OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） combined with neoadjuvant chemotherapy in the treatment of early triple-negative breast cancer （TNBC）. METHODS Randomized controlled trials （RCTs） comparing ICIs combined with neoadjuvant chemotherapy （experimental group） versus neoadjuvant chemotherapy alone （control group） were retrieved from PubMed， Cochrane Library， Embase， Web of Science， CNKI， Wanfang Data， and VIP databases， as well as relevant studies published at oncology academic conferences. The search period was from database inception to June 30， 2025. After literature screening， data extraction， and quality assessment， a meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 6 RCTs involving 3 786 patients were finally included. The meta-analysis results showed that the experimental group had superior event-free survival [HR＝0.73， 95%CI （0.62， 0.85）， P＜0.000 1]， overall survival [HR＝0.69， 95%CI （0.57， 0.84）， P＝0.000 3]， and pathological complete response （pCR） [OR＝1.57， 95%CI （1.37， 1.80）， P＜0.000 01] compared to the control group. The incidence of ≥grade 3 adverse event （AE）， severe AE （SAE）， and ≥ grade 3 immune-related adverse event （irAE） in the experimental group was significantly higher than that in the control group. There was no statistically significant difference between the two groups in the incidence of any AE or any irAE （P＞0.05）. Subgroup analysis revealed that， regardless of programmed cell death ligand 1 expression status （negative or positive），the pCR in the experimental group was significantly higher than that in the control group （P＜0.05）. Additionally， the pCR of the patients with positive lymph nodes in the experimental group was significantly higher to that in the ontrol group （P＜0.05）. There was no statistically significant difference in pCR between the two groups with negative lymph nodes （P＝0.09）. CONCLUSIONS ICIs combined with neoadjuvant chemotherapy can significantly improve event-free survival and overall survival in patients with TNBC， providing patients with long-term survival benefits. However， the risk of ≥ grade 3 AE， SAE and ≥ grade 3 irAE has increased.

Hepatic fibrosis is not only a pathological process of hepatic self-repair after chronic liver injury， but also a critical stage in the progression of chronic liver disease to liver cirrhosis. Studies have shown that as a pro-inflammatory form of programmed cell death， pyroptosis plays an important role in various diseases and is also considered a potential therapeutic target for hepatic fibrosis. This article systematically reviews the association of pyroptosis in hepatocytes， hepatic stellate cells， and hepatic macrophages with hepatic fibrosis and discusses pyroptosis-mediated therapeutic strategies targeting hepatic fibrosis.

Objective To investigate the impact of holiday effects and prevention/control measures on the development characteristics and incidence trends of influenza in Hefei City using a Prophet-LSTM hybrid model, and to validate the applicability of the Prophet-LSTM model in influenza prediction by comparing the performance of different forecasting models. Methods Influenza incidence data from Hefei City (2016–2024) were collected to construct a Prophet-LSTM feature analysis and prediction model to analyze the impact of holiday effects and intervention measures on influenza incidence trends. Comparative models (ARIMA, GRU, and TimeGPT) were established and evaluated on the same test set. Results The data analysis revealed significantly increased influenza incidence during holidays (e.g., New Year's Day, Spring Festival, and National Day), while prevention and control measures led to declining trends. The Prophet-LSTM model demonstrated high consistency between the predicted and actual values, outperforming the comparative models with superior MAE (0.209), MSE (0.195), and IA (0.914), indicating higher prediction accuracy and trend-fitting capability. Conclusion The Prophet-LSTM model effectively captures spatiotemporal characteristics of influenza incidence, exhibits enhanced predictive performance when incorporating holiday effects and intervention measures, and demonstrates significant advantages and application value in influenza forecasting.

OBJECTIVE To establish a method for simultaneous determination of plasma concentration of lamotrigine（LTG）， levetiracetam（LEV） and perampanel（PER） in children with epilepsy and apply this method in clinical practice. METHODS Plasma proteins were precipitated with acetonitrile. Using PER-D 5 as internal standard， ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method was adopted. The determination was performed on ACQUITY UPLC HSS T3 C 18 column with mobile phase consisted of 0.1% formic acid with 5 mmol/L ammonium acetate-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and sample size was 5 μL. The analysis time was 5 min. The electrospray ionization source and multiple reaction monitoring mode were used for positive ion scanning. The ion pairs used for quantitative analysis of LTG， LEV， PER and internal standard were m / z 255.9→144.9， m / z 171.1→126.1， m / z 350.1→219.0 and m / z 354.9→220.2， respectively. The steady-state trough concentrations of the aforementioned drugs in the plasma of 14 pediatric epilepsy patients receiving combination therapy were determined using the same UPLC-MS/MS method as above. RESULTS The linear ranges of LTG， LEV and PER were 0.15-24 μg/mL （ R 2 ＞0.993）， 0.312 5-50 μg/mL （ R 2 ＞0.997） and 6.25-1 000 ng/mL （ R 2 ＞0.997）， respectively. The lower limits of quantification were 0.15 μg/mL， 0.312 5 μg/mL and 6.25 ng/mL， respectively. RSDs of intraday and interday precision tests of the three drugs were no more than 9.83%， and the accuracies （relative errors） were between －9.33% and 13.72%（ n ＝6 or n ＝18）； the average extraction recovery rates were 86.4%-97.9%， and the average matrix effects were 86.9%-110.0% （ n ＝6）. The absolute values of the relative errors in the stability tests were all below 15%. The steady-state trough concentrations of LTG， LEV and PER were （5.64±4.03）μg/mL， （10.67±8.78）μg/mL and（450.20±251.27）ng/mL， respectively； the rates of achieving target trough concentrations were 71.4%， 37.5% and 84.6%， respectively. CONCLUSIONS The established UPLC-MS/MS method is specific， rapid and suitable for the plasma concentration monitoring in epileptic children receiving combination therapy.

Primary biliary cholangitis （PBC） is a cholestatic autoimmune liver disease characterized by the injury of small intrahepatic bile ducts， and at present， the pathogenesis of PBC remains unclear. Recent studies have shown that bile acid metabolism disorder and gut microbiota imbalance play a key role in the development and progression of PBC， and they form a complex and dynamic interaction network via the “gut-liver axis” and regulate core physiopathological processes such as immune response， metabolic homeostasis， and inflammatory response in a synergistic manner. This article systematically elaborates on the abnormal features of bile acid metabolism and gut microbiota in PBC， discusses their synergistic mechanisms in PBC， and then proposes a combined strategy of targeting bile acid receptors and modulating gut microbiota， in order to overcome the limitations of current treatment modalities and provide new insights and directions for the clinical management of PBC.

Objective To investigate the expression characteristics of the transcription factor E2F2 in clear cell renal cell carcinoma (ccRCC), its impact on patient prognosis, and its potential role in the tumor immune microenvironment, with validation using clinical samples and functional assays. Methods RNA sequencing data and clinical information of ccRCC patients were obtained from the TCGA database; GSE53757 and GSE66272 datasets were downloaded from the GEO database as external validation cohorts. The expression difference of E2F2 between ccRCC tissue and normal tissue was compared, and the relationship between E2F2 expression and clinical pathological characteristics was analyzed. Kaplan-Meier (KM) survival analysis with log-rank test was performed to evaluate the effects of E2F2 on overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The prognostic efficacy of E2F2 in predicting 1-, 3- and 5-year survival was evaluated using receiver operating characteristic (ROC) curve. GSEA was performed to identify E2F2-related signaling pathways, and the ESTIMATE and CIBERSORT algorithms were used to assess the relationship between E2F2 expression level and tumor immune cell infiltration and immune microenvironment. Twenty pairs of surgically resected and pathologically confirmed ccRCC tissues and matched adjacent non-tumor tissues were collected from our hospital, and immunohistochemistry (IHC) was performed to detect the protein expression of E2F2. Human ccRCC cell line 786-O was used for functional assays;shRNA was used to knock down E2F2 expression (constructing stable shE2F2#1 and shE2F2#2 cell lines), and qRT-PCR and Western blot were performed to verify knockdown efficiency, followed by MTT, colony formation, and Transwell migration assays to evaluate the effects of E2F2 on the biological behaviors of ccRCC cells. Results E2F2 was significantly upregulated in ccRCC tissues (the same results in the verification set). Higher E2F2 expression was associated with advanced histological grade, clinical stage and higher TNM classification (P＜0.05). KM analysis showed that patients in the E2F2 high-expression group had worse OS, PFS, and DSS (P=0.019, 0.036, ＜0.001); the ROC curves showed area under the curve (AUC) of E2F2 of predicting 1-, 3- and 5- year survival of ccRCC patients were 0.844, 0.851 and 0.815, respectively. GSEA revealed that the E2F2 low-expression group was enriched in multiple metabolism-related pathways, whereas the E2F2 high-expression group was associated with immune-related pathways. Immune analysis demonstrated that high E2F2 expression was associated with increased immune scores, increased proportion of immune cells, higher tumor mutation burden, and potentially stronger immunotherapy response. IHC results showed that the E2F2 immunoreactivity score in ccRCC tissues was significantly higher than that in adjacent non-tumor tissues (P＜0.05). Functional assays indicated that E2F2 knockdown significantly inhibited the proliferation, colony formation, and migration of ccRCC cells. Conclusion E2F2 is highly expressed in ccRCC and may be involved in tumorigenesis and progression through modulation of the immune microenvironment. Its expression level is closely associated with patient prognosis, and E2F2 has the potential to serve as a prognostic biomarker and immunotherapeutic target in ccRCC.

Objective:To systematically review and evaluate prediction models for aspiration risk in enteral nutrition patients, providing a reference for the development and application of future models.Methods:Literature related to prediction models for aspiration risk in enteral nutrition patients was searched in China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, Web of Science, Cochrane Library, Embase, and PubMed, with the search period covering from the inception of the databases to August 30, 2024. Two researchers independently conducted literature screening and data extraction, and the PROBAST tool was used to assess the risk of bias and applicability of the included studies.Results:A total of 18 studies were included, involving 24 prediction models, with sample sizes ranging from 103 to 512 and an event rate of 9.46% to 49.87%. The top six predictive variables reported most frequently were baseline age, history of aspiration, length of nasogastric tube insertion, nutritional risk, impaired consciousness, and Acute Physiology and Chronic Health Evaluation-Ⅱscore. The area under the receiver operating characteristic curve of the models ranged from 0.756 to 0.992. Twelve studies reported model calibration, six studies conducted internal validation only, one study conducted external validation only, and four studies performed both internal and external validation. The overall applicability of the 18 studies was good, but the risk of bias was high, mainly due to improper handling of continuous variables and missing data.Conclusions:The aspiration risk prediction models developed in various studies for enteral nutrition patients show good applicability but carry a high risk of bias. Future efforts should focus on further optimizing the model construction process, internal and external validation, and result analysis to provide more reliable and scientific tools for clinical aspiration risk assessment.

Depression is a chronic brain dysfunctional disease mainly due tomood disorders.Currently,the pathogenesis of depression is unclear,and its pathogenesis,pathophysiology and treatment have consistently been a major focus of academic research.This review provides an overview of the role of serum inflammatory factors in the pathogenesis,diagnosis,and treatment of depression.The inflammatory factor pathway provides a theoretical basis for the development of diagnostic and therapeutic methods for depression.It is expected to provide accurate personalized treatment for patients with depression through the treatment of inflammatory factors,improve the treatment outcomest,and reduce the risk of disease progression.

Objective:To systematically review and evaluate prediction models for aspiration risk in enteral nutrition patients, providing a reference for the development and application of future models.Methods:Literature related to prediction models for aspiration risk in enteral nutrition patients was searched in China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, Web of Science, Cochrane Library, Embase, and PubMed, with the search period covering from the inception of the databases to August 30, 2024. Two researchers independently conducted literature screening and data extraction, and the PROBAST tool was used to assess the risk of bias and applicability of the included studies.Results:A total of 18 studies were included, involving 24 prediction models, with sample sizes ranging from 103 to 512 and an event rate of 9.46% to 49.87%. The top six predictive variables reported most frequently were baseline age, history of aspiration, length of nasogastric tube insertion, nutritional risk, impaired consciousness, and Acute Physiology and Chronic Health Evaluation-Ⅱscore. The area under the receiver operating characteristic curve of the models ranged from 0.756 to 0.992. Twelve studies reported model calibration, six studies conducted internal validation only, one study conducted external validation only, and four studies performed both internal and external validation. The overall applicability of the 18 studies was good, but the risk of bias was high, mainly due to improper handling of continuous variables and missing data.Conclusions:The aspiration risk prediction models developed in various studies for enteral nutrition patients show good applicability but carry a high risk of bias. Future efforts should focus on further optimizing the model construction process, internal and external validation, and result analysis to provide more reliable and scientific tools for clinical aspiration risk assessment.

Objective To investigate the efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis(CPA)based on CYP2C19 gene polymorphism detection and examine the factors affecting the efficacy for improving targeted therapy in clinical practice.Methods A total of 207 patients with pulmonary tuberculosis complicated with CPA treated in the Third People's Hospital of Kunming from December 2018 to November 2022 were randomly assigned to an observation group(105 cases)or a control group(102 cases).The patients in the control group received standard voriconazole treatment,while the patients in the observation group had their voriconazole regimen tailored based on CYP2C19 genotyping results.Plasma drug concentration levels,efficacy,and safety were compared between the two groups and in terms of CYP2C19 genotypes.Logistic regression analysis was used to identify the factors affecting treatment efficacy.Results The observation group showed significantly higher plasma voriconazole concentrations and overall antifungal efficacy compared to the control group(P＜0.05).In the observation group,CYP2C19 genotyping identified 37 extensive metabolizers(EM),47 intermediate metabolizers(IM),and 21 poor metabolizers(PM).Plasma concentration of voriconazole did not show significant difference between EM and IM(P＞0.05),but both PM and IM were associated with significantly lower plasma concentration of voriconazole than PM(P＜0.05).The clinical efficacy rate was 100％for PM,91.5％for IM,and 83.8％for EM(P＜0.05).The incidence of adverse events did not show significant difference among the three genotypes(P＞0.05).Logistic regression analysis revealed that lung cavitation,hypoalbuminemia,and agranulosis were significantly correlated with therapeutic efficacy(P＜0.05).Conclusions CYP2C19 gene polymorphism detection is valuable in clinical practice.It can inform anti-aspergillus therapy with voriconazole to effectively improve symptoms and clinical efficacy in patients with pulmonary tuberculosis complicated with CPA.Meanwhile,clinicians should be aware of the factors such as hypoproteinemia,agranulocytosis,and lung cavitation that may affect the efficacy of voriconazole.