Objective To analyze the effect of Roflumilast combined with Budesonide in the treatment of chronic bronchitis complicated with chronic obstructive pulmonary disease(COPD).Methods A total of 98 patients with chronic bronchitis complicated with COPD admitted from February 2023 to February 2025 were selected and divided into group A(n=49)and group B(n=49)by random number table method.Group A was given Budesonide,and group B was given Roflumilast combined with Budesonide.The clinical efficacy,symptom scores[Chronic Obstructive Pulmonary Disease Assessment Test(CAT),modified British medical research council(mMRC)],pulmonary function[forced vital capacity(FVC),peak exploratory flow(PEF),forced exploratory volume in one second(FEV1)],respiratory mechanics indexes[airway resistance(Raw),dynamic compliance(Cdyn),peak inspiratory pressure(PIP)],inflammatory factors[interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP)],oxidative stress markers[8-iso-prostaglandin F2α(8-iso-PGF2α),malondialdehyde(MDA),super oxide dismutase(SOD),glutathione peroxidase(GSH-Px)],adverse reactions and prognosis were compared between the two groups.Results The total effective rate of group B[95.92%(47/49)]was higher than that of group A[83.67%(41/49)](P<0.05).After treatment,CAT,mMRC score,PIP,Raw,8-iso-PGF2α,MDA,hs-CRP,TNF-α and IL-8 in group B were lower than those in group A,while FVC,PEF,FEV1,Cdyn,SOD and GSH-Px were higher than those in group A(P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).The number of acute exacerbation in group B was less than that in group A at 3 and 6 months after treatment(P<0.01).Conclusion The combination therapy of Roflumilast and Budesonide is significantly effective in the treatment of chronic bronchitis complicated with COPD.It can alleviate clinical symptoms,improve patients'pulmonary function and respiratory mechanics,inhibit inflammation and oxidative stress response,and has a favorable safety profile and good prognosis.

Objective To investigate the efficacy of Vericiguat combined with Sacubitril/Valsartan(Sac/Val)in the treatment of heart failure in elderly patients with dilated cardiomyopathy(DCM).Methods From January 2023 to January 2024,96 elderly patients with DCM and heart failure were selected and randomly divided into two groups by the random number table method,with 48 patients in each group.The control group was treated with Sac/Val,while the combination group was treated with Vericiguat combined with Sac/Val for a course of 3 months.The clinical efficacy,adverse reactions,parameters of cardiac structure and function[left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),stroke volume(SV)],myocardial injury indicators[N-terminal pro-brain natriuretic peptide(NT-proBNP),troponin I(cTnI),creatine kinase isoenzyme(CK-MB)],and serum miR-133a and miR-433 expression levels before and after treatment were compared between the two groups.The patients were followed up for 6 months to statistically analyze the occurrence of major adverse cardiovascular events(MACE).Results Compared with 77.08%(37/48)in the control group,the total effective rate of the combination group was significantly increased to 93.75%(45/48)after treatment(P<0.05).Compared with the control group,SV and LVEF increased,while LAD and LVEDD decreased in the combination group after treatment(P<0.05).Compared with the control group,the levels of serum NT-proBNP,cTnI,CK-MB and the expression levels of serum miR-133a and miR-433 in the combination group decreased after treatment(P<0.05).During the treatment period,there was no significant difference in the total incidence of adverse reactions between the two groups(P>0.05).After a 6-month follow-up,there was no significant difference in the incidence of MACE between the two groups(P>0.05).Conclusion Vericiguat combined with Sac/Val has a definite therapeutic effect in the treatment of heart failure in elderly patients with DCM,which can reduce the levels of myocardial injury markers in patients,improve cardiac structure and function,and has favorable safety profile.It may be related to the regulation of miR-133a and miR-433 expression.

Objective To analyze the clinical characteristics of immune checkpoint inhibitor(ICI)-related hepatotoxicity(ICIH)in cancer patients.Methods A retrospective analysis was conducted on clinical data of cancer patients with ICIH from January 2019 to December 2024.Patients with Grade 1-2 liver injury were defined as the mild group,and those with Grade 3-4 liver injury were defined as the severe group.Results Among 13 patients with ICIH,10(76.92%)were males and 3(23.08%)were females,with a mean age of 67.8±5.2 years.Twelve patients(92.3%)were aged 60 years or above.ICIH first occurred between cycle 1 and cycle 14 after initial treatment,with the highest incidence observed within cycles 1-5.Combination therapy(combination chemotherapy or targeted agents)was used in 10 patients(76.92%).Among the 13 patients,the distribution of liver injury grades was as follows:1 case of Grade 1(7.69%),2 cases of Grade 2(15.38%),5 cases of Grade 3(38.46%),and 5 cases of Grade 4(38.46%).Liver injury types included hepatocellular(38.46%),cholestatic(38.46%),and mixed(23.08%).After drug discontinuation and supportive care,9 patients(69.23%)fully recovered,2(15.38%)improved,and 2(15.38%)showed no improvement.No significant differences were observed between the mild and severe groups in terms of age,body mass index,baseline lymphocyte count,platelet count,neutrophil count,monocyte count,alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,alkaline phosphatase,lymphocyte-to-monocyte ratio,neutrophil-to-lymphocyte ratio,and platelet-to-lymphocyte ratio(P>0.05).Conclusion ICIH typically occurs within 1 to 5 cycles after ICI administration,with non-specific clinical manifestations,which lead to a diagnosis of exclusion.Despite a generally favorable prognosis,severe ICIH can be fatal,particularly in patients with primary liver cancer.Prompt discontinuation of ICIs and initiation of Corticosteroid therapy can lead to timely improvement of patient's condition.

Objective To investigate the effects of Remimazolam combined with Esketamine on cellular immunity,cognitive function,and sleep quality in elderly patients with lung cancer during surgery.Methods A total of 106 elderly lung cancer patients who underwent elective thoracoscopic lobectomy from September 2023 to March 2025 were selected and divided into the control group(n=53)and the research group(n=53)according to random number table method.The control group received Midazolam combined with Esketamine for general anesthesia,while the research group received Remimazolam combined with Esketamine for general anesthesia.The intraoperative and postoperative conditions,hemodynamic parameters[heart rate(HR),mean arterial pressure(MAP)]before anesthesia induction(T0),at tracheal intubation(T1),at 1 min before one-lung ventilation(OLV)(T2),at skin incision(T3),at 1 h after OLV(T4),and immediately after extubation(T5),as well as pain and inflammatory factors[5-hydroxytryptamine(5-HT),prostaglandin E2(PGE2),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α)],cellular immunity[peripheral blood natural killer(NK)cells,CD3+,CD4+,CD4+/CD8+],the levels of serum interleukin(IL)-2,interferon-γ(IFN-γ),cognitive function[Mini-Mental State Examination(MMSE)],sleep quality[Pittsburgh Sleep Quality Index(PSQI)],and recovery quality[Postoperative Quality of Recovery-15(QoR-15)score]were compared between the two groups of patients.The adverse reactions and complications were also compared between the two groups.Results There was no significant difference in duration of surgery,duration of anesthesia,intraoperative blood loss,and time to spontaneous breathing recovery of patients between the two groups(P>0.05).The total dosage of Sufentanil in the research group was less than that in the control group,and time to postoperative eye opening,duration of recovery room stay and length of postoperative hospitalization were shorter than those in the control group(P<0.05).At T0 and T5,there was no significant difference in HR and MAP between the two groups(P>0.05),and at T1-T4,HR and MAP in the research group were higher than those in the control group(P<0.05).At the time of recovery,the levels of serum 5-HT,PGE2,hs-CRP,and TNF-α in the research group were lower than those in the control group(P<0.05),and at the time of recovery,the peripheral blood NK cells,CD3+,CD4+,and CD4+/CD8+ratio,serum IL-2 and IFN-γ levels in the research group were higher than those in the control group(P<0.05).At 1 d after surgery,the MMSE and QoR-15 scores of the research group were higher than those of the control group,while the PSQI score was lower than that of the control group(P<0.05).The incidence of adverse reactions and complications in the research group[5.66%(3/53)and 3.77%(2/53)],was lower than that of the control group[18.87%(10/53)and 15.09%(8/53)](P<0.05).Conclusion The combination of Remimazolam and Esketamine in elderly patients undergoing thoracoscopic lobectomy can better maintain intraoperative hemodynamics,stabilize cellular immune function,reduce serum pain and inflammatory factor levels,improve postoperative cognitive function and sleep quality,reduce adverse reactions and complications,and promote postoperative recovery.

Objective To investigate the prognostic value of mitochondrial autophagy-related genes(MRGs)in prostate cancer(PCa),and to reveal their regulatory relationship with interstitial epidermal transforming factor(C-Met)based on the Gene Expression Database(GEO).Methods Single-cell RNA sequencing(scRNA-seq)data of three PCa samples were obtained from the GSE153892 dataset of GEO,and MRGs were collected from the Genecards database and previous literature.The scRNA-seq data were processed and analyzed using the Seurat software package,including quality control,gene expression screening,cell type annotation,differentially expressed genes(DEGs)identification,and intersection analysis with MRGs.The transcriptome data of PCa and control samples were downloaded from the Cancer Genome Atlas Database(TCGA)-PRAD cohort,and differential expression analysis and copy number variation analysis were conducted.The non-negative matrix factorization algorithm is adopted to conduct cluster analysis on PCa samples to identify different PCa subtypes.A prognostic risk model based on intersection genes was constructed,and the predictive ability of the model was analyzed through Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic(ROC)curve analysis.Conduct independent prognostic analysis,construct a nomogram model based on risk scores and clinical characteristics,and evaluate its ability to predict patient survival rates.The possibility of immune infiltration and tumor immune escape in PCa samples was evaluated by using the single-sample Gene Set Enrichment analysis(ssGSEA)algorithm and the TIDE database.The relationship between intersection genes and C-Met expression was analyzed using Pearson correlation analysis.Results scRNA-seq data analysis identified five cell types including B lymphocytes,epithelial cells,monocytes,natural killer cells and T lymphocytes,and discovered the intersection genes that were highly expressed in different cell types.Through differential expression analysis,genes significantly related to the prognosis of PCa patients were screened out,and a prognostic risk model was constructed.Six genes such as ADH5 and CAT were retained through LASSO analysis.A diagnostic model was constructed and grouped.There was a significant difference in survival time between the two groups in the internal test set(P<0.05).ROC curve evaluation showed that the model had a good predictive ability for 1-,3-,and 5-year survival rates.The external test set verified that there was a statistically significant difference in the expression of intersection genes(P<0.05).Independent prognostic analysis identified T stage and risk score as independent prognostic factors.A nomogram model was constructed.Calibration curve and ROC curve analyses showed that the predictive ability of this model was superior to that of the simple risk model.ssGSEA analysis revealed differences in the abundance of immune cell inflammation and immune function scores between the two groups.Most immune cells,immune function,and risk scores were related to the modeling genes.There were significant differences in TIDE scores and multiple immune checkpoints between the high-risk and low-risk groups(P<0.05).BCAT2,DCXR,OGT and FUS were positively correlated with the expression of C-Met,while ADH5 and CAT were negatively correlated with the expression of C-Met(P<0.05).Conclusion The prognostic risk model based on intersection genes can effectively predict the prognosis of patients with PCa,and the risk score and T stage are independent prognostic factors for PCa.The correlation analysis of intersection genes and C-Met expression provides a new idea for the targeted therapy of PCa.

Objective To analyze the relationship between the expression levels of post-meiosis isolated protein 2(PMS-2)and p-glycoprotein(PGP)in gastric cancer tissues and clinicopathological characteristics,prognosis and immune function.Methods The clinical data of 100 patients with gastric cancer who visited the hospital from May 2018 to February 2022 were selected for retrospective analysis.All patients received radical surgical treatment.The expression levels of PGP and PMS-2 proteins in adjacent tissues and cancer tissues were determined by immunohistochemistry,and the correlations between the expression of PGP and PMS-2 proteins in cancer tissues and the clinicopathological characteristics and immune function of patients with gastric cancer were analyzed.The patients were followed up for 3 years after the operation to analyze the influencing factors of prognosis in patients with gastric cancer,as well as the correlation between the protein expressions of PGP and PMS-2 in cancer tissues and prognosis.Results The positive expression rates of PGP and PMS-2 proteins in cancer tissues were higher than those in adjacent tissues(P<0.05).Positive expression of PMS-2 and PGP protein was significantly associated with advanced clinical stage(stage Ⅲ),presence of lymph node metastasis,and poorer tumor differentiation(P<0.05).However,their expression showed no significant correlation with age,gender,Lauren classification,vascular invasion,or tumor diameter(P>0.05).The preoperative CD4+/CD8+levels of gastric cancer patients with positive expression of PMS-2 and PGP proteins were respectively lower than those of patients with negative expression of PMS-2 and PGP proteins(P<0.05).Cox multivariate regression analysis showed that clinical stage Ⅲ,degree of differentiation,distant metastasis,lymph node metastasis,positive expression of PMS2 protein,positive expression of PGP protein,and preoperative CD4+/CD8+were all influencing factors for the prognosis of patients with gastric cancer(P<0.05).After a 3-year follow-up,the survival curves of gastric cancer patients with negative expressions of PMS2 and PGP protein were respectively higher than those of patients with positive expressions of PMS-2 and PGP protein(P<0.05).Conclusion The expressions of PMS-2 and PGP proteins in gastric cancer tissues are closely associated with clinical stage,presence or absence of lymph node metastasis,degree of tumor differentiation,prognosis and preoperative CD4+/CD8+level.Moreover,patients with positive expressions of PMS-2 and PGP proteins have a worse prognosis.

Psoriasis is a chronic,inflammatory,recurrent,and systemic disease mediated by immune dysregulation,which is often accompanied by psychological issues such as depression and anxiety.Recent research on the gut microbiota and depression and anxiety has made significant progress,with studies demonstrating that the gut microbiota plays a crucial role in the pathogenesis of psoriasis.Dysbiosis of the gut microbiota may be an important comorbidity mechanism linking psoriasis with depression and anxiety.This article summarizes the changes in the abundance of gut microbiota in patients with psoriasis and those with depression and anxiety,as well as how the gut microbiota influences this comorbidity through neural pathways and immune-endocrine pathways.It aims to provide novel perspectives for the study of the comorbidity mechanisms and clinical treatment of psoriasis and depression and anxiety.In the future,targeting the gut microbiota may enable the development of personalized treatments.

Objective To investigate the clinical application value of detection of interleukin-6(IL-6),C reactive protein(CRP),and neutrophic-to-lymphocyte ratio(NLR)alone and in combination in the prognosis assessment of severe pneumonia(SP).Methods A total of 81 patients with SP admitted from December 2022 to December 2023 were selected as the research subjects.According to the discharge outcomes of the patients,they were divided into the survival group(n=62)and the death group(n=19).The general clinical data at admission and laboratory parameters of the two groups were collected and compared.The receiver operating characteristic(ROC)curve was used to analyze the value of serum IL-6,CRP and NLR detection in the prognosis assessment of SP.Results At admission,the pulse of the death group was higher than that of the survival group,while the systolic blood pressure(SBP)was lower than that of the survival group(P<0.05,P<0.01).The incidence of chest tightness in the death group at admission was significant higher than that in the survival group(P<0.05).Compared with the survival group,the number of lymphocyte counts and albumin levels in the death group were lower,while the percentage of neutrophils,NLR and procalcitonin were higher than those in the survival group(P<0.05,P<0.01).ROC curve analysis showed that the area under the curve(AUC)for predicting poor prognosis of SP by the combined detection of IL-6,CRP and NLR was 0.75,which was higher than that predicted by each indicator alone.Conclusion Compared with the detection of IL-6,CRP and NLR alone,the combined detection of the three has a more significant value in predicting the risk of death in patients with SP.It suggests that clinicians should promptly,comprehensively and dynamically monitor the above infection indicators during diagnosis and treatment,and take prompt and effective intervention measures to reduce the mortality rate of patients.

Objective To investigate the predictive efficacy of complete blood count(CBC)parameters for the prognosis of acute pancreatitis(AP),and to construct a machine learning model.Methods The clinical data of 120 patients with AP admitted from January 2021 to December 2024 were retrospectively analyzed.Based on the prognostic outcomes within 28 d of treatment,they were divided into the poor prognosis group and the good prognosis group.On the first day of admission,CBC parameters[red blood cell count,hemoglobin,hematocrit,white blood cell count,neutrophil count,lymphocyte count,monocyte count,red blood cell distribution width(RDW),platelet count,mean platelet volume,platelet distribution width,neutrophil/lymphocyte ratio(NLR),platelet/lymphocyte ratio(PLR),lymphocyte/monocyte ratio(LMR)were detected in the two groups.The general data and CBC parameters of the two groups were compared.The clinical variables were screened using the Lasso regression equation.Four models,namely Support Vector Machine(SVM),logistic regression(LR),deep neural network(DNN),and Random Forest(RF),were constructed for external validation.The predictive efficacy of the four models for the prognosis of AP was evaluated by using the receiver operating characteristic(ROC)curve,the precision-recall(PR)curve,the calibration curve and the clinical decision curve.Results The APACHE Ⅱ score,bedside severity index score,proportion of vasoactive drug use,and proportion of severe hypoproteinemia in the poor prognosis group were all higher than those in the good prognosis group(P<0.01).The levels of RDW,NLR and PLR in the poor prognosis group were all higher than those in the good prognosis group,while the level of LMR was lower than that in the good prognosis group(P<0.01).The Lasso regression equation ultimately screened out four non-zero coefficient variables:NLR,RDW,APACHE Ⅱ score,and severe hypoproteinemia.Based on the above variables,SVM,LR,RF and DNN machine learning models were constructed.The RF model had the highest area under the ROC curve(AUC),PR AUC,accuracy rate and F1 score for predicting the prognosis of AP,and had the optimal comprehensive performance.The calibration curve showed that the curve of the RF model for predicting the prognosis of AP was relatively close to the ideal curve.The decision curve showed that when the threshold probability value of the RF model was 15%to 100%,it had a significance clinical net benefit rate.External validation also showed that the RF model had the optimal predictive efficacy.The calibration curve indicated that the predictive curve of the RF model for the prognosis of AP highly coincided with the actually observed curve.The decision curve showed that the RF model provided clinical net benefits to patients across the decision threshold range of 0 to 100%.Conclusion Machine learning models constructed based on CBC parameters can make relatively accurate predictions about the prognosis of AP.Among them,the RF model has the optimal predictive efficiency,which can be used as an auxiliary tool for clinical prediction of AP prognosis,and can also provide reference for clinical treatment.

Objective To analyze the clinical distribution,drug resistance characteristics,molecular prevalence,and impact of immunocompromised status on the infection rate of carbapenem-resistant Enterobacteriaceae(CRE)isolated from pediatric respiratory tract samples(sputum,bronchoalveolar lavage fluid).Methods A retrospective analysis was conducted on clinical data of hospitalized children from 2019 to 2023.A total of 1 235 non-repetitive strains of Enterobacteriaceae bacteria were obtained from pediactric respiratory tract samples.Drug susceptibility testing,multilocus sequencing typing(MLST),and resistance-related gene sequencing were performed on 100 isolated CRE strains,to study the clinical distribution,drug resistance characteristics,and molecular prevalence of CRE,and to further analyze the impact of immunocompromised status on the respiratory CRE infection rate in children.Results From 2019 to 2023,the detection rate of CRE in 1 235 strains of Enterobacteriaceae bacteria was 8.10%(100/1 235).Among them,51.0%(51/100)of CRE were isolated from the intensive care unit(ICU),of which 33.0%(33/100)were isolated from the Surgical ICU,18.0%(18/100)of CRE was isolated from the Medical ICU;32.0%(32/100)of CRE were isolated from Department of Neonatology,with the majority(74.0%)isolated from infants under 6 months of age.Of all pediatric patients,85.0%recovered and were discharged after treatment.Immunocompromised status was identified as an independent risk factor for CRE infection.Among 100 strains of CRE,Carbapenem-resistant Klebsiella pneumoniae(CRKP)was the most commonly detected strain,accounting for 88.0%(88/100),followed by Escherichia coli at 6.0%(6/100)and Enterobacter cloacae at 4.0%(4/100).CRE strains were highly resistant to carbapenems and cephalosporins,with prevalent resistance to amikacin,ciprofloxacin,and levofloxacin.However,their resistance rates were relatively low to tigecycline,colistin,minocycline,ceftazidime/avibactam,meropenem/vaborbactam,and imipenem/relebactam.The screening results of carbapenem resistance genes showed that blaKPC-2 was the most prevalent gene(74.0%),followed by blaNDM-1(14.0%)and blaNDM-5(11.0%).Molecular typing showed that ST11 type CRE was the dominant type,comprising 72.0%(72/100)and was the primary epidemic clone.Conclusions CRKP is the most prevalent CRE strain isolated from pediatric respiratory tract samples,primarily identified in the ICU,Department of Neonatology,and among infants under 6 months of age.Immunocompromised status is an independent risk factor for respiratory CRE infection in children.CRE generally has high resistance to antibacterial drugs,with blaKPC-2 being the dominant resistance genotype,and ST11 as the predominant multilocus sequence type.Clinical management should account for these characteristics to implement timely interventions and rational therapeutic strategies.