BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Objective To investigate the longitudinal relationship between sleep duration(SD)and positive youth development(PYD)among primary and secondary school students in Chengdu city using a cross-lagged model,and to provide scientific evidence for enhancing sleep management practices for students.Methods A total of 4061 students of grades 3 through 9 from the Chengdu Child Positive Development Cohort were included in this three-wave longitudinal study.There was a one-year interval between one survey and the following round of survey,and the time points for the baseline,12-month follow-up,and 24-month follow-up surveys were designated T0,T1,and T2.The PYD of the participants was assessed using the Chinese version of the Positive Youth Development Scale.The demographic data and the average daily SD over the past month were collected.Spearman correlation analysis was performed to examine the associations between SD and PYD,and a cross-lagged model was used to investigate the longitudinal relationship between them.Results The average daily SD for the 3 rounds of surveys conducted at T0,T1,and T2 was 9.00(8.04,10.00)hours,10.44(9.67,11.11)hours,and 10.39(9.83,11.00)hours,respectively,while the PYD scores were 5.30(4.73,5.71),5.27(4.73,5.73),and 5.39(4.89,5.77),respectively.Statistical significance was found in the differences of SD and PYD scores across the 3 rounds(P＜0.05).Spearman correlation analysis revealed synchronous correlations between SD and PYD at all three time points(r=0.10 at T0,r=0.18 at T1,and r=0.21 at T2,P＜0.05)and significant lagged correlations(e.g.,r=0.10 for T1-PYD and T2-SD,and likewise,significant correlation was found for the 3 other cross-lagged paths).The cross-lagged model demonstrated that PYD at T0 and T1 positively predicted SD at T1 and T2,respectively(β0-1=0.116[95％CI,0.083-0.150],β1-2=0.097(95％CI,0.067-0.127),P＜0.05),and that SD at T0 and T1 also positively predicted PYD at T1 and T2(β0-1=0.028[95％CI,0-0.056],β1-2=0.042[95％CI,0.010-0.074],P＜0.05).According to these findings,a bidirectional predictive relationship between SD and PYD across different time points was observed in primary and secondary school students.Furthermore,PYD demonstrated better performance for predicting SD than SD did for PYD.Subgroup analysis by sex confirmed the robustness of the predictive power of PYD for SD.Conclusion This study reveals a positive bidirectional predictive relationship between SD and PYD among primary and secondary school students,suggesting that higher levels of PYD may contribute to adequate sleep.These findings provide critical scientific evidence for schools and families to strengthen sleep management and promote the holistic development and well-being of adolescents.

Objective:To investigate the levels of osteoporosis-related biomarkers in individuals with subclinical hypothyroidism complicated by type 2 diabetes mellitus.Methods:A cross-sectional study. From January 2021 to June 2022, 40 patients with subclinical hypothyroidism, 40 patients with type 2 diabetes, 40 patients with type 2 diabetes complicated with subclinical hypothyroidism, and 40 individuals receiving physical examination in Shanxi Bethune Hospital were selected as subjects in this study. The glucose and lipid metabolism indexes and bone metabolism indexes of the subjects were detected, and the differences and correlations of the metabolic indexes among the groups were analyzed by t-tests, nonparametric tests or correlation analysis. Results:Compared with healthy group, beta C-terminal cross-linked telopeptides of type Ⅰ collagen (β-CTX) level in type 2 diabetes group was higher [(344.60±125.61) vs (227.56±68.33) pg/ml] ( t=-5.176, P<0.001), osteocalcin (OC) and total procollagen type 1 aminoterminal peptide (t-PINP) were both lower [(15.76±4.70) vs (28.02±5.83)ng/ml, (43.49±13.63) vs (59.58±15.80) ng/ml] ( t=10.352, t=4.874, P<0.001). The β-CTX level in type 2 diabetes patients complicated with hypothyroidism was higher than that in patients with simple subclinical hypothyroidism [(380.51±122.22) vs (212.41±44.17) pg/ml] ( t=-8.180 ,P<0.001), but the levels of OC and t-PINP were both lower [(13.67±4.06) vs (26.12±4.55) ng/ml, (38.76±9.53) vs (61.50±12.31) ng/ml] ( t=12.897, P<0.001); but there was no significant difference in the three biomarkers between patients with type 2 diabetes mellitus complicated by subclinical hypothyroidism and those with type 2 diabetes mellitus alone. [β-CTX: (380.51±122.22) vs (344.60±125.61) pg/ml, OC: (13.67±4.06) vs (15.76±4.70) ng/ml, t-PINP: (38.76±9.53) vs (43.49±13.63) ng/ml] ( t=1.296,1.890,-1.799 ,all P>0.05). In the patients with type 2 diabetes mellitus complicated by subclinical hypothyroidism, the β-CTX was positively correlated with fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c)( r=0.293,0.487,all P<0.05), while OC and t-PINP were negatively correlated with FBG and HbA1c ( r=-0.560,-0.502,-0.289,-0.326, P<0.05). Conclusion:Changes of serum osteoporosis-related biomarkers in subclinical hypothyroidism patients with type 2 diabetes indicate the increased risk of osteoporosis in those patients.

Objective:This study aimed to explore the effect of Vaspin on adipose tissue macrophage polarization and its underlying mechanism.Methods:Fifty male SD rats, aged 8 weeks, were chosen and randomly allocated into three groups: the normal control(NC), the type 2 diabetes(T2DM), and various concentrations of Vaspin intervention(V1: 480 ng/kg, V2: 960 ng/kg, V3: 1 440 ng/kg). Vaspin was administered via intraperitoneal injection for 8 weeks. Glucose tolerance and insulin sensitivity were evaluated via intraperitoneal glucose tolerance test(IPGTT), intraperitoneal insulin tolerance test(IPITT) and hyperinsulinemic-euglycemic clamp. Adipose tissue inflammation and macrophage polarization were assessed using immunofluorescence, RT-PCR and western blotting.Results:After 8 weeks of intervention, there were no statistically significant differences in body weight and blood lipid levels among groups. IPGTT, IPITT, and hyperinsulinemic-euglycemic clamp experiments demonstrated that Vaspin intervention improved blood glucose and insulin sensitivity, exhibiting a dose-dependent manner( P<0.05). IF and RT-PCR showed that Vaspin downregulated the expression of CD11c, IL-1β, and TNF-α in eWAT, while upregulating the expression of CD206, IL-10, and PPARγ, which correlated with Vaspin concentration( P<0.05). ELISA revealed that Vaspin intervention reduced the concentrations of IL-1β and TNF-α in serum, while increasing the concentration of IL-10( P<0.05). Western blotting demonstrated that Vaspin downregulated iNOS protein expression, while upregulating Arg1, p-Akt, and PPARγ expression in a dose-dependent manner( P<0.05). Conclusion:Vaspin promotes M2 polarization of adipose tissue macrophages via PPARγ pathway, leading to reduced inflammation and improved insulin sensitivity in T2DM rats.

Objective To compare the survival outcomes of bladder cancer with non-pure urothelium(BCa with n-pU)and bladder cancer with pure urothelium(BCa with pU)treated with robot-assisted radical cystectomy(RARC).Methods Clinical data of BCa patients treated with RARC in Nanjing Drum Tower Hospital during Oct.2014 and Mar.2022 were retrospectively analyzed.The patients were divided into n-pU group and pU group.After the baseline differences between groups were balanced with propensity score matching(PSM),the overall survival(OS)and recurrence-free survival(RFS)curve were plotted using Kaplan-Meier method and compared using Log-rank test.Univariate and multivariate analysis were performed with Cox model to identify the influencing factors of prognosis.Based on the results,a secondary grouping was performed to compare the survival differences between subgroups and further investigate the prognostic factors.Results After PSM,there were 53 pairs of BCa patients.There were no significant differences in the baseline data between the pU and n-pU groups(P＜0.05).Regardless of T stage,there were no significant differences in OS and RFS between the two groups(P=0.217,P=0.109).Univariate Cox regression analysis showed that T stage(＞T2)was a significant risk factor of OS and RFS(P＜0.05).In the early pathological stage(≤T2),there were no significant differences in OS and RFS(P=0.565,P=0.344).In the advanced pathological stage(＞T2),the OS and RFS of n-pU were significantly worse than those of pU patients(P=0.025,P=0.034).Conclusion The prognosis of BCa patients with n-pU who received RARC is significantly correlated with pathological status.At＞T2 stage,n-pU patients have worse prognosis than pU patients in the same pathological status.

Objective:To investigate the value of 3D CT reconstruction in diagnosis of chronic lateral ankle instability (CLAI) combined with syndesmotic diastasis (SD).Methods:A retrospective study was conducted to analyze the clinical data of 160 patients with CLAI who had been examined by arthroscopy from January 2018 to September 2022 at Department of Foot and Ankle Surgery, Wuhan Fourth Hospital. There were 64 males and 96 females with an age of (39.8±12.6) years. Eighty-one left and 79 right feet were affected; the time from injury to surgery was (27.3±11.6) months. The patients were divided into a widened interval group and a normal interval group according to the syndesmotic width measured, with 2 mm as a critical value. After preoperative 3D CT reconstruction, the differences in anterior tibiofibular distance, posterior tibiofibular distance, the narrowest tibiofibular distance, fibular translation, fibular rotation, and syndesmotic area (SA) were compared between the 2 groups. Univariate and multivariate analyses were performed successively to identify the risk factors. The receiver operating characteristic (ROC) curve was used to identify the best predictive factor and critical value. According to the findings of previous research, the above analyses were repeated to determine the best predictive factor and critical value respectively in the sex subgroup, fibular morphology subgroup and incisura feature subgroup.Results:The binary logistic regression showed that SA was a risk factor for CLAI combined with SD ( OR=1.196, 95% CI: 1.122 to 1.275, P < 0.001). The ROC curve revealed an area under curve of 0.847 and the difference critical value of 22.06 mm 2 that indicated a sensitivity of 80.4% and a specificity of 78.9%, respectively. Subgroup analyses showed that SA was suitable for male and female patients and patients with different fibular morphologies and incisura features but the difference critical values were different. Conclusion:In 3D CT reconstruction, measurement of SA may help the diagnosis of CLAI combined with SD.

Background/Aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options. Results: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. Conclusions Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.

Objective:Through meta-analysis, the association of three common adipokines (leptin, adiponectin, and chemerin) with bone nutrition of senile osteoporosis (SOP) in China was systematically evaluated.Methods:CNKI, CBM, VIP, Wanfang, PubMed, Web of Science, Embase, Cochrane Library, and other databases were searched for articles published from the establishment of the database to July 30, 2022. After literature screening, data extraction, and quality evaluation of the included studies were independently conducted by two researchers, a meta-analysis was performed using RevMan5.4 and Stata17.0 softwares.Results:A total of 13 studies in the Chinese population were included, including 897 patients with SOP and 673 elderly with normal bone mineral density . The results of the meta-analysis showed that compared with the control group, the serum leptin levels were significantly lower ( MD -2.64, 95% CI -4.04 to -1.23, P < 0.001), chemerin levels were significantly higher ( MD 25.23, 95% CI 14.57 to 35.90, P < 0.001), and adiponectin levels were not significantly different ( MD -0.55, 95% CI -2.26 to 1.17, P > 0.05) in SOP patients. After subgroup analysis according to the measurement method, leptin levels remained lower in SOP patients than in the control group. Conclusions:Compared with the control group, leptin levels were lower and chemerin levels were higher in SOP patients. Therefore, dysregulation of adipokines may play an important role in the occurrence and development of SOP, and regulation of adipokine levels and functions may play a role in the treatment of SOP and the improvement of bone nutrition as a nutritional intervention.

Objective:To explore the clinical efficacy of reconstructing the calcaneocuboid and calcaneonavicular ligaments with the autologous semitendinosus for chronic bifurcate ligament injury.Methods:A retrospective study was conducted to analyze the clinical data of 12 patients with chronic bifurcate ligament injury who had been treated by anatomical reconstruction with the autologous semitendinosus from March 2018 to January 2021 at Department of Foot and Ankle Surgery, The Fourth Hospital of Wuhan. There were 4 males and 8 females with an age of (41.4±9.6) years. Seven left and 5 right feet were affected; the time from injury to surgery was (9.3±4.3) months. The surgical efficacy was evaluated based on anteroposterior and lateral imaging assessments of foot weight-bearing at 6 months postoperation, comparison of the visual analogue scale (VAS) pain scores for foot weight-bearing walking and the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot scores between preoperation and the last follow-up, stress test for stability of the transverse tarsal joint, recovery of movement, and occurrence of complications.Results:All patients were followed up for (18.4±4.0) months. Their sports activities were completely resumed after postoperative (6.8±3.9) months. Primary wound healing was achieved in all patients. One patient suffered from cutaneous nerve lesion and skin numbness, the symptoms of which disappeared after conservative treatment. Double harmonic curves were observed on the anteroposterior and lateral imaging films of foot weight-bearing in all patients. The spaces in the calcaneocuboid and the calcaneonavicular joints were normal, the articular positions were matched, and the calcaneocuboid joint was stable without recurrence or worsening of displacement. The VAS decreased significantly from preoperative 6.5 (5.6, 7.0) to 0.0 (0.0, 1.0) at the last follow-up, and the AOFAS mid-foot score increased significantly from preoperative (55.6±8.8) points to (92.3±2.6) points at the last follow-up ( P<0.05). The stress test for the stability of the transverse tarsal joint showed joint stability. Conclusion:Reconstruction of the calcaneocuboid and calcaneonavicular ligaments using the autologous semitendinosus is an alternative treatment for patients with chronic bifurcate ligament injury, because it can restore the stability of the bifurcate ligament and obviously improve the foot and ankle functions with limited postoperative complications.