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.

Objective: To investigate the epidemiological and spatio-temporal characteristics of influenza in Jiaxing City, Zhejiang Province, so as to provide insights into perfecting the prevention and control strategies of influenza. Methods: Data of influenza in Jiaxing City from 2019 to 2023 were collected from the Chinese Disease Prevention and Control Information System. Population data of the same period were collected from the Zhejiang Health Information Network Reporting System. The epidemiological characteristics of influenza were analyzed using descriptive analysis. Vector map information was collected from the Open Street Map, and the spatio-temporal clustering characteristics of influenza were analyzed using spatial autocorrelation and spatio-temporal scanning. Results: A total of 181 501 cases of influenza were reported in Jiaxing City from 2019 to 2023, with an average annual reported incidence of 653.93/105. The majority of cases were aged 5 to <15 years (59 785 cases, 32.94%). The majority of the occupations were students (78 239 cases, 43.11%) and pre-school children (33 715 cases, 18.58%). The county (city, district) with the highest reported incidence was Haining City (1 451.70/105), and the town (street) with the highest reported incidence was Chang'an Town (1 932.78/105). Spatial autocorrelation analysis showed that the incidence of influenza in Jiaxing City from 2019 to 2023 had positive spatial correlations (all Moran's I>0, all P<0.05), with a high-high clustering in the southern region. Spatio-temporal scanning analysis showed that there was a spatio-temporal clustering of influenza in Jiaxing City from 2019 to 2023, with the southern region being the primary-type clustering area and the period between November and January of the following year being the clustering time. Conclusion There was a significant spatio-temporal clustering of influenza in Jiaxing City from 2019 to 2023, with winter being the peak season and the southern region being the primary area.

It is believed that diabetes complicated with coronary heart disease is closely related to the functional interplay of the heart， spleen， and kidneys. This paper proposed the concept of the heart-spleen-kidney as a unified system for understanding and treating the disease. At the early stage， spleen and kidney deficiency leads to the internal accumulation of phlegm， dampness， and turbid lipids， causing impaired blood circulation and vascular obstruction， so treatment should focus on tonify the kidneys and strengthening the spleen， activating blood circulation and resolving stasis， using the self-prescribed Tangxin Maiwen Formula （糖心脉温方）. As the disease progresses， further decline of spleen and kidney function results in inadequate nourishment of the heart， leading to blood stasis and the accumulation of phlegm， dampness， and turbid lipids， which may transform into pathogenic heat and toxins， causing heart damage， then treatment should emphasize on boosting qi and nourishing yin， clearing heat， activating blood and resolving toxins， using the self-prescribed Tangxin Maiqing Formula （糖心脉清方）. In advanced stages， three zang organs， the heart， spleen， and kidneys， become severely impaired， leading to mental activity fail to be nourished and abnormal cognitive functions， so treatment should focus on harmonizing the three zang organs simultaneously， using the self-prescribed Yunpi Tiaoxin Decoction （运脾调心汤）. This approach aims to provide a clinical framework for the diagnosis and treatment of diabetes with coronary heart disease.

AIM:To investigate the mechanism by which exosomes(EXOs)derived from neural stem cells(NSCs)pretreated with astragaloside IV(ASIV)alleviate brain damage in rats after ischemic stroke.METHODS:Rat NSCs were isolated from fetal rats within 24 h of birth,cultured for 3 d,and subsequently treated with ASIV for additional 5 d.The EXOs from untreated NSCs and ASIV-pretreated NSCs(ASIV-EXOs)were isolated via ultracentrifugation of the cell supernatant.These EXOs were characterized using Western blot to detect specific markers such as CD63,tumor sus-ceptibility gene 101(TSG101)and calnexin.Nanoparticle analysis was employed to determine the size,and the morpholo-gy of the EXOs was observed under electron microscope.Six to eight-week-old SD male rats were randomly assigned to 6 groups:sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)model group,edaravone(EDA)treatment(MCAO/R+EDA)group,EXOs treatement(MCAO/R+EXOs)group and ASIV-EXOs treatment(MCAO/R+ASIV-EXOs)group.Tail vein injections were administered within 2 h following the successful establishment of the MCAO/R model.The Zea Longa method was utilized to evaluate neurological deficits,while the TTC method was employed to assess brain infarc-tion.Pathological changes were examined through HE staining,and TUNEL and caspase-1 immunofluorescence double staining were conducted to detect cellular pyroptosis.Serum levels of interleukin-1β(IL-1β)and IL-18 were measured us-ing ELISA,and Western blot was performed to evaluate the expression of caspase-1,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),gasdermin D(GSDMD),and IL-18 proteins in the ischemic area of the rat cerebral cortex across all groups.RE-SULTS:The MCAO/R group exhibited significantly higher neurological deficit scores compared to the sham group(P＜0.01)and lower scores in the administered groups relative to the MCAO/R group(P＜0.05).Cerebral infarction was mark-edly increased in the MCAO/R group compared to the sham group(P＜0.01),whereas the infarction area was reduced in the administered groups compared to the MCAO/R group(P＜0.05).Serum levels of IL-1β and IL-18 were significantly el-evated in the MCAO/R group versus the sham group(P＜0.01)and were lower in the administered groups compared to the MCAO/R group(P＜0.01).Moreover,IL-1β and IL-18 levels in the MCAO/R+ASIV-EXOs group were lower than those in the MCAO/R+EXOs group(P＜0.05).HE staining revealed pronounced sieve-like infarction foci in the ischemic area of the rat cerebral cortex in MCAO/R group,characterized by disorganized neuronal arrangements,reduced or absent Nys-trom's vesicles,shrunken or fragmented nuclei,and numerous red neurons.In contrast,drug-treated groups exhibited milder pathological changes with clearer neuronal structures and a significant reduction in red neuron counts.Immunofluo-rescence double staining indicated a significant increase in double-positive cells in the MCAO/R group compared to the sham group(P＜0.01),with a decrease in double-positive cells in the administered groups relative to the MCAO/R group(P＜0.05)and a further reduction in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).The expression levels of caspase-1,NLRP3,ASC,IL-18 and GSDMD proteins in the ischemic region of the rat cerebral cortex were significantly reduced in the administered groups compared to the MCAO/R group(P＜0.01),with further re-duction observed in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).CONCLU-SION:Exosomes derived from ASIV-pretreated NSCs attenuate brain damage in ischemic stroke rats,potentially through a mechanism involving the inhibition of pyroptosis mediated by the NLRP3/caspase-1 pathway.

Objective To investigate the effects and molecular mechanisms of ginsenoside Rg1(GSRG1)on the proliferation,mi-gration,and inflammatory cytokine expression of human gingival fibroblasts(HGFs)induced by lipopolysaccharide(LPS).Methods HGFs were isolated and cultured using the tissue block method.The effects of different concentrations of LPS(0,1,5,10,20μg/mL)on inflammatory cytokines in HGFs were detected by ELISA.Cells were divided into three groups:control group(no treat-ment),LPS group(20 μg/mL LPS),and LPS+GSRG1 group(20 μg/mL LPS and 100 mg/L GSRG1).Cell proliferation was detec-ted by cell counting kit-8(CCK-8);cell migration was assessed by Transwell assay;intracellular reactive oxygen species(ROS)lev-els were compared using flow cytometry;and the expression levels of TNF-α,IL-6,NLRP3,p-p38,and p38 proteins were detected by Western blot.Results LPS concentrations of 5,10,and 20 μg/mL significantly increased the expression of IL-6 and TNF-α in HGFs(P＜0.05),with 20 μg/mL showing the strongest pro-inflammatory effect.Compared with the control group,there was no notable difference in the proliferation of HGFs in the LPS group at Day 1 and 2.However,on Day 3,4 and 5,decreased cell proliferation,re-duced migration,significantly increased ROS levels(P＜0.001),elevated protein expression of TNF-α,IL-6,and NLRP3(P＜0.001),and reduced p-p38 protein expression(P＜0.001)were exhibited.Compared with the LPS group,the LPS+GSRG1 group showed significantly enhanced cell proliferation and migration(P＜0.05),reduced ROS levels,decreased protein expression of TNF-α,IL-6,and NLRP3,and increased p-p38 protein expression(P＜0.001).There was no significant change in p38 expression among the three groups.Conclusion GSRG1 can alleviate the inhibitory effects of LPS on the proliferation and migration of HGFs and inhibit the inflammatory response,potentially through mechanisms involving p-p38 protein regulation.

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 differential responses of the endoplasmic reticulum stress-to-apoptosis cascade induced by proton ultra-high dose rate (FLASH) irradiation between lung epithelial and lung cancer cells.Methods:Human lung epithelial cells (KT) and lung adenocarcinoma cells (A549) were irradiated with protons, and divided into Ctrl, CONV and FLASH groups. Survival curves were generated using colony formation assay. Protein and mRNA expressions of the endoplasmic reticulum (ER) stress and apoptosis regulators were assessed via Western blot and RT-qPCR. The concentration of IL-6 secreted into the culture supernatant was determined by enzyme-linked immunosorbent assay(ELISA).Results:In KT cells, compared to the CONV group, FLASH irradiation resulted in a significantly higher survival fraction ( P<0.05), increased GRP78 protein expression ( t= 7.52, P < 0.05) and UPR-related genes PERK, ATF4, and CHOP. In A549, the cell survival rate did not differ significantly between the CONV and FLASH groups ( P > 0.05). UPR pathway was not activated in either group. However, both CONV and FLASH irradiation significantly promoted secretion of IL-6 ( t=4.31, 4.47, P<0.05), while no difference was identified between two groups. In KT, both irradiation promoted secretion of IL-6 ( t=7.43, 3.07, P<0.05) while IL-6 concentration in FLASH group was significantly lower than that in CONV group ( t=7.63, P<0.05). Additionally, a pro-apoptotic propensity in KT cells following FLASH irradiation and in A549 cells following both FLASH and CONV irradiation was identified. Conclusions:In KT cells, FLASH irradiation cleared misfolded proteins through activating UPR pathway, promoted apoptosis of damaged cells, suppressed IL-6 secretion to attenuate inflammatory injury, and ultimately enhanced cell survival. Furthermore, proton FLASH irradiation bypasses ER stress activation in A549 cells, instead directly priming an apoptotic disposition with concomitant IL-6 hypersecretion. This paracrine damage amplification cascade potentiates radiation-induced tumoricidal efficacy through sustained cytotoxic microenvironment remodeling.

[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0～74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80～84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23％,P＜0.001),ASMRC showed a marginal increase(AAPC=0.78％,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.

Objective:To explore the efficacy of percutaneous vertebroplasty (PVP) using the partition injection technique in the treatment of Kümmell’s disease of stages Ⅰ and Ⅱ.Methods:A retrospective study was conducted of the 30 patients with stage Ⅰ or Ⅱ Kümmell’s disease (the partition group) who had been treated by PVP using the partition injection technique at Department of Spinal Surgery, Zhengzhou Orthopedic Hospital from January 2020 to January 2022. The data of another 30 patients who had been treated at the same department and the same period using conventional PVP for stage Ⅰ or Ⅱ Kümmell's disease were selected as the conventional group. In the partition group, there were 13 males and 17 females, with an age of (72.3±10.1) years and disease duration of (3.1±1.5) months. Seventeen thoracic and 13 lumbar vertebrae were affected. In the conventional group, there were 11 males and 19 females, with an age of (75.5±12.7) years and disease duration of (3.5±1.8) months. Eighteen thoracic and 12 lumbar vertebrae were affected. Surgical time, volume of bone cement injected, bone cement leakage, and bone cement distribution were compared between the 2 groups. The heights of the anterior and middle vertebral bodies, kyphotic Cobb angle, visual analog scale (VAS) pain score, and Oswestry disability index (ODI) were assessed postoperatively at 1 day, 6 months, and the last follow-up and compared between the 2 groups.Results:No significant differences were found in the baseline data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (17.3±3.1) months. There were no significant differences in the surgical time or bone cement leakage between the 2 groups ( P>0.05). The volume of bone cement injected in the partition group was significantly higher [(6.3±1.5) mL] than that in the conventional group [(4.9±1.0) mL] ( P<0.05). Bone cement distribution was significantly better in the partition group than that in the conventional group ( P<0.05). At postoperative 1 day, 6 months, and the last follow-up, the partition group was significantly better than the conventional group in anterior vertebral body height, middle vertebral body height, and kyphotic Cobb angle ( P<0.05). At the 6-month and the last follow-ups, the partition group was also significantly better than the conventional group in VAS pain score and ODI ( P<0.05). Conclusion:In the treatment of Kümmell’s disease of stages Ⅰ and Ⅱ, compared with conventional PVP, PVP using the partition injection technique may lead to better long-term outcomes due to its better bone cement distribution, more adequate cement injection, and better restoration of vertebral body heights and correction of local deformity.