ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Objective:To explore the prevalence and risk factors of insomnia in Chinese Air Force servicemen deployed to highland areas.Methods:A total of 718 Air Force servicemen deployed to Qinghai-Tibetan plateau were recruited at May 2024.Sleep quality was assessed with the Pittsburgh Sleep Quality Index.Social-demograph-ic,military service,and psychological characteristics were measured with a self-administered general question-naire.Bivariable and multivariable logistic regressions were performed to identify independent risk factors.Missing data were handled by the multiple imputation.Results:The average sleep duration was(6.9±1.2)h and the aver-age PSQI score was(5.9±4.1).Totally 53.8％of participants experienced clinically significant insomnia.The multivariable analysis revealed that age≥35(aOR=4.07,95％CI=1.11-17.76),stressful event(aOR=3.27,95％CI=2.00-5.49),dysfunctional sleep beliefs and attitudes(aOR=2.59,95％CI=1.75-3.85),and caffeine product usage(aOR=1.69,95％CI=1.17-2.43)were risk factors for insomnia,while Tibetan-indigenous ethnic(aOR=0.44,95％CI=0.20-0.91),higher perceived social support(aOR=0.96,95％CI=0.96-0.99),and positive coping style(aOR=0.96,95％CI=0.93-0.99)were protective factors.Conclusion:Air force service-men deployed to highland areas have sufficient sleep time,but reduced sleep quality.Age,exposed to stress event during deployment,dysfunctional sleep beliefs and attitudes,and caffeine product usage are risk factors for insomni-a,while Tibetan-indigenous ethnic,higher perceived social support and positive coping style act as protective fac-tors.

Objective:To explore the prevalence and risk factors of insomnia in Chinese Air Force servicemen deployed to highland areas.Methods:A total of 718 Air Force servicemen deployed to Qinghai-Tibetan plateau were recruited at May 2024.Sleep quality was assessed with the Pittsburgh Sleep Quality Index.Social-demograph-ic,military service,and psychological characteristics were measured with a self-administered general question-naire.Bivariable and multivariable logistic regressions were performed to identify independent risk factors.Missing data were handled by the multiple imputation.Results:The average sleep duration was(6.9±1.2)h and the aver-age PSQI score was(5.9±4.1).Totally 53.8％of participants experienced clinically significant insomnia.The multivariable analysis revealed that age≥35(aOR=4.07,95％CI=1.11-17.76),stressful event(aOR=3.27,95％CI=2.00-5.49),dysfunctional sleep beliefs and attitudes(aOR=2.59,95％CI=1.75-3.85),and caffeine product usage(aOR=1.69,95％CI=1.17-2.43)were risk factors for insomnia,while Tibetan-indigenous ethnic(aOR=0.44,95％CI=0.20-0.91),higher perceived social support(aOR=0.96,95％CI=0.96-0.99),and positive coping style(aOR=0.96,95％CI=0.93-0.99)were protective factors.Conclusion:Air force service-men deployed to highland areas have sufficient sleep time,but reduced sleep quality.Age,exposed to stress event during deployment,dysfunctional sleep beliefs and attitudes,and caffeine product usage are risk factors for insomni-a,while Tibetan-indigenous ethnic,higher perceived social support and positive coping style act as protective fac-tors.

Objective To construct a predictive model for the occurrence of lower extremity deep vein thrombosis(DVT)after internal fixation surgery for thoracolumbar fractures by using extreme gradient boosting(XGBoost).Methods Data of 220 patients who underwent internal fixation surgery for thoracolumbar fractures in the First Affiliated Hospital of Wenzhou Medical University from January 2019 to December 2022 was collected.The dataset was divided into a training set(154 cases)and a testing set(66 cases).The training set was processed by using the synthetic minority over-sampling technique and the predictive model was build based on XGBoost.The performance was compared on the testing set by using area under receiver operating characteristic curve,accuracy,F1 score,sensitivity and specificity.The interpretability analysis base on SHAP was conducted to quantify the degree of contribution of influencing factors.Results The XGBoost model outperformed logistic regression,support vector machine and random forest models on multiple metrics,with an area under the curve of 0.761 on the original testing set.The decision curve indicated that the XGBoost model has clinical application value.Conclusion The XGBoost model based on factors such as age,body mass index,and postoperative albumin,D-dimer,total protein,erythrocyte sedimentation rate,prothrombin time can effectively predict the occurrence of lower extremity DVT after internal fixation surgery for thoracolumbar fractures,which has good potential for clinical application.

The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

ObjectiveTo observe the effect of Shenling Baizhusan on the intervention of the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway by regulating ferroptosis in rats with alcoholic liver injury. MethodForty SD rats were randomly divided into model group， polyene phosphatidylcholine group， and high， medium， and low-dose Shenling Baizhusan groups， with 8 rats in each group. Another 8 SD rats were taken as blank group. The model group， polyene phosphatidylcholine group， high， medium， and low-dose Shenling Baizhusan groups were given 10 mL·kg^-1 liquor by gavage for modeling， and the blank group was given equal volume of distilled water by gavage. After 4 h of daily alcoholic administration， 143.64 mg·kg^-1 of polyene phosphatidylcholine group was given to the polyene phosphatidylcholine group， 15， 7.5， 3.75 mg·kg^-1 of Shenling Baizhusan were given to Shenling Baizhusan high， medium， and low-dose groups， respectively， and the blank group and the model group were given equal volume of distilled water. The gavage lasted for 6 weeks. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， glutamyl transpeptidase （GGT）， total cholesterol （TC）， and triglyceride （TG） were detected by automatic biochemical analyzer. The levels of tumor necrosis factor-α （TNF-α） and interleukin-β （IL-β） were detected by the enzyme-linked immunosorbent assay （ELISA）. The levels of lipopolysaccharide （LPS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， and Fe⁺ were detected by biochemical assay. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The mRNA expression levels of Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， ferritin heavy polypeptide 1 （FTH1）， and nuclear factor-κB （NF-κB） were detected by Real-time polymerase chain reaction （Real-time PCR）. The protein expression levels of Nrf2， HO-1， GPX4， FTH1， p65， and phosphorylation （p）-p65 were detected by Western blot. ResultAs compared with the blank group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the model group were significantly increased （P<0.05）. The liver showed obvious steatosis， with a large number of fat deposition， the oxidative stress and inflammatory factors were significantly increased （P<0.05）， and the level of Fe⁺ was significantly increased in model group （P<0.05）. The protein expression levels of Nrf2， HO-1， GPX4， and FTH1 was significantly down-regulated （P<0.05）， and those of p65 and p-p65 was significantly up-regulated in the model group （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly down-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly up-regulated （P<0.05）. As compared with the model group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the high-dose and medium-dose Shenling Baizhusan groups were significantly decreased （P<0.05）， liver steatosis was significantly improved， fat deposition was significantly reduced， oxidative stress and inflammatory factors were significantly decreased （P<0.05 ）， and Fe⁺ level was significantly decreased （P<0.05）. In the high-dose and medium-dose Shenling Baizhusan， the protein expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and those of p65， p-p65 were significantly down-regulated （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly down-regulated （P<0.05）. ConclusionShenling Baizhusan can effectively reduce liver injury in rats with ALD， regulate steatosis and fat deposition， and play an antioxidant and anti-inflammatory role in the liver. Its mechanism may be related to the inhibition of ferroptosis in hepatocytes by up-regulating the Nrf2 signaling pathway to improve oxidative stress

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.