ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Objective: Machine learning (ML) has been reported to have better predictive capability than traditional statistical techniques. The aim of this study was to assess the efficacy of ML algorithms and logistic regression (LR) for predicting depressive symptoms during the COVID-19 pandemic. Methods: Analyses were carried out in a national cross-sectional study involving 21,916 participants. The ML algorithms in this study included random forest (RF), support vector machine (SVM), neural network (NN), and gradient boosting machine (GBM) methods. The performance indices were sensitivity, specificity, accuracy, precision, F1-score, and area under the receiver operating characteristic curve (AUC). Results: LR and NN had the best performance in terms of AUCs. The risk of overfitting was found to be negligible for most ML models except for RF, and GBM obtained the highest sensitivity, specificity, accuracy, precision, and F1-score. Therefore, LR, NN, and GBM models ranked among the best models. Conclusion Compared with ML models, LR model performed comparably to ML models in predicting depressive symptoms and identifying potential risk factors while also exhibiting a lower risk of overfitting.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Objective To explore the safety of establishing the veno-arterial extracorporeal membrane oxygenation(VA-ECMO)pipeline through percutaneous puncture and the effectiveness of high-risk percutaneous coronary intervention(HR-PCI)under VA-ECMO assistance.Methods In this single-center retrospective study,patients who underwent HR-PCI assisted by VA-ECMO at Wuhan Asian Heart Hospital from December 2022 to December 2023 were included.The primary endpoint was the safety of establishing the VA-ECMO pipeline through percutaneous puncture,mainly characterized by extracorporeal membrane oxygenation(ECMO)-related complications,including severe bleeding/hematoma at the wound,arteriovenous fistula,pseudoaneurysm,peripheral arterial dissection,etc.The secondary endpoint was the effectiveness of HR-PCI under VA-ECMO assistance,defined as major adverse cardiovascular and cerebrovascular events(MACCE)at 6-month follow-up,including the composite events of all-cause death,non-fatal myocardial infarction,repeat revascularization,and ischemic stroke.Results Among the 189 patients included in the study,15(7.9％)had severe bleeding/hematoma at the puncture wound caused by VA-ECMO,8(4.2％)had wound infection,1(0.5％)had arteriovenous fistula,4(2.1％)had pseudoaneurysm,3(1.6％)had peripheral arterial dissection,8(4.2％)had systemic embolism,8(4.2％)had acute kidney injury,3(1.6％)had acute neurological injury,and 1(0.5％)died.percutaneous coronary intervention(PCI)was successful in 182 cases(96.3％),and a total of 36 cases(19.0％)had PCI-related complications.164 patients completed 6-month follow-up,among which 4(2.4％)had all-cause death,11(6.7％)had non-fatal myocardial infarction,11(6.7％)had unplanned repeat revascularization,and 2(1.2％)had the composite event of ischemic stroke.Conclusions Ultrasound-guided percutaneous puncture for establishing the VA-ECMO pipeline has high safety,and HR-PCI patients assisted by VA-ECMO have good short-term effects.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

The principe of electrical impedance tomography(EIT)was described,and the research progress of EIT technology in the field of gesture recognition was reviewed from the aspects of hardware system and gesture recognition algorithm.The challenges of EIT technology applied in the field of gesture recognition were analyzed,and the future development trends were envisioned.[Chinese Medical Equipment Journal,2025,46(4):93-99]

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

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.

Objective: Machine learning (ML) has been reported to have better predictive capability than traditional statistical techniques. The aim of this study was to assess the efficacy of ML algorithms and logistic regression (LR) for predicting depressive symptoms during the COVID-19 pandemic. Methods: Analyses were carried out in a national cross-sectional study involving 21,916 participants. The ML algorithms in this study included random forest (RF), support vector machine (SVM), neural network (NN), and gradient boosting machine (GBM) methods. The performance indices were sensitivity, specificity, accuracy, precision, F1-score, and area under the receiver operating characteristic curve (AUC). Results: LR and NN had the best performance in terms of AUCs. The risk of overfitting was found to be negligible for most ML models except for RF, and GBM obtained the highest sensitivity, specificity, accuracy, precision, and F1-score. Therefore, LR, NN, and GBM models ranked among the best models. Conclusion Compared with ML models, LR model performed comparably to ML models in predicting depressive symptoms and identifying potential risk factors while also exhibiting a lower risk of overfitting.