As the core hub of energy metabolism in eukaryotes, mitochondria participate in a variety of cellular activities, including metabolic regulation of the cell matrix, apoptosis, and the activation of signal transduction pathways. Their functional status is closely linked to the initiation and progression of various diseases. Neurodegenerative diseases are primarily characterized by the progressive loss and dysfunction of neurons, and mitochondrial dysfunction is considered one of the key triggers in this process. The specific mechanisms by which mitochondrial dysfunction contributes to neurodegenerative diseases have attracted widespread attention. When misfolded or unfolded proteins are detected, a process known as the mitochondrial unfolded protein response (mtUPR) is activated to promote proper protein folding or degradation, thereby restoring mitochondrial function. As a mitochondrial stress defense mechanism, mtUPR primarily regulates the expression of nuclear-encoded genes, such as chaperones and proteases, to alleviate mitochondrial stress. Studies have shown that, in addition to misfolded and unfolded proteins, other mitochondrial stresses—such as mitochondrial DNA abnormalities and reactive oxygen species (ROS)—can also induce mtUPR. The biological functions of mtUPR extend beyond mitochondria and are crucial for the health of the entire cell and even the whole organism. The mtUPR process involves communication between mitochondria and the nucleus, a phenomenon that is highly conserved and has been observed across different species. Abnormal activation or inhibition of mtUPR is closely associated with the development of various neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. An in-depth exploration of the dynamic regulatory role and molecular mechanisms of mtUPR is therefore of great significance for understanding the pathogenesis of these disorders. In addition to neuron loss, neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain, including insoluble fibrils of amyloid beta, phosphorylated tau, or α-synuclein. While the molecular pathways of mtUPR are largely conserved across different diseases, the possibility of differential regulatory factors cannot be excluded. Although mtUPR activation is predominantly recognized for its cytoprotective role, it may exert deleterious effects when overstimulated or sustained. Chronic mtUPR activity has been linked to mitochondrial dysfunction and increased neuronal vulnerability, contributing to the pathogenesis of various neurodegenerative diseases. This review summarizes the fundamental concepts, major inducers, and signaling pathways of the mtUPR. We focus on the intrinsic relationship and regulatory patterns between mtUPR and neurodegenerative diseases, providing insights that may aid the development of targeted therapies. Finally, we discuss the challenges and future directions of mtUPR research in this field, aiming to pave the way for new therapeutic breakthroughs. A major limitation arises from the experimental models currently used; most findings rely on model organisms or cultured cells, which cannot fully replicate the complexity of human neurons. Future research should therefore focus on three main directions: (1) defining the molecular switches that determine whether mtUPR acts in a protective or detrimental manner; (2) elucidating differences in mtUPR molecular pathways across various models of neurodegenerative diseases; and (3) establishing robust biomarkers for mtUPR activity.

Objective To investigate the value of machine learning models based on contrast-enhanced CT radiomics in differentia-ting renal oncocytoma(RO)from chromophobe renal cell carcinoma(chRCC).Methods A total of 65 patients with RO and chRCC confirmed by pathology with complete clinical and imaging data were analyzed retrospectively.The patients were randomly divided into training set(n=45)and test set(n=20)according to a ratio of 7︰3.The tumor boundaries were delineated on the preoperative CT images using 3D Slicer software,and radiomics features were extracted using the Radiomics plugin.Univariate analysis,recursive fea-ture elimination(RFE),least absolute shrinkage and selection operator(LASSO)algorithms were used to select the best radiomics features.Three machine learning models were constructed on the training set and the grid search method was used to select the best combination of hyperparameters.The receiver operating characteristic(ROC)curve,calibration curve and decision curve were used to evaluate the performance of each machine learning model on the training set and test set.Results Random forest model,logistic regres-sion model and support vector machine model can better identify RO and chRCC.In the training set,the area under the curve(AUC)of random forest model and support vector machine model were 0.950[95%confidence interval(CI)0.901-0.998]and 0.955(95%CI 0.908-1.000),respectively,which were higher than the AUC of logistic regression model 0.882(95%CI 0.806-0.956).Statistical differences were found by DeLong test(P<0.05);In the test set,the AUC of random forest model,logistic regression model and support vector machine model were 0.876(95%CI 0.758-0.993),0.883(95%CI 0.768-0.997)and 0.883(95%CI 0.768-0.997),respectively.There was no significant statistical difference in the AUC of each model by DeLong test(P>0.05).The decision curve showed that all three models had significant net clinical benefits.Conclusion The machine learning model based on contrast-enhanced CT radiomics can effectively distinguish RO from chRCC.

Objective:To construct a key item checklist for the Mini-HTA report specification,providing scientific guidance for drafting each section of Mini-HTA research reports,enhancing their standardization,scientific rigor,and completeness,thereby improving the efficiency and quality of health decision-making.Methods:Based on preliminary literature review and qualitative systematic review,a pool of problem items for the Mini-HTA report specification was formed.Delphi questionnaires were distributed,and the Delphi technique was employed through two rounds of expert consultation to optimize and select key items.Results:Through two rounds of Delphi expert consultation,the initial Mini-HTA report specification item checklist was screened,integrated,and supplemented.A finalized key item checklist was constructed,comprising 8 first-level items(Title,Abstract,Introduction,Methods,Results,Discussion,Conclusion,and Other Relevant Information)and 48 second-level items.Conclusion:The constructed key item checklist for the Mini-HTA report specification provides scientific guidance for drafting Mini-HTA research reports.It helps enhance the standardization and transparency of the assessment process and the reliability of results,thereby optimizing the efficiency and quality of health decision-making.

Time rhythm and the immune system play crucial roles in the pathogenesis of allergic rhinitis.Traditional Chinese medicine(TCM)believes that the circulation of qi and blood in lung meridian follows the principle of"yang during the day,yin at night",which has a defensive function to protect the body from external pathogens.Qi stagnation in lung meridian and impaired qi and blood circulation can lead to the invasion of external pathogens,exacerbating allergic reactions,especially during the active period of the lung meridian,when the immune system is most sensitive to allergens.Based on this,this paper proposes the concept of"bidirectional regulation among meridian,time rhythm,and immune system",and in combination with TCM theory of midnight-noon and ebb-flow doctrine,analyzes the fluctuations of allergic rhinitis symptoms and the temporal changes of meridian qi and blood,and reveals the rhythmic relationship between meridian activity and immune response.This paper combines existing clinical and experimental studies to support this hypothesis,integrating the time dimension into traditional TCM syndrome differentiation and treatment,offering a more individualized treatment approach.This concept not only provides novel scientific evidence for TCM treatment of allergic rhinitis,but also offers theoretical support for optimizing treatment timing and intervention strategies.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90％,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68％).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

Objective To investigate the effect of esketamine on postoperative depression in frail elderly patients undergoing thoracoscopic radical resection of lung cancer.Methods A total of 88 frail elderly patients undergoing elective thoracoscopic radical resection of lung cancer were assigned randomly(using a randomization table)and in a double-blind way(blinding applies to both researchers and patients)to an esketamine group(Esk group,n=44)and a normal saline group(NS group,n=44).In the Esk group,0.25 mg/kg esketamine was injected intravenously during anesthesia induction,followed by continuous infusion of esketamine at 0.125 mg/kg per hour until 20 min before the end of surgery.In the NS group,equivalent volumes of normal saline were administered using the same method.The primary outcome was the score for the 17-item Hamilton Rating Scale for Depression(HAMD-17)on days 7 and 30 after surgery.The secondary outcomes included sleep quality and cognitive function.Sleep quality was assessed using the numerical rating scale(NRS)on days 1,3,and 7 after surgery and the Pittsburgh Sleep Quality Index(PSQI)on day 30 after surgery.Cognitive function was assessed using the Mini-Mental State Examination(MMSE)on days 1,3,7,and 30 after surgery.The other indicators included the levels of serum brain-derived neurotrophic factor(BDNF),5-hydroxytryptamine(5-HT),S100β protein,and neuron specific enolase(NSE)at 24 hours(T1),48 hours(T2),and 72 hours(T3)after surgery,as well as perioperative data and postoperative safety outcomes.Results Three patients were excluded from the Esk group and the NS group,respectively,and eventually,41 patients in each group were included in the statistical analysis.There were no statistically significant differences between the two groups in terms of age,sex,body mass index,American Society of Anesthesiologists(ASA)classification,comorbidities,educational attainment,and the scores for HAMD-17,PSQI,and MMSE 1 day before surgery(P＞0.05).Concerning the primary outcome,compared with those of the NS group,the HAMD-17 scores of patients in the Esk group were significantly lower at 7 days(median[P25,P75])(7[6,8]vs.7[6,12],P=0.045)and 30 days(6[6,7]vs.7[6,9],P=0.020)after surgery.Concerning the secondary outcomes,compared with those of the NS group,the sleep NRS scores of patients in the Esk group were significantly lower at 1,3,and 7 days after surgery(P＜0.01),and the MMSE scores were significantly higher(P＜0.05).Concerning the other indicators,compared with those of the NS group,the concentrations of serum BDNF and 5-HT in the Esk group were significantly higher(P＜0.05 or 0.01)at T1-T3,while the content of S100β was significantly lower(P＜0.01)at T1-T3;the levels of serum NSE were significantly lower at T1 and T2(P＜0.01);the consumption of propofol,sufentanil,remifentanil,and sevoflurane during surgery in the Esk group was significantly reduced(P＜0.05 or 0.01);the incidence of postoperative nausea/vomiting and hyperalgesia was significantly lower(P＜0.01);the duration of postoperative mechanical ventilation,length-of-stay in postanesthesia care unit(PACU),and postoperative length-of-stay in the hospital were significantly shorter(P＜0.01).Conclusion Esketamine can improve the postoperative depressive state,sleep quality,and cognitive function in frail elderly patients undergoing thoracoscopic radical resection of lung cancer.

Objective To evaluate the efficacy and safety of ibuprofen in treating hemodynamically significant patent ductus arteriosus(hsPDA)in preterm infants of different postnatal ages at treatment initiation.Methods Clinical records of infants with gestational age<37 weeks who received ibuprofen for hsPDA in the Department of Neonatology,Fourth Hospital of Shijiazhuang,from January 2020 to December 2023 were retrospectively reviewed.One hundred eligible infants were divided by the postnatal age at the first ibuprofen administration into three groups:group A(≤4 days),group B(5-7 days),and group C(>7 days).Clinical efficacy and safety indicators were compared among groups.Results After treatment,cure rates were 92%in group A,72%in group B,and 60%in group C,and effective rates were 8%,25%,and 33%,respectively.Differences in clinical efficacy among the three groups were statistically significant(P<0.05).No significant differences were observed among groups in the incidence of pulmonary hemorrhage,gastrointestinal bleeding,cholestasis,bronchopulmonary dysplasia,necrotizing enterocolitis,intracranial hemorrhage,or acute kidney injury(P>0.05).Conclusions For hsPDA requiring pharmacologic therapy,earlier oral ibuprofen administration yields a higher ductal closure rate and does not increase the incidence of adverse events.

Objective:To explore the expression regulation of lipid metabolism gene ABHD5 in testes.Methods:Differential gene analysis was performed by integrating databases of TCGA and GTEx to identify the target gene ABHD5.The expression trends of ABHD5 gene in testicular carcinoma tissue were analyzed.Human testis single-cell atlases were obtained from the Human Protein Atlas and Male Health Atlas databases to determine the expression distribution of ABHD5 across different testicular cell types.Additionally,the GTEx database was utilized to visualize the expression pattern of ABHD5 in the testis,thereby enhancing the understanding of its transcriptional profile.The relationship between ABHD5 expression and age was assessed through integrated database analysis.Western blotting and immunofluorescence were performed to detect differential expressions of ABHD5 in testicular tissues of young and aged mice respectively.Results:The TCGA database indicated that the expression of ABHD5 in human testicular carcinoma tissue was significantly lower than that in normal testicular tissue which showed a negative correlation with patient survival.ABHD5 was highly ex-pressed in germ cells of the testis reveaked from Human Protein Atlas and Male Health Atlas databases.The stability of ABHD5 protein was crucial for testicular tissue,and its expression decreased with age.Furthermore,Western blot and immunofluorescence staining demonstrated that ABHD5 expression in the testicular tissue of aged mice was significantly lower than that in young mice.Conclu-sion:ABHD5 plays an important role in testicular tissue,and may be inseparable from testicular tumors and reproductive aging.How-ever,its mechanism of action remains to be further studied.