This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

Objective To analyze the influencing factors of death in the elderly with coronavirus disease 2019(COVID-19).Methods The case data of death caused by COVID-19 in West China Fourth Hospital from January 1 to July 8,2023 were collected,and surviving cases from the West China Elderly Health Cohort infected with COVID-19 during the same period were selected as the control.LASSO-Logistic regression was adopted to analyze the data after propensity score matching and the validity of the model was verified by drawing the receiver operating characteristic curve.Results A total of 3 239 COVID-19 survivors and 142 deaths with COVID-19 were included.The results of LASSO-Logistic regression showed that smoking(OR=3.33,95%CI=1.46-7.59,P=0.004),stroke(OR=3.55,95%CI=1.15-10.30,P=0.022),malignant tumors(OR=19.93, 95%CI=8.52-49.23, P<0.001),coronary heart disease(OR=7.68, 95%CI=3.52-17.07, P<0.001),fever(OR=0.51, 95%CI=0.26-0.96, P=0.042),difficulty breathing or asthma symptoms(OR=21.48, 95%CI=9.44-51.95, P<0.001),and vomiting(OR=8.19,95%CI=2.87-23.58, P<0.001)increased the risk of death with COVID-19.The prediction model constructed based on the influencing factors achieved an area under the curve of 0.889 in the test set.Conclusions Smoking,stroke,malignant tumors,coronary heart disease,fever,breathing difficulty or asthma symptoms,and vomiting were identified as key factors influencing the death risk in COVID-19.
Humans ; COVID-19/mortality* ; Aged ; Propensity Score ; China/epidemiology* ; Risk Factors ; Logistic Models ; Smoking ; SARS-CoV-2 ; Male ; Female ; Stroke ; Neoplasms

The purpose of this study was to evaluate the diagnostic performance of multiparametric ultrasound (mpUS; grayscale US, color Doppler US, strain elastography, and contrast-enhanced US) in the assessment of testicular lesions with negative tumoral markers. MpUS imaging data, patient age, serum tumor markers, scrotal pain, cryptorchidism, and related clinical information were retrospectively collected for patients who underwent mpUS examination between January 2013 and December 2019. Histologic results or follow-up examinations were used as the reference standard. In total, 83 lesions from 79 patients were included in the analysis. Fifty-six patients were finally diagnosed with benign tumors, and 23 patients were ultimately diagnosed with malignant tumors. Chi-square tests or Fisher's exact tests were used to assess the difference between the two groups. Stepwise multivariate logistic regression analysis showed that lesion diameter (odds ratio [OR] = 1.072, P = 0.005), vascularization on color Doppler US (OR = 4.066, P = 0.001), and hyperenhancement during the early phase (OR = 6.465, P = 0.047) were significant independent risk factors for malignancy; however, when compared with neoplastic lesions, pain (OR = 0.136, P < 0.001), absence of vascularization on color Doppler US (OR = 1.680, P = 0.042), and nonenhancement during the late phase (OR = 3.461, P = 0.031) were strongly associated with nonneoplastic lesions. MpUS features are useful for differentiating testicular lesions with negative tumoral markers and improving the preoperative diagnosis, which may avoid inappropriate radical orchiectomy.
Male ; Humans ; Testicular Neoplasms/pathology* ; Biomarkers, Tumor ; Retrospective Studies ; Contrast Media ; Ultrasonography/methods*

Objective:To investigate the long-term clinical value of composite biomaterial mesh in inguinal hernia repair.Methods:The prospective randomized controlled non-inferiority study was conducted. The clinical data of 172 adult patients with inguinal hernia who were admitted to 3 medical centers, including Huadong Hospital Affiliated to Fudan University et al, from July 2014 to February 2015 were selected. Based on random number table, patients were divided into two groups. Patients underwent technique of abdominal wall reinforcement with biological mesh. Patients using the electrospun composite biomaterial mesh were allocated into experimental group, and patients using the small intestinal submucosa mesh were allocated into control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) endpoint of the study. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Taking the recurrence rate of hernia at 6 years after surgery as the basis of efficacy evaluation, the Cochran-Mantel-Haenszel test was used for comparison between groups. The confidence interval method was used to conduct non-inferiority statistical analysis. If the lower limit of 95% confidence interval of the difference of recurrence rate of hernia between the experiment group and the control group was more than -10%, the experiment group was considered to be non-inferior to the control group. If the lower limit of 95% confidence interval is more than 0, the experiment group was considered to be superior to the control group. Results:(1) Grouping situations of the enrolled patients. A total of 172 adult patients with inguinal hernia were selected for eligibility. They were males, aged (61±2)years. All 172 patients were randomly divided into to the experimental group and the control group with 86 cases in each group. At 6 years after surgery, 20 patients in the experi-mental group and 19 patients in the control group was lost to follow-up. (2) Endpoint of the study. ① The primary endpoint of study. At 6 years after surgery, no patient had recurrence in the 66 patients of experimental group and 4 patients had recurrence in the 67 patients of control group. Results of non-inferiority statistical analysis showed that the 95% confidence interval of the difference of recurrence rate of hernia between the two groups was 0.27% to 14.41%, with the lower limit as 0.27%, which was more than -10% and simultaneously more than 0. ② The secondary endpoint of study. There was no significant difference in the simple verbal scale between the two groups after 6 months and 6 years at rest or cough status ( P>0.05). At a follow-up of 6 months after surgery, 2 cases of the experimental group and 5 patients of the control group had complications, showing no significant difference between the two groups( χ2=1.38, P>0.05). At a follow-up of 6 years after surgery, no complication occurred in either group. Conclusion:Composite biological mesh in inguinal repair is safe and feasible, which can have low long-term recurrence and achieve good long-term efficacy.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Prescriptions ; Reproducibility of Results ; Research

Recurrent anterior dislocation of shoulder with bone defect is one of the common diseases of shoulder joint. How to effectively repair glenoid bone defect and reduce recurrence rate of shoulder dislocation is a problem that clinicians focus on. Bone grafting could stimulate bone, promote bone regeneration and bone remodeling, and restore the normal anatomical structure of glenoid. Among them, Bristow-Latarjet procedure is a classic operation for recurrent shoulder dislocation. Latarjet procedure could repair larger glenoid bone defects, but with higher surgical skills for surgeons;autogenous iliac grafting is the first choice for revision once Latarjet procedure failed;osteochondral grafting (autogenous and allogenous) has certain advantages in reconstructing original articular surface and preventing joint degeneration, but autologous osteochondral grafting may cause secondary injury, while immune rejection is difficult to avoid for allogenous osteochondral grafting. With the improvement of composite materials, and the mechanism of bone regeneration and remodeling, as well as the advantages and disadvantages of bone grafting, tissue engineering technology may become an effective method for the treatment of glenoid bone defect in the future.
Bone Transplantation ; Humans ; Joint Instability ; Recurrence ; Shoulder ; Shoulder Dislocation/surgery* ; Shoulder Joint

Biopsy ; Deep Learning ; Humans ; Male ; Neoplasm Grading ; Prostatectomy ; Prostatic Neoplasms

Anti-Arrhythmia Agents ; Brugada Syndrome/complications* ; Bundle-Branch Block/complications* ; Electrocardiography ; Humans ; Quinidine ; Ventricular Fibrillation

Objective:To investigate the manifestations of liver injury in hospitalized patients with coronavirus disease 2019 (COVID-19), to investigate the prognosis indicators of the disease, and to provide the reference for clinical diagnosis and treatment.Methods:From January 10 to February 14, 2020, at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the data of 333 hospitalized patients with COVID-19 were collected. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil) and albumin of the first liver function test after admission and the reexaminations of liver function test during hospitalization period in patients with liver injury were retrospectively analyzed. Student t test and Chi-square test were used for statistical analysis. Results:Liver injury occurred in 39.6% (132/333) of COVID-19 patients. There was no statistically significant difference in the rate of liver injury between patients in intensive care unit (ICU) and in general ward (45.6%, 26/57 vs. 38.4%, 106/276; χ2=1.026, P>0.05). 67.4% (89/132) of COVID-19 patients with liver injury presented with increased ALT or AST level on admission. During hospitalization, the level of ALT was higher than that of the first examination after admission ((60.28±50.44) U/L vs. (42.25±32.21) U/L), and the difference was statistically significant ( t=-3.230, P<0.05). The levels of ALT and AST of 71.2% (94/132) patients were both <80 U/L, which indicated that most of the patients showed mild liver injury. The patients with elevated level of TBil, DBil and IBil accounted for 3.9% (13/333), 5.4% (18/333) and 2.4% (8/333) of the COVID-19 patients, respectively. The albumin level of COVID-19 patients with liver injury during hospitalization was lower than that of the first examination after admission ((31.8±5.1) g/L vs. (33.7±5.4) g/L), and the difference was statistically significant ( t=2.712, P<0.05). The albumin levels at first examination on admission and reexamination during hospitalization of patients in ICU were both significantly lower than those of patients in general ward ((29.3±3.7) g/L vs. (34.8±5.1) g/L and (27.6±2.8) g/L vs. (32.9±5.1) g/L), and the differences were statistically significant ( t=4.928 and 4.783, both P<0.05). Conclusions:The incidence of liver injury in COVID-19 patients is high. A slight increase in aminotransferase levels is particularly common. Bilirubin abnormality is relatively rare and mild. The level of albumin may be one of the indicators for the severity and prognosis of COVID-19.