Small Transjugular Intrahepatic Portosystemic Shunt Plus Variceal Embolization for Gastric Varices: A Multicenter Cohort Study.

BACKGROUND AND AIMS: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs. METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at seven medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality. RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% versus 13.6%, P=0.005) and OHE (31.0% versus 39.4%, P=0.02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% versus 9.7%, P=0.42). In patients with GOV2 and IGV1, TIPS+E reduced both rebleeding (GOV2: 7.8% versus 25.1%, P=0.01; IGV1: 5.6% versus 30.8%, P=0.03) and OHE (GOV2: 31.8% versus 51.5%, P=0.008; IGV1: 11.6% versus 38.5%, P=0.04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% versus 8.7%, P=0.37) or OHE (33.1% versus 35.3%, P=0.60). CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

Mental health literacy, mental health experiences and help-seeking behaviours of Chinese elite athletes: a qualitative study.

Introduction: Elite athletes' help-seeking on mental health might be influenced by their mental health literacy (MHL) and mental health experiences. The current study aimed to explore the MHL, experiences and help-seeking behaviours among elite athletes using a qualitative approach. Methods: Face-to-face semi-structured interviews were conducted among 20 Chinese elite athletes, 12 coaches, and 5 team officials. Interview data was analyzed using content analysis. Results: Seven main themes emerged from the analysis. The current study revealed that Chinese elite athletes suffered from various mental health issues and athletes' MHL levels, help-seeking attitudes and intentions, Chinese sports environments, and Chinese cultural background could impact their help-seeking behaviours. Conclusion: Support for Chinese elite athletes' mental health and help-seeking requires improvement.

[Antioxidative effect of wheat-grain moxibustion on cyclophosphamide-induced liver injury in mice based on Nrf2-Keap1 signaling pathway].

OBJECTIVE: To observe the protective effect of wheat-grain moxibustion on cyclophosphamide (CTX)-induced liver injury in mice, and explore its mechanism based on the nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signaling pathway. METHODS: Twenty-four male CD-1 (ICR) mice were randomly divided into a blank group, a model group, and a moxibustion group, with 8 mice in each group. The mice in the model group and the moxibustion group were intraperitoneally injected with CTX (80 mg/kg) to induce liver injury. The mice in the moxibustion group were treated with wheat-grain moxibustion at "Guanyuan" (CV 4) and bilateral "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with each acupoint being treated by 3 cones, approximately 30 seconds per cone, once daily for 7 days. After intervention, the general condition of the mice was observed; the liver mass was measured and the liver index was calculated; HE staining was used to observe the morphology of the liver, and the liver tissue pathological score was assessed; ELISA was used to detect the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in the liver; Western blot and real-time fluorescence quantitative PCR were used to detect the protein and mRNA expression of Nrf2, Keap1, and quinione acceptor oxidoreductase 1 (NQO1) in the liver. RESULTS: Compared with the blank group, the mice in the model group showed sluggishness, unsteady gait, and decreased body weight; liver index was increased (P<0.01); liver cells were loosely arranged, with a small number of cell swollen and exhibiting balloon-like changes; liver tissue pathological score was increased (P<0.05); the serum levels of AST, ALT, GLDH, and level of MDA in the liver were increased (P<0.05), and the levels of SOD and GSH-Px in the liver were decreased (P<0.05); protein and mRNA expression of Nrf2 and NQO1 in the liver was decreased (P<0.01), protein and mRNA expression of Keap1 in the liver was increased (P<0.01). Compared with the model group, the mice in the moxibustion group showed improvement in general condition; liver index was decreased (P<0.01); liver cell structure was relatively intact and clear, and liver tissue pathological score was decreased (P<0.05); the serum levels of AST, ALT, GLDH, and level of MDA in the liver were decreased (P<0.05), and the levels of SOD and GSH-Px in the liver were increased (P<0.05, P<0.01); protein and mRNA expression of Nrf2 and NQO1 in the liver was increased (P<0.05), protein and mRNA expression of Keap1 in the liver was decreased (P<0.05). CONCLUSION: The wheat-grain moxibustion may alleviate CTX-induced liver injury by activating the Nrf2-Keap1 signaling pathway and enhancing the expression of antioxidative enzyme system in the body.

Growth hormone promotes myelin repair after chronic hypoxia via triggering pericyte-dependent angiogenesis.

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.

The α-1 Adrenergic Receptor Antagonist Doxazosin Attenuates Liver Fibrosis by Alleviating Sinusoidal Capillarization and Liver Angiogenesis.

Liver fibrosis and cirrhosis, which are caused by chronic liver injury, represent common and intractable clinical challenges of global importance. However, effective therapeutics are lacking. Therefore, the study examines the effect of doxazosin on liver fibrosis. Carbon tetrachloride (CCl4 ) is injected into mice to establish a liver fibrosis model. Doxazosin (5 and 10 mg/kg) is administered daily by gavage. HE staining, Masson staining, Sirius Red staining, scanning electron microscopy, western blotting, real-time PCR, and immunofluorescence analysis are performed to estimate liver fibrosis and sinusoidal capillarization in mice. Cell Counting Kit-8 assays, western blotting, immunofluorescence analysis, tube formation, and transwell migration assays are performed on human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs) to elucidate the potential mechanism of doxazosin. Doxazosin alleviates liver fibrosis and sinusoidal capillarization in CCl4 -induced mice. Angiogenesis is attenuated by doxazosin in HUVECs and HHSECs. This study demonstrates that doxazosin attenuated liver fibrosis by alleviating sinusoidal capillarization and liver angiogenesis.

Ligustilide inhibits Purkinje cell ferritinophagy via the ULK1/NCOA4 pathway to attenuate valproic acid-induced autistic features.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in which social impairment is the core symptom. Presently, there are no definitive medications to cure core symptoms of ASD, and most therapeutic strategies ameliorate ASD symptoms. Treatments with proven efficacy in autism are imminent. Ligustilide (LIG), an herbal monomer extracted from Angelica Sinensis and Chuanxiong, is mainly distributed in the cerebellum and widely used in treating neurological disorders. However, there are no studies on its effect on autistic-like phenotypes and its mechanism of action. PURPOSE: Investigate the efficacy and mechanism of LIG in treating ASD using two Valproic acid(VPA)-exposed and BTBR T + Itpr3tf/J (BTBR) mouse models of autism. METHODS: VPA-exposed mice and BTBR mice were given LIG for treatment, and its effect on autistic-like phenotype was detected by behavioral experiments, which included a three-chamber social test. Subsequently, RNA-Sequence(RNA-Seq) of the cerebellum was performed to observe the biological changes to search target pathways. The autophagy and ferroptosis pathways screened were verified by WB(Western Blot) assay, and the cerebellum was stained by immunofluorescence and examined by electron microscopy. To further explore the therapeutic mechanism, ULK1 agonist BL-918 was used to block the therapeutic effect of LIG to verify its target effect. RESULTS: Our work demonstrates that LIG administration from P12-P14 improved autism-related behaviors and motor dysfunction in VPA-exposed mice. Similarly, BTBR mice showed the same improvement. RNA-Seq data identified ULK1 as the target of LIG in regulating ferritinophagy in the cerebellum of VPA-exposed mice, as evidenced by activated autophagy, increased ferritin degradation, iron overload, and lipid peroxidation. We found that VPA exposure-induced ferritinophagy occurred in the Purkinje cells, with enhanced NCOA4 and Lc3B expressions. Notably, the therapeutic effect of LIG disappeared when ULK1 was activated. CONCLUSION: LIG treatment inhibits ferritinophagy in Purkinje cells via the ULK1/NCOA4-dependent pathway. Our study reveals for the first time that LIG treatment ameliorates autism symptoms in VPA-exposed mice by reducing aberrant Purkinje ferritinophagy. At the same time, our study complements the pathogenic mechanisms of autism and introduces new possibilities for its therapeutic options.

Efficacy of TIPS plus extrahepatic collateral embolisation in real-world data: a validation study.

OBJECTIVES: The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) plus extrahepatic collateral embolisation (TIPS+E) in reducing rebleeding and hepatic encephalopathy (HE) post-TIPS was recently reported in a meta-analysis, but further validation is essential. This study aims to confirm the effectiveness of TIPS+E using real-world data. METHODS: The multicentre retrospective cohort included 2077 patients with cirrhosis who underwent TIPS±E (TIPS: 631, TIPS+E: 1446) between January 2010 and December 2022. Regression and propensity score matching (PSM) were used to adjust for baseline characteristic differences. After PSM, clinical outcomes, including rebleeding, HE, survival and further decompensation (FDC), were analysed. Baseline data from all patients contributed to the construction of prognostic models. RESULTS: After PSM, 1136 matched patients (TIPS+E: TIPS=568:568) were included. TIPS+E demonstrated a significant reduction in rebleeding (HR 0.77; 95% CI 0.59 to 0.99; p=0.04), HE (HR 0.82; 95% CI 0.68 to 0.99; p=0.04) and FDC (HR 0.85; 95% CI 0.73 to 0.99; p=0.04), comparing to TIPS. Significantly, TIPS+E also reduced rebleeding, HE and FDC in subgroup of using 8 mm diameter stents and embolising of gastric varices+spontaneous portosystemic shunts (GV+SPSS). However, there were no differences in overall or subgroup survival analysis. Additionally, the random forest models showed higher accuracy and AUROC comparing to other models. Controlling post-TIPS portal pressure gradient (pPPG) within 7 mm Hg

Preventing variceal rebleeding in cirrhotic patients with portal vein thrombosis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Preventing rebleeding is crucial, but the best prevention technique for patients with cirrhosis and portal vein thrombosis (PVT) remains debatable. Therefore, this systematic review and meta-analysis compared a transjugular intrahepatic portosystemic shunt (TIPS) with endoscopic therapy (ET) plus nonselective beta-blockers (NSBBs) for preventing variceal rebleeding in this patient population. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from their inception until May 18, 2023. The studies were screened using predetermined criteria, relevant data were extracted, and pooled analyses were performed using the Reviewer Manager 5.4.1 software. RESULTS: We retrieved 1032 studies, of which 5 studies comprising a total of 272 patients were included. The postoperative variceal rebleeding rate was significantly lower in the TIPS group than in the ET + NSBBs group (odds ratio [OR] = 0.19, 95% confidence interval [CI] = 0.11-0.35, P < 0.05, I2 = 0%), but the portal vein recanalization rate was higher (OR = 7.92, 95% CI = 3.04-20.67, P < 0.05, I2 = 0%). The rates of hepatic encephalopathy (HE) and mortality did not differ between the groups. CONCLUSIONS: Our results suggest that TIPS prevents variceal rebleeding without increasing the hepatic encephalopathy risk more effectively than ET plus NSBBs, but this benefit did not translate into improved survival. Thus, it may be preferable to ET plus NSBBs for preventing variceal rebleeding in patients with cirrhosis and PVT. However, more large-scale and multicenter randomized controlled trials involving other patient populations are required to verify the clinical efficacy of both these treatments and ensure generalizability.

Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

Skeletal muscle alterations indicate poor prognosis in cirrhotic patients: a multicenter cohort study in China.

INTRODUCTION: We aimed to determine the diagnostic criteria of myosteatosis in a Chinese population and investigate the effect of skeletal muscle abnormalities on the outcomes of cirrhotic patients. METHODS: Totally 911 volunteers were recruited to determine the diagnostic criteria and impact factors of myosteatosis, and 480 cirrhotic patients were enrolled to verify the value of muscle alterations for prognosis prediction and establish new noninvasive prognostic strategies. RESULTS: Multivariate analysis showed age, sex, weight, waist circumference, and biceps circumference had a remarkable influence on the L3 skeletal muscle density (L3-SMD). Based on the cut-off of a mean - 1.28 × SD among adults aged < 60 years, the diagnostic criteria for myosteatosis was L3-SMD < 38.93 Hu in males and L3-SMD < 32.82 Hu in females. Myosteatosis rather than sarcopenia has a close correlation with portal hypertension. The concurrence of sarcopenia and myosteatosis not only is associated with poor liver function but also evidently reduced the overall and liver transplantation-free survival of cirrhotic patients (p < 0.001). According to the stepwise Cox regression hazard model analysis, we established nomograms including TBil, albumin, history of HE, ascites grade, sarcopenia, and myosteatosis for easily determining survival probabilities in cirrhotic patients. The AUC is 0.874 (95% CI 0.800-0.949) for 6-month survival, 0.831 (95% CI 0.764-0.898) for 1-year survival, and 0.813 (95% CI 0.756-0.871) for 2-year survival prediction, respectively. CONCLUSIONS: This study provides evidence of the significant correlation between skeletal muscle alterations and poor outcomes of cirrhosis, and establishes valid and convenient nomograms incorporating musculoskeletal disorders for the prognostic prediction of liver cirrhosis. Further large-scale prospective studies are necessary to verify the value of the nomograms.

Development and validation of a prognostic score to identify the optimal candidate for preemptive TIPS in patients with cirrhosis and acute variceal bleeding.

BACKGROUND AND AIM: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining "high-risk" have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. APPROACH AND RESULTS: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). CONCLUSIONS: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.

Integrating perceived physical environments and the theory of planned behaviors when explaining adherence to 24-hour movement guidelines in Chinese adolescents.

PURPOSES: Most adolescents worldwide do not meet 24-h movement guidelines, which recommend specific level of physical activity, sedentary behavior, and sleep for optimal health. Nevertheless, there remains a lack of understanding regarding how social cognitive and physical environmental factors influence adolescents' compliance with these guidelines. This prospective study aimed to examine the associations between perceived physical environments, constructs of the theory of planned behavior (TPB), habit strength, and adherence to 24-h movement guidelines in Chinese adolescents over a three-month period. METHODS: A total of 629 Chinese adolescents (Mage = 14.59 years, SD = 0.64) completed a set of questionnaires comprising perceived physical environmental characteristics, constructs of the TPB, habit strength, and 24-h movement behaviors at baseline and 3 months later. Data analysis was conducted using variance-based structural equation modeling. RESULTS: Attitude, subjective norm, and perceived behavioral control had a direct effect on intention and intention had a direct effect on number of the guidelines being met. Habit strength was a significant predictor of adherence to the guidelines, although its moderating effect on the intention-behavior relationship was not significant. Perceived neighborhood facility accessibility, school facility availability, and home physical activity equipment had significant indirect effects on intention through attitude, subjective norm, and perceived behavioral control. However, constructs of the TPB did not serve as mediators in the relationship between perceived physical environments and the number of guidelines being met. CONCLUSION: This study offers preliminary evidence supporting the integration of perceived physical environments and the TPB in predicting adolescents' adherence to 24-h movement guidelines. Future research should consider using experimental study designs with rigorous measures of 24-h movement behaviors to establish causal relationships.

Upregulation of ATG9b by propranolol promotes autophagic cell death of hepatic stellate cells to improve liver fibrosis.

Proranolol has long been recommended to prevent variceal bleeding in patients with cirrhosis. However, the mechanisms of propranolol in liver fibrosis have not yet been thoroughly elucidated. Autophagic cell death (ACD) of activated hepatic stellate cells (HSCs) is important in the alleviation of liver fibrosis. Our study aims to assess the mechanisms of propranolol regulating HSC ACD and liver fibrosis. ACD of HSCs was investigated using lentivirus transfection. The molecular mechanism was determined using a PCR profiler array. The role of autophagy-related protein 9b (ATG9b) in HSC ACD was detected using co-immunoprecipitation and co-localization of immunofluorescence. Changes in the signalling pathway were detected by the Phospho Explorer antibody microarray. Propranolol induces ACD and apoptosis in HSCs. ATG9b upregulation was detected in propranolol-treated HSCs. ATG9b upregulation promoted ACD of HSCs and alleviated liver fibrosis in vivo. ATG9b enhanced the P62 recruitment to ATG5-ATG12-LC3 compartments and increased the co-localization of P62 with ubiquitinated proteins. The PI3K/AKT/mTOR pathway is responsible for ATG9b-induced ACD in activated HSCs, whereas the p38/JNK pathway is involved in apoptosis. This study provides evidence for ATG9b as a new target gene and propranolol as an agent to alleviate liver fibrosis by regulating ACD of activated HSCs.

Predictive model for epileptogenic tubers from all tubers in patients with tuberous sclerosis complex based on 18F-FDG PET: an 8-year single-centre study.

BACKGROUND: More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. METHODS: Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. RESULTS: PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70-0.83) than the LDA (AUC = 0.7506; 95% CI 0.68-0.82) and ANN models (AUC = 0.7425; 95% CI 0.67-0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71-0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71-0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74-0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75-0.87). CONCLUSIONS: The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.

The burden of epilepsy in the People's Republic of China from 1990 to 2019: epidemiological trends and comparison with the global burden of epilepsy.

Background: Epilepsy is associated with a significant global burden of disease, affecting over 50 million people worldwide. The specific aim of this study is to compare the burden of epilepsy in the People's Republic of China (PRC) with the global burden, and to analyze the epidemiological trends of epilepsy, the relationship between the burden of epilepsy and social demographic index (SDI), and the relative contributions of epidemiological factors. Methods: This is a retrospective population-based study, data were obtained from the Global Burden of Disease (GBD) study in 2019. We employed Joinpoint software and the age-period-cohort (APC) model to analyze epilepsy's epidemiological trends. Health inequality analysis was conducted to investigate the impact of SDI on epilepsy burden. Decomposition analysis was performed to examine the relative contributions of age, population, and epidemiological changes to epilepsy. Results: Between 1990 and 2019, the incidence rate in the PRC increased by 45%, significantly surpassing the global incidence of epilepsy. However, Disability-Adjusted Life Years (DALY) decreased notably, and the proportion of Years of Life Lost (YLL) decreased from 62.73 to 39.03%. Concerning incidence, the period Rate Ratio (RR) in the PRC initially increased and then decreased, while the cohort RR in the PRC and globally exhibited a consistent upward trend. In terms of mortality, period RR and cohort RR in the PRC displayed a gradual decrease, with mortality starting higher but eventually falling below the global mortality. The net drifts of incidence were greater than 0, whereas the net drifts of mortality were less than 0, both were lower in the PRC than at the global level. Decomposition analysis indicated that the changes of incidence and mortality in the PRC were mainly attributed to epidemiological changes. Additionally, global disparities in epilepsy decreased, with the burden concentrating in low SDI countries. Conclusion: The incidence of epilepsy in the PRC rose during the 30-year study period, while epilepsy mortality decreased. The improved survival rate in the PRC is predominantly attributable to epidemiological changes. The burden of epilepsy in the PRC predominantly affects males, children, and the elderly, Chinese government should focus on specific populations.

Enhancing Physical and Psychosocial Health of Older Adults in Saudi Arabia through Walking: Comparison between Supervised Group-Based and Non-Supervised Individual-Based Walking.

Walking is widely recognized as one of the most common and effective forms of physical activity, particularly for older adults. This study examined the comparative effects of two types of walking interventions, including supervised group-based intervention (SGBI) and non-supervised individual-based intervention (NSIBI), on frailty syndrome, cognitive functions or skills, and health-related quality of life among sedentary older Saudi individuals. A 15-week double-blinded, randomized controlled trial (RCT) including three groups (two were intervention groups while the other was the control group) was conducted among older adults who were inactive to examine the effect of different forms of walking interventions on frailty syndrome, cognitive functions, and health-related quality of life. A total of 107 participants, including 65 males and 42 females, were divided into three groups, which include SGBI, NSIBI, and the control group. Frailty syndrome was measured using the physical performance test (PPT), while cognitive function and health-related quality of life were assessed using the Mini-mental State Examination (MMSE) and the Short Form 36 (SF 36) health survey questionnaire. One-way repeated measures analysis of variance (ANOVA) and one-way analysis of covariance (ANCOVA) with the pre- and post-tests were performed for within- and between-group differences. while post-test data for the control group participants were absent due to the change in elderly center regulation, and they were excluded from the analysis. Hence, the comparison was stated only between the intervention groups. Both of the intervention groups (SGBI and NSIBI) showed significant within-subject differences in the Physical Function subscale of the health-related quality of life scale only, with F(1,20) = 23.03, p < 0.001, and F(1,18) = 27.22, p < 0.001, respectively. On the other hand, the Physical Performance Test revealed significant [F(2,51) = 9.21, p < 0.001] between-group differences in the post-test based on the baseline values. In addition, the average step count of older adults was increased from 4000 steps per session to around 7000 steps per session in the intervention group. The average heart rate of the NSIBI group did not show a visible change, and the resting heart rate of both groups showed a slightly declining trend throughout the intervention period. The walking intervention significantly increased participants' physical function, which is a component of health-related quality of life and physical performance (frailty level), along with average daily step counts for older adults in Saudi Arabia. Regular engagement in the recommended level of walking is strongly advisable for Saudi Arabian older adults to maintain their overall quality of life at this stage.

Expression profiles of α-synuclein in cortical lesions of patients with FCD IIb and TSC, and FCD rats.

Background: Focal cortical dysplasia (FCD) IIb and tuberous sclerosis complex (TSC) are common causes of drug-resistant epilepsy in children. However, the etiologies related to the development of FCD IIb and TSC are not fully understood. α-synuclein (α-syn) is a member of synucleins family that plays crucial roles in modulating synaptic transmission in central nervous system. Here, we explored the expression profiles and potential pathogenic functions of α-syn in cortical lesions of epileptic patients with FCD IIb and TSC. Methods: Surgical specimens from epileptic patients with FCD IIb and TSC, as well as FCD rats generated by in utero X-ray-radiation were adopted in this study and studied with immunohistochemistry, immunofluorescence, western blotting, and co-immunoprecipitation etc. molecular biological techniques. Result: Our results showed that α-syn expression was reduced in FCD IIb and TSC lesions. Specifically, α-syn protein was intensely expressed in dysplastic neurons (DNs) and balloon cells (BCs) in FCD IIb lesions, whereas was barely detected in DNs and giant cells (GCs) of TSC lesions. Additionally, p-α-syn, the aggregated form of α-syn, was detected in DNs, BCs, GCs, and glia-like cells of FCD IIb and TSC lesions. We previous showed that the function of N-methyl-D-aspartate receptor (NMDAR) was enhanced in FCD rats generated by X-ray-radiation. Here, we found the interaction between α-syn and NMDAR subunits NMDAR2A, NMDAR2B were augmented in cortical lesions of FCD patients and FCD rats. Conclusion: These results suggested a potential role of α-syn in the pathogenesis of FCD IIb and TSC by interfering with NMDAR.

Recompensation in treatment-naïve HBV-related decompensated cirrhosis: a 5-year multi-center observational study comparing patients with ascites and bleeding.

BACKGROUND AND AIMS: Recompensation between patients with ascites and bleeding was unknown in treatment-naïve HBV-related decompensated cirrhosis. METHODS: In this retrospective multi-center study, treatment-naïve HBV-related decompensated patients were enrolled at first decompensating event of ascites and/or variceal bleeding. Further complications and clinical characteristics were collected using standard case report form every 6 months to year-5 of antiviral treatment. Recompensation was defined as maintaining free of decompensation for one year and achieving liver function within Child-Pugh A and/or MELD < 10. RESULTS: Totally, 170 (170/298, 57.0%) patients in ascites group of 298 (298/383, 77.8%) treatment-naïve decompensated patients and 33 (33/85, 38.8%) in bleeding group of 85 (85/383, 22.2%) patients, achieved recompensation. Ascites group had higher 5-year rate of recompensation than bleeding group (63.3% vs. 46.5%, p = 0.012), respectively. Patients achieving recompensation in ascites group maintained lower rate of second decompensation than these in bleeding group (at year-5: 26.7% vs. 43.3%, p = 0.032). Specifically, recompensated patients in ascites group had predominantly 5-year rate of further ascites (24.0%) and lower rate of further bleeding (6.0%), which differed from the pattern of these in bleeding group, with lower rate of further ascites (16.0%, p = 0.599) and significantly higher rate of further bleeding (33.9%, p < 0.001). Both patients had superior long-term prognosis (death/LT rate at year-5: 0.6% vs. 3.0%, p = 0.196). CONCLUSION: Ascites patients could achieve higher rate of recompensation through antiviral therapy than bleeding patients. Recompensated patients in ascites group had better prognosis in terms of preventing further bleeding.

The effects of walking on frailty, cognitive function and quality of life among inactive older adults in Saudi Arabia: a study protocol of randomized control trial by comparing supervised group-based intervention and non-supervised individual-based intervention.

BACKGROUND: Kingdom of Saudi Arabia (KSA) demographics are also changing with the increase in life expectancy in the country and the rise in the number of older Saudi Arabians. Saudi Arabia has a higher rate of physically inactive people, and most of them are between the ages of 55-64. Walking is one of the most prevalent forms of physical activity in Saudi Arabia and the study showed that most people prefer walking for recreational and health benefits. Therefore, the purpose of the proposed study is to compare the effects of supervised group-based walking and non-supervised individual-based walking interventions on frailty, cognitive function and quality of life among inactive older adults in Saudi Arabia. METHOD: This study will apply a three-group (2 intervention groups and 1 control group), double-blinded, randomized controlled trial (RCT) to examine the effect of different forms of walking interventions on Saudi Arabia older adults' frailty, cognitive function and quality of life immediately after a 16-week intervention, as well as the residual effects 12 weeks after completion of the interventions. DISCUSSION: This study aims to determine whether supervised group walking and non-supervised individual walking lead to different effects. Given the limited evidence in the literature regarding Saudi Arabia older adults' physical fitness and health, it is worthwhile to explore the effect of walking, as well as the forms of walking on improving the overall physical fitness and psychological status of older adults in Saudi Arabia. The findings of the current study could also create awareness of the government and the general public in Saudi Arabia of the ageing problems and the effective ways of achieving better intervention results. TRIAL REGISTRATION: The trial is registered at the ClinicalTrials.gov PRS (Trial ID: NCT05151575; Date of first posted: 12/07/2021).