Hepatic fibrosis is a pathological repair response of the liver to various chronic injuries, commonly seen in chronic liver diseases such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, etc. Hepatic fibrosis is a necessary stage for the development of chronic liver disease into cirrhosis or even hepatocellular carcinoma. Reversing or delaying the progression of hepatic fibrosis is crucial for the treatment of chronic liver disease, but there are currently no safe and effective therapeutic drugs in clinical practice. In recent years, research has found that many alkaloids in traditional Chinese medicine have anti-fibrotic activity, and their mechanisms involved multiple aspects such as cell autophagy, antioxidation, and anti-inflammation. The anti-fibrotic effects and mechanisms of alkaloids from traditional Chinese medicine were reviewed, which could provide reference for the application of alkaloids in the prevention and treatment of hepatic fibrosis.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Objective To Study the value of effected ejection fraction(eEF)in assessment of cardiac function in elderly patients with heart failure.Methods A total of 1 134 elderly inpatients in this hospital from January 2019 to December 2023 were selected as the research subjects.After admission,relevant examinations and tests were completed,and the cardiac function classification of the New York Heart Association(NYHA)was carried out.Sequential electrocardiogram(ECG)and echocardiogram examinations were completed before treatment.Age,under-lying diseases,left ventricular ejection fraction(LVEF),N-terminal pro-brain natriuretic peptide(NT-proB-NP),and QT interval(QTc)of the ECG were included for classification and statistics,and eEF was obtained,and the evaluation value of eEF on cardiac function was analyzed.Results The numbers of patients with NY-HA cardiac function grades Ⅰ—Ⅳ were 86,434,454 and 160,respectively,and LVEF decreased with the in-crease of the NHYA cardiac function grade.There was statistically significant differences in LVEF among dif-ferent NHYA cardiac function classifications(P＜0.05).The QTc of the patients was(434.71±40.96)ms,the eEF was(8.73±2.03)ms,and the ln(NT-proBN)was 7.05±1.70.QTc,eEF,and ln(NT-proBN)all in-creased with the increase of the NHYA cardiac function classification,and there were statistically significant differences in indicators above among different NHYA cardiac function classfications(P＜0.05).There was a low correlation between QTc of the ECG,age and cardiac insufficiency(r＜0.5,P＜0.05);there was a high correlation between eEF,LVEF,and ln(NT-proBNP)and cardiac insufficiency(r≥0.5,P＜0.05).Conclusion eEF still has discriminatory value for patients with heart failure with preserved ejection fraction,and it is a good indicator for evaluating the cardiac function of elderly patients with heart failure.

Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To investigate the status quo,driving factors and clinical intervention measures of intrinsic capacity(IC)in elderly patients with cerebrovascular disease.Methods Clinical data of 206 elderly patients with cerebrovascular disease admitted to our hospital from January to December 2024 were retrospectively collected.According to the IC score,they were divided into a low IC group(123 cases,IC score＜4)and a good IC group(83 cases,IC score≥4).The IC scores were compared between the two groups,and the driving factors affecting the IC were analyzed.Results The low IC group exhibited significantly lower IC score than the good IC group(1.94±0.49 vs 4.52±0.15,P＜0.01).The age ≥80 years,dysfunctions,three or more chronic diseases,frailty,albumin ≤ 35 g/L,pre-albumin ≤280 mg/L,rehabilitation guidance and regular exercises were the influencing factors of IC in elderly patients with cerebrovascular disease(P＜0.05,P＜0.01).Conclusion The IC of elderly patients with cerebrovascular disease is associated with many factors,and corresponding clinical intervention measures should be implemented to promote the improvement of patient's IC.

Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.