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.

Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.

Objective To investigate the effect of Dex on neurological function in PD rats through the receptor interacting protein kinase 1(RIPK1)/RIPK3/mixed lineage kinase domain-like pro-tein(MLKL)pathway.Methods After rat PD model was constructed,the PD rats were assigned into PD group,L-,M-and H-Dex groups(intraperitoneal injection of 25,50,and 100 μg/kg Dex,respectively),and Dex+recombinant RIPK1 protein(rRIPK1)group(intraperitoneal injection of 100 μg/kg Dex+8 μg/kg rRIPK1),with 6 animals in each group.Another 6 rats served as sham-operation(Sham)group.The rats from the Sham group and PD group were intragastrically ad-ministered and injected with an equal amount of normal saline solution once a day.After 21 con-secutive days,the rotational behavior was observed of in each group rats.HE staining was per-formed to detect the pathological changes in dopaminergic neurons in the substantia nigra.TUNEL staining was conducted to measure the apoptosis of dopaminergic neurons.ELISA was used to determine the levels of neurotransmitters[DA,HVA,3,4-dihydroxyphenylacetic acid(DOPAC),5-hydroxytrptamine(5-HT)]and inflammatory factors(TNF-α,IL-1β)in the sub-stantia nigra.Western blotting was applied to detect the expression of RIPK1/RIPK3/MLKL pathway related proteins in the substantia nigra tissues.Results Intact and well-arranged mor-phology and structure were observed in the neurons of the Sham group.The PD group presented prominently less neurons,in scattered arrangement,with obviously reduced volume,irregular nu-clear deformation,indicating notably neuronal damage.The severity of neuronal damage was at-tenuated sequentially in the L-Dex,M-Dex,and H-Dex groups,but the damage in the Dex+rRIPK1 group was further worsened.The PD group had significantly larger number of rotations,longer escape latency,higher apoptotic rate,increased TNF-α and IL-1β contents,and elevated lev-els of p-RIPK1/RIPK1(1.07±0.18 vs 0.36±0.11),p-RIPK3/RIPK3(1.32±0.21 vs 0.47±0.14),and p-MLKL/MLKL(0.79±0.11 vs 0.18±0.05),but lower DA,DOPAC,5-HT,and HVA con-tents than the Sham group(P＜0.05).Dex treatment of low,medium and high doses reserved all above changes induced by PD modeling(P＜0.05).The Dex+rRIPK1 group obtained larger num-ber of rotations,longer escape latency,higher apoptotic rate,increased TNF-α and IL-1β contents,and elevated levels of p-RIPK1/RIPK1(0.95±0.17 vs 0.41±0.12),p-RIPK3/RIPK3(1.14±0.20 vs 0.51±0.15),and p-MLKL/MLKL(0.72±0.09 vs 0.24±0.06),but decreased DA,DOPAC,5-HT,and HVA contents when compared with the H-Dex group(P＜0.05).Conclusion Dex protects the neurological function of PD rats by inhibiting the RIPK1/RIPK3/MLKL pathway.

Objective:To investigate the differences in clinical characteristics and antibiotic resistance of neonatal sepsis（NS）caused by different Gram-staining pathogens.Methods:A retrospective study was conducted on confirmed NS cases admitted to the Neonatal Ward of the Pediatric Department at The First Affiliated Hospital of Dali University，from June 1，2014，to May 31，2024.Patients were divided into Gram-positive and Gram-negative groups based on blood or cerebrospinal fluid（CSF）culture results.Clinical characteristics，pathogen distribution，and antibiotic resistance were compared between the two groups.Results:A total of 98 cases were included，with 81 in the Gram-positive group and 17 in the Gram-negative group.Multivariate logistic regression analysis revealed that NS cases with a high neutrophil percentage（ OR=0.933，95% CI：0.899-0.969）or hemorrhagic symptoms/signs（ OR=0.059，95% CI：0.008-0.458）were less likely to have Gram-positive pathogens detected in blood or CSF cultures（ P<0.05）.Common Gram-positive pathogens included Staphylococcus epidermidis with 35 strains（33.65%）and Staphylococcus hominis with 22 strains（21.15%）.The predominant Gram-negative pathogen was Escherichia coli with 14 strains（13.46%）.Gram-positive pathogens exhibited high resistance to oxacillin（91.30%），erythromycin（90.91%），and penicillin G（90.00%），but low resistance to tigecycline（0），linezolid（0），and vancomycin（0）.Gram-negative pathogens showed high resistance to ampicillin（92.31%），cefazolin（90.00%），and ampicillin/sulbactam（75.00%），but low resistance to amikacin（6.25%），latamoxef（0），and ertapenem（0）.The incidence of concurrent purulent meningitis was lower in the Gram-positive group than in the Gram-negative group（9.88% vs.47.06%， χ2=11.628， P<0.05），and there was significant difference. Conclusion:NS cases with high neutrophil percentages or hemorrhagic symptoms/signs are less likely to be caused by Gram-positive pathogens.Staphylococcus epidermidis and Staphylococcus hominis are common Gram-positive pathogens，while Escherichia coli is the predominant Gram-negative pathogen in NS.Both Gram-positive and Gram-negative pathogens exhibit resistance to specific antibiotics.NS caused by Gram-positive pathogens is less likely to be complicated by purulent meningitis compared to those caused by Gram-negative pathogens.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

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.

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.

Objective To observe the effect of RAW264.7 cells on calcium sparks in a insulin resistance model of C2C12 cells induced by sodium palmitate.Methods C2C12 cells and RAW264.7 cells were co-cultured to simulate the in vivo state of skeletal muscle.C2C12 cells were cultured in high-glucose medium containing 2%horse serum to induce differentiation into mature myotubes,and then divided into 5 groups:control(RAW264.7 cells),co-culture of C2C12 with RAW264.7,C2C12 alone,co-culture of C2C12 with RAW264.7 plus sodium palmitate(PA),and C2C12 alone with PA.PA of 5 mmol/L was used to induce insulin resistance in C2C12 cells for 24 hours.Revived and expanded RAW264.7 cells were evenly added to C2C12 cells and co-cultured for two days.Subsequently,cells were maintained in modified suspension culture,and both cell types were loaded with the calcium ion fluorescent probe Fluo-4 AM.Finally,Paraxanthine was used to induce intracellular calcium sparks,which was captured and recorded under a laser confocal microscope.Results No significant calcium signal change was observed in the control group.Co-cultured C2C12 cells exhibited rapid and pronounced calcium signal changes,whereas calcium signals in C2C12 cells cultured alone increased slowly throughout the observation period without a sharp decline.The peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).With PA induction,calcium signal changes in C2C12 cells were not markedly altered,while distinct calcium fluctuations were still observed in co-cultured C2C12 cells,and the peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).Conclusion RAW264.7 cells enhance the dynamic responsiveness of calcium signaling in both normal and PA-stimulated C2C12 cells.