Objective To explore the causal relationship between sarcopenia and cognitive impairment by using a two-sample Mendelian randomization(MR)study design.Methods Hand grip strength,usual walking pace,and appendicular lean mass(ALM)were identified as the primary exposure factors for sarcopenia,while cognitive function and cognitive performance associated with cognitive impairment were considered as the outcome.The MR statistical method was applied to examine the causal associations between both variables.Results The analysis revealed a positive correlation between sarcopenia,as indicated by hand grip strength,usual walking pace and ALM,and cognitive performance.Usual walking pace and ALM were positively associated with cognitive function.No significant causal relationship was detected between hand grip strength and cognitive function.In the reverse MR analysis,cognitive performance showed a positive correlation with usual walking pace and ALM,but no significant causal link was found with hand grip strength.Cognitive function was positively related to usual walking pace,but no significant associations were observed with hand grip strength and ALM.Conclusion Sarcopenia is associated with an increased risk of cognitive impairment,and a bidirectional causal relationship appears to exist between ALM and cognitive performance.

Objective To explore the causal relationship between sarcopenia and cognitive impairment by using a two-sample Mendelian randomization(MR)study design.Methods Hand grip strength,usual walking pace,and appendicular lean mass(ALM)were identified as the primary exposure factors for sarcopenia,while cognitive function and cognitive performance associated with cognitive impairment were considered as the outcome.The MR statistical method was applied to examine the causal associations between both variables.Results The analysis revealed a positive correlation between sarcopenia,as indicated by hand grip strength,usual walking pace and ALM,and cognitive performance.Usual walking pace and ALM were positively associated with cognitive function.No significant causal relationship was detected between hand grip strength and cognitive function.In the reverse MR analysis,cognitive performance showed a positive correlation with usual walking pace and ALM,but no significant causal link was found with hand grip strength.Cognitive function was positively related to usual walking pace,but no significant associations were observed with hand grip strength and ALM.Conclusion Sarcopenia is associated with an increased risk of cognitive impairment,and a bidirectional causal relationship appears to exist between ALM and cognitive performance.

Objective To evaluate the role of calcium channel in the mechanism of the generation and maintenance of bursting firing of substantia nigra pars compacta (SNc) dopaminergic neurons in rats.Methods Using the patch clamp technique,we observed the firing pattern switching features after adding 10 μmol/L N-methyl-D-aspartic acid (NMDA),compared the changes of whole-calcium current and L-type calcium current with or without NMDA,and analyzed the correlation between the generation of burst firing and L-type calcium channel activation.Results After NMDA treatment,the firing pattern of SNc dopaminergic neurons changed to burst firing,which was compromised by a charastistic high plateau potential and series of action potential on it.The current density of L-type calcium current increased significantly after adding NMDA,which,from (2.86 ±0.26) pA/pF (n =28),significantly increased to (3.75 ± 0.18) pA/pF (n =34 ; t =7.52,P =0.002 8).The high plateau potential was almost abolished with the application of verapamil,a specific antagonist of L-type calcium channel.Consiusion NMDA could induce the firing pattern changed to burst firing in SNc dopaminergic neurons,while L-type calcium channel contributes to the process of generation and maintenance of burst firing.

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.