Objective To identify the key biomarkers for diagnosing chronic obstructive pulmonary disease(COPD)complicated with pulmonary arterial hypertension(PAH)using bioinformatics,and validate their clinical significance.Methods High-throughput sequencing data analysis was employed to identify differentially expressed genes(DEGs)in COPD-PAH.Functional enrichment analysis was then conducted to explore the biological functions of these DEGs.Machine learning methods,including least absolute shrinkage and selection operator(LASSO),random forest(RF),and support vector machine-recursive feature elimination(SVM-RFE),were utilized to screen 5 potential biomarkers.Single-cell analysis was performed to reveal the expression patterns of these key genes in macrophages.The clinical significance of these biomarkers was further validated using peripheral blood mononuclear cells(PBMC)data.A mouse model of COPD-PAH was established using hypoxia exposure.Sixteen mice(either sexes,8 weeks old,weighing 20～22 g)were randomly divided into a hypoxia group[O2(10.0±0.5)%,COPD-PAH,n=8]and a normoxia group(COPD,n=8).Immunofluorescence assay was used to label the key biomarkers,and their expression levels were quantified.Results A total of 28 DEGs(|Log2FC|≥2,P<0.05)were identified in COPD-PAH patients.Functional enrichment analysis indicated that DEGs in COPD were primarily associated with major histocompatibility complex(MHC)Ⅱ and cell division,and involved in lysosomes,oxidative phosphorylation,and cell cycle pathways(P<0.05).Machine learning identified 5 potential biomarkers(GRN,KLF4,SHTN1,LRP1,and GPNMB),and subsequent single-cell analysis revealed that these markers exhibited reverse expression patterns during disease progression.A nomogram model constructed based on PBMC data yielded an area under the curve(AUC)of 0.907 in diagnosing COPD-PAH.GRN,KLF4,SHTN1,LRP1 and GPNMB were significantly upregulated in the COPD-PAH group(P<0.05).Conclusion GRN,KLF4,SHTN1,LRP1 and GPNMB are identified as key biomarkers for the prediction and diagnosis of COPD-PAH,which providing new insights for the clinical and treatment of the condition.

Proteolysis-targeting chimeras (PROTACs) have emerged as a promising therapeutic strategy for targeted protein degradation. However, the clinical application of PROTACs may be hindered by off-target toxicity resulting from non-tissue-specific protein degradation and ingenious prodrug strategies may open new avenues to addressing this concern. Herein, we propose a light-induced positive feedback strategy to use photodynamic therapy (PDT) to improve the activation efficiency of PROTAC prodrugs, monitor PROTAC release, and combine PROTAC to induce tumor cell apoptosis. In the hypoxic tumor microenvironment, the azo bond in AZO-PRO selectively cleaves, triggering the release of the potent protein degrader PRO and the multifunctional photosensitizer. Once activated, the fluoresce signal of the photosensitizer dramatically recovers, allowing monitoring of prodrug activation. Additionally, upon irradicating the tumor site using near-infrared (NIR) laser, PDT exacerbates tumor hypoxia, further promoting AZO-PRO activation. Our work introduces a novel approach to efficiently track and activate PROTAC prodrugs, enhance their antitumor efficacy, and mitigate off-target systemic toxicity.

Objective To explore the risk factors of adverse pregnancy outcomes in the patients with cervical incompetence(CI),and to establish a risk warning model of adverse pregnancy outcomes in CI pa-tients based on decision tree model.Methods The clinical data of 159 patients with CI admitted and treated in this hospital from February 2022 to April 2023 were retrospectively analyzed,and the risk factors for adverse pregnancy outcomes were screened and the decision tree model for postoperative adverse pregnancy outcomes was constructed.The internal verification method was 5-fold cross-validation.Results The incidence rate of adverse pregnancy outcome was 22.64%.The pregnant weeks of cervical cerclage,amniotic cystocele,multiple cervical cerclage,preoperative cervical length and amniotic fluid sediment were all influential factors for ad-verse pregnancy outcome occurrence(P＜0.05).The amniotic fluid sediment was the most important factor affecting the postoperative adverse pregnancy outcome in CI patients,and the preoperative cervical length had little influence on the postoperative adverse pregnancy outcomes in CI patients.The area under the curve(AUC)value of logistic regression model was slightly higher than that of the decision tree model.The accura-cy rate of the 5-fold cross-validation model was 78.3%.Conclusion During clinical treatment,the above two models can be combined to find the influencing factors of postoperative adverse pregnancy outcomes in CI pa-tients from different aspects,and provide references for clinical medical staff to evaluate the disease condition of CI patients and formulate the intervention plans.

Objective:To analyze the biological characteristics, phylogeny and the taxonomic status of strain 7712 (=CGMCC 1.17031=NBRC 113783=KCTC 15766) isolated from a clinical blood sample.Methods:Strain 7712 was identified by the cultural properties, cellular and colonial morphology, physiological and biochemical reactions, matrix-assisted laser desorption ionization time-of-flight mass spectrometry system, and genome correlation index analysis. The genomic phylogenetic tree was construct to analyze the taxonomic position. The virulence factors and resistance genes of strain 7712 and related strains were then compared by the online virulence factor database and online comprehensive antibiotic research database respectively.Results:Strain 7712 was urease negative, gram-negative nonfermenters, which was identified as Ochrobactrum anthropi by VITEK GN card. The 16S rRNA gene analysis showed that the strain was closely related to the members of genera Ochrobactrum and Brucella. The phylogenetic tree showed that strain 7712 was clustered together with Ochrobactrum teleogrylli LCB8 T and Ochrobactrum haematophilum CCUG 38531 T, along with genus Brucella and other Ochrobactrum species. The genome relatedness indexes analysis showed that the average nucleotide identity between strain 7712 and Ochrobactrum teleogrylli LCB8 T was 98.16%, which was higher than the threshold for prokaryotic species. Genetic prediction showed that strain 7712 carried several virulence-related genes and resistance-related genes, of which the existence of OCH gene might be responsible to the resistance to cephalosporin. Conclusions:A case of human infection caused by Ochrobactrum teleogrylli is identified, which would help promote the understanding of biodiversity of genus Ochrobactrum.

Objective:Analysis of surgical strategies for atrial functional mitral regurgitation with atrial fibrillation.Methods:Retrospective analysis of 112 patients with mitral regurgitation and atrial fibrillation between June 2017 and January 2023. Among them, 56 cases were severe atrial functional mitral regurgitation with atrial fibrillation, and the other 56 cases were degenerative mitral regurgitation with atrial fibrillation. All patients underwent maze Ⅳ procedure and mitral valve surgery. Follow up will be conducted through outpatient follow-up and telephone calls. The condition of postoperative mitral valve is obtained through echo. The postoperative cardiac rhythm is based on the patient's conscious symptoms, electrocardiogram, 24 hour dynamic electrocardiogram.Results:The comparison of preoperative basic data shows that the age, duration of atrial fibrillation, and comorbidity of patients with atrial functional mitral regurgitation are significantly higher than those in the degenerative mitral regurgitation group. All patients successfully completed the surgery. Postoperative death occurred in 2 cases in the atrial mitral regurgitation group. The causes of death were ARDS and pulmonary infection, respectively. The main postoperative complications include bleeding, low cardiac output, pulmonary infection, and acute kidney injury. During follow-up, 43 patients (79.6%) in the atrial mitral regurgitation group maintained sinus rhythm, while 49 patients (87.5%) in the degenerative group. However, there was no statistically significant difference in the Kaplan- Meier curves. In the atrial mitral regurgitation group, there were 47 cases with no mitral regurgitation, 4 cases with mild regurgitation, and 1 case with moderate regurgitation. In the degenerative group, there were 42 cases with no mitral regurgitation, 6 cases with mild regurgitation, 1 case with moderate regurgitation, and 1 case with severe regurgitation. The risk for atrial fibrillation recurrence in the atrial mitral regurgitation is related to postoperative left atrial diameter greater than 50 mm, while in the degenerative group, atrial fibrillation recurrence is related to postoperative left atrial diameter greater than 50 mm and residual mitral regurgitation. Conclusion:Mitral valve repair combined with maze Ⅳ procedure is an effective treatment for patients with severe atrial functional mitral regurgitation and atrial fibrillation. Further improving the success rate of atrial fibrillation and reducing surgical trauma will benefit patients in the future.

Objective:To the investigate the predictive value of preoperative systemic inflammatory response index (SIRI) for postoperative clinical outcome in patients with spontaneous intracerebral hemorrhage (ICH) in basal ganglia region.Methods:Patients with ICH in basal ganglia region underwent surgical treatment at the Department of Neurosurgery, the Affiliated Hospital of Qingdao University from January 2015 to December 2021 were retrospectively included. At 3 months after surgery, the modified Rankin Scale was used to evaluate the clinical outcome, with a score of 0-2 defined as good outcome and >2 defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent correlation between SIRI and poor outcome in patients with ICH. Receiver operating characteristic (ROC) curve analysis was used to identify the predictive value of SIRI. Results:A total of 258 patients with ICH in basal ganglia region underwent surgical treatment were enrolled, including 176 males (68.22%), aged 57.00 years (interquartile range, 49.00-65.25 years); median hematoma volume was 50.00 ml (interquartile range, 40.00-70.00 ml), and median SIRI was 4.12 (interquartile range, 2.28-7.30); 143 patients (55.43%) had poor outcome. Multivariate logistic regression analysis showed that older age (odds ratio [ OR] 1.070, 95% confidence interval [ CI] 1.030-1.111; P<0.001), lower Glasgow Coma Scale score ( OR 0.669, 95% CI 0.575-0.779; P<0.001), higher platelet count ( OR 1.010, 95% CI 1.003-1.017; P=0.004), and higher SIRI ( OR 1.434, 95% CI 1.255-1.638; P<0.001) were the independent predictors of poor outcome. ROC curve analysis showed that the area under the curve for predicting poor outcome by SIRI was 0.791 (95% CI 0.737-0.845; P<0.001), with an optimal cutoff value of 4.53. The predictive sensitivity and specificity were 67.8% and 81.7%, respectively. Conclusion:Preoperative SIRI can effectively predict the clinical outcome of patients with ICH in basal ganglia area at 3 months after surgery, and SIRI >4.53 indicates poor outcome.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.