Objective:To investigate the risk factors of skin adverse events associated with immune checkpoint inhibitor (ICI) therapy in patients with urologic neoplasms, and establish a predictive model.Methods:A single-center retrospective case-control study enrolled 91 advanced urologic neoplasms patients who received ICI therapy at the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2025. Patients were divided into the skin lesion group ( n=44) and the control group ( n=47). Patients in the skin lesion group experienced related skin adverse events during ICI treatment, while patients in the control group did not experience such events during ICI treatment. The general data and laboratory indicators were compared between the two groups. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; the non-normally distributed measurement data were expressed as the median (interquartile range) [ M ( Q1, Q3)], and the Kruskal-Wallis test was used for comparison between groups. The count data were expressed as the number of cases and percentages, and the Chi-test was used for comparison between groups. First, a univariate analysis was conducted on the influencing factors of skin adverse events in patients with urologic neoplasms after ICI treatment. Then, the indicators with statistically significant differences in the univariate analysis were further included in the multivariate Logistic regression model to screen the independent risk factors for predicting skin adverse events. The R software was used to incorporate the factors with significant differences from multivariate analysis into the prediction model and construct a Nomogram. The calibration curve was utilized to evaluate the consistency between predicted values and actual observed results. Meanwhile, the discrimination of the model was verified by the receiver operating characteristic (ROC) curve and the area under the curve (AUC), so as to comprehensively verify the reliability and clinical application value of the prediction model. Results:The results of univariate analysis showed that there were statistically significant differences between the skin lesion group and the control group in terms of the proportion of other immune responses, serum albumin level, absolute eosinophil count, and C-reactive protein (CRP) levels ( P<0.05). These factors were included in multivariate Logistic regression, which identified elevated absolute eosinophil count and elevated CRP as the independent risk factors for related skin adverse events in patients with urologic neoplasms after ICI treatment. A predictive nomogram was built based on these factors. The calibration curve showed high consistency between predicted and actual probabilities, and ROC analysis confirmed the combined model had high predictive value (AUC=0.883, P<0.001). Conclusions:Elevated absolute eosinophil count and elevated CRP level are independent predictors of immune-related skin adverse events in urologic neoplasms patients after ICI treatment. The prediction model constructed based on these two factors facilitates early clinical screening and identification of high-risk patients.

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To analyze the results of lymphocyte subsets and 12 plasma cytokines in patients with tuberculosis by flow cytometry and to evaluate their diagnostic efficacy in these patients.Methods:This is a retrospective case-control study. A total of 128 patients with evidence of tuberculosis disease or clinically confirmed tuberculosis who were admitted to the 8th Medical Center of PLA General Hospital from January 2022 to December 2023 were included. According to the location of mycobacterium tuberculosis infection, the patients were divided into the pulmonary tuberculosis group (83 cases) and the extrapulmonary tuberculosis group (45 cases), and 100 healthy age-and sex matched people who underwent health check up during the study period were selected as the control group. Flow cytometry was used to detect peripheral blood lymphocyte subsets and 12 plasma cytokines [including 10 pro-inflammatory factors: interleukin (IL)-5, interferon (IFN)-α, IL-2, IL-6, IL-1β, IFN-γ, IL-8, IL-17, IL-12P70, Tumor necrosis factor (TNF)-α, and two anti-inflammatory factors: IL-4, IL-10] in participants of all groups. Spearman correlation method was used to analyze the correlation between lymphocyte subsets and cytokines, binary Logistic regression was used to screen the TB related factors, and receiver operating curve (ROC) was used to evaluate the diagnostic efficacy of TB related factors.Results:Compared with the control group, the absolute number of CD3 +T lymphocytes, CD3 +CD8 +T lymphocytes, CD3 +CD4 +T lymphocytes, NK cells and B cells were lower in pulmonary tuberculosis group and extrapulmonary tuberculosis group (all P<0.05). Except for IL-1β, the levels of other 11 cytokines are all significantly higher in the pulmonary tuberculosis group (all P<0.01), and the levels of IL-6, IFN-γ, IL-17, TNF-α, IL-4 and IL-10 were significantly higher in extrapulmonary tuberculosis group (all P<0.05). Compared with extrapulmonary tuberculosis group, the level of IL-8 was higher in pulmonary tuberculosis group ( P=0.026). Spearman correlation analysis showed that IL-6, IFN-γ and IL-8 were negatively correlated with the absolute numbers of CD3 +T lymphocytes, CD3 +CD8 +T lymphocytes, CD3 +CD4 +T lymphocytes, NK cells and B cells (IL-6: R2=-0.30, -0.28, -0.32, -0.26, -0.28; IFN-γ: R2=-0.36, -0.31, -0.37, -0.25, -0.36; IL-8: R2=-0.14, -0.13, -0.16, -0.14, -0.22; all P<0.05), IL-10 was negatively correlated with the absolute number of CD3 +CD4 +T lymphocytes, NK cells and B cells ( R 2=-0.14, -0.19, -0.21, all P<0.05); Binary Logistic regression analysis showed that IL-6, IFN-γ, IL-8 and IL-10 were the related factors of tuberculosis ( OR=1.809, 1.136, 0.910, 2.218, all P<0.05), ROC curve analysis showed that the AUC of IL-6, IFN-γ, IL-8 and IL-10 in the joint diagnosis of tuberculosis was 0.845, the sensitivity was 0.766, and the specificity was 0.820. Conclusion:The lower absolute number of lymphocyte subsets and cytokine levels in patients with pulmonary tuberculosis and extrapulmonary tuberculosis indicate that their immune function is in a low state, and the higher levels of pro-inflammatory factors (IL-6, IFN-γ, IL-8) and anti-inflammatory factor (IL-10) indicates the higher inflammatory status, and evaluation of these 4 cytokines has satisfactory diagnostic efficacy for tuberculosis.

Objective To explore the postmortem diffusion rule of Aconitum alkaloids and their metabo-lites in poisoned rabbits,and to provide a reference for identifying the antemortem poisoning or post-mortem poisoning of Aconitum alkaloids.Methods Twenty-four rabbits were sacrificed by tracheal clamps.After 1 hour,the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration.Then,they were placed supine and stored at 25℃.The biological samples from 3 randomly selected rabbits were collected including heart blood,peripheral blood,urine,heart,liver,spleen,lung and kidney tissues at 0 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h after intragastric administration,respectively.Aconitum alkaloids and their metabolites in the biological samples were ana-lyzed by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Results At 4 h after intragastric administration,Aconitum alkaloids and their metabolites could be detected in heart blood,peripheral blood and major organs,and the contents of them changed dynamically with the preservation time.The contents of Aconitum alkaloids and their metabolites were higher in the spleen,liver and lung,especially in the spleen which was closer to the stomach.The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration.In contrast,the contents of Aconitum alkaloids and their metabolites in kidney were all lower.Aconi-tum alkaloids and their metabolites were not detected in urine.Conclusion Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits,diffusing from high-content organs(stomach)to other major organs and tissues as well as the heart blood.The main mechanism is the dispersion along the concentration gradient,while urine is not affected by postmortem diffusion,which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.

Aim To observe the behavioral effects of exogenous allopregnanolone(ALLO)and its inhibitor finasteride on the receptive period(R)and non-recep-tive period(NR)of PMDD liver-qi inversion model rats and the expression of GABAARα4,GABAARδ mR-NA and protein effects to explore its pathogenesis.Methods The PMDD liver-qi reverse syndrome rat model was prepared.The rats were divided into the normal group R and NR(control-R,control-NR),model group R and NR(Model-R,Model-NR),nor-mal group R+ALLO and NR+ALLO(Control+A-R,Control+A-NR),and model group R+ALLO and NR+ALLO(Model+A-R,Model+A-NR),model group R+finasteride and NR+finasteride(Model+F-R,Model+F-NR).The elevated cross labyrinth ex-periment and social interaction experiment were used to detect the behaviors of rats;fluorescence quantitative PCR and immunofluorescence were used to detect the expression of GABAARα4 and 8 mRNA and protein in rat amygdala and hippocampus.Results In the be-havioral evaluation,in the NR period,in the elevated cross maze test and in the social interaction test,the rats in the model group had anxiety behavior and de-creased social communication ability(P＜0.05),while the rats in the Model+A group could effectively relieve anxiety symptoms and improve their social com-munication ability(P＜0.05),and the rats in the Model+F group had increased anxiety behavior and social disorder(P＜0.05).In fluorescence quantita-tive PCR and immunofluorescence experiments,the ex-pression of GABAARα4 subunit in the model group was up-regulated in the hippocampus(P＜0.01),and the expression of δ subunit was down-regulated(P＜0.01);the expression of GABAARα4 subunit in the a-mygdala and hippocampus of the Model+A group de-creased(P＜0.01),and the expression of δ subunit increased in the hippocampus(P＜0.01).Conclu-sions The abnormal expression of GABAARα4 and 8 subunits mediated by ALLO improves the anxiety symptoms and social interaction ability of PMDD,which is the pathogenesis of PMDD liver-qi reverse syndrome,and provides basis and support for subse-quent exploration of the pathogenesis of PMDD liver-qi reverse syndrome.

Objective To analyze the distribution and antimicrobial resistance of pathogens from wounds of burned patients,providing reference for the rational use of antimicrobial agents and healthcare-associated infection(HAI)prevention and control.Methods Clinical data of burned patients admitted to a tertiary first-class hospital from Ja-nuary 2020 to December 2022 were analyzed retrospectively,pathogens in the wound was cultured,identified,and performed antimicrobial susceptibility analysis.Results From 2020 to 2022,a total of 588 burned patients were ad-mitted,734 strains of pathogens were detected,including 415 strains(56.54％)of Gram-negative bacteria,306 strains(41.69％)of Gram-positive bacteria,and 13(1.77％)strains of fungi.The top 5 pathogens were Staphy-lococcus aureus,Escherichia coli,Pseudomonas aeruginosa,Klebsiella pneumoniae,and Enterobacter cloacae.Staphylococcus aureus had higher resistance rates(93.02％-97.37％)to penicillin G,resistance rate to oxacillin increased from 11.63％to 21.92％.Pseudomonas aeruginosa mainly exhibited resistance to ticarcillin/clavulanic acid,aztreonam,and levofloxacin,resistance rates to imipenem and meropenem were 15.00％-38.10％and 10.00％-33.33％,respectively.Susceptibility of Enterobacterales bacteria to cephalosporins enhanced with the increased of cephalosporin generations,and exhibited higher resistance to commonly used antimicrobial agents.Conclusion Over the past three years,there has been no significant change in the detection of major pathogens and antimicrobial resistance in wounds of burned patients in this hospital.Antimicrobial resistance of Staphylococcus aureus and En-terobacterales is relatively severe,and it is necessary to carry out surveillance on pathogens from burn wounds in corresponding areas.

Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.