Epilepsy-Associated SCN2A-L1342P Mutation Drives Network Hyperexcitability and Widespread Transcriptomic Changes in Human Cortical Organoids.

Objective: pathogenic mutations, such as the recurrent heterozygous Nav1.2-L1342P, are monogenic causes of epilepsy. In this human-induced pluripotent stem cell model system, we aim to investigate the molecular and cellular mechanisms underlying the SCN2A-L1342P-associated pathology.

The mechanism of Ningxin-Tongyu-Zishen formula regulating probdnf/mbdnf balance through PAI-1/tPA signaling pathway in the treatment of premature ovarian insufficiency.

Background: Premature ovarian insufficiency (POI) is a refractory gynecological endocrine disorder. Ningxin-Tongyu-Zishen formula (NTZF), developed based on the 'simultaneous heart-kidney regulation' principle, exhibits therapeutic efficacy in treating POI, potentially through regulating proBDNF/mBDNF balance. This study aimed to elucidate the molecular mechanism by which NTZF treats POI via proBDNF/mBDNF modulation.

The Pathological Role and Therapeutic potential of ALDH2 in acrolein detoxification Following Spinal Cord Injury in Mice.

Oxidative stress and lipid peroxidation-derived aldehydes, such as acrolein, play a central role in the pathology of spinal cord injury (SCI) and have emerged as promising therapeutic targets. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is a key oxidoreductase responsible for detoxifying reactive aldehydes. Pharmacological activation of ALDH2 using Alda-1, a selective agonist, has been shown to reduce aldehyde accumulation, alleviate inflammation, and enhance functional recovery in experimental SCI models.

Gene therapies alleviate absence epilepsy associated with deficiency in DBA/2J mice.

Mutations in the voltage-gated sodium channel gene , which encodes the Na1.2 channel, cause severe epileptic seizures. Patients with loss-of-function (LoF) mutations, such as protein-truncating mutations, often experience later-onset and drug-resistant epilepsy, highlighting an urgent unmet clinical need for new therapies.

Autism-associated deficiency disrupts cortico-striatal circuitry in human brain assembloids.

Profound autism spectrum disorder (ASD) is frequently attributable to single-gene mutations, with (voltage-gated sodium channel Na1.2) protein-truncating variants (PTVs) being one of the most penetrant. Although cortico-striatal circuitry is implicated as a key node in ASD, the impact of deficiency on human neural circuits is unknown.

Restoration of excitation/inhibition balance enhances neuronal signal-to-noise ratio and rescues social deficits in autism-associated deficiency.

Social behavior is critical for survival and adaptation, which is profoundly disrupted in autism spectrum disorders (ASD). Social withdrawal due to information overload was often described in ASD, and it was suspected that increased basal noise, i.e.

Ningxin-Tongyu-Zishen formula alleviates the senescence of granulosa cells on D-galactose-induced premature ovarian insufficiency mice.

Ningxin-Tongyu-Zishen formula (NTZF) is a clinical experience formula for the treatment of premature ovarian insufficiency (POI) in traditional Chinese medicine (TCM), and the potential mechanism is unknown. For experiments, POI mouse models (C57BL/6 mice), were constructed by subcutaneous injection of D-galactose (D-gal, 200 mg/kg). After treatment of NTZF (10.

Deficiency of autism-related Scn2a gene in mice disrupts sleep patterns and circadian rhythms.

Autism spectrum disorder (ASD) affects ~2% of the population in the US, and monogenic forms of ASD often result in the most severe manifestation of the disorder. Recently, SCN2A has emerged as a leading gene associated with ASD, of which abnormal sleep pattern is a common comorbidity. SCN2A encodes the voltage-gated sodium channel Na1.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

Background: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate.

Aim: To investigate whether RL can improve the prognosis of patients with T1b GBC.

Methods: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.

Protocol for a gallbladder cancer registry study in China: the Chinese Research Group of Gallbladder Cancer (CRGGC) study.

Introduction: Gallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population.

Methods And Analysis: The Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study.