Objective To investigate the perioperative safety of patients with myasthenia gravis who take high doses of oral glucocorticoids. Methods A retrospective analysis was conducted on the clinical data of patients with myasthenia gravis who received oral glucocorticoids and underwent thoracoscopic thymectomy at the Department of Thoracic Surgery, the University of Hong Kong-Shenzhen Hospital from April 2013 to October 2019. Patients were divided into a high-dose steroid group and a medium-to-low dose steroid group based on the dosage of oral steroids, and the clinical data of the two groups were compared. Results A total of 102 patients were included, including 19 (18.62%) males and 83 (81.37%) females, with an average age of (32.25±9.83) years. There were 75 patients in the medium-to-low dose steroid group and 27 patients in the high-dose steroid group. All patients in both groups successfully completed the surgery without major intraoperative bleeding, conversion to open chest surgery, delayed extubation, severe infection, or perioperative death. The daily oral steroid dose for the high-dose steroid group was (35.81±4.29) mg, and for the medium-to-low dose steroid group it was (15.29±2.17) mg. There was no statistical difference in the operation time [(124.69±23.51) min vs. (117.89±21.46) min, P=0.172] and intraoperative blood loss [(21.19±3.48) mL vs. (20.56±3.41) mL, P=0.419] between the two groups. Postoperatively, 12 (11.76%) patients developed complications: one patient of myasthenic crisis (the medium-to-low dose steroid group), which was improved after short-term respiratory support and intravenous immunoglobulin treatment; 11 patients of respiratory/swallowing difficulties (9 in the medium-to-low dose steroid group and 2 in the high-dose steroid group), which were improved after anticholinergic treatment to reduce oral secretions and sputum suction, and the patients were discharged smoothly. There was no statistical difference in the incidence of postoperative complications between the two groups (P=0.637). Conclusion On the basis of good perioperative management, it is safe and feasible for patients with myasthenia gravis who take high dose of oral steroids to undergo thymectomy, and they have the same perioperative safety as patients with medium-to-low dose steroids.

Metabolic dysfunction-associated fatty liver disease （MAFLD）， as one of the most common chronic liver diseases in the world， poses a severe challenge to precision diagnosis and treatment due to its complex pathogenesis and highly heterogeneous disease progression. Existing clinical classification systems cannot meet the needs for comprehensively analyzing the complexity of the disease and the heterogeneity of its adverse outcomes. In recent years， data-driven prognostic risk classification methods have gradually emerged， optimizing the ability for predicting adverse outcomes and enhancing the accuracy of identifying different endpoint outcomes. However， such paradigm of “classify first， associate outcomes later” suffers from a “black-box” nature， and there are various indicators for classification， leading to limited stability and generalizability in clinical application. Future research needs to integrate or establish large-scale population cohorts， develop outcome-oriented prognostic risk classification models， incorporate dynamic data， refine classification algorithms， and validate their generalizability across multiple populations， thereby providing reliable support for the precision diagnosis and treatment of MAFLD.

ObjectiveAbnormal lipids in neurons can cause the accumulation of α-synuclein（α-syn）. This study aimed to explore the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） mice using lipidomics combined with network pharmacology. MethodsMice were divided into the blank group， model group and ASH （45.5 mg·kg^-1） group. Motor ability was evaluated by pole climbing time and autonomous activity count； The oxidative stress indicators were detected by enzyme-linked immunosorbent assay （ELISA）. Lipid biomarkers in brain tissues were screened and identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and metabolic pathway analysis was conducted. The key targets of ASH for PD treatment were explored using network pharmacology. The Kyoto Encyclopedia of Genes and Genomes （KEGG） database was used for pathway enrichment analysis， and the "compound-reaction-enzyme-gene" network was constructed using the MetScape plugin. The protein expression levels of glutathione S-transferase P1 （GSTP1）， glutathione S-transferase Mu 2 （GSTM2）， prostaglandin peroxide synthase 1 （PTGS1）， prostaglandin peroxide synthase 2 （PTGS2）， and prostaglandin E synthase （PTGES） were validated by Western blot. ResultsCompared with the blank group， the model group showed significantly prolonged pole climbing time and reduced autonomous activity count （P<0.01）. Compared with the model group， the ASH group demonstrated significantly faster pole climbing and increased autonomous activity count （P<0.01）. The model group exhibited significantly decreased superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） levels， and increased malondialdehyde （MDA） level in brain tissues compared with the blank group （P<0.01）. The ASH group showed increased SOD and GSH-Px levels and decreased MDA level compared with the model group （P<0.05， P<0.01）. Lipidomics analysis identified 10 differential metabolites and 8 differential metabolic pathways. Network pharmacological analysis revealed 213 intersection targets between ASH components and PD， with KEGG enrichment involving the sphingolipid signaling pathway， lipid arteriosclerosis， phosphoinositide 3-kinase/protein kinase B（PI3K/Akt） signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway， and hypoxia inducible factor-1（HIF-1） signaling pathway. Integrated lipidomics and network pharmacology analysis highlighted the central role of the arachidonic acid metabolic pathway. The Western blot results showed that ASH effectively up-regulated GSTP1， GSTM2， and PTGS1 protein expression， and down-regulated PTGS2 and PTGES protein expression. ConclusionASH can ameliorate behavioral deficits， exert antioxidant effects， regulate lipid differential metabolites and the arachidonic acid metabolic pathway， thereby exerting therapeutic effects in PD model mice.

Neurodegenerative diseases are a group of disorders characterized by chronic progressive degeneration of neurons in the brain and/or spinal cord.Their etiology remains unclear,the pathogenesis is complex,and no effective treatments exist.Importantly,the roles of mitochondria-localized silent information regulator(SIRT)family members,including SIRT3,SIRT4,and SIRT5,in neurodegenerative diseases are attracting increasing attention.Accumulating evidence demonstrates their involvement in critical processes of neuronal degeneration by regulating,for example,mitochondrial function and inflammatory responses.This review summarizes the research advances on mitochondrial SIRTs in neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,and aims to provide new insights for elucidating disease pathogenesis and developing prevention/therapeutic strategies.

Objective:To explore the distribution of HIV-1 genetic subtypes and drug resistance profiles among HIV-1 infected patients with antiretroviral treatment (ART) failure in Henan Province and to provide evidence for optimizing ART regimens.Methods:HIV-1 infected patients who had received ART for at least 6 months with viral loads (VL) ≥200 copies/ml in 18 cities of Henan from January to December 2023. The plasma samples were collected, and partial pol gene sequences and full-length integrase ( int) gene sequences of HIV-1 were amplified using nested RT-PCR. HIV-1 subtypes were determined using the REGA HIV-1 subtyping tool, and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database ( http://hivdb.stanford.edu/). Chi-square tests and multivariate logistic regression were used to identify risk factors associated with drug resistance of HIV-1 infected patients. Results:Among 697 HIV-1 infected patients with ART failure, 14 HIV-1 genetic subtypes were identified. Subtype B was predominant (58.68%, 409/697), followed by CRF01_AE (21.95%, 153/697) and CRF07_BC (12.91%, 90/697). The overall drug resistance rate was 72.31% (504/697), with CRF55_01B exhibiting a resistance rate of 91.30% (21/23). Non-nucleoside reverse transcriptase inhibitors (NNRTIs) had the highest resistance mutation rate (67.29%, 469/697), followed by nucleoside reverse transcriptase inhibitors (NRTIs)(56.81%, 396/697), protease inhibitors (PIs)(5.74%, 40/697), and integrase strand transfer inhibitors (INSTIs)(2.75%, 19/691). The results of multivariate analysis showed that the positive correlation factor for drug resistance in HIV-1 infected individuals with failed ART was baseline CD4 +T lymphocyte counts <200 cells/μl (a OR=3.84, 95% CI: 1.69-8.72), and the negative correlation factor was ART duration of 3-5 years (a OR=0.32, 95% CI: 0.13-0.77), the initial treatment ART protocol used two types of NRTIs plus one type of PIs (a OR=0.14, 95% CI: 0.05-0.43) and two types of NRTIs plus one type of INSTIs protocol (a OR=0.12, 95% CI: 0.03-0.57). Conclusions:The drug resistance rate of HIV-1 infected patients with ART failure was relatively higher in Henan Province in 2023. Strengthening the monitoring of HIV-1 drug resistance is of great significance to improve the ART effect of HIV-1 infected patients.

Objective:To analyze risk factors associated with false-positive results of quantitative fecal immunochemical testing (FIT), evaluate its performance for detecting advanced colorectal neoplasia across different subgroups, and explore the optimal positivity thresholds for each subgroup.Methods:Individuals who participated in the Zhejiang Colorectal Cancer Screening Program in 2020-2021, completed questionnaire-based risk assessment and quantitative FIT for initial screening, and undertook colonoscopy for confirmed diagnosis were included in this study. The information of individuals, including demographic characteristics, lifestyles, history of diseases, and family history of colorectal cancer (CRC), was collected by using questionnaires. The diagnostic outcomes of the individuals were obtained through colonoscopy and pathological examination. Multivariate logistic regression analyses were conducted to identify factors associated with false-positive FIT results. The optimal threshold of FIT was determined based on the receiver operating characteristic (ROC) curve and 10-fold cross-validation. The effectiveness of FIT screening in different subgroups was compared using the unified threshold of 100 ng/ml or optimal positivity thresholds.Results:There were 25 874 individuals included in the analysis, with 14 694 (56.79%) having fecal hemoglobin concentrations ≥100 ng/ml. A total of 3 830 advanced adenoma cases (14.80%) and 362 CRC cases (1.40%) were identified. Age below 60 years old, females, underweight, smoking, drinking, use of nonsteroidal anti-inflammatory drugs, no family history of CRC, no history of intestinal disease, no history of hypertension, and physical inactivity were associated with an elevated risk of false-positive results in FIT ( P<0.05). Compared to the predetermined threshold of 100 ng/ml, the false positive rate (FPR) of quantitative FIT decreased from 52.3% to 37.3% in all individuals, and decreased by more than 20% in females, individuals with normal weight, smokers, and those without a history of intestinal disease when adopting the optimal threshold (all P<0.001). Conclusion:The risk of false-positive results in quantitative FIT varies across different subgroups. Adopting the optimal thresholds could improve the specificity and reduce the FPR of quantitative FIT for CRC screening.

Objective:To analyze the drug resistance characteristics and influencing factors in human immunodeficiency virus (HIV)-1 treated patients in Henan Province.Methods:HIV-1 treated patients who had received anti-retroviral therapy (ART) for more than six months and had a viral load >200 copies/mL in the Zhengzhou Sixth People′s Hospital from January to December 2024 were enrolled. Plasma samples were collected. Partial pol region gene sequences and integrase gene sequences of HIV-1 were amplified by reverse transcription nested polymerase chain reaction. The REGA HIV-1 subtype analysis tool was used to determine the subtypes of HIV-1 isolates, and the HIV drug resistance database of Stanford University in the United States was used to analyze the genetic drug resistance mutations and antiviral drug susceptibility. The multivariate logistic regression analysis was used to analyze the factors related to drug resistance. Results:Among 933 HIV-1 treated patients with ART failure, 825 samples were successfully amplified, with the amplification success rate of 88.42%. The overall drug resistance rate was 70.06%(578/825), among which the drug resistance rates of nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), and integrase inhibitor (INSTI) were 55.15%(455/825), 64.36%(531/825), 5.70%(47/825), and 2.31%(19/821), respectively. The most common drug resistance mutations included M184I/V (47.88%(395/825)), K103N/S (38.18%(315/825)), and K70E/G/N/Q/R/S/T/del (16.61%(137/825)). Multivariate analysis showed that the baseline CD4 + T cell count <200 cells/μL (adjusted odds ratio ( OR)=2.239, 95% confidence interval ( CI)1.011 to 4.960), an initial 2NRTI+ NNRTI-based treatment regimen (adjusted OR=44.332, 95% CI 5.191 to 378.593), initial 2NRTI+ PI/r (r means ritonavir)-based regimen (adjusted OR=14.391, 95% CI 1.304 to 158.805) and a change in the ART regimen (adjusted OR=5.941, 95% CI 2.373 to 14.878) were independent risk factors for drug resistance (all P<0.05). Conclusions:The drug resistance rate after virological failure in HIV-1 treated patients in Henan Province is relatively high, which is mainly characterized by NNRTI resistance. The baseline immune status and the choice of the initial treatment regimen are important factors affecting the occurrence of drug resistance. The treatment monitoring and drug resistance monitoring should be strengthened.

Neurodegenerative diseases are a group of disorders characterized by chronic progressive degeneration of neurons in the brain and/or spinal cord.Their etiology remains unclear,the pathogenesis is complex,and no effective treatments exist.Importantly,the roles of mitochondria-localized silent information regulator(SIRT)family members,including SIRT3,SIRT4,and SIRT5,in neurodegenerative diseases are attracting increasing attention.Accumulating evidence demonstrates their involvement in critical processes of neuronal degeneration by regulating,for example,mitochondrial function and inflammatory responses.This review summarizes the research advances on mitochondrial SIRTs in neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,and aims to provide new insights for elucidating disease pathogenesis and developing prevention/therapeutic strategies.

Objective:To explore the distribution of HIV-1 genetic subtypes and drug resistance profiles among HIV-1 infected patients with antiretroviral treatment (ART) failure in Henan Province and to provide evidence for optimizing ART regimens.Methods:HIV-1 infected patients who had received ART for at least 6 months with viral loads (VL) ≥200 copies/ml in 18 cities of Henan from January to December 2023. The plasma samples were collected, and partial pol gene sequences and full-length integrase ( int) gene sequences of HIV-1 were amplified using nested RT-PCR. HIV-1 subtypes were determined using the REGA HIV-1 subtyping tool, and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database ( http://hivdb.stanford.edu/). Chi-square tests and multivariate logistic regression were used to identify risk factors associated with drug resistance of HIV-1 infected patients. Results:Among 697 HIV-1 infected patients with ART failure, 14 HIV-1 genetic subtypes were identified. Subtype B was predominant (58.68%, 409/697), followed by CRF01_AE (21.95%, 153/697) and CRF07_BC (12.91%, 90/697). The overall drug resistance rate was 72.31% (504/697), with CRF55_01B exhibiting a resistance rate of 91.30% (21/23). Non-nucleoside reverse transcriptase inhibitors (NNRTIs) had the highest resistance mutation rate (67.29%, 469/697), followed by nucleoside reverse transcriptase inhibitors (NRTIs)(56.81%, 396/697), protease inhibitors (PIs)(5.74%, 40/697), and integrase strand transfer inhibitors (INSTIs)(2.75%, 19/691). The results of multivariate analysis showed that the positive correlation factor for drug resistance in HIV-1 infected individuals with failed ART was baseline CD4 +T lymphocyte counts <200 cells/μl (a OR=3.84, 95% CI: 1.69-8.72), and the negative correlation factor was ART duration of 3-5 years (a OR=0.32, 95% CI: 0.13-0.77), the initial treatment ART protocol used two types of NRTIs plus one type of PIs (a OR=0.14, 95% CI: 0.05-0.43) and two types of NRTIs plus one type of INSTIs protocol (a OR=0.12, 95% CI: 0.03-0.57). Conclusions:The drug resistance rate of HIV-1 infected patients with ART failure was relatively higher in Henan Province in 2023. Strengthening the monitoring of HIV-1 drug resistance is of great significance to improve the ART effect of HIV-1 infected patients.

Objective To evaluate the longitudinal imaging features of coronary artery plaques in elderly male patients with CHD and myocardial bridges and explore the longitudinal changing pat-terns.Methods A total of 117 elderly male CHD patients who underwent two examinations of coronary computed tomography angiography in our medical center from January 2018 to Septem-ber 2023 were enrolled in this study.Then 216 small plaques(0.1-50 mm3 in size)were subjec-ted,and classified into the proximal myocardial bridge group(98 plaques)and other heart part group(118 plaques)according to the site of the plaques.Plaque volume,plaque composition vol-ume,FAI,and CT-derived fraction flow reserve(CT-FFR)were calculated and recorded.Results In the 2 groups of plaques,there were no statistically differences in the plaque length,plaque nec-rotic core volume,and FAI derived from the second examination than the baseline one(P＞0.05).The plaque volume,intra-plaque fibers,and dense calcified volume of plaques in the second exami-nation were significantly greater than those at baseline,and CT-FFR was obviously smaller than the baseline level in both groups(P＜0.05,P＜0.01).In the proximal myocardial bridge group,the intra-plaque fibrofat volume in the second examination was significantly larger than that of baseline,while opposite phenomenon was observed in the plaques of the other heart part group(P＜0.05).The annual changing rates of intraplaque fibrofat volume and FAI were significantly higher in the proximal myocardial bridge group than the other heart part group[0.51％(-0.32％,0.51％)vs 0.02％(-0.46％,0.20％),P=0.046;0.55％(-2.44％,1.76％)vs 0.33％(-1.36％,2.63％),P=0.044].Conclusion In elderly male patients,the intraplaque fibrofat vol-ume,FAI and CT-FFR are more likely to change in the proximal plaques of the left anterior de-scending artery myocardial bridge than the plaques of other parts of heart,so the proximal plaques of the left anterior descending artery need more clinical attention and early intervention.