Objective To explore the molecular mechanism of Guben Zhike Pingchuan Granules in treating cough variant asthma(CVA)through network pharmacology and molecular docking technology;To use CVA model rats for validation;To provide a basis for the basic research and clinical application of Guben Zhike Pingchuan Granules.Methods TCMSP and BATMAN-TCM databases were used to retrieve the active components and corresponding targets of Guben Zhike Pingchuan Granules,and CVA disease targets were screened using OMIM,GeneCards,DrugBank,PharmGKB databases to obtain drug disease intersection targets.Cytoscape 3.10.1 software was used to construct the drug-component-target network and screen the key components;STRING database was used to construct protein-protein interaction(PPI)network and screen core targets;GO and KEGG enrichment analysis was conducted using DAVID platform;AutoDock Vina software was used to conduct molecular docking on the core targets and key components with high degree value respectively.CVA rat model was established by smoking combined with intraperitoneal and subcutaneous multi-point injection of ovalbumin.The rats were randomly divided into blank group,model group,montelukast sodium tablets group,Guben Zhike Pingchuan Granules low-and high-dosage groups.The groups received corresponding medicine for 15 d.HE staining was used to observe the morphology of lung tissue;ELISA was used to detect the contents of serum interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α);immunohistochemistry was used to detect the positive expressions of AKT,EGFR and NFKB1 in lung tissue.Results A total of 9 996 active components and 1 119 potential targets of Guben Zhike Pingchuan Granules,2 740 CVA targets,467 drug and disease intersection targets were screened out;PPI network topology analysis showed that AKT1,STAT3,EGFR,NFKB1 and MTOR were the core targets;the results of enrichment analysis showed that Guben Zhike Pingchuan Granules played an anti-inflammatory role in the treatment of CVA mainly through the interaction of EGFR/PI3K-Akt/NF-κB signaling pathway;molecular docking showed good binding ability between the core targets and key components,with a binding energy of<-7.0 kcal/mol for EGFR and Quercetin.Animal experiment results showed that after intervention with Guben Zhike Pingchuan Granules,the alveolar walls of the lung tissue in the model rats narrowed,the size of the alveoli became uniform,lymphocyte infiltration improved significantly,bronchioles contracted,and mucus in the lumen decreased;compared with the model group,the serum contents of IL-1β and TNF-α decreased in Guben Zhike Pingchuan Granules low-and high-dosage groups and montelukast sodium tablets group,and the positive expressions of AKT,EGFR and NFKB1 in lung tissue decreased(P<0.05,P<0.01).Conclusion Guben Zhike Pingchuan Granules may mediate the inflammatory response through the EGFR/PI3K-Akt/NF-κB signaling pathway,significantly improve the structural damage of CVA lung tissue,inhibit inflammatory cell infiltration,down-regulate the expressions of inflammatory factors,and thus exert therapeutic effects on CVA.

Objective To investigate the correlation between platelet-to-albumin ratio(PAR)and occurrence of cerebral infarction after left atrial appendage closure(LAAC)in patients with non-valvular atrial fibrillation(NVAF).Methods A retrospective study was conducted on 259 NVAF patients undergoing LAAC in our department between 2019 and 2023.According to occurrence of cerebral infarction after LAAC or not,they were divided into a control group(241 cases)and a study group(18 cases).Their general data were collected,and Cox proportional hazards regression model was used to identify the risk factors for cerebral infarction.ROC curve was plotted to assess the predictive value of PAR for cerebral infarction in NVAF patients after LAAC,and the AUC value was calculated.Kaplan-Meier survival curve was drawn to analyze the incidence of cerebral infarction after LAAC in NVAF patients with different PAR values.Results The study group had significantly advanced age,higher SBP at admission,increased WBC,neutrophil,monocyte and platelet counts,longer thrombin time,elevated international normalized ratio(INR)and high-sensitivity C-reactive protein(hs-CRP)level,and higher PAR than the control group(P＜0.05,P＜0.01).Multivariate Cox regression analysis showed that PAR(HR=2.286,95％CI:1.182-4.420,P＜0.05)was an independent risk factor for cerebral infarction in NVAF patients after LAAC.ROC curve indicated that the AUC value of PAR in predicting cerebral infarction after LAAC in NVAF patients was 0.721(95％CI:0.586-0.856,P＜0.01),with an optimal cut-off value of 4.137,a sensitivity of 66.39％,and a specificity of 77.78％.Kaplan-Meier survival curve revealed that the higher the PAR value was,the higher the risk of cerebral infarction was(P＜0.01).Conclusion PAR is significantly correlated with cerebral infarction in NVAF patients after LAAC.The higher the PAR,the higher the risk of cerebral infarction,demonstrating its predictive value and being worthy of clinical promotion.

Very-late-onset schizophrenia-like psychosis(VLOSLP)is considered the most common mental disorder in the elderly following dementia and depression, and its clinical symptomatology is different from that of schizophrenia with onset around the average age.The diagnostic classification system and prognosis of VLOSLP are very complicated, and it is still controversial whether it should be classified as a prodromal symptom of dementia or as a type of late-onset schizophrenia.This article reviewed studies concerning the epidemiology, clinical features, diagnosis, prognosis, and neuroimaging of VLOSLP, hoping to provide value as a reference for future clinical research and treatment.

Objective:This study sought to examine the clinicopathological features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and to discuss its differential diagnosis.Methods:A total of 36 MEITL cases, collected between June 2015 and January 2024 from the Fourth Affiliated Hospital of Soochow University and the First Affiliated Hospital, College of Medicine, Zhejiang University, were analyzed. Patients underwent immunohistochemistry, in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER), and T-cell receptor (TCR) gene rearrangement testing. Clinical data, laboratory results, and follow-up information were collected for correlation analysis.Results:The cohort included 36 patients (20 males and 16 females) aged 17-76 years (median: 57 years). Tumors outside the intestine were observed in 22 cases (61%). A total of 32 patients (89%) underwent surgical intervention and/or chemotherapy, and one patient received auto-HSCT. The median follow-up duration was 11.5 months (range: 8-73 months), with a median overall survival of 6 months (range: 1-67 months) ; 34 patients died during the follow-up period. Morphologically, nine cases (25%) exhibited significant pleomorphism. Immunohistochemical analysis revealed that high expression levels of both P53 and c-Myc were correlated with atypical morphology ( P=0.003 and P=0.016, respectively). Notably, patients with high P53 expression had significantly shorter survival times than those with low P53 expression ( χ2=4.922, P=0.027), whereas survival did not differ significantly based on c-Myc expression levels ( χ2=0.034, P=0.854). Furthermore, a PD-L1 CPS score ≥10 was observed in 22 cases (68.8%). Scattered EBER positivity in background cells was identified in four cases. All tested cases (17/17, 100.0%) showed clonal TCR gene rearrangements. Conclusions:MEITL is a rare but highly aggressive lymphoma with distinct clinical and pathological features. A subset of cases may exhibit atypical morphological patterns, complicating the diagnostic process. Improving awareness of this neoplasm is helpful for early and precise diagnosis as well as the estabolishment of novel therapy regimen.

Objective:To identify risk factors influencing clinical efficacy of endoscopic resection of small rectal neuroendocrine tumor (NETs).Methods:A retrospective analysis was conducted on patients with rectal NETs ≤10 mm who underwent endoscopic resection from 2013 to 2022. Patients were divided into the endoscopic submucosal dissection (ESD) group and the endoscopic mucosal resection with ligation (EMRL) group according to the treatment methods. After comparing the baseline data, propensity score matching was performed to compare the rates of R1 resection and adequacy of vertical margin distance.Results:A total of 186 patients were included in this study, with 139 receiving ESD and 47 receiving EMRL. The R1 resection rates were 12.2% (17/139) and 2.1% (1/47) in the ESD and EMRL group, respectively ( χ2=3.027, P=0.082). A significant difference in vertical margin adequacy was observed between the two groups [69.1% (96/139) VS 85.1% (40/47), χ2=4.598, P=0.032]. After propensity score matching, 46 pairs of cases were included, and there were no significant differences in the R1 resection rate [6.5% (3/46) VS 2.2% (1/46), χ2=0.261, P=0.609] and vertical margin adequacy [78.3% (36/46) VS 84.8% (39/46), χ2=0.649, P=0.420] between the two groups. Univariate and multivariate Logistic regression analyses revealed that operator experience and preoperative biopsy were independent risk factors for inadequate margin. Conclusion:Treatment method may not be the key factor affecting the distance of the vertical margin after endoscopic resection, but preoperative biopsy and operator experience have a significant impact on margins. Biopsy before endoscopic resection should be avoided, and less experienced doctors are recommended to use EMRL method for small NETs due to its ease of execution.

Objective To investigate necroptosis-related diagnostic biomarkers of bronchopulmo-nary dysplasia(BPD)and their relationships with the immune microenvironment through the analysis of necroptosis-related genes(NRGs)in BPD.Methods The dataset GSE32472 was downloaded from the Gene Expression Omnibus(GEO)database,and NRGs were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Cards databases.Differentially expressed necroptosis-related genes(DE-NRGs)were screened,and their biological functions and pathways were explored through functional enrichment analysis.Machine learning algorithms,inclu-ding least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE),were applied to screen feature genes.The Cell-type Ⅰdentification By Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression Data(ESTIMATE)algo-rithm were used to explore the immune infiltration characteristics of BPD.Spearman correlation anal-ysis between feature genes and immune cells was performed using the"corrplot"package in R lan-guage.Results A total of 19 DE-NRGs were identified.The main biological functions and path-ways of DE-NRGs included the regulation of necroptosis and inflammatory responses.Three feature genes,namely flotillin-2(FLOT2),CASP8 and FADD-like apoptosis regulators(CFLAR),and charged multivesicular body protein 7(CHMP7),were further screened to construct a nomogram.In the validation sets GSE8586 and GSE188944,the area under the curve(AUC)values were all greater than 0.7.CIBERSORT analysis revealed that BPD group presented a higher proportion of naive B cells,neutrophils,eosinophils and resting mast cells compared to control group(P＜0.05).Meanwhile,the proportion of CD8+T cells,CD4+naive T cells,CD4+resting memory T cells,regulatory T cells,resting natural killer(NK)cells,M0 macrophages,M2 macrophages and activated dendritic cells was lower than that in the control group(P＜0.05).ESTIMATE analysis showed that the stromal score in the BPD group was higher than that in the control group,while the immune score was lower,with statistically significant differences(P＜0.05).Correlation analysis between the three feature genes and ESTIMATE scores indicated that FLOT2 and CFLAR were posi-tively correlated with the stromal score and negatively correlated with the immune score,whereas CHMP7 was positively correlated with the immune score and negatively correlated with the stromal score.Conclusion The three necroptosis-related feature genes can serve as diagnostic biomarkers for BPD-related necroptosis,with high diagnostic efficacy.They may play an important roles through immune mechanisms,providing new insights and theoretical references for the early diagnosis and immune intervention of BPD.

Catheter-based percutaneous coronary intervention has become a crucial approach for treating obstructive coronary artery disease and is widely applied in clinical practice.Although the new generation of drug-eluting stents(DES)has significantly reduced the incidence of post-procedur-al restenosis and improved long-term clinical outcomes,in-stent restenosis(ISR)remains one of the key challenges affecting the long-term efficacy of percutaneous coronary intervention.Recent studies have demonstrated that DES still have certain inherent limitations.From the metallic stent platform,drug coating to the polymer carrier,each component may exert varying degrees of biological effects on the vascular intima.Optical coherence tomography(OCT),as a high-resolution intravascular imaging technique,has shown significant value in the mechanism research,etiological diagnosis,and clinical classification of ISR.It can clearly identify the tissue composition and morphological characteristics of ISR,providing a precise basis for the formulation of individualized treatment strategies.This review aimed to systematically search the existing literature,comprehensively review the clinical and patho-logical features of ISR after DES implantation,focus on the OCT-based ISR classification system,and summarize the current treatment strategies and latest advances for ISR.

Objective To determine the pathogenicity of a novel mutation(c.109_111del)in DKC1 gene of an adult patient,and to analyze the clinical phenotype,immunophenotype and telomere length,so as to provide clues for early clinical identification and diagnosis.Methods The clinical data and peripheral blood samples of the patient were collected for genetic testing and family analysis.The lymphocyte subsets of the patient were detected by Flow cytometry,and the telomere length of the patient and healthy controls were detected by Flow-FISH.Results The main clinical manifestations of the patient were mucocutaneous triad,bone marrow failure and infection.The telomere length of lymphocytes in the patient was significantly shorter than that of healthy controls of the same age,and the absolute value and percentage of lymphocyte subsets were abnormal.Conclusion The clinical manifestations of DC patients are diverse.Flow-FISH detection of telomere length is helpful for early diagnosis of DC patients.

Diamond-Blackfan anemia(DBA),also known as congenital pure red cell aplasia,is a rare genetic disorder characterized by bone marrow failure,congenital anomalies,and severe red blood cell abnormalities.The rarity of the condition,and consequently limited patient pool and scarcity of research models,means that the pathogenic mechanisms associated with genetic mutations in DBA remain uncertain,and the clinical treatment options are limited.This review synthesizes the findings from zebrafish,mouse,and human cellular models of DBA mutations.We clarify the pathogenic mechanisms and monitor the progression of drugs into clinical trials,thereby aiding further in-depth explorations into the etiology and therapeutic advancements for DBA.

Objective:To investigate the effects of C-reactive protein(CRP)and fibrinogen(FIB)on activated partial thromboplastin time(APTT)and anti Xa activity in extracorporeal membrane oxygenation(ECMO)patients.Methods:The clinical data of 33 patients undergoing ECMO support treatment at Guangxi Zhuang Autonomous Region People's Hospital from January 2024 to July 2024 were retrospective analysis.Patients undergoing ECMO support treatment were divided into low-CRP group and high-CRP group.FIB,APTT and anti-Xa activity between low-CRP group and high-CRP group were compared.The correlation between APTT and anti-Xa activity in low-CRP group and high-CRP group were analyzed by Pearson method.Results:The APTT levels in the high CRP group was higher than that in the low CRP group(P＜0.05).There was no statistically significant difference in anti Xa activity between the low CRP group and the high CRP group(P＞0.05).The FIB levels in the high CRP group was higher than that in the low CRP group(P＜0.05).The correlation between APTT and anti-Xa activity in the low-CRP group was positively correlated(r=0.698,P＜0.05),while the correlation between APTT and anti-Xa activity in the high-CRP group was positively correlated(r=0.650,P＜0.05),there was no strong in the correlation between APTT and anti-Xa activity between the low-CRP group and high-CRP group.Conclusion:Abnormal elevation of CRP levels can affect the detection of APTT in patients undergoing ECMO supportive therapy,but does not affect the detection of anti-Xa activity.The correlation between APTT and anti-Xa activity is not strong,so multiple monitoring indicators should be combined to comprehensively evaluate the anticoagulant efficacy of heparin.