OBJECTIVE:Most of the existing studies are based on traditional Meta-analysis to study the efficacy of single stimulation protocols such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor dysfunction in stroke patients,and it is not possible to clarify which stimulation protocol is the optimal choice.This study used network meta-analysis to systematically evaluate the clinical efficacy of different regimens of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke.METHODS:CNKI,WanFang,VIP,CBM,PubMed,Medline and Web of Science databases were searched to collect randomized controlled trials on different regimens of non-invasive brain stimulation for lower limb motor dysfunction after stroke from inception to October 1,2024.Data extraction was performed on the included studies.RevMan 5.4.1 software was used for traditional meta-analysis and the quality of the included studies was evaluated.Stata 17.0 software was used for network meta-analysis.RESULTS:(1)A total of 39 studies involving 2 920 patients were included,involving 6 treatment methods:conventional rehabilitation training,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation.(2)The results of network meta-analysis showed that high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training in the Fugl-Meyer assessment for lower extremity motor function.(3)In terms of improving Berg balance scale score,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,and intermittent theta burst stimulation were significantly different from conventional rehabilitation training(P＜0.05),and there was a significant difference between high-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation(P＜0.05).(4)In improving modified Barthel index and Barthel index,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training.(5)Under the cumulative ranking chart,high-frequency repetitive transcranial magnetic stimulation showed the best efficacy in Fugl-Meyer assessment for lower extremity motor function,Berg balance scale score,modified Barthel index and Barthel index,followed by low-frequency repetitive transcranial magnetic stimulation.CONCLUSION:Both high-and low-frequency repetitive transcranial magnetic stimulation can improve the lower limb motor function and balance function of patients with stroke,and can improve the activities of daily living of patients to varying degrees.Moreover,the effect of high-frequency repetitive transcranial magnetic stimulation is better than that of low-frequency repetitive transcranial magnetic stimulation.

OBJECTIVE:Most of the existing studies are based on traditional Meta-analysis to study the efficacy of single stimulation protocols such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor dysfunction in stroke patients,and it is not possible to clarify which stimulation protocol is the optimal choice.This study used network meta-analysis to systematically evaluate the clinical efficacy of different regimens of non-invasive brain stimulation in the treatment of lower limb motor dysfunction after stroke.METHODS:CNKI,WanFang,VIP,CBM,PubMed,Medline and Web of Science databases were searched to collect randomized controlled trials on different regimens of non-invasive brain stimulation for lower limb motor dysfunction after stroke from inception to October 1,2024.Data extraction was performed on the included studies.RevMan 5.4.1 software was used for traditional meta-analysis and the quality of the included studies was evaluated.Stata 17.0 software was used for network meta-analysis.RESULTS:(1)A total of 39 studies involving 2 920 patients were included,involving 6 treatment methods:conventional rehabilitation training,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation.(2)The results of network meta-analysis showed that high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training in the Fugl-Meyer assessment for lower extremity motor function.(3)In terms of improving Berg balance scale score,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,and intermittent theta burst stimulation were significantly different from conventional rehabilitation training(P＜0.05),and there was a significant difference between high-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation(P＜0.05).(4)In improving modified Barthel index and Barthel index,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,and transcranial direct current stimulation were superior to conventional rehabilitation training.(5)Under the cumulative ranking chart,high-frequency repetitive transcranial magnetic stimulation showed the best efficacy in Fugl-Meyer assessment for lower extremity motor function,Berg balance scale score,modified Barthel index and Barthel index,followed by low-frequency repetitive transcranial magnetic stimulation.CONCLUSION:Both high-and low-frequency repetitive transcranial magnetic stimulation can improve the lower limb motor function and balance function of patients with stroke,and can improve the activities of daily living of patients to varying degrees.Moreover,the effect of high-frequency repetitive transcranial magnetic stimulation is better than that of low-frequency repetitive transcranial magnetic stimulation.

Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry* ; Sesquiterpenes/chemical synthesis* ; Molecular Structure ; Humans ; Liver Cirrhosis/genetics* ; Biomimetics ; Plant Extracts/pharmacology*

Objective To investigate the therapeutic effect of gabapentin combined with hemoperfusion on skin pruritus in the patients on maintenance hemodialysis(MHD).Methods A total of 72 patients with MHD complicating moderate to severe skin itching treated in Lianyungang Municipal Oriental Hospital from January 2023 to March 2024 were selected as the study subjects and divided into the observation group and control group by the random number table method,36 cases in each group.On the basis of symptomatic treat-ment,the control group was given hemodialysis 3 times a week and hemoperfusion twice a month;on the basis of the control group,the observation group orally took 1 gabapentin capsule every night,and the patients in the two groups continued to be treated for 12 weeks.The visual analogue scale(VAS)score,Pittsburgh Sleep Quality Index(PSQI)score,molecular toxin level and calcium and phosphorus metabolism were evaluated be-fore treatment,in 4,12 weeks after treatment respectively,and the occurrence of adverse reactions during treatment in the two groups was observed.Results After 4 weeks and 12 weeks of treatment,the VAS and PSQI scores of the observation group were decreased compared with those before treatment,moreover the scores of the observation group were lower than those of the control group in the same period,and the differ-ences were statistically significant(P<0.05);the VAS and PSQI scores after 4 weeks of treatment in the control group were decreased compared with those before treatment,but the difference was not statistically significant(P>0.05);and the VAS and PSQI scores after 12 weeks of treatment in the control group were decreased compared with before treatment,and the difference was statistically significant(P<0.05).After 4 weeks of treatment,the levels of Scr,BUN and β2-MG in the two groups were decreased compared with those before treatment,but the differences were not statistically significant(P>0.05);after 12 weeks of treatment,the levels of Scr,BUN and β2-MG in the two groups were decreased compared with those before treatment and after 4 weeks of treatment,and the differences were statistically significant(P<0.05),but there was no sta-tistically significant difference between the two groups(P>0.05).After 4 weeks of treatment,there was no statistically significant difference in the levels of blood Ca,P and iPTH between the two groups compared with before treatment(P>0.05);after 12 weeks of treatment,except for blood Ca,the levels of blood P and iPTH in the two groups were decreased compared with those before treatment and in 4 weeks of treatment(P<0.05),and the differences were statistically significant(P<0.05),but there was no statistical difference be-tween the two groups(P>0.05).There were no adverse reactions in the control group,and there were 3 cases of drowsiness,1 case of fatigue and 1 case of dizziness at the beginning of treatment in the observation group.The symptoms were mild without treatment and spontaneously relieved in about 1 week.Conclusion Gabap-entin combined with hemoperfusion could quickly and effectively alleviate the itchy symptoms of skin,improve the sleep quality,reduce the uremic toxin levels,and improve the calcium and phosphorus metabolism in MHD patients,with few adverse reactions,and the patients are easy to tolerate.

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Objective:To investigate the association between the triglyceride-glucose(TyG)index and the incidence and mortality of cardiovascular disease(CVD)in a large population-based cohort.Methods:Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHi-nese Electronic health Records Research in Yinzhou(CHERRY)study between January 1,2010,and May 31,2020.The TyG index was calculated using baseline triglyceride and fasting blood glucose.Cox proportional hazards models were used to assess the association between the TyG index and the composite outcome of CVD(incidence and mortality),adjusting for age,gender,education,region,smoking sta-tus,body mass index,systolic blood pressure,and total cholesterol.Hazard ratios(HR)and 95％confi-dence intervals(CI)were calculated.Nonlinear associations between the TyG index and CVD were fur-ther evaluated using restricted cubic splines,and subgroup analyses by gender and age were conducted to explore potential differences.Results:A total of 226 406 individuals were included,with a mean age of(55.0±9.7)years at baseline,46.8％of whom were men,and a median TyG index of 8.68.Over a median follow-up of 7.99 years,9 815(4.34％)participants experienced CVD incidence or mortality.After adjusting for age,gender,education,region,smoking status,body mass index,systolic blood pressure and total cholesterol,the risk of CVD increased with higher TyG index levels(P＜0.001).The risk in the highest TyG quartile(TyG＞9.10)was 42％higher than in the lowest quartile(TyG ≤8.32)(HR=1.42,95％CI:1.34-1.51).Individuals under 60 years had a higher HR for CVD compared with those aged 60 years and above(HR:1.71 vs.1.27,P＜0.05).Restricted cubic spline analysis revealed a reverse L-shaped association between the TyG index and CVD risk in the overall population(P＜0.001 for nonlinear trend),with risk increasing after the TyG index exceeded 8.67.However,the threshold varied by gender,with a lower threshold in women(8.51)than in men(8.67).Conclusion:A significant nonlinear relationship was revealed between the TyG index and CVD risk,with a threshold effect.The risk of CVD increased once the TyG index surpassed a certain threshold,with a lower threshold in women than in men.These findings suggest that cardiovascular risk prediction and interven-tions based on the TyG index should be gender-stratified,and early intervention for individuals under 60 years old might have important public health implications.

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

Objective:To investigate the association between the triglyceride-glucose(TyG)index and the incidence and mortality of cardiovascular disease(CVD)in a large population-based cohort.Methods:Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHi-nese Electronic health Records Research in Yinzhou(CHERRY)study between January 1,2010,and May 31,2020.The TyG index was calculated using baseline triglyceride and fasting blood glucose.Cox proportional hazards models were used to assess the association between the TyG index and the composite outcome of CVD(incidence and mortality),adjusting for age,gender,education,region,smoking sta-tus,body mass index,systolic blood pressure,and total cholesterol.Hazard ratios(HR)and 95％confi-dence intervals(CI)were calculated.Nonlinear associations between the TyG index and CVD were fur-ther evaluated using restricted cubic splines,and subgroup analyses by gender and age were conducted to explore potential differences.Results:A total of 226 406 individuals were included,with a mean age of(55.0±9.7)years at baseline,46.8％of whom were men,and a median TyG index of 8.68.Over a median follow-up of 7.99 years,9 815(4.34％)participants experienced CVD incidence or mortality.After adjusting for age,gender,education,region,smoking status,body mass index,systolic blood pressure and total cholesterol,the risk of CVD increased with higher TyG index levels(P＜0.001).The risk in the highest TyG quartile(TyG＞9.10)was 42％higher than in the lowest quartile(TyG ≤8.32)(HR=1.42,95％CI:1.34-1.51).Individuals under 60 years had a higher HR for CVD compared with those aged 60 years and above(HR:1.71 vs.1.27,P＜0.05).Restricted cubic spline analysis revealed a reverse L-shaped association between the TyG index and CVD risk in the overall population(P＜0.001 for nonlinear trend),with risk increasing after the TyG index exceeded 8.67.However,the threshold varied by gender,with a lower threshold in women(8.51)than in men(8.67).Conclusion:A significant nonlinear relationship was revealed between the TyG index and CVD risk,with a threshold effect.The risk of CVD increased once the TyG index surpassed a certain threshold,with a lower threshold in women than in men.These findings suggest that cardiovascular risk prediction and interven-tions based on the TyG index should be gender-stratified,and early intervention for individuals under 60 years old might have important public health implications.