Objective To investigate the impact of vestibular dysfunction on various domains of cognitive function, providing a basis for developing comprehensive vestibular-cognitive intervention strategies. Methods A total of 33 patients with confirmed unilateral vestibular dysfunction treated at Eye & ENT Hospital, Fudan University between June 2024 and December 2024. Vestibular function was assessed using vestibular evoked myogenic potential (VEMP), caloric testing, video head impulse test (vHIT), and sensory organization test (SOT). Cognitive function was evaluated using mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), Stroop color-word test, trail making test (TMT), and auditory verbal learning test (AVLT). Subjective symptoms were assessed using dizziness handicap inventory (DHI). Results In the vestibular function assessment of patients, abnormalities in caloric testing, utricle VEMP and saccule VEMP results were most common, with rates of 87.9%, 57.6%, and 66.7%, respectively; SOT abnormality primarily characterized by impaired vestibular function (21.2%). Spearman correlation analysis showed age, years of education, hearing ability, and emotional state were associated with overall or specific domains of cognitive function in patients. Greater vestibular dysfunction severity was associated with longer TMT-A time (r＝0.443，P＝0.010), most severe damage of short-term (r＝－0.405，P＝0.019) and long-term delayed recalls (r＝－0.537，P＝0.001). Patients with 31-60 of DHI scores showed longer TMT-A time than patients with 0-30 of DHI scores (P＝0.033). Conclusions Patients with vestibular dysfunction exhibit significant impairment in low-frequency semicircular canal and utricle function, which affects attention allocation, information processing speed, and memory performance in cognitive tasks.

【Objective】 To monitor the effectiveness and accuracy of the blood transfusion compatibility test system by self-made weakly positive internal quality control products. 【Methods】 Red blood cells from DAT(-) healthy subjects were selected, and B/RhD(-)E(-) red blood cells were selected as tube 1. A/RhD(+ )E(+ ) was selected as tube 2 to prepare blood group quality control products according to the principle of blood group antigen compatibility, and red blood cell preservation solution and corresponding ABO blood group reagent antibody were added to make the agglutination intensity of microcolumn gel method in reverse blood typing reach a low positive value (1+ ). Tube 3 and tube 4 were prepared with five different preservation media: plasma, serum, antibody diluent, mixture of equal plasma and antibody diluent, and mixture of equal serum and antibody diluent, respectively. IgM anti-E antibody was added to tube 3, and IgG anti-D antibody was added to tube 4, so that the agglutination intensity of microcolumn gel method reached a low positive value (1+ ). 【Results】 Comparison between the 5 different preservation media showed that the preservation medium of antibody diluent was the most stable for weakly positive antibody (F=11.35, P<0.05), Agglutination intensity 1+ is assigned 5 points by AABB Technical Manual, and its score was 5.25±1.75 points. 【Conclusion】 The use of self-made weakly positive quality control products can improve the effectiveness, accuracy and sensitivity of the monitoring system, thus achieving internal quality control and ensuring the safety of clinical blood use.

OBJECTIVE To investigate the protective effect of paeoniflorin(PF) on cardiac dysfunction and myocardial cell injury induced by cisplatin(CDDP) in rats. METHODS SD male rats were randomly divided into control group, CPPD group, and CDDP PF+low-dose, high-dose group. PowerLab multifunctional recorder was used to detect the related indexes of cardiac function: the changes of left ventricular peak pressure(LVSP), left ventricular end-diastolic pressure(LVEDP) and left ventricular pressure change rate(±dp/dt). Serum levels of inflammatory factors TNF-α, IL-1β and IL-6 were measured in each group. Myocardial tissue was stained to observe the changes of tissue structure. H9c2 cardiomyocytes were divided into control group, CDDP group, PF group and CDDP+PF group. The activity of H9c2 cardiomyocytes was measured by CCK-8. The apoptosis of cardiomyocytes in each group was detected by flow cytometry. The expressions of MAPK signaling pathway related proteins p38, ERK, JNK and their phosphorylated proteins and apoptosis-related proteins Bax, Bcl-2, Casp3, Cl-casp3 were detected in cardiomyocytes by Western blotting. RESULTS Compared with the control group, LVSP and ±dp/dt decreased, LVEDP increased in rats of CDDP group(P<0.01). Compared with CDDP group, both CDDP+low-dose and high-dose PF pretreatment increased LVSP and ±dp/dt value(P<0.05 or P<0.01), decreased LVEDP(P<0.01), and could decrease the serum inflammatory factor TNF-α, IL-1β and IL-6(P<0.01). Cell level results showed that compared with control group, in CDDP group, the cell activity decreased, the apoptosis-related protein Bax, Cl-casp3 increased(P<0.01), expression of anti-apoptotic protein Bcl-2 decreased(P<0.01), and the expression of p38 and ERK phosphorylation also increased(P<0.01). Compared with CDDP group, PF could restore cell activit, down-regulate apoptosis-related protein Bax, Cl-casp3(P<0.05 or P<0.01), and increase anti-apoptotic protein Bcl-2 expression(P<0.01), inhibit MAPK pathway p38 and ERK phosphorylation expression(P<0.01). CONCLUSION PF can restore cardiac dysfunction and myocardial cell injury induced by cisplatin in rats, which may be related to inhibiting inflammation and apoptosis by regulating ERK/p38 MAPK signal expression.

Objective To investigate the effect of dioscin on uric acid(UA)-induced oxidative stress injury of human renal tubular epithelial cells(HK-2)and its molecular mechanism.Methods HK-2 cells were cultured and divided into four groups:blank group(normal group),model group(uric acid-stimulation modeling),condition control group(UA+DMSO)and dioscin group(UA+dioscin).Oxidative stress injury model was induced by UA in HK-2 cells.Cells viability was detected by CCK-8.ROS level was detected by flow cytometry.Real-time PCR was used to detect the expressions of glycogen synthase kinase 3β(GSK3β),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)at mRNA level,and Western Blot was used to detect the expressions of phosphorylated glycogen synthesis kinase 3β(p-GSK3β),GSK3β,Nrf2 and HO-1 at protein level.Results After stimulation by UA,HK-2 cells viability was obviously decreased,and ROS level was significantly increased(all P＜0.001).When treated with dioscin,HK-2 cells viability was obviously increased,and the ROS level of HK-2 cells was significantly decreased(all P＜0.001).The expressions of Nrf2 and HO-1 decreased at the protein and mRNA levels after stimulation with UA.But the expressions of Nrf2 and HO-1 significantly increased after treated with dioscin(all P＜0.001).Compared with the blank group,the p-GSK3β/GSK3β ratio in the model group decreased significantly at the protein level,but the p-GSK3β/GSK3β ratio increased after treated with dioscin(all P＜0.001).Conclusion Dioscin can alleviate UA-induced oxidative stress injury in HK-2 cells.The mechanism might be that dioscin can promote phosphorylation of GSK3β,and activate Nrf2/HO-1 pathway.

【Objective】 To explore the causal relationship between education level and pancreatitis risk through Mendelian randomization. 【Methods】 A two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) summary data. The GWAS data for education level and pancreatitis were obtained from SSGAC database and the FinnGen database (version R9). Causal relationship between education level and pancreatitis was explored using the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Heterogeneity and directional pleiotropy were evaluated using Cochran’s Q test and funnel plots. 【Results】 Totally 604 SNPs associated with education level were included. The results provided evidence that there was negative relationship between education level and pancreatitis risk. For acute pancreatitis, OR=0.52, 95% CI: 0.44-0.62, P=2.43×10^-14 while for chronic pancreatitis, OR=0.51, 95% CI: 0.41-0.64, P=7.20×10^-9. Results from MR-Egger and weighted median analyses obtained the same results. The results of sensitivity analysis indicated that this study did not violate the basic assumptions of Mendelian randomization. 【Conclusion】 There is a causal relationship between education level and the occurrence of pancreatitis. The educational level is negatively correlated with the risk of pancreatitis.

BACKGROUND:Many clinical research observations have indicated a close association between rheumatoid arthritis and osteoporosis as well as bone mineral density(BMD).However,it remains unclear whether there is a causal genetic relationship between rheumatoid arthritis and the development of osteoporosis and alterations of BMD. OBJECTIVE:To assess the potential causal relationship between rheumatoid arthritis and osteoporosis as well as BMD using a two-sample Mendelian randomization approach,provide meaningful insights from a genetic perspective into the underlying mechanisms and offer a reference for early prevention of osteoporosis and improvement in the progression of the disease. METHODS:We conducted a study using data from publicly available genome-wide association studies databases to identify single nucleotide polymorphisms associated with rheumatoid arthritis as instrumental variables(P＜5×10-8).The main outcomes of the study included osteoporosis and BMD at five different sites,including total body BMD,lumbar spine BMD,femoral neck BMD,heel BMD,and forearm BMD.The inverse variance-weighted method was used as the primary analysis method to evaluate causal effects.Weighted median,simple median,weighted mode and MR-Egger regression were used as supplementary analyses.Causal relationships between rheumatoid arthritis and the risk of osteoporosis and BMD were assessed using odds ratios(OR)and 95%confidence intervals(CI).Heterogeneity was assessed using Cochran's Q test and horizontal pleiotropy was evaluated using MR-Egger intercept tests. RESULTS AND CONCLUSION:The inverse variance-weighted analysis demonstrated a positive association between genetically predicted rheumatoid arthritis and osteoporosis(OR=1.123,95%CI:1.077-1.171;P=4.02×10-8).Heterogeneity test(P=0.388)indicated no significant heterogeneity among the single nucleotide polymorphisms.MR-Egger intercept(P=0.571)tests did not detect horizontal pleiotropy,and sensitivity analysis showed no evidence of bias in the study results.There was no causal relationship between rheumatoid arthritis and BMD at the five different sites.The total body BMD(OR=1.000,95%CI:0.988-1.012;P=0.925),lumbar spine BMD(OR=0.999,95%CI:0.982-1.016;P=0.937),femoral neck BMD(OR=1.001,95%CI:0.986-1.016;P=0.866),heel BMD(OR=0.996,95%CI:0.989-1.004;P=0.419),and forearm BMD(OR=1.063,95%CI:0.970-1.031;P=0.996)indicated no significant association.MR-Egger intercept analysis did not detect potential horizontal pleiotropy(total body BMD:P=0.253;lumbar spine BMD:P=0.638;femoral neck BMD:P=0.553;heel BMD:P=0.444;forearm BMD:P=0.079).Rheumatoid arthritis may contribute to the development of osteoporosis through the interaction between chronic inflammation and bone formation,resorption,and absorption.Additionally,the use of glucocorticoids and the presence of autoantibodies(such as anti-citrullinated protein antibody)in patients with rheumatoid arthritis showed associations with osteoporosis.Future research should focus on monitoring systemic inflammatory markers,standardized use of glucocorticoids,and regular screening for osteoporosis risk in patients with rheumatoid arthritis.

BACKGROUND:Observational studies have suggested that statins may have a protective effect against osteoarthritis,including knee osteoarthritis and hip osteoarthritis.However,the association between statins and the risk of osteoarthritis remains unclear. OBJECTIVE:To investigate the association between statins and the risk of osteoarthritis through Mendelian randomization analysis using summary data from large-scale population-based genome-wide association studies(GWAS). METHODS:Firstly,single nucleotide polymorphism data related to statins were obtained from the latest 9th edition of the FinnGen database,while data of osteoarthritis,knee osteoarthritis and hip osteoarthritis were obtained from the IEU Open GWAS,UK Biobank,and ArcOGEN(Genetics of Osteoarthritis)databases,respectively.The inverse variance weighted method was used as the primary analysis approach to evaluate the causal effects.The weighted median method,simple median method,weighted mode-based method,and MR-Egger regression were used as supplementary analyses.The causal relationship between statins and the risk of osteoarthritis,knee osteoarthritis and hip osteoarthritis was assessed using odds ratios(OR)with 95%confidence intervals(CI).Sensitivity analyses were conducted to validate the reliability of the results,including the Cochran's Q test for heterogeneity and the MR-Egger-intercept test for horizontal pleiotropy,as well as leave-one-out analysis to identify potentially influential single nucleotide polymorphisms. RESULTS AND CONCLUSION:The inverse variance weighted analysis demonstrated a negative causal relationship between genetically predicted statins and the risk of osteoarthritis(OR=0.998,95%CI:0.996-0.999,P=0.01),knee osteoarthritis(OR=0.964,95%CI:0.940-0.989,P=0.005),and hip osteoarthritis(OR=0.928,95%CI:0.901-0.955,P=4.28×10-7).MR-Egger intercept analysis did not detect potential horizontal pleiotropy(osteoarthritis:P=0.658;knee osteoarthritis:P=0.600;hip osteoarthritis:P=0.141).The results of this study provide evidence that statins reduce the risks of osteoarthritis,knee osteoarthritis and hip osteoarthritis as described in observational studies.Further research is needed to explore the specific mechanisms of statin treatment for osteoarthritis.

BACKGROUND:Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level,and the mechanism of related signaling pathways is an important way to further understand osteoporosis.At present,traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis.Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action. OBJECTIVE:To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature. METHODS:"Kaempferol,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathways"were used as Chinese and English search terms to search CNKI,WanFang,VIP,PubMed,Web of Science and Embase databases for relevant literature published from database inception to February 2023. RESULTS AND CONCLUSION:Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation,proliferation and apoptosis of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts.Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways.Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex.Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis.Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification.Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway.Kaempferol inhibits the expression of ERK,JNK,p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway,thus protecting osteogenesis.Kaempferol enhances the expression of osteogenic factors,bone morphogenetic protein-2,p-Smad1/5/8,β-catenin and Runx2,inhibits the expression of Peroxisome proliferation-activated receptor,and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.

BACKGROUND:Recent studies have shown that research on naringin anti-osteoporosis mostly stays in in vitro and in vivo experiments.Understanding the mechanism of related signaling pathways and the expression of related proteins and some specific genes is an important way to deeply understand naringin anti-osteoporosis.At present,traditional Chinese medicine has been confirmed to have a significant role in anti-osteoporosis.Naringin is one of the main active ingredients in Rhizoma Drynariae.Its effectiveness and mechanism of action against osteoporosis have been gradually recognized by scholars,and its clinical and basic research has been gradually emphasized. OBJECTIVE:To analyze and summarize the research progress of naringin in anti-osteoporosis in vitro and in vivo,thereby providing some ideas for the next step to study its related mechanism of action. METHODS:The relevant literatures included in CNKI and PubMed database were searched with the Chinese search terms of"naringin,osteoporosis,traditional Chinese medicine compound,pathogenesis,signaling pathway,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English,respectively.The corresponding criteria were established according to the research needs,and finally 69 articles were included for review. RESULTS AND CONCLUSION:Naringin blocks the increase in the number of osteoclasts and adipocytes,the decrease in the number of osteocytes and osteocalcin(+)cells induced by fructose-rich diet,and promotes the secretion of Sema3A from osteoblasts and osteocytes,thereby enhancing local bone formation and inhibiting osteoclast production by activating the Wnt/β-catenin pathway.Naringin is an important way to induce autophagy of osteoblasts,but autophagy-related proteins participate in osteoblast differentiation and bone formation.Lack of autophagy in osteoblasts reduces mineralization and leads to an imbalance in the number of osteoblasts and osteoclasts,which results in bone loss and decreased bone density.The composite scaffold loaded with naringin can be used as a necessary carrier for bone defect repair and has excellent bone repair properties.Naringin can also accelerate the growth of new bone tissue by increasing the local contents of bone morphogenetic protein 2 and vascular endothelial growth factor.Naringin can regulate bone metabolism and inhibit oxidative stress via ERK,PI3K/Akt and Wnt signaling pathways to improve osteoporosis,which can play a good role in preventing and controlling the disease.However,the depth and breadth of the relevant research is insufficient.Based on the mechanism of the current study,we should investigate the specific mechanisms by which naringin regulates different pathways and inter-pathway interactions in the future,which will be beneficial to the multifaceted development of naringin used in the treatment of osteoporosis..

Objective To determine the reference red blood cells with weak agglutination intensity of low positive quali-ty control products by comparing RhD antigen expression intensity difference according to the serological results.Methods The RhD(+)red blood cells were detected by microcolumn gel method with 1 500 times diluted anti-D typing reagent.The samples with weak and strong RhD antigen expression intensity were selected as the reference red blood cells for weak agglu-tination intensity of low positive quality control products,and verification was performed.Results Ten RhD(+)red blood cells were detected with diluted anti-D typing reagent,of which 8 were 1+and 2 were±.Red blood cells with agglutination intensity of 1+were used as the benchmark to determine the maximum dilution ratio of anti-D typing reagent when their ag-glutination intensity was 1+.As the preparation standard of low positive quality control products,the agglutination intensity of red blood cells with low RhD antigen expression intensity was extremely weak±,which was difficult to ensure the stability of its control limit properties.Based on red blood cells with agglutination intensity of±,the maximum dilution ratio of anti-D typing reagent with agglutination intensity of 1+was re-determined as the preparation standard of low positive quality con-trol products,and the results met the requirements of quality control product setting.Conclusion Using red blood cells with low RhD antigen expression intensity as the benchmark to set the weak agglutination intensity of the low positive quality control products can avoid the loss of control due to the low target value.