Objective:To investigate the correlation between metabolic syndrome (MS), its different components and the risk of cholecystolithiasis and gallbladder polyp in Uygur population in rural areas of southern Xinjiang.Methods:This study was a prospective cohort study. A baseline survey was conducted in August 2016. A typical sampling method was used to select 10 476 Uygur people in rural areas of southern Xinjiang as the research objects. Baseline clinical data were collected, including demographic data such as age, gender, and education level, and laboratory examination indicators such as blood glucose and triglyceride levels. According to the MS diagnostic criteria of the relevant guidelines, 10 476 subjects were divided into the MS group (3 475 cases) and the non-MS group (7 001 cases). The incidence of cholecystolithiasis and gallbladder polyp was followed up in 2019, 2021 and 2023, respectively. Cox regression was used to analyze the correlation between MS, its different components and the risk of cholecystolithiasis and gallbladder polyp. Chi-square test and independent sample t test were used for statistical analysis. Results:The median follow-up time was 6.43 years in 10 476 subjects, and the overall cumulative incidence of cholecystolithiasis and gallbladder polyp was 5.43% (569/10 476). The cumulative incidence of cholecystolithiasis and gallbladder polyp in the MS group was 10.73% (373/ 3 475), which was significantly higher than that in the non-MS group (2.80% (196/7 001)); χ2= 284.62, P<0.001). The results of multivariate Cox regression analysis showed that, 41 to 59 years old ( HR=1.26, 95% confidence interval (95% CI): 1.03 to 1.54, P=0.025), ≥60 years old ( HR=1.88, 95% CI: 1.45 to 2.45, P<0.001), female ( HR=1.34, 95% CI: 1.13 to 1.60, P=0.001), MS ( HR=2.19, 95% CI: 1.59 to 3.01, P<0.001), hypertriglyceridemia ( HR=1.47, 95% CI: 1.18 to 1.83, P=0.001), hypertension ( HR=1.30, 95% CI: 1.04 to 1.62, P=0.023), and hyperglycemia ( HR=1.24, 95% CI: 1.01 to 1.52, P=0.041) were independent risk factors for cholecystolithiasis and gallbladder polyp. After the adjustment of age and gender, MS ( HR=3.39, 95% CI: 2.82 to 4.07, P<0.001), hypertriglyceridemia ( HR=2.37, 95% CI: 2.00 to 2.81, P<0.001), hypertension ( HR=2.00, 95% CI: 1.66 to 2.41, P<0.001), and hyperglycemia ( HR=1.86, 95% CI: 1.55 to 2.23, P<0.001) were still correlated with cholecystolithiasis and gallbladder polyp, and there was the srtongest correlation between MS and cholecystolithiasis and gallbladder polyp. The results of univariate Cox regression analysis showed that along with the increase of accumulated of MS components, the risk of cholecystolithiasis and gallbladder polyp significantly increased (1 to 5 components corresponding HR (95% CI) were 1.92 (1.13 to 3.24), 2.21 (1.32 to 3.69), 6.91 (4.22 to 11.30), 8.56 (5.15 to 14.22), and 10.73 (5.66 to 20.33); P=0.015, =0.002, <0.001, <0.001, and <0.001); after age and gender were adjusted, this trend still existed (1 to 5 components corresponding HR (95% CI) were 1.81(1.07 to 3.06), 1.95(1.16 to 3.27), 5.64(3.42 to 9.32), 6.69(3.97 to 11.25), and 7.76(4.04 to 14.91); P=0.028, =0.012, <0.001, <0.001, and <0.001). Conclusion:MS and its components can increase the risk of cholecystolithiasis and gallbladder polyp, and the risk of cholecystolithiasis and gallbladder polyp significantly increases along with the increase of accumulated of MS components.

Objective:To investigate the correlation between metabolic syndrome (MS), its different components and the risk of cholecystolithiasis and gallbladder polyp in Uygur population in rural areas of southern Xinjiang.Methods:This study was a prospective cohort study. A baseline survey was conducted in August 2016. A typical sampling method was used to select 10 476 Uygur people in rural areas of southern Xinjiang as the research objects. Baseline clinical data were collected, including demographic data such as age, gender, and education level, and laboratory examination indicators such as blood glucose and triglyceride levels. According to the MS diagnostic criteria of the relevant guidelines, 10 476 subjects were divided into the MS group (3 475 cases) and the non-MS group (7 001 cases). The incidence of cholecystolithiasis and gallbladder polyp was followed up in 2019, 2021 and 2023, respectively. Cox regression was used to analyze the correlation between MS, its different components and the risk of cholecystolithiasis and gallbladder polyp. Chi-square test and independent sample t test were used for statistical analysis. Results:The median follow-up time was 6.43 years in 10 476 subjects, and the overall cumulative incidence of cholecystolithiasis and gallbladder polyp was 5.43% (569/10 476). The cumulative incidence of cholecystolithiasis and gallbladder polyp in the MS group was 10.73% (373/ 3 475), which was significantly higher than that in the non-MS group (2.80% (196/7 001)); χ2= 284.62, P<0.001). The results of multivariate Cox regression analysis showed that, 41 to 59 years old ( HR=1.26, 95% confidence interval (95% CI): 1.03 to 1.54, P=0.025), ≥60 years old ( HR=1.88, 95% CI: 1.45 to 2.45, P<0.001), female ( HR=1.34, 95% CI: 1.13 to 1.60, P=0.001), MS ( HR=2.19, 95% CI: 1.59 to 3.01, P<0.001), hypertriglyceridemia ( HR=1.47, 95% CI: 1.18 to 1.83, P=0.001), hypertension ( HR=1.30, 95% CI: 1.04 to 1.62, P=0.023), and hyperglycemia ( HR=1.24, 95% CI: 1.01 to 1.52, P=0.041) were independent risk factors for cholecystolithiasis and gallbladder polyp. After the adjustment of age and gender, MS ( HR=3.39, 95% CI: 2.82 to 4.07, P<0.001), hypertriglyceridemia ( HR=2.37, 95% CI: 2.00 to 2.81, P<0.001), hypertension ( HR=2.00, 95% CI: 1.66 to 2.41, P<0.001), and hyperglycemia ( HR=1.86, 95% CI: 1.55 to 2.23, P<0.001) were still correlated with cholecystolithiasis and gallbladder polyp, and there was the srtongest correlation between MS and cholecystolithiasis and gallbladder polyp. The results of univariate Cox regression analysis showed that along with the increase of accumulated of MS components, the risk of cholecystolithiasis and gallbladder polyp significantly increased (1 to 5 components corresponding HR (95% CI) were 1.92 (1.13 to 3.24), 2.21 (1.32 to 3.69), 6.91 (4.22 to 11.30), 8.56 (5.15 to 14.22), and 10.73 (5.66 to 20.33); P=0.015, =0.002, <0.001, <0.001, and <0.001); after age and gender were adjusted, this trend still existed (1 to 5 components corresponding HR (95% CI) were 1.81(1.07 to 3.06), 1.95(1.16 to 3.27), 5.64(3.42 to 9.32), 6.69(3.97 to 11.25), and 7.76(4.04 to 14.91); P=0.028, =0.012, <0.001, <0.001, and <0.001). Conclusion:MS and its components can increase the risk of cholecystolithiasis and gallbladder polyp, and the risk of cholecystolithiasis and gallbladder polyp significantly increases along with the increase of accumulated of MS components.

Objective:To construct the intracranial venous sinus thrombosis (CVST) models under plateau hypoxia by simulating plateau hypoxic condition, and further clarify the role of plateau hypoxa in CVST.Methods:Forty-eight 8-week-old male SD rats were randomly divided into sham-operated group, plateau sham-operated group, CVST group, and plateau CVST group ( n=12). CVST models in the CVST group and plateau CVST group were established by ferric chloride wet dressing, and rats in the plateau CVST group were kept in a low-pressure oxygen chamber for 2 d immediately after modeling to simulate plateau hypoxic condition at an altitude of 5,000 m (barometric pressure of 54.047 kPa, oxygen concentration of 10%-11%, and temperature of 18-23 °C). Only the bone flap and dura mater were separated in rats of the sham-operated group, without low-pressure oxygen condition or filter paper dressing. Only the bone flap and dura mater were separated in rats of the plateau sham-operated group, with plateau hypoxic condition at an altitude of 5,000 m for 2 d and without filter paper dressing. Intracranial venous sinus blood flow was detected by Doppler flowmetry before and 48 h after modeling. At 6, 24, and 48 h after modeling, 4 rats in each group were sacrificed; blood vessels at the thrombus of superior sagittal sinus (blood vessels at the superior sagittal sinus in the sham-operated group and plateau sham-operated group) were cut out and weighed; meanwhile, water contents of the brain tissues were calculated. HE staining was employed in the brain, heart, liver, lung, and kidney tissues and veins, and toluidine blue staining was peformed in the brain tissues only at 48 h after modeling. Results:(1) Doppler flowmetry indicated that intracranial venous sinus blood flow was normal in the 4 groups before modeling; intracranial venous sinus blood flow signals were normal in the sham-operated group and plateau sham-operated group and obviously weakened in the CVST group and plateau CVST group 48 h after modeling. (2) No thrombus was formed in the sham-operated group 48 h after modeling. At 6, 24 and 48 h after modeling, the thrombus in the CVST group ([15.44±1.90] mg, [12.63±1.26] mg, and [7.85±0.68] mg) and plateau CVST group ([20.38±1.67] mg, [24.93±2.37] mg, and [20.90±1.30] mg) weighted significantly heavier than those in the plateau sham-operated group ([2.55±0.38] mg, [2.19±0.30] mg, [1.75±0.31] mg), and that in the plateau CVST group weighted significantly heavier than that in the CVST group ( P<0.05); the thrombus weight in both plateau sham-operated group and CVST group decreased sequentially at 6, 24 and 48 h after modeling, with significant differences ( P<0.05); whereas, the thrombus weight in the plateau CVST group at 24 h after modeling increased compared with that at 6 h after modeling, and that at 48 h after modeling decreased compared with that at 24 h after modeling, with significant differences ( P<0.05). (3) At 6 h after modeling, the brain water contents in the sham-operated group, plateau sham-operated group, CVST group and plateau CVST group were (77.56±0.52)%, (77.57±0.92)%, (78.91±0.53)%, and (78.90±0.63)%, respectively, with statistical differences ( P<0.05); the CVST group and plateau CVST group had increased water content compared with the sham-operated group and plateau sham-operated group without significant differences ( P>0.05). At 24 and 48 h after modeling, the brain water content among the 4 groups was not statistically different ( P>0.05). (4) HE staining and toluidine blue staining indicated limited infarction, neuronal edema, and necrotic apoptosis in the brain tissues of plateau CVST group at 24 h after modeling. HE staining showed no obvious pathological changes in the myocardium, liver, lung, or kidney tissues in the 4 groups. Conclusion:CVST models can be successfully established by simulating plateau hypoxic condition through ferric chloride wet dressing and feeding in low-pressure oxygen chamber.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Objective To investigate and study the relationship between abnormal monitoring and prognosis of long range video electroencephalogram(VEEG)in patients with intractable epilepsy. Methods 100 patients from March 2012 to May 2017 in our hospital whose diagnosis and treatment of refractory epilepsy were the research object,all patients were given VEEG monitoring records,epilepsy typing characteristics and antiepileptic drug(AEDs)use survey,prognosis of all patients and the correlation analysis. In 100 cases,GTCS 60 cases,CPS 30 cases,CPS-GTCS 10 cases;56 cases treated with sodium valproate,lamotrigine treatment in 44 cases. Results VEEG monitored 80 cases of epileptiform discharge in 100 patients and 20 cases without epileptiform discharge. There was no significant difference in the incidence of epileptiform discharges between different epileptic patients in VEEG monitoring(P > 0.05),and there was no significant difference in the incidence of epileptiform discharges between VEEG patients in different medication groups(P > 0.05). The total effective rate of treatment in the VEEG epileptiform discharge group was 91.3%,which was significantly lower than that of the VEEG non epileptic discharge group (100%,P < 0.05). The main adverse reactions during treatment were drowsiness , abnormal behavior, abnormal sensation and gastrointestinal reaction. There was no significant difference in monitoring epileptiform discharges between VEEG patients (P > 0.05). All adverse reactions were improved after symptomatic treatment. Conclusion The VEEG plays an important role in guiding the patients with refractory epilepsy for epilepsy typing characteristics and AEDs treatment ,so it has significant correlation to the prognosis , and it also has an important significance in assessing the prognosis.