BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.

Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE 02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD 01/RHD 01; RHAG genotype was RHAG 01/RHAG 01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE 02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.

Objective:To explore the therapeutic effect of Banxia Baizhu Tianma Decoction on phlegm-dampness-blocking cervical vertigo and its influence on neck hemodynamics.Methods:96 patients with phlegm-dampness block type cervical vertigo admitted to our hospital from January 2022 to January 2024 were divided into control group and observation group,48 cases in each group.The control group was treated with conventional Western medicine,and the observation group was treated with Banxia Baizhu Tianma Decoction.Both groups were treated for 4 weeks and followed up for 6 months.The reduction time and disappearance time of vertigo were recorded.The score of cervical vertigo Symptom and Function Assessment Scale(ESCV)was performed before treatment and 1 day after treatment.The average blood flow level of basilar artery,right vertebral artery and left vertebral artery was detected,and the total clinical effective rate,recurrence rate and adverse reaction rate of the two groups were compared.Results:The reduction time and disappearance time of vertigo in the observation group were shorter than those in the control group(P＜0.05).Post-treatment,the ESCV score of both groups was higher than that before treatment;compared with the control group,the ESCV score of the observation group was higher post-treatment(P＜0.05).The total clinical effective rate of observation group was higher than that of control group,and the recurrence rate was lower than that of control group(P＜0.05).The hemodynamic index were higher after treatment than in the control group(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Banxia Baizhu Tianma Decoction has certain curative effect on phlegm-dampness block type cervical vertigo,can effectively relieve vertigo symptoms,reduce recurrence,improve neck hemodynamics,and is safe,worthy of popularization and application.

Atherosclerosis(As)is a chronic inflammatory arterial wall injury process,and vessel wall cells play an important role in the occurrence and development of As.Vascular endothelial cell(VEC)act as a semi-permeable barrier between vascular smooth muscle cell(VSMC)and vascular lumen,and its injury is the initial stage of As.In addition,Through phenotypic transformation,VSMC could transform into many cell phenotype of the plaques,including macrophage,foam cell,mesenchymal stem cell and so on,and these cells further involved in the occurrence of As.Fibroblast is the main component of vascular adventitia,in pathological conditions,fibroblast differentiate into myofibroblast and participate in the occurrence of As.In this article,we will review the involvement of vascular wall cells in the mechanism of As and its potential therapeutic targets for the treatment of As,which provide new therapeutic ideas for As.

AIM:To investigate whether total alkaloids of Cocculus orbiculatus(COTA)attenuate ulcerative colitis(UC)in mice via PINK1/parkin mitophagy pathway.METHODS:Sixty C57BL/6 mice were randomly divided into normal control group,model group,positive drug mesalazine group,and low-,medium-and high-dose(0.162,0.324 and 0.486 g/kg)COTA groups,with 10 mice in each group.Except for normal control group,the mice in all groups were given free access to 3%dextran sulfate sodium(DSS)solution for 7 consecutive days to establish a UC model in mice,and were then treated with COTA or mesalazine via oral gavage.The general condition of the mice was observed,and the colon length and disease activity index(DAI)score were determined.Colon histopathological damage was observed by HE staining.The serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The pro-tein levels of PINK1,parkin,microtubule-associated protein 1 light chain 3(LC3),P62 and beclin-1 in colon tissues were determined by Western blot.The protein expression of LC3 and parkin was detected by immunofluorescence.RE-SULTS:Compared with normal control group,the mice in model group showed varying degrees of soft stools or bloody stools,decreased body weight(P<0.05),increased DAI score,shortened colon length(P<0.05),and obvious pathologi-cal damage in the colon tissue.The serum levels of IL-1β,IL-6 and TNF-α were elevated(P<0.05).The protein levels of parkin,PINK1,LC3-II and beclin-1 were significantly decreased(P<0.05),while P62 protein expression was in-creased(P<0.05).Immunofluorescence showed a small number of autophagosomes in the colon tissue.In contrast,com-pared with model group,the mice in total alkaloids of Cocculus orbiculatus groups exhibited increased body weight(P<0.05),decreased DAI score,increased colon length(P<0.05),and reduced levels of IL-1β,IL-6 and TNF-α(P<0.05).The protein levels of parkin,PINK1,LC3 and beclin-1 were elevated(P<0.05),while P62 expression was re-duced(P<0.05),with numerous autophagosomes visible in the colon tissue via immunofluorescence.CONCLUSION:Total alkaloids of Cocculus orbiculatus can enhance the expression of mitophagy-related proteins PINK1,parkin,LC3 and beclin-1,activate mitophagy,and reduce the expression of inflammatory factors,thereby attenuating the inflammatory re-sponse in the colon mucosa of DSS-induced UC mice.

Objective:Through the comparative analysis of the payment program for the therapeutic value of Traditional Chinese Medicine dominant diseases in 8 provinces,we found the shortcomings of the existing program and put forward the perfect policy suggestions.Methods:Comparative analysis of the core content of the programs in various places,the selection of disease types,efficacy evaluation indexes,the application of the payment link and the protection mechanism.Results:The fragmentation of existing programs is an obvious problem,the specific content settings of each item are quite different,reflecting differences in the understanding of the core content of the program,the existence of inconsistent understanding of Chinese medicine's therapeutic value,the failure to link the payment standard to the results of the therapeutic value evaluation,and the lack of recognition of the value of Chinese medicine's technical labor,among other problems.Conclusions:We can select disease types based on the prominent advantages of Traditional Chinese medicine,learn from the evaluation framework of western medicine value-based medical care,construct the evaluation system of Chinese medicine therapeutic value,and carry out"equal price"payment based on the"same effect"of health results,set performance indicators and payment standards in stages,realize the whole process management of disease,and enhance the Traditional Chinese Medicine's therapeutic value,and promote the development of Traditional Chinese Medicine inheritance and innovation.

AIM:To investigate whether total alkaloids of Cocculus orbiculatus(COTA)attenuate ulcerative colitis(UC)in mice via PINK1/parkin mitophagy pathway.METHODS:Sixty C57BL/6 mice were randomly divided into normal control group,model group,positive drug mesalazine group,and low-,medium-and high-dose(0.162,0.324 and 0.486 g/kg)COTA groups,with 10 mice in each group.Except for normal control group,the mice in all groups were given free access to 3%dextran sulfate sodium(DSS)solution for 7 consecutive days to establish a UC model in mice,and were then treated with COTA or mesalazine via oral gavage.The general condition of the mice was observed,and the colon length and disease activity index(DAI)score were determined.Colon histopathological damage was observed by HE staining.The serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The pro-tein levels of PINK1,parkin,microtubule-associated protein 1 light chain 3(LC3),P62 and beclin-1 in colon tissues were determined by Western blot.The protein expression of LC3 and parkin was detected by immunofluorescence.RE-SULTS:Compared with normal control group,the mice in model group showed varying degrees of soft stools or bloody stools,decreased body weight(P<0.05),increased DAI score,shortened colon length(P<0.05),and obvious pathologi-cal damage in the colon tissue.The serum levels of IL-1β,IL-6 and TNF-α were elevated(P<0.05).The protein levels of parkin,PINK1,LC3-II and beclin-1 were significantly decreased(P<0.05),while P62 protein expression was in-creased(P<0.05).Immunofluorescence showed a small number of autophagosomes in the colon tissue.In contrast,com-pared with model group,the mice in total alkaloids of Cocculus orbiculatus groups exhibited increased body weight(P<0.05),decreased DAI score,increased colon length(P<0.05),and reduced levels of IL-1β,IL-6 and TNF-α(P<0.05).The protein levels of parkin,PINK1,LC3 and beclin-1 were elevated(P<0.05),while P62 expression was re-duced(P<0.05),with numerous autophagosomes visible in the colon tissue via immunofluorescence.CONCLUSION:Total alkaloids of Cocculus orbiculatus can enhance the expression of mitophagy-related proteins PINK1,parkin,LC3 and beclin-1,activate mitophagy,and reduce the expression of inflammatory factors,thereby attenuating the inflammatory re-sponse in the colon mucosa of DSS-induced UC mice.

Designation of ideological and political teaching of Medical Immunology courses focuses on"cultivate talent for Party and the State",and adheres to goal of"build morality and cultivate people".From perspective of big ideology and politics,with basic foundation of"major guiding,disciplines supporting and curriculum shaping",principle of"six combinations"is applied to con-struct ideological and political cases of Medical Immunology courses,to create an infiltrating teaching pattern,which simultaneously cultivate talent for the Party and the State,and forms a synergistic effect of professional course learning and ideological and political learning.