were exposed to OMC plus PB, confirming their potent synergism.Conclusion: OMC monotherapy is ineffective against KPC-producing CRKP strains, but OMC plus PB has a potent synergistic effect on them, suggesting that OMC plus PB is the preferred combination therapy against KPC-producing CRKP in vitro.Keywords: Klebsiella pneumoniae, carbapenem resistance, omadacycline, polymyxin B, antibiotic combination treatment, time-kill test

Yi Liu, Weina Jin,&ast; Ke Wang,&ast; Zheng Chang, Li Zhang Department of Nursing, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weina Jin; Ke Wang, Department of Nursing, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China, Email jinweina@51mch.com; wangkeyfy@126.comObjective: To investigate the effect of traditional Chinese medicine nursing scheme on gastrointestinal function recovery in patients with uterine fibroids after high-intensity focused ultrasound treatment.Methods: By convenient sampling method, 110 patients who received high-intensity focused ultrasound treatment for uterine fibroids from January 2023 to December 2023 in HIFU Treatment Center, a Grade-III obstetrics and gynecology hospital in Shanghai were selected as the study objects and were divided into a control group (n = 54) and experimental group (n = 56) by non-synchronous control study. The control group was treated with conventional nursing mode, and the experimental group was treated with traditional Chinese medicine nursing plan for gastrointestinal function recovery of patients with uterine fibroids after sea aid treatment. The postoperative gastrointestinal function recovery, comfort level, mental health and nursing satisfaction of the two groups were compared.Results: The gastrointestinal function recovery time, comfort status scale, anxiety self-rating scale, depression self-rating scale and nursing service satisfaction scale of experimental group were better than those of control group (P < 0.05).Conclusion: The main finding of this study is that through traditional Chinese medicine nursing programs, early gastrointestinal function can be improved in patients with uterine fibroids treated with high-intensity focused ultrasound, promoting gastrointestinal function recovery. The secondary finding is that the implementation of traditional Chinese medicine nursing programs can alleviate the negative emotions of such patients and improve clinical nursing satisfaction, which is worthy of clinical promotion.Keywords: traditional Chinese medicine nursing program, HIFU treatment, gastrointestinal function, post-HIFU treatment

Yuqin Wang,1 Xiuxiu Song,1 Siqi Wang,2 Ting Bai,3 Rui Li,3 Haonan Liu,4 Yuping Liu,3 Zhengxiang Han4 1Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China; 2Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China; 3Nursing Department, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China; 4Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Zhengxiang Han; Yuping Liu, The Affiliated Hospital of Xuzhou Medical University, No. 99 huaihai West Road, Quanshan District, Xuzhou City, Jiangsu Province, People’s Republic of China, Email cnhzxyq@163.com; 1647221333@qq.comPurpose: To develop and summarize pain management strategies after hepatectomy for liver cancer based on the best evidence summary, and to improve the strategy of the Delphi study.Methods: According to the “ 6S” evidence pyramid model, the database was systematically searched, with a search deadline of December 2023. Two researchers independently conducted literature screening and quality evaluation. Relevant evidence on pain management was extracted and integrated. Relevant evidence for pain management formed a preliminary strategy through a one-day, face-to-face meeting. Subsequently, a Delphi process was performed to improve the strategy. The scientific soundness of the Delphi method was expressed by the effective response rate, authority coefficient (Cr), and coordination coefficient. The coordination of expert opinions was assessed using the coefficient of variation (CV) and Kendall’s coefficient (W). Cr should be above 0.700 and the coefficient of variation (CV) should be below 0.25. Data analysis was performed using SPSS V.25.0.Results: A total of 14 studies were included, and we summarized 13 first-level items and 48 second-level items by two rounds of Delphi. The effective response rate of the two rounds of Delphi was 100.00%, and the authority coefficient of the experts was 0.832. The coefficients of variation were 0.00– 0.41 and 0.05– 0.17, respectively. The Kendall’s W values for the two rounds were 0.114– 0.222 (p< 0.05).Conclusion: Pain management strategy after hepatectomy is scientific and applicable. We plan to translate this into a plan and confirm its feasibility in the future.Keywords: pain management, hepatectomy, evidence-based nursing, Delphi method, liver cancer

Qin Chen,1,&ast; Lele Zang,1,&ast; Qin Xu,1 Min Wang,1 Huaqin Lin,1 Yanyan Liu,2 Yi Fang1 1Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, 350014, People’s Republic of China; 2Department of Oncology, Wuping County Hospital, Longyan, Fujian Province, 364300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Chen; Yi Fang, Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 420&num; Fuma Road, Fuzhou, Fujian Province, 350014, People’s Republic of China, Tel +86-15359734658, Email 15359734658@189.cn; fang_april@126.comPurpose: This study was conducted to analyze the relationship between plasma D-dimer levels and the risk of recurrence after surgical treatment in patients with early-stage cervical cancer (CC).Methods: In this cohort study, 888 participants with early-stage CC undergoing surgical treatment in Fujian Cancer Hospital between June 2016 and December 2019 were identified. Univariate logistic regression was used to screen confounding factors affecting the recurrence of early CC after surgical treatment. Variables significantly associated with the recurrence of early CC after surgical treatment were confounding factors. Univariate and multivariate logistic regression models were established to explore the association between D-dimer levels and the risk of recurrence of early CC after surgical treatment. ORs and 95% CIs were calculated.Results: The end of follow-up was when CC recurred or 3 years after surgery. In sum, 80 patients suffered CC recurrence, accounting for 9% of all participants. The risk of recurrence was elevated in CC patients from the elevated group (EG), with an adjusted OR of 2.16 (95% CI 1.28– 3.62). The risk of recurrence was increased in the EG in patients with cervical squamous cell carcinoma undergoing surgery in the adjusted model (OR 3.58, 95% CI 1.02– 12.89). As for cervical adenocarcinoma patients, the increased risk of recurrence was identified in patients from the EG (OR 1.87, 95% CI 1.01– 3.48).Conclusion: High levels of D-dimer were associated with increased recurrence risk of CC in patients at the early stage of surgical treatment.Keywords: D-dimer, cervical cancer, surgical treatment, recurrence

Jinye Gu,1,&ast; Yang Liu,1,&ast; Xiaoyan Lin,1 Lei Fu,1 Jianbo Liu,1 Bona Sun,2 Xiaoyu Li,3 Bo Lu3 1Department of Anesthesiology, Zhenhai Hospital of Traditional Chinese Medicine, Ningbo, 315200, People’s Republic of China; 2Department of Gynaecology, Zhenhai Hospital of Traditional Chinese Medicine, Ningbo, 315200, People’s Republic of China; 3Department of Anesthesiology, Ningbo No. 2 hospital, Ningbo, 315010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Lu, Department of Anesthesiology, Ningbo No. 2, Hospital, No. 41, Northwest Street, Ningbo, Zhejiang Province, 315010, People’s Republic of China, Tel/Fax +86 574 83870920, Email nblbmz@hotmail.comObjective: This study aims to compare the recovery profiles of remimazolam combined with flumazenil against those of propofol in patients undergoing painless surgical abortion, focusing on psychomotor function and emergence. Rapid recovery and restoration of psychomotor function are critical for enhancing patient safety and satisfaction in outpatient procedures like surgical abortion.Methods: A total of 110 patients scheduled for surgical abortion were randomly assigned to either the remimazolam group (Group R) or the propofol group (Group P) in a 1:1 ratio. Both groups received intravenous sufentanil for induction, followed by either remimazolam or propofol. Psychomotor function was assessed using the Digit Symbol Substitution Test (DSST) and Trieger Dot Test (TDT) at 30, 60, and 90 minutes post-anesthesia. Emergence parameters, including time to first eye opening and first verbal response, were recorded. Adverse events and hemodynamic parameters were also monitored.Results: The DSST scores at 30, 60, and 90 minutes post-anesthesia were similar between the Remimazolam group and the Propofol group (F=50.61, P> 0.05, η²=0.0051). The TDT results were also comparable between the groups at all time points (F=0.12, 0.11 and 0.30, all P> 0.05, η²=0.0002, 0.0003 and 0.0008). At 30 or 60 minutes post-anesthesia, DSST scores or TDT performance were significantly worse compared to preoperative baseline in both groups, indicating reduced psychomotor function (P< 0.05). The Remimazolam group showed significantly shorter times to first eye opening (54.48± 3.45 s vs 99.22± 11.78 s, P=0.0014, Cohen’s d=5.15) and to obey verbal commands (61.85± 3.78 s vs 131.1± 12.79 s, P< 0.0001, Cohen’s d=7.34) compared to the Propofol group.The incidence of injection pain and respiratory depression was significantly lower in the remimazolam group (P< 0.05), while hiccups were more common. Hemodynamic stability was maintained in both groups, with no significant differences in blood pressure or oxygen saturation (P> 0.05).Conclusion: Remimazolam combined with flumazenil provides faster emergence and comparable psychomotor function to propofol in patients undergoing painless surgical abortion. This combination offers a promising anesthetic profile for procedures requiring quick recovery and minimal postoperative complications.Trial Registration: ChiCTR2300075375, date of registration: 03/09/2023.Keywords: remimazolam, flumazenil, propofol, psychomotor function, emergence, surgical abortion, anesthesia recovery

Junfei Xu,&ast; Yongyong Ding,&ast; Bing Liu, Xuehai Wu, Xiaofeng Yang, Yi Liu, Hong Deng Department of Pain, The First People’s Hospital of Zunyi City, Zunyi, Guizhou Province, 563000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Deng, Email dengqiao303@163.comObjective: To compare the application effects of short-term peripheral nerve stimulation (st-PNS) and pulsed radiofrequency (PRF) technology in postherpetic neuralgia (PHN).Methods: A retrospective analysis was conducted on the clinical data of 127 PHN patients from our hospital. Based on the treatment interventions received, patients were divided into a control group (n=63, treated with PRF) and an observation group (n=64, treated with st-PNS). The clinical treatment effects, pain conditions, sleep quality, inflammatory factors [interleukin-6 (IL-6)] levels, quality of life levels, and complication rates were compared between the two groups.Results: The observation group showed significantly higher total treatment effectiveness (93.75%) compared to the control group (80.95%) (P < 0.05). VAS and PSQI scores were significantly improved at 1 week, 1 month, and 3 months post-treatment in both groups (P < 0.05), with the observation group consistently showing better outcomes. Additionally, IL-6 levels decreased significantly, and SF-36 scores improved more in the observation group (P < 0.05). No significant difference was found in complication rates between the two groups (P > 0.05).Conclusion: Compared to PRF treatment, the st-PNS treatment method further improves patients’ pain and sleep quality, reduces inflammatory responses, and enhances quality of life, while also demonstrating better safety.Keywords: short-term peripheral nerve stimulation, pulsed radiofrequency technology, postherpetic neuralgia, application effects, comparative study

Jingfeng Zou,&ast; Yiting Liu,&ast; Chunhui Tian,&ast; Liping Wang, Shaotian Li, Jiajia Ran, Xin Yang,&ast; Guqiao Nie, Wen Peng Department of General Practice, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, WuHan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guqiao Nie; Wen Peng, Department of General Practice, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang avenue, WuHan, Hubei, 1227, People’s Republic of China, Email 313848396@qq.com; pengwen666@sina.comObjective: The scientometric analysis was aim to focus on recent studies and clarify new research directions on hypertension with sarcopenia. We hope to provide comprehensive insights or actionable recommendations for clinicians or policymakers.Methods: The Web of Science Core Collection database (WoSCC) from 2004 to 2023 for analysis was used. And VOSviewer, CiteSpace, and Origin software were utilized for scientometric analyses.Results: The United States was the primary contributor to 1,994 studies on hypertension with sarcopenia. The University of São Paulo emerged as the most prolific institution, with Morrell Nicholas W. being the most influential scholar and Cruz-Jentoft A.J. being the most co-cited author. PLoS One was the most prolific journal, whereas Circulation was the most relevant journal. Research has focused not only on physiological, biochemical, and cell biological mechanisms but also on sarcopenia associated with other diseases and involved in various fields, highlighting the complexity of the area and the need for integrative treatment. Keyword analysis revealed that, in addition to hypertension and sarcopenia, other topics such as obesity, pulmonary hypertension, old age, metabolic syndrome, inflammation, hypoxia, exercise, insulin resistance, and revascularization attracted attention. In recent years, COVID-19, mitochondria, handgrip strength, etc. have been hot topics, but aging, skeletal muscle, weight loss, diabetes, obesity, metabolic syndrome, insulin resistance, heart failure, mitochondria, mortality, exercise, and physical activity seems to bridge hypertension and sarcopenia research.Conclusion: This study highlights the distribution of fields, the structure of knowledge and the evolution of major research topics related to hypertension in patients with sarcopenia. Identifying keyword hotspots enhanced the comprehension of occurrence, development, and future research trends related to the topic.Keywords: hypertension, sarcopenia, scientometric analysis, visualization

Cong Peng,1 Zhenyun Zhang,2 Yuhua Wang,1 Yan Liu,3 Xingyue Li,1 Yujie Yao,1 Xinyu Zheng,1 Huiying Fan1 1School of Education and Psychology, Hubei Engineering University, Xiaogan, People’s Republic of China; 2School of Computer and Information Science, Hubei Engineering University, Xiaogan, People’s Republic of China; 3School of Education, Hunan University of Science and Technology, Xiangtan, People’s Republic of ChinaCorrespondence: Cong Peng, Email pengcong2023@hbeu.edu.cnPurpose: While previous studies have investigated the adverse effects of hyper-competitiveness on individual development, research addressing its underlying causes from a family systems perspective remains relatively scarce. This study provides a comprehensive, longitudinal analysis of how the father hunger impacts adolescent hyper-competitiveness, thoroughly investigating the roles of basic psychological needs satisfaction and mother-child attachment within the broad context of family dynamics.Methods: We employ Father Presence Theory, Attachment Theory and Basic Psychological Needs Theory as our theoretical frameworks. Data were gathered from 417 high school students in Central China at two time points (December 15, 2023, and May 15, 2024). Descriptive statistics and tests of the moderated mediation model were performed using SPSS 23.0.Results: Our results reveal that increased levels of father hunger are associated with greater adolescent hyper-competitiveness. Basic psychological needs satisfaction (BPNS) functions as a significant mediator, with higher levels of satisfaction correlating with lower hyper-competitiveness. Additionally, mother-child attachment serves as a significant moderator in both the first and second halves of the model, indicating its protective role in mitigating the adverse effects of elevated father hunger on BPNS. Furthermore, mother-child attachment can buffer the negative impact of unmet psychological needs on adolescent hyper-competitiveness.Conclusion: The present study reveals that father hunger leads to adolescent hyper-competitiveness through the basic psychological needs satisfaction whilst mother-child attachment moderates the indirect effects of father hunger on hyper-competitiveness. The findings enhance our theoretical understanding of the interplay between father hunger and adolescent hyper-competitiveness and provides a foundational basis for future research aimed at improving father-child relationships and developing targeted interventions for managing adolescent hyper-competitiveness.Keywords: father hunger, hyper-competitiveness, basic psychological needs satisfaction, mother-child attachment, longitudinal study

Fei Liu,1,&ast; Tianqing Cao,1,&ast; Yacong Liu,1 Dian Huang,2 Jingxin Zhang3 1Department of Cardiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225001, People’s Republic of China; 2Department of Radiology, Affiliated hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 3Department of General Surgery, People’s Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu, 212002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingxin Zhang, Email zfynjykd@163.comObjective: The main purpose of this study is to evaluate the changes in sleep quality among patients with cirrhotic cardiomyopathy (CCM).Methods: The study included liver cirrhosis patients aged 18– 75 from Northern Jiangsu People’s Hospital Affiliated to Yangzhou University and collected their clinical examination results to assess the clinical characteristics and related risk factors of patients with CCM.Results: The study found that the onset of CCM was not related to the etiology of inducing cirrhosis. Pittsburgh Sleep Quality Index (PSQI) score (odds ratio (OR) = 13.476, 95% confidence interval (CI) = 1.514– 119.923, P = 0.020), absolute GLS (OR = 0.328, 95% CI = 0.210– 0.510, P < 0.001), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR = 1.050, 95% CI = 1.025– 1.076, P < 0.001) were identified as independent risk factors for inducing CCM.Conclusion: In patients with CCM, a decrease in sleep quality often occurs. When cirrhotic patients also have poor sleep quality, along with a decrease in absolute Global Left Ventricular Strain (GLS) levels and an increase in NT-proBNP levels, these factors may pose a higher risk for CCM development. However, further validation of these research findings is required in larger sample sizes.Keywords: cardiomyopathy, liver cirrhosis, sleep quality, cirrhotic cardiomyopathy

Yumeng Liu,1 Huizhen Xin,1 Yongqiang Shu,1,2 Lifeng Li,1 Ting Long,1 Li Zeng,1 Ling Huang,1 Xiang Liu,1 Yingke Deng,1 Yu Zhu,1 Haijun Li,1,2 Dechang Peng1,2 1Department of Radiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2PET Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of ChinaCorrespondence: Dechang Peng; Haijun Li, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwai Zheng Street, Donghu District, Nanchang, Jiangxi Province, 330006, People’s Republic of China, Tel +86 79186427565, Email pengdcdoctor@163.com; haijunli1990@163.comPurpose: This study is to evaluate the altered number of functional connection (s) in patients with obstructive sleep apnea (OSA) by functional connectivity density (FCD), to investigate its relationship with cognitive function, and to explore whether these features could be used to distinguish OSA from healthy controls (HCs).Methods: Seventy-six OSA patients and 72 HCs were included in the analysis. All participants underwent resting-state functional magnetic resonance imaging scan. Subsequently, intergroup differences between long-and short-range FCD groups were obtained in the Matlab platform by using the degree centrality option with a 75 mm cutoff. The partial correlation analysis were used to assess the relationship between the altered FCD value and clinical assessments in OSA patients. The FCD values of the different brain regions were used as classification features to distinguish the two groups by support vector machine (SVM).Results: Compared to HCs, OSA patients had decreased long-range FCD in the right superior frontal gyrus (SFG), right precuneus, and left middle frontal gyrus (MFG). Simultaneously, increased long-range FCD in the right cingulate gyrus (CG). Meanwhile, the short-range FCD were decreased in the right postcentral gyrus (PoCG), right SFG, left MFG, and right CG. The short-range FCD values of the right PoCG were correlated with the Montreal Cognitive Assessment scores in OSA patients. SVM analysis showed that FCD in differential brain regions could differentiate OSA patients from HCs.Conclusion: Long- and short-range FCD values in different brain regions of OSA patients may be related to cognitive decline, and also be effective in distinguishing OSA patients from HCs. These findings provide new perspectives on neurocognition in OSA patients.Keywords: cognitive function, functional magnetic resonance imaging, functional connectivity density, obstructive sleep apnea

Hua-Bin Peng,1 Ying Liu,1 Fei Hou,1 Shuang Zhao,1 Yi-Zhi Zhang,1 Zhi-Ying He,1 Jing-Yi Liu,1 Hao-Feng Xiong,1 Li-Ying Sun1– 4 1Department of Critical Liver Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Laboratory for Clinical Medicine, Capital Medical University, Beijing, People’s Republic of China; 3Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Li-Ying Sun; Hao-Feng Xiong, Department of Critical Liver Diseases, Beijing Friendship Hospital, Capital Medical University, Number 101, Luyuan East Road, Tongzhou District, Beijing, 101100, People’s Republic of China, Email sunxlx@outlook.com; Xionghaofengmd@qq.comPurpose: To examine the clinical utility of metagenomic next-generation sequencing (mNGS) in individuals with early pulmonary infection following liver transplantation.Patients and Methods: mNGS and traditional detection results were retrospectively collected from 99 patients with pulmonary infection within one week following liver transplantation. These patients were admitted to the Department of Critical Liver Diseases at Beijing Friendship Hospital from February 2022 to February 2024, along with their general clinical data.Results: mNGS exhibited a significantly higher detection rate than traditional methods (92.93% vs 54.55%, P < 0.05) and was more effective in identifying mixed infections (67.68% vs 14.81%, P < 0.05). mNGS identified 303 pathogens in 92 patients, with Enterococcus faecium, Pneumocystis jirovecii, and human herpesvirus types 5 and 7 being the most prevalent bacteria, fungi, and viruses. A total of 26 positive cases were identified through traditional culture methods (sputum and bronchoalveolar lavage fluid), with 18 cases consistent with mNGS detection results, representing 69.23% consistency. Among the three drug-resistant bacteria that showed positivity in mNGS and traditional culture, the presence of drug-resistance genes—mecA in Staphylococcus aureus; KPC-2, KPC-9, KPC-18, KPC-26, OXA27, OXA423 in Klebsiella pneumoniae; and OXA488 and NDM6 in Pseudomonas aeruginosa—reliably predicted drug-resistance phenotype. The treatment regimen for 76 of the 92 patients with positive mNGS relied on these results; 74 exhibited significant symptom improvement, yielding a 97.37% recovery rate. The overall prognosis was favorable.Conclusion: mNGS offers rapid detection, a high positivity rate, insensitivity to antibiotics, and a superior ability to detect mixed infections in patients with early post-transplant pulmonary infections. Additionally, mNGS shows good consistency with traditional culture and can predict drug-resistant phenotypes to guide targeted antibiotic therapy for early-stage post-transplant pulmonary infection after liver transplantation. Patients whose antibiotic therapy is based on mNGS results have experienced decreased mortality rates and overall improved prognosis.Keywords: Liver transplantation, Pulmonary infection, Metagenomic next-generation sequencing, Clinical value

Yunfan He,1,2 Jun Liang,3– 5 Wenguang Fu,6 Yongcheng Liu,7 Fangyu Yang,8 Shunjing Ding,9 Jianbo Lei10– 12 1School of International Relations and Public Affairs, Fudan University, Shanghai, People’s Republic of China; 2National Institute of Intelligent Evaluation and Governance, Fudan University, Shanghai, People’s Republic of China; 3Department of AI and IT, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Center for Health Policy Studies, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 5Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 7Netease Group, Hangzhou, Zhejiang, People’s Republic of China; 8School of Nursing, Capital Medical University, Beijing, People’s Republic of China; 9Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 10Clinical Research Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 11School of Medical Informatics and Engineering, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 12Center for Medical Informatics, Health Science Center, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Jianbo Lei, Center for Medical Informatics, Peking University, Beijing, 100191, People’s Republic of China, Tel +86 (10) 8280-5901, Fax +86 (10) 8280-5900, Email jblei@hsc.pku.edu.cn Shunjing Ding, Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email dsj6890@sina.comBackground: Online health-related misinformation poses a serious threat to public health. As the coronavirus disease 2019 (COVID-19) pandemic aggravated the spread of misinformation regarding COVID-19, relevant research has surged.Objective: To systematically summarize Chinese and English articles regarding health-related misinformation about COVID-19 on social media and quantitatively describe research progress.Methods: Using bibliometrics, we systematically analyzed and compared the characteristics of scientific articles in English and Chinese, examining article numbers, journals, authors, countries, institutions, funding, and research topics, and compared changes in popular research topics.Results: This study analyzed 1,294 articles, revealing a significant increase in article numbers and citations during the COVID-19 pandemic (1.94 times and 2.95 times, respectively, compared to pre-pandemic data). However, high-impact articles were scarce and the field lacked a core group of authors and collaborative networks. China had the largest number of papers (n=266) and funds (n=292), but articles in English exceeded by far those in Chinese (1,131 vs 163, respectively). Regarding article topics, the transformation from qualitative small-data analyses to quantitative empirical big-data research has been realized.Conclusion: With the maturity of natural language processing technology, in-depth mining of massive user-generated content has become a hot spot. The outbreak of the COVID-19 pandemic has prompted the research focus to shift from misinformation-related health problems to social problems involving the sources, content, channels, audiences, and effects of communication networks. Using artificial intelligence technology like machine learning to deeply mine large amounts of user-generated content on social media will be a future research hot spot.Keywords: misinformation, online health information, social media, COVID-19, Chinese, English

Yajing Liu,1 Chunming Li,2 Xiaoya Yang,1 Shufen Guo,1 Zhaobo Cui,1 Hongshan Kang,1 Zhen Ma,1 Huiqing Wang1 1Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), Hengshui, 053000, People’s Republic of China; 2Department of Pain, Hengshui Second People’s Hospital, Hengshui, 053000, People’s Republic of ChinaCorrespondence: Yajing Liu; Hongshan Kang, Intensive Care Unit, Hengshui People’s Hospital (Harrison International Peace Hospital), 180 Renmin East Road, Taocheng District, Hengshui, Hebei, 053000, People’s Republic of China, Tel +8618732891639, Email liuyajingbs@163.com; kanghongshan@163.comObjective: We assessed the predictive value of blood neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in predicting the onset of acute kidney injury (AKI) in sepsis patients in the intensive care unit (ICU).Methods: In this retrospective analysis, we examined the medical records of sepsis patients admitted to the ICU. After ICU admission, blood samples were taken at 0 h, 6 h, 12 h, 24 h, and 48 h. Using an enzyme-linked immunosorbent assay, the concentrations of serum creatinine, NGAL, and IL-18 were determined.Results: This study comprised a total of 197 participants, 104 of whom had AKI and 93 of whom did not. Blood concentrations of NGAL and IL-18 increased prior to serum creatinine levels. Between 6– 48 hours after ICU administration, NGAL and IL-18 levels in the AKI group were considerably higher than those in the non-AKI group, and creatinine levels between the two groups were significantly different after 48 hours. Based on receiver operating characteristic (ROC) curve analysis, the area under the curve of NGAL and IL-18 for predicting AKI was 0.781 and 0.883, respectively.Conclusion: Blood NGAL and IL-18 are potential biomarkers for the early prediction of AKI in sepsis patients in the ICU.Keywords: acute kidney injury, intensive care unit, interleukin-18, neutrophil gelatinase-associated lipocalin sepsis

Yi Liu,1,2 Changqing He,1 Quanhai Zhong,3 Xianbao Shi,4 Hongyan Li,1 Gaoge Fu,1 Lixuan Guo,1 Churong Zhao,1 Lei Tian,1 Xin Li,1 Xue Jiao,1 Lina Shan1 1Department of Respiratory Disease, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, 121000, People’s Republic of China; 2Department of Critical Care Medicine, Panzhihua Central Hospital, Panzhihua, 61700, People’s Republic of China; 3Clinical Drug Laboratory, People’s Hospital of Yichun City, Yichun, Jiangxi, 336000, People’s Republic of China; 4Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of ChinaCorrespondence: Lina Shan, Email shanlina321@163.comIntroduction: Pulmonary hypertension (PH) is a progressive and life-threatening condition. Recent research has demonstrated that exosomes derived from mesenchymal stem cells (MSC) exhibit significant therapeutic potential in the treatment of PH. The composition of these exosomes is often substantially influenced by the characteristics of their parental cells. This study aimed to identify an intervention strategy to enhance the efficacy of mesenchymal stem cell exosomes in treating PH.Methods: Exosomes were isolated from control MSC and tadalafil-pretreated MSCs. In vitro and in vivo studies were conducted.Results: MSCTAD-Exo attenuated macrophage inflammation and improved endothelial cell (EC) apoptosis while also reducing pulmonary arterial pressure in a hypoxia-induced rat model. Furthermore, MSC exosomes can mitigate hypoxia-induced proliferation and migration of smooth muscle cells (SMC) by influencing the secretion of endothelial exosomes. MiR-29a-3p has been identified as a crucial mediator in this process, with its expression regulated by cAMP responsive element binding protein 1 (CREB1). MiR-29a-3p exerts anti-inflammatory effects by modulating the expression of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2). Notably, the anti-inflammatory and anti-vascular remodeling activities of exosomes were diminished following the depletion of MiR-29a-3p.Discussion: MSC treated with tadalafil can secrete better exosomes. MSCTAD-Exo may enhance anti-inflammatory and anti-vascular remodeling properties by upregulating mir-29a-3p expression, providing a novel idea for PH therapy. Future studies could explore the clinical application of this finding. Keywords: exosome, tadalafil, hypoxia pulmonary hypertension, mesenchymal stem cell, miR-29a-3p

Jie Wang, Yan Dong, Zhaoling Li, Yun Zhang, Lanchun Liu, Guang Yang, Yongmei Liu, Jun Li, Lian Duan Department of Cardiology, Guang Anmen Hospital, Beijing, People’s Republic of ChinaCorrespondence: Lian Duan, Email popale2003@163.comBackground: Improving angiogenesis in the ischemic myocardium is a therapeutic strategy for preventing, reducing, and repairing myocardial injury of coronary artery disease (CAD). Panax notoginseng saponins (PNS) have been widely used in the clinical treatment of cardiovascular diseases, demonstrating excellent efficacy, and can potentially improve angiogenesis in the ischemic myocardium. However, the effects of PNS on angiogenesis and its underlying mechanism of action remain unclear.Purpose: In this study, we aimed to evaluate the role of PNS in improving angiogenesis after myocardial infarction (MI) and explain the mechanism of PNS in improving angiogenesis in CAD from an epigenetic perspective.Study Design: The MI rat model was established by ligating the left anterior descending coronary artery permanently. The in vitro model comprised hypoxic human coronary artery endothelial cells (HCEACs). The mice and cells were then treated with PNS.Methods: Blood tests, histomorphology, polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and MassARRAY targeted methylation detection analyses were conducted in vivo and in vitro to investigate the potential mechanisms of PNS.Results: Oral PNS significantly improved myocardial injury and activated angiogenesis in MI rats. DNA methylation analysis in vitro revealed that PNS decreased the hypermethylation of microRNA 200a (miR200a). PNS improved angiogenesis in hypoxic human coronary artery endothelial cells (HCEACs) by regulating the vascular endothelial growth factor (VEGF) pathway.Conclusion: Our research shows that PNS can improve angiogenesis in rats with MI and hypoxic HCEACs and affect the level of miR200a promoter methylation and miR200a and VEGF molecular pathways.Keywords: Panax notoginseng saponins, coronary artery disease, DNA methylation, miRN200a, angiogenesis

Wenjing Pan,1,&ast; Zhaoyang Jia,1,&ast; Jingtong Du,1,&ast; Kexin Chang,2 Yiming Liu,2 Wei Liu,1 Xibo Zhao,3 Wenhua Tan1 1Department of Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 3Department of Gynecological Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xibo Zhao; Wenhua Tan, Email zhaoxb8@mail.sysu.edu.cn; tanwenhua1962@126.comIntroduction: The NLRP3 inflammasome has been implicated in the initiation of inflammation and tumorigenesis; however, its role in epithelial ovarian cancer (EOC) remains unclear.Methods: This study employed high-throughput sequencing data, ELISA, clone formation assay, Western blot, and flow cytometric analysis to investigate the specific role of the NLRP3 inflammasome in EOC.Results: NLRP3 was highly expressed in human EOC tissues and correlated with an unfavorable prognosis. Activation of the NLRP3 inflammasome by LPS and ATP promoted EOC cell proliferation and increased IL-1 and PD-L1 levels. MCC950, a NLRP3 inflammasome blocker, reduced IL-1 and PD-L1 levels and diminished tumor-immune suppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and PD-1+ CD4+ T cells, in a murine model of ovarian cancer. This intervention also suppressed tumor growth.Conclusion: Our investigation revealed the pro-tumorigenic role of the NLRP3 inflammasome and its regulation of PD-L1 expression in EOC. Blockade of the NLRP3 inflammasome led to reduced PD-L1 expression, fewer immunosuppressive cells, and suppressed tumor growth. These findings suggest that targeting the NLRP3 inflammasome-PD-L1 axis could be a novel treatment approach for ovarian cancer.Keywords: NLRP3 inflammasome, PD-L1, immunosuppressive cells, EOC, inflammation

Shaotian Li,&ast; Jingfeng Zou,&ast; Jiajia Ran,&ast; Liping Wang, Guqiao Nie, Yiting Liu, Chunhui Tian, Xin Yang, Yun Liu, Jingjing Wan, Wen Peng General Practice Department, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Peng; Jingjing Wan, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan City, Hubei Province, People’s Republic of China, Tel +86 13986074846, Email pengwen666@sina.com; 8735174@qq.comAbstract: Osteosarcopenia (OS) is a geriatric syndrome characterized by the concurrent presence of osteoporosis and sarcopenia, predominantly affecting the elderly population. Osteoporosis (OP) is a systemic skeletal disorder characterized by decreased bone mass, compromised bone microarchitecture, and heightened bone fragility, substantially elevating fracture risk. Sarcopenia (SP) is defined by decreased muscle mass, strength, and/or functional capacity. Both conditions are age-related degenerative diseases with overlapping pathophysiological mechanisms, commonly co-occurring in elderly individuals and substantially increasing fracture risk. Denosumab, a targeted anti-osteoporotic agent, mediates therapeutic effects by inhibiting bone resorption through the RANK-RANKL-OPG (RRO) pathway, consequently enhancing bone mineral density. International studies indicate that Denosumab not only treats osteoporosis but also improves sarcopenia-related metrics, suggesting its potential as a sarcopenia treatment. However, research focusing on the Chinese population remains limited. Additionally, the pathophysiological mechanisms of sarcopenia and the pathways through which Denosumab ameliorates sarcopenia are not yet fully understood, warranting further experimental investigation. In summary, Denosumab’s therapeutic efficacy in osteoporosis treatment and its potential impact on sarcopenia are of substantial research interest. However, research and literature on these topics in China remain notably scarce. This article aims to offer a systematic review and critical analysis of these topics.Keywords: osteoporosis, sarcopenia, denosumab, RANK-RANKL-OPG pathway, comorbidity

Yan Liu,&ast; Shuai Li,&ast; Rong Liu Department of Obstetrics and Gynecology, Tianjin First Central Hospital, Nankai University, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liu, Department of Obstetrics and Gynecology, Tianjin First Central Hospital, Nankai University, No. 24 Fukang Road Nankai District, Tianjin, 300192, People’s Republic of China, Email liuyantj663@outlook.com; 30819007@nankai.edu.cnPurpose: Outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, leading to over 6 million deaths worldwide. Pregnant women suffer from a higher risk facing the pandemic COVID-19, while their related clinical information is limited.Methods: The clinical information of SARS-CoV-2 positive (n = 30) and negative pregnant women (n = 134) in Tianjin First Central Hospital (from November 30, 2022, to January 20, 2023) were collected. All statistical analyses were conducted in R language, employing t test or Chi-square test methods.Results: Significantly higher heart rate, temperature, and intrapartum hemorrhage were observed in positive pregnant women, besides fetal placentation grading, umbilical cord around the neck, cardiac B-scan ultrasound, and ultrasonic examination of lower limb vessels were significantly differential between positive and negative individuals. As for coagulation test, significantly higher activated partial thromboplastin time (APTT), Thrombin Time (TT), and D-dimer (DD2) were found in SARS-CoV-2 positive patients. Liver function test results indicated that six indicators were significantly differential between positive and negative individuals.Conclusion: Compared to negative pregnant women, significantly abnormal liver function and coagulopathy were observed in positive patients. As the unique vulnerable population, SARS-CoV-2 infected pregnant women should be payed more attention in clinical practice.Keywords: COVID-19, pregnant women, clinical feature, coagulopathy