OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

ObjectiveTo investigate the influencing factors and independent risk factors for lower extremity deep vein thrombosis （DVT） in patients with acute necrotizing pancreatitis （ANP）， to analyze the effectiveness of three commonly used risk assessment models for thrombosis （Caprini score， Padua score， and Wells score）， and to provide a reference for clinical identification of high-risk individuals and optimization of prevention and treatment strategies. MethodsA retrospective analysis was performed for the clinical data of 320 patients with ANP who were admitted to Luzhou People’s Hospital and The Affiliated Hospital of Southwest Medical University from April 2013 to April 2024， and according to the presence or absence of DVT during hospitalization， the patients were divided into thrombosis group with 25 patients and control group with 295 patients. After propensity score matching， the two groups were compared in terms of past history and various examination results during hospitalization. The risk factors for lower extremity DVT in ANP patients during hospitalization were analyzed through univariate and multivariate Logistic regression， and a DVT risk prediction model was established based on independent influencing factors. The receiver operating characteristic （ROC） curve was used to assess the performance of models， and the DeLong test was used for comparison of the area under the ROC curve （AUC）， sensitivity， and specificity. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. ResultsAfter matching， the patients were divided into thrombosis group with 24 patients and control group with 112 patients. The clinical characteristics analysis showed that compared with the control group， the thrombosis group had significantly higher degree of pancreatic necrosis， D-dimer level， Bedside Index for Severity in Acute Pancreatitis （BISAP） score， and proportion of patients undergoing dialysis （all P<0.05）. The multivariable Logistic regression analysis showed that BISAP score， degree of pancreatic necrosis， and D-dimer level were independent risk factors for lower extremity DVT in ANP patients during hospitalization （all P<0.05）. The BISAP-Caprini score model had an AUC of 0.832 （95% confidence interval： 0.722 — 0.942， P<0.001） in predicting the risk of lower extremity DVT， with a Youden index of 1.661， an optimal cut-off value of 0.26， a sensitivity of 75.0%， and a specificity of 91.1%. ConclusionD-dimer， BISAP score， and the degree of pancreatic necrosis are independent risk factors for lower extremity DVT in patients with ANP during hospitalization， and the BISAP-Caprini score model can effectively predict the risk of DVT in ANP patients.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

OBJECTIVES: Stress urinary incontinence (SUI) is a common condition among women that severely impairs quality of life. Pelvic floor proprioceptive training (PFPT) has attracted increasing attention for its potential to enhance pelvic floor muscle function and alleviate SUI symptoms. This study aims to observe and compare the clinical efficacy of PFPT combined with electroacupuncture, electrical stimulation, and biofeedback therapy versus conventional therapy consisting of electroacupuncture, electrical stimulation, and biofeedback alone in women with SUI, and to explore the role of PFPT in improving symptom and functional outcomes. METHODS: In this randomized controlled trial, 72 women with mild to moderate SUI were recruited from the Department of Rehabilitation Medicine at Third Xiangya Hospital, Central South University, between December 2021 and October 2023. Participants were randomly assigned to an experimental group (n=36) or a control group (n=36). Both groups received health education. The control group underwent electroacupuncture combined with electrical stimulation and biofeedback therapy, while the experimental group additionally received PFPT 3 times per week for 4 weeks. The primary outcome was assessed using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Secondary outcomes included pelvic floor muscle strength, bladder neck mobility, and balance ability. The ICIQ-SF was reassessed at 1, 3, 6, and 12 months post-treatment. RESULTS: Both groups showed statistically significant improvements in all parameters after treatment (all P<0.05). However, there were no statistically significant differences between groups in most measures (all P>0.05). The experimental group demonstrated longer single-leg stance duration with eyes closed than the control group (left leg: P=0.026; right leg: P=0.006), with a significant increase from baseline (P<0.001). At 6 months post-treatment, the cure rate in the experimental group was significantly higher than that in the control group (P=0.037). CONCLUSIONS Conventional therapy effectively improves SUI symptoms, but adding PFPT provides notable additional benefits, including enhanced balance ability and sustained mid-term cure rates. These findings suggest that PFPT is a valuable adjunct to standard SUI management strategies.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Middle Aged ; Biofeedback, Psychology ; Adult ; Exercise Therapy/methods* ; Proprioception ; Electroacupuncture/methods* ; Quality of Life ; Electric Stimulation Therapy/methods* ; Treatment Outcome ; Combined Modality Therapy

Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE: To explore the timing of weaning extracorporeal membrane oxygenation (ECMO) and analyze the risk factors that affect survival outcomes before weaning. METHODS: A retrospective case-control study was conducted. Patients who received ECMO treatment and were weaned according to physicians' orders at the Second Xiangya Hospital of Central South University from January 2020 to June 2024 were enrolled as the study subjects. The general information, underlying diseases, indications and processes of ECMO, vital signs and arterial blood gas analysis 1 hour before weaning test, and biochemical indicators 24 hours before weaning test were collected through the hospital electronic medical record system. The primary outcome measure was the hospital mortality. The variables with P < 0.1 in univariate analysis and correlation analysis were included into binary Logistic regression analysis to identify risk factors. A nomogram model was constructed to predict the risk of weaning death in patients with ECMO, and receiver operator characteristic curve (ROC curve) and calibration curve were drawn to evaluate the model. Decision curve analysis (DCA) was used to evaluate the clinical net benefit rate of the model. RESULTS: A total of 32 ECMO patients were included, among whom 10 received veno-arterial ECMO (VA-ECMO) and 22 received veno-venous ECMO (VV-ECMO). During the hospitalization period, 23 patients survived, while 9 died. The time from mechanical ventilation to ECMO activation in the death group was significantly longer than that in the survival group, and the time from ECMO cessation to discharge was significantly shorter than that in the survival group. The levels of diastolic blood pressure (DBP) and albumin (Alb) before weaning were significantly lower than those in the survival group, and the level of procalcitonin (PCT) was significantly higher than that in the survival group (all P < 0.05). Spearman correlation analysis showed that DBP, PCT, Alb, and thrombin time (TT) were correlated with the weaning outcomes of ECMO patients (r values were -0.450, 0.373, -0.376, -0.346, all P < 0.1). Binary Logistic regression analysis showed that the final indicators entering the regression equation included DBP [odds ratio (OR) = 0.864, 95% confidence interval (95%CI) was 0.756-0.982], PCT (OR = 1.157, 95%CI was 0.679-1.973), and TT (OR = 0.852, 95%CI was 0.693-1.049), and a nomogram model was constructed to predict the weaning outcomes of ECMO patients. ROC curve analysis showed that the area under the curve (AUC) of the nomogram model for predicting the weaning outcome of ECMO patients was 0.831, with a sensitivity of 77.8% and a specificity of 65.2%. Its predictive value was better than that of single indicators DBP, PCT, and TT (AUC of 0.787, 0.739, and 0.722, respectively). The calibration curve showed that the prediction probability of the model was in good consistency with the actual observed results, the Hosmer-Lemeshow goodness of fit test showed that, χ ² = 8.3521, P = 0.400, indicating that the model fits well. DCA showed that across risk threshold of 0-0.8, the net benefit rate was greater than 0, which was significantly better than that of single indicator. CONCLUSIONS The nomogram model constructed with DBP, PCT, and TT has certain predictive value for the weaning outcomes of ECMO patients and can be used as a screening indicator for ECMO weaning timing.
Humans ; Extracorporeal Membrane Oxygenation ; Retrospective Studies ; Risk Factors ; Case-Control Studies ; Hospital Mortality ; Male ; Female ; Nomograms ; Logistic Models ; ROC Curve ; Middle Aged ; Adult ; Ventilator Weaning ; Time Factors

OBJECTIVE: To identify the risk factors related to the timing of patients receiving extracorporeal membrane oxygenation (ECMO) initiation and construct a risk prediction model for ECMO initiation timing. METHODS: Patients who received ECMO admitted to the Second Xiangya Hospital of Central South University from January 2020 to January 2024 were retrospectively collected. The case data mainly included physiological and biochemical indicators 1 hour before ECMO initiation. According to the outcome of the patients, they were divided into survival group and death group. Univariate and multivariate Logistic regression analysis were used to analyze the predictors of mortality risk in patients with ECMO, and a nomogram prediction model was constructed. The discrimination, calibration accuracy, and goodness of the model were evaluated by the receiver operator characteristic curve (ROC curve), calibration curve, and the Hosmer-Lemeshow test, respectively. Decision curve analysis (DCA) evaluated the clinical net benefit rate of the model. RESULTS: A total of 81 ECMO patients were included, including 59 males and 22 females; age range from 16 to 61 years old, with a median age of 56.0 (39.5, 61.5) years old; 20 patients received veno-arterial (V-A) ECMO, and 61 patients received veno-venous (V-V) ECMO; 23 patients ultimately survived and 58 patients died. Univariate analysis showed that age, blood urea nitrogen, serum creatinine, D-dimer, arterial blood carbon dioxide partial pressure, and prothrombin time of the death group were all higher than those of the survival group, while albumin was slightly lower than that of the survival group. There was a statistically significant difference in the direct cause of ECMO initiation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.069, 95% confidence interval (95%CI) was 1.015-1.125, P = 0.012], direct cause of ECMO initiation [with heart failure as the reference, return of spontaneous circulation (ROSC) after cardiopulmonary support (OR = 30.672, 95%CI was 1.265-743.638, P = 0.035), novel coronavirus infection (OR = 8.666, 95%CI was 0.818-91.761, P = 0.073), other severe pneumonia (OR = 4.997, 95%CI was 0.558-44.765, P = 0.150)], pre-ECMO serum creatinine (OR = 1.008, 95%CI was 1.000-1.016, P = 0.044), prothrombin time (OR = 1.078, 95%CI was 0.948-1.226, P = 0.252), and D-dimer (OR = 1.135, 95%CI was 1.047-1.231, P = 0.002) were entered into the final regression equation. A nomogram prediction model was developed based on these five factors. The area under the ROC curve (AUC) of the model was 0.889 (95%CI was 0.819-0.959), higher than the AUC of the sequential organ failure assessment (SOFA; AUC = 0.604, 95%CI was 0.467-0.742). The calibration curve showed good consistency between the model predictions and the observed results. The Hosmer-Lemeshow goodness-of-fit test showed that χ ² = 4.668, P = 0.792. DCA analysis showed that when the risk threshold was 0-0.8, the net benefit rate was greater than 0, which was significantly better than that of SOFA score. CONCLUSIONS The risk prediction model for the timing of ECMO initiation, constructed using five factors (age, direct cause of ECMO initiation, thrombin time, serum creatinine, and D-dimer), demonstrated good discrimination and calibration. It can serve as a pre-initiation assessment tool to identify and predict post-initiation mortality risk in ECMO patients.
Humans ; Extracorporeal Membrane Oxygenation ; Middle Aged ; Male ; Female ; Retrospective Studies ; Adult ; Risk Factors ; Adolescent ; Young Adult ; Logistic Models ; Nomograms ; ROC Curve ; Time Factors ; Risk Assessment

Traditional Chinese medicine(TCM) processing is a unique and highly distinctive pharmaceutical technology in China. Utilizing modern scientific methods to elucidate the connotations of traditional processing theory and its effects is expected to facilitate the inheritance, development, innovation, and enhancement of TCM processing, and lead to more original research outcomes in the field of TCM. The breakthrough in TCM processing lies in the study of its underlying principles, and analyzing these principles involves researching the transformation mechanisms of chemical components and the biological effect mechanisms of the transformed components. This paper proposed the concept of "TCM processing chemical biology"(TCMPCB) for the first time. Under the guidance of TCM theory, the active components transformed during TCM processing were used as chemical tools to study their targets and molecular regulatory mechanisms, aiming to clarify the scientific principles by which TCM processing affected biological effects in the organism. The research findings also provided new directions for discovering novel active components, new lead compounds, creating new decoction pieces, and developing new TCM drugs. This paper provided a detailed introduction to the background, definition, research content, research ideas, research methods, and prospects of TCMPCB, with the aim of offering new research perspectives for analyzing the principles of TCM processing and providing new pathways for achieving the "four new and eight transformations" in TCM processing.
Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/methods* ; Humans ; Animals