Objective: To analyze the relationship between asthma and nocturia in women based on the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2018,so as to provide reference for the prevention and treatment of female nocturia. Methods: Female respondents aged ≥20 years with nocturia or asthma were selected from the 2005-2018 NHANES database.Those with both diabetes stroke and obstructive sleep apnea syndrome were excluded.A weighted analysis was conducted using a complex sampling design.The association between asthma and nocturia in women was evaluated with univariate analysis，propensity score matching (PSM)，and multivariate logistic regression models. Results: A total of 14 718 respondents were selected，of whom 1426 (9.7%) were diagnosed with asthma，and 4664 (31.7%) with nocturia.There is a significant correlation between asthma and nocturia (χ =39.846，P<0.01). Age，body mass index (BMI)，smoking and race were also associated with nocturia (P<0.01).Multivariate logistic regression analysis showed that，the age，BMI，smoking，race and asthma were correlated with the risk of nocturia，before PSM matching (P<0.05).To eliminate confounding bias，PSM was applied，and generalized linear mixed model analysis after matching showed that the risk of nocturia remained high in asthma patients (OR=1.540，95% CI：1.320-1.800，P<0.01). Conclusion: Asthma is associated with nocturia in women，indicating that it may be an important risk factor for female nocturia.

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.

Objective To identify potential drug target genes associated with idiopathic pulmonary fibrosis(IPF)and predict therapeutic candidates using a two-sample Mendelian randomization(MR)approach across the druggable genome.Methods Druggable genome data from the DGIdb database and Finan were integrated to identify overlapping genes.A two-sample MR analysis was performed to infer causal relationships between genes and IPF.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),were conducted to explore biological pathways.Drug-target interactions were predicted via DSigDB database screening,followed by molecular docking simulations to evaluate binding affinities.Results Among the 2588 overlapping druggable genes,thirty exhibited significant causal associations with IPF(P＜0.05).Four hub genes(NOD2,LATS2,LTA,and TCF7L2)were enriched in IPF-related pathways,notably Hippo and TNF signaling.Six potential therapeutics were identified:oxyphenbutazone,moexipril,α-galactosylceramide,GSK429286A,CGP74514A,and JW-7-24-1.Molecular docking confirmed strong binding affinities between these drugs and their targets.Conclusion This study has identified thirty druggable gene targets and six candidate drugs for IPF.The enrichment of hub genes in key pathways and validated drug-target interactions provide insights into IPF therapies.

Liver fibrosis and cirrhosis are the common outcomes of various chronic liver diseases after progression,and studies have shown that liver fibrosis and early liver cirrhosis can be reversed.Compound traditional Chinese medicine prescriptions have a marked therapeutic effect in reversing liver fibrosis and early liver cirrhosis,and their mechanism of action remains unclear.By reviewing related articles in China and globally,this article summarizes the six main phenotypic mechanisms involved in the efficacy of compound traditional Chinese medicine prescriptions,i.e.,inhibiting liver inflammation and regulating liver immune response,regulating hepatic stellate cell activation and extracellular matrix(ECM)generation,promoting ECM degradation,reversing hepatic sinusoidal capillarization,regulating hepatocyte regeneration,and regulating gut microbiota,and in addition,this article also analyzes the advances and shortcomings in current studies on each phenotype.Future studies on compound traditional Chinese medicine prescriptions should focus on experimental exploration and rescue experiments to verify the above phenotypes and further explore the upstream and downstream signaling pathways with a marked effect.This article aims to help clarify the direction and ideas of studies on the therapeutic mechanism of compound traditional Chinese medicine prescriptions,in order to provide a basis for clarifying the scientific essence of compound traditional Chinese medicine prescriptions.

Objective To investigate the effect of Kangxian Yiai Prescription(KXYA)on the mTOR/HIF-1α/VEGF signaling pathway in a rat model of precancerous lesions of liver cancer.Methods A total of 40 male Wistar rats were divided into normal group,model group,KXYA group,and Biejia Rangan Tablets(BJRG)group,with 10 rats in each group.The rats in the normal group were given intraperitoneal injection of normal saline at a dose of 0.4 mL/100 g,and those in the other three groups were given intraperitoneal injection of diethylnitrosamine at a dose of 50 mg/kg to establish a rat model of the precancerous lesions of liver cancer.Immunohistochemistry and Western Blot were used to measure the expression level of GST-Pi,and quantitative real-time PCR and Western Blot were used to measure the mRNA and protein expression levels of mTOR,HIF-1α,VEGF,PKM2,and GLUT1.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the normal group,the model group had a significant increase in the protein expression level of GST-Pi in liver tissue(P＜0.01),and compared with the model group,the KXYA group had a significant reduction in the protein expression level of GST-Pi(P＜0.05).Compared with the normal group,the model group had significant increases in the mRNA expression levels of GLUT1 and PKM2 in liver tissue(P＜0.01),and compared with the model group,the BJRG group and the KXYA group had a significant reduction in the mRNA expression level of GLUT1(P＜0.05).Compared with the normal group,the model group had significant increases in the protein expression levels of GLUT1 and PKM2 in liver tissue(P＜0.01).Compared with the normal group,the model group had significant increases in the mRNA expression levels of mTOR,HIF-1α,and VEGF in liver tissue(P＜0.01);compared with the model group,the BJRG group had significant reductions in the mRNA expression levels of mTOR and VEGF(P＜0.05),and the KXYA group also had significant reductions in the mRNA expression levels of mTOR and VEGF(P＜0.01).Compared with the normal group,the model group had significant increases in the protein expression levels of mTOR,HIF-1α,and VEGF in liver tissue(P＜0.01);compared with the model group,the BJRG group had a significant reduction in the protein expression level of mTOR(P＜0.01),and the KXYA group had significant reductions in the protein expression levels of mTOR,HIF-1α,and VEGF(P＜0.05);compared with the BJRG group,the KXYA group had a significantly higher protein expression level of mTOR(P＜0.01).Conclusion KXYA can inhibit the precancerous lesions of liver cancer by regulating the mTOR/HIF-1α/VEGF signaling pathway.

OBJECTIVE To investigate the modulating effect of neotropics on form deprivation myopia(FDM)in guinea pigs.METHODS Tricolour guinea pigs were randomly divided into normal control group,FDM model group,FDM+saline group,FDM+atropine group,and FDM+neotropine group,with eight animals in each group.Except for the normal control group,the right eyes of the guinea pigs were covered for 14 d to establish a guinea pig FDM model.The drug administration groups were injected with 10 μL of saline,1%atropine,or 1%neotropine into the vitreous cavity once every other day.The changes in the refractive error and axial length of both eyes were recorded for 1 d before the intervention and for 14 d after the intervention.Then,the eyeballs of guinea pigs were taken from the right eyes.HE staining was used to evaluate the histopathological structure of the sclera while sirius red staining was used to detect the collagen protein content in the sclera.RT-qPCR was used to detect the mRNA expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)in guinea pigs'sclera.The protein expression levels of collagen type Ⅰ(Col-Ⅰ)and TGF-β1 in guinea pig sclera were detected by Western blotting while those of MMP-2,TIMP-2 and Ki-67 were detected by immunohistochemical staining.RESULTS Compared with the nor-mal control group,eyes of guinea pig in the FDM model group showed a significantly lower refractive error(P<0.01),significant elongation of the ocular axis(P<0.01),scattered distribution of scleral fibre bundles,sparse collagen cells,reduced scleral thickness(P<0.01),and a significantly lower collagen protein content(P<0.01).The mRNA and protein expressions of TIMP-2 and TGF-β1 were lower(P<0.05,P<0.01),and MMP-2 was higher(P<0.01)in scleral tissue.The protein expression level of Col-Ⅰwas lower(P<0.05)while that of Ki-67 was elevated(P<0.01)in scleral tissue.Compared with the FDM model group,there were no significant changes in any of the indexes in the FDM+saline group.The refractive error of the right eyes of guinea pigs in the FDM+neotropium group and the FDM+atropium group were significantly higher(P<0.05),the length of the ocular axis was significantly shorter(P<0.05),the collagen fibres were arranged more tightly,the fibre bundles were distributed more orderly,the distribution of the collagen cells was more uniform,and the thickness of the sclera was significantly increased(P<0.01).Collagen protein contents were significantly higher(P<0.05,P<0.01),the mRNA and protein expressions of TIMP-2 and TGF-β1 were significantly higher(P<0.01),MMP-2 mRNA and protein expressions were significantly lower(P<0.05,P<0.01).The protein expression level of Col-Ⅰwas higher(P<0.05,P<0.01),and that of Ki-67 was lower(P<0.05,P<0.01)in scleral tissue.CONCLU-SION The muscarinic antagonist neotropine inhibits the development of myopia in guinea pigs in the FDM model by reversing both the down-regulation of TGF-β1 and the up-regulation of MMP-2 in scleral tissues and inhibiting the remodeling of the scleral extracellular matrix.

Objective:To compare the effectiveness of the Moses holmium laser and the traditional holmium laser in the treatment of kidney stones using flexible ureteroscopy.Methods:The data of 425 patients with kidney stones treated with flexible ureteroscopic holmium laser lithotripsy at Hebei University Affiliated Hospital from January 2017 to January 2023 were retrospectively analysed. Among them, 136 cases were treated with traditional holmium laser (traditional group), and 289 cases were treated with Moses holmium laser (Moses group). To minimize selection bias due to non-random allocation, 1∶1 propensity score matching (PSM) was employed, ensuring comparability between the two groups in baseline characteristics (age, gender) and stone characteristics (stone location, number, diameter, CT value, and stone composition). The differences in operation time, laser action time, stone clearance rate (SFR), postoperative complications and secondary treatment rate were compared between the two groups after matching. The risk factors affecting SFR were analyzed by multivariate logistic regression. The efficacy of Moses group and traditional group in treating kidney stones with diameter ≥20 mm was also compared.Results:After PSM, 108 patients were selected from each group for data analysis. Traditional group and Moses group demonstrated good consistency in baseline characteristics, including age [57.0(49.0, 65.0) years old vs. 58.5(51.8, 66.0) years old], male gender [58.3% (63/108) vs. 60.2% (65/108)], stone location(upper calyx / mid calyx / lower calyx / pelvis: 33/35/38/42 cases vs. 35/33/40/42 cases), multiple stones [33.3% (36/108) vs. 35.2% (38/108)], diameter [14.0(11.0, 16.0)mm vs. 14.0(12.0, 17.0)mm], CT value [1 115.5(993.2, 1 228.2) HU vs. 1 114.5(1 000.2, 1 216.5) HU], and the presence of calcium stones [83.3% (90/108) vs. 79.6% (86/108)], and all showing absolute standardized mean difference(ASMD) <0.1. The Moses group had shorter operation time [48.5(36.0, 56.0)min vs. 60.0(48.8, 68.0)min, P<0.01], higher post-operative stone-free rate (SFR) [88.9%(96/108) vs. 67.6(73/108), P<0.01], and lower rate of secondary surgery [1.8%(2/108) vs. 9.3%(10/108), P=0.04], indicating advantages in surgical efficiency and post-operative outcomes. Multivariable logistic regression analysis revealed that using Moses holmium laser ( OR=0.029, P<0.01), stone diameter ( OR=1.492, P<0.01), stone CT value ( OR=1.007, P<0.01), presence of calcium stones ( OR=1.551, P<0.01), holmium laser application time ( OR=0.863, P<0.01), preoperative placement of a double-J stent ( OR=0.193, P<0.01), and preoperative moderate to severe hydronephrosis ( OR=1.651, P<0.01) were significant factors affecting SFR. In treating stones with a diameter of 20-30 mm, the surgery time of Moses group was shorter than that of traditional group [50.5(43.8, 58.3)min vs. 72.0(68.0, 78.0)min, P<0.05], and the laser application time of Moses group was also shorter [29.5(22.8, 36.0)min vs. 36.0(32.0, 41.0)min, P<0.05]. The post-operative SFR of Moses group was higher than that of traditional group [65.6%(42/64) vs. 35.3%(6/17), P<0.05], and the rate of secondary surgery was lower[7.8%(5/64) vs. 29.4(5/17), P<0.05]. Conclusions:Flexible ureteroscopy combined with Moses holmium laser lithotripsy demonstrated significant advantages over traditional holmium laser in enhancing stone clearance rate, reducing operation time, and lowering the need for secondary surgeries in the treatment of kidney stones. Flexible ureteroscopy combined with Moses holmium laser lithotripsy also proves its efficacy and clinical value in managing complex kidney stone cases.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore the risk factors for early trauma-induced coagulopathy (TIC) following severe trauma in the elderly patients.Methods:A case-control study was used to analyze the clinical data of 317 elderly patients with severe trauma admitted to Second Affiliated Hospital of Zhejiang University School of Medicine between February 2015 and November 2020. There were 212 males and 105 females, aged 65-96 years [(72.6±6.8)years]. The patients were divided into TIC group ( n=32) and non-TIC group ( n=285) using the international normalised ratio (INR)>1.5 as the reference standard. Sex, age, trauma sites, injury severity score (ISS), Glasgow coma scale (GCS), first body temperature on admission, shock index(SI), first laboratory results of arterial blood gas, routine blood and coagulation, blood transfusion, usage of blood product, hospitalization days and clinical outcomes were compared between the two groups. Univariate and multivariate Logistic regression analysis were used to identify the risk factors for early TIC in patients with severe trauma. Results:Differences in sex, age, injuries to the face, chest and abdomen, GCS, first body temperature and hospitalization days were not statistically significant between the two groups (all P>0.05). The two groups showed statistical differences in the ratio of injuries to head, neck and extremities, ISS, SI, pH value, base excess (BE), lactate, hemoglobin (Hb), platelet (PLT) count (first detection, lowest level), activated partial thromboplastin time (APTT), thrombin time (TT), plasma fibrinogen (FIB), blood transfusion and usage of blood product and clinical outcomes (all P<0.05). According to the univariate analysis, injuries to the head, neck and extremities, ISS, first body temperature, SI, pH value, BE, lactate, Hb, PLT, APTT, TT and FIB were correlated with the occurrence of early TIC (all P<0.05). Multiple Logistic regressions analysis showed that SI ( OR=1.54, 95% CI 1.10-2.17, P<0.05), PLT ( OR=0.67, 95% CI 0.49-0.91, P<0.05) and FIB ( OR=0.56, 95% CI 0.40-0.78, P<0.01) were significantly correlated with the occurrence of early TIC. Conclusion:For elderly patients with severe trauma, higher SI, lower PLT count and lower concentration of FIB are independent risk factors for the incidence of early TIC.

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.