Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

China is one of the countries with the fastest growth in diabetes. The prevalence of diabetes among adults in China is as high as 12.4%, while the awareness rate of patients is only 36.7%, the standardized diagnosis and treatment rate is 32.9%, and the rate of achieving control targets is 50.1%. Diabetes prevention and control has become a major issue related to national economy and people′s livelihood. The data from 2015 to 2017 in Shanxi indicate that the prevalence of diabetes among adults aged 18 and above is 10.4%, while the prevalence of prediabetes is 34.5%. Moreover, the awareness, treatment, and control rates of diabetes among patients remain suboptimal. How to adhere to the principle of innovation while maintaining the core values, and efficiently apply and fully promote the standardized diabetes prevention and control model of National Diabetes Prevention and Control Center (DPCC) in Shanxi Province, is undoubtedly an important topic with great significance for exploration and practice. The Shanxi sub-center of DPCC has sorted out some working ideas based on more than two years of specific practical experience for reference.

China is one of the countries with the fastest growth in diabetes. The prevalence of diabetes among adults in China is as high as 12.4%, while the awareness rate of patients is only 36.7%, the standardized diagnosis and treatment rate is 32.9%, and the rate of achieving control targets is 50.1%. Diabetes prevention and control has become a major issue related to national economy and people′s livelihood. The data from 2015 to 2017 in Shanxi indicate that the prevalence of diabetes among adults aged 18 and above is 10.4%, while the prevalence of prediabetes is 34.5%. Moreover, the awareness, treatment, and control rates of diabetes among patients remain suboptimal. How to adhere to the principle of innovation while maintaining the core values, and efficiently apply and fully promote the standardized diabetes prevention and control model of National Diabetes Prevention and Control Center (DPCC) in Shanxi Province, is undoubtedly an important topic with great significance for exploration and practice. The Shanxi sub-center of DPCC has sorted out some working ideas based on more than two years of specific practical experience for reference.

[Objectives]To investigate the effect of METTL3 on the malignant biological behaviors of uveal melanoma cells and to verify whether this effect is related to m6A methylation.[Methods]Uveal melanoma cell models with METTL3 knockdown,overexpression,and point mutations at m6A-related catalytic sites were constructed via lentivirus transfection.Transwell assays were used to assess cell migration and invasion;CCK8 assays were used to measure cell proliferation and flow cytometry was used to analyze apoptosis and cycle changes.[Results]The proliferation,migration and invasion abilities of C918 and MUM-2B cells with METTL3 knockdown were significantly decreased(P<0.001),while the apoptosis rate was increased.The proportion of cells in G1 phase significantly increased,whereas the proportion in the S phase significantly decreased.Cells overexpressing METTL3 showed significantly enhanced proliferation,migration and invasion abilities(P<0.001),along with a decreased apoptosis rate.In C918 cells,the proportion of cells in G1 phase decreased significantly,while the proportion in S phase increased significantly.The cell cycle distribution of MUM-2B cells did not change remarkably.Following point mutation of m6A-related catalytic sites,cell proliferation,migration and invasion decreased,and the apoptosis rate increased.In MUM-2B cells,the percentage of cells in G1 phase significantly increased;the percentage in S phase significantly decreased and the percentage in G2 phase slightly decreased.In C918 cells,the percentage of G1 phase cells significantly increased,with no significant changes in the proportions of S and G2 phases.[Conclusions]The proliferation,invasion and metastasis of uveal melanoma cells were positively correlated with the expression of METTL3,while the apoptosis rate was negatively correlated.Changes in METTL3 levels differentially affect the cell cycles in different cell lines.The effects of METTL3 on the proliferation,migration and invasion of uveal melanoma cells are related to m6A methylation modification.

[Objectives]To investigate the effect of METTL3 on the malignant biological behaviors of uveal melanoma cells and to verify whether this effect is related to m6A methylation.[Methods]Uveal melanoma cell models with METTL3 knockdown,overexpression,and point mutations at m6A-related catalytic sites were constructed via lentivirus transfection.Transwell assays were used to assess cell migration and invasion;CCK8 assays were used to measure cell proliferation and flow cytometry was used to analyze apoptosis and cycle changes.[Results]The proliferation,migration and invasion abilities of C918 and MUM-2B cells with METTL3 knockdown were significantly decreased(P<0.001),while the apoptosis rate was increased.The proportion of cells in G1 phase significantly increased,whereas the proportion in the S phase significantly decreased.Cells overexpressing METTL3 showed significantly enhanced proliferation,migration and invasion abilities(P<0.001),along with a decreased apoptosis rate.In C918 cells,the proportion of cells in G1 phase decreased significantly,while the proportion in S phase increased significantly.The cell cycle distribution of MUM-2B cells did not change remarkably.Following point mutation of m6A-related catalytic sites,cell proliferation,migration and invasion decreased,and the apoptosis rate increased.In MUM-2B cells,the percentage of cells in G1 phase significantly increased;the percentage in S phase significantly decreased and the percentage in G2 phase slightly decreased.In C918 cells,the percentage of G1 phase cells significantly increased,with no significant changes in the proportions of S and G2 phases.[Conclusions]The proliferation,invasion and metastasis of uveal melanoma cells were positively correlated with the expression of METTL3,while the apoptosis rate was negatively correlated.Changes in METTL3 levels differentially affect the cell cycles in different cell lines.The effects of METTL3 on the proliferation,migration and invasion of uveal melanoma cells are related to m6A methylation modification.

Objective To analyze the biomechanical characteristics of the landing movements of com-petitive aerobics athletes,compare the laterality between their dominant and non-dominant limbs,and to explore the primary factors influencing landing stability.Methods Taking 26 female aerobics athletes in universities as the research objects,their kinematics and kinetics data of double-leg vertical land-ing with the height of 40 cm were simultaneously recorded.A comparison was made between the two limbs in terms of joint angles at initial contact,range of motion(ROM)of joint,ground reaction force(GRF),load-rate,the displacement and envelope area of the center of pressure(COP).The symmetry index(SI),reflecting laterality,was computed,and a multiple stepwise regression analysis was conduct-ed to examine the correlation between parameter asymmetry and COP envelope area.Results Compared with the non-dominant limbs,the dominant limbs had significantly greater knee external rotation and hip abduction angle at initial contact(P<0.05),significantly greater ROM of the ankle and hip flexion-extension and hip adduction-abduction,and smaller ROM of ankle rotation during landing(P<0.05).Moreover,the peak knee extension moment of the dominant limbs was significantly higher than the non-dominant limbs(P<0.01).The SI of vertical load rate and peak knee extension moment were signif-icantly positively correlated with the COP envelope area(P<0.05).In addition,the SI of vertical load rate,peak knee extension moment and knee rotation angle could explain 83.6%of the difference in the COP envelope area.Conclusion There is laterality between the dominant and non-dominant limb of competitive aerobics athletes during landing:the greater laterality of the load rate and peak knee ex-tension moment,the worse the landing stability.Furthermore,the SI of vertical load rate,peak knee extension moment,and knee rotation angle can be used as predictors of the landing stability.

Objective:To explore the association between weight change from age 20 to middle age and diabetes risk.Methods:A total of 10 104 residents over 40 years old were recruited in Guangzhou. The final analysis data set is a cohort of 6 272 patients from the REACTION study. Quartile of weight changes from age 20 to middle-age was used as an independent variable to explore its association with newly diagnosed diabetes. Simple and multivariable logistic regression analysis were used to calculate OR and 95% CI. Results:The prevalence of newly diagnosed diabetes in study cohort was 15.7%. Weight changes from age 20 to middle-age was significantly higher in diabetes group( P<0.001). Logistic regression analysis found in general population and overweight people [24.0≤body mass index(BMI)<28.0 kg/m 2], after adjusting for gender, age, educational level, family history of diabetes, drinking, SBP, waist circumference, cholesterol, high-density lipoprotein-cholesterol(HDL-C), TG, ALT, AST, the risk of diabetes increased in line with the magnitude of weight change( P=0.081). While in group of lean, normal and obese adult, no significant association has been found. Conclusion:The risk of diabetes increased with weight change in general population and overweight people, indicating that weight change in adults after age of 20 was positively associated with diabetes. It is suggested the importance of weight management in the prevention of dialetes.

Objective: To investigate the change in intestinal flora in Mongolian students with anxiety,so as to provide basis for exploring the relationship between flora and secretion expression in vivo. Methods: The Self rating Anxiety Scale(SAS)was used to assess anxiety in medical college students; then a semi structured interview was administered. Fecal samples that met the inclusion criteria were collected and divided into anxiety (SAS score≥50) and control groups (no anxiety, SAS score<50) according to the standard score of SAS. Samples provided by Mongolian female students were selected from each group. The total bacterial DNA was extracted from the fecal samples for PCR amplification and NovaSeq 2x250bp high throughput sequencing was performed for the V3- V4 region of 16S rDNA gene to obtain the biological information of the intestinal flora. The intergroup OTU, structural diversity, significant difference, and LEfSe analyses were performed with information mining of the literature think tanks. Results: Anxiety existed in 23.86% of the Mongolian students,and 16.96% of the Han people. A Chi square test showed no significant difference in detection of anxiety between Mongolian and Han college students ( P =0.07). Analysis of the alpha diversity index showed that the Shannon index, Simpson index, Chao1 index, and Observed species did not differed significantly between the two groups( t =8.0， 9.0 ，6.0，6.5). The difference in abundance of some bacteria was significant at the Class, Order, Family, and Genus levels between the two groups( t =-2.26-2.57，-5.08-3.58，-2.65-2.09， P <0.05). Conclusion The alpha diversity index showed that there was no significant difference in the abundance and diversity of intestinal flora between the two groups. While there were significant differences at different classification levels, the results suggest that the structure of intestinal flora can change in students with anxiety.

[Abstract] Objective: Elevated levels of soluble PD-L1 (sPD-L1) are associated with worse prognosis of renal cell carcinoma and multiple myeloma. However, the regulatory roles and functions of sPD-L1 in advanced melanoma are not fully understood. This study was designed to evaluate the association between circulating sPD-L1 concentrations and prognosis of patients with advanced acral or mucosal melanoma. Methods: A total of 102 untreated patients with advanced acral and mucosal melanoma admitted to Peking University Cancer Hospital between January 2012 and December 2015 were enrolled in this study. In the meanwhile, peripheral blood samples were obtained from 40 healthy donors. Circulating sPD-L1 concentrations were determined using an enzyme-linked immunosorbent assay. Results: The advanced melanoma cohort included 58 acral melanoma patients and 44 mucosal melanoma patients. The pre-treatment concentration of sPD-L1 (2.91±2.23 ng/ml) in plasma of patients group was elevated as compared with that in healthy donors (0.59 ng/ml). The concentration of sPD-L1 in serum was significantly upregulated in 39/102 (38.2%) patients and significantly associated with increased LDH level (P=0.021) and number of Tregs (P=0.017). The overall survival rates of patients with high or low concentrations of sPD-L1 were statistically different (8.5 months [high level] vs 11.6 months [low level], P=0.022). Conclusion: sPD-L1 concentration is elevated in patients with advanced acral or mucosal melanoma, which may play an important role in predicting prognosis.

[Abstract] Objective: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients. Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed. Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores (S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94). Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.