Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Objective:To evaluate the efficacy and safety of immunotherapy with or without radiotherapy in the treatment of recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC).Methods:A retrospective analysis was conducted on the data of 75 patients with R/M ESCC treated with sintilimab at Anyang Tumor Hospital from January 2020 to October 2021. The patients were divided into the radiotherapy (RT) group ( n=37) and non-radiotherapy (NRT) group ( n=38) based on whether they received radiotherapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse effects were compared between two groups. Count data were expressed as composition ratios and analyzed using Chi-square test or Fisher's exact test. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:There was no statistically significant difference in ORR and DCR between the RT and NRT groups (70% vs. 61%, P=0.375; 95% vs. 89%, P=0.414). However, the complete response (CR) rate in the RT group was higher compared to that in the NRT group (19% vs. 3%, P=0.022). The median follow-up duration was 25.4 months. There was no statistically significant difference in the median PFS and OS between the RT and NRT groups (13.8 months vs. 9.9 months, P=0.221; 20.2 months vs. 18.9 months, P=0.214). Subgroup analysis demonstrated that among patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes, there was no statistically significant difference in the median PFS between the RT and NRT groups (15.1 months vs. 8.4 months, P=0.115), but the median OS in the RT group was better than that in the NRT group (not reached vs. 12.3 months, P=0.036). Compared to the NRT group, besides an increase in grade 1-2 pneumonitis (41% vs. 18%, P=0.035), no significant increase in treatment-related toxicity was observed in the RT group. Conclusion:Immunotherapy combined with radiotherapy is safe in patients with R/M ESCC, and shows survival benefit in patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes.

Humans ; Epilepsy, Temporal Lobe/surgery* ; Mossy Fibers, Hippocampal ; Brain-Derived Neurotrophic Factor ; Dentate Gyrus

OBJECTIVE Epileptic networks are char-acterized as two states,seizures or more prolonged inter-ictal periods.However,cellular mechanisms underlying the contribution of interictal periods to ictal events remain unclear.METHODS Here,we present the procedure for labeling seizure-activated and interictal-activated neuro-nal ensembles in mouse hippocampal kindling model using an enhanced-synaptic-activity-responsive element.This technique is combined with genetically encoded effectors to characterize and manipulate neuronal ensembles recruited by focal seizures(FS-Ens)and interictal periods(IP-Ens)in piriform cortex,a region that plays a key role in seizure generation.RESULTS Ca2+ activities and histo-logical evidence reveal a disjointed correlation between the two ensembles during FS dynamics.Optogenetic acti-vation of FS-Ens promotes further seizure development,while IP-Ens protects against it.Interestingly,both ensem-bles are functionally involved in generalized seizures(GS)due to circuit rearrangement.IP-Ens bidirectionally modulates FS but not GS by controlling coherence with hippocampus.CONCLUSION This study indicates that the interictal state may represent a seizure-preventing environment,and the interictal-activated ensemble may serve as a potential therapeutic target for epilepsy.

Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain. Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons. Calretinin (CR) is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons. The functions of CR and its role in neural excitability are still unknown. Recent data suggest that CR neurons have diverse neurotransmitters, morphologies, distributions, and functions in different brain regions across various species. Notably, CR neurons in the hippocampus, amygdala, neocortex, and thalamus are extremely susceptible to excitotoxicity in the epileptic brain, but the causal relationship is unknown. In this review, we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy. Importantly, we provide perspectives on future investigations of the role of CR neurons in epilepsy.
Amygdala/metabolism* ; Calbindin 2/metabolism* ; Epilepsy ; GABAergic Neurons ; Hippocampus/metabolism* ; Humans

Basal Forebrain ; Cholinergic Agents ; Cholinergic Neurons ; Humans ; Receptors, Histamine H1 ; Schizophrenia

Objective:To summarize the nursing experience of medical rescue mission of Chinese manned spaceflight and space station astronauts returning to Dongfeng landing site, to analyze the characteristics of different mission stages of Shenzhou-12 manned spacecraft and Dongfeng landing site, and to take steps to implement effective medical rescue support of the space station missions.Methods:The relevant literature and reports at home and abroad were consulted, the nursing experience of previous medical rescue support tasks was summarized, and the corresponding clinical measures were put forward according to the orbit time of Shenzhou-12 and the complex terrain and climate of the main landing site.Results:Based on the existing experience, the rescue process had been further detailed, the emergency plan had been formulated, the clinical process in each plan had been refined, the clinical process in front of the cabin, in the carrier and in the evacuation process of nurses under different injury conditions had been formulated and improved, and the special training of nurses' own quality and nursing skills was carried out to improve the overall quality and combat ability of the nursing echelon.Conclusions:The improvement and refinement of clinical process in the medical rescue support task of the main landing site of Shenzhou-12 has provided a solid assurance for the successful completion of manned aerospace medical rescue support task.

Objective:To study the environmental characteristics of launch section during the space medical rescue mission of Shenzhou-13 spacecraft, evaluate the influence of special environment on peripheral veins, and investigate the coping strategies.Methods:Combined with the practice of launch section during space medical rescue mission of Shenzhou-13 spacecraft, the main factors of aerospace special environment, cold and faint light, were selected and the related literature was reviewed to explore the feasibility, advantages and disadvantages of peripheral venipuncture, central venous catheter and bone marrow puncture. The experience of the space medical rescue mission was summarized and the coping strategies were provided for follow-up task training.Results:The environmental characteristics of launch section during the space medical rescue mission of Shenzhou-13 spacecraft included cold, faint light, sand-wind and complex terrain. The vascular filling, vascular elasticity and visibility of peripheral vein decreased in different degrees under special environmental, the vascular visibility was most affected. The literature analysis showed that bone marrow puncture was a suitable method to establish infusion access in cold and faint light environment.Conclusions:The special environment of space launch mission has greater impact on peripheral veins. In order to assurance the successful implementation of manned space project, the training of basic operational skills should be consolidated, the training of ability in special environment should be enhanced and the advanced clinical auxiliary equipment should be equipped in follow-up space medical mission training.

Renal clear cell carcinoma metastasis to the gallbladder is rare. This paper reported a case of gallbladder metastasis of renal clear cell carcinoma detected after two years of left radical nephrectomy. The patient underwent laparoscopic cholecystectomy and followed by postoperative targeted therapy of sunitinib. No new metastasis was found after 5 months of follow-up.

Folliculogenesis is essential for production of female gametes in vertebrates. However, the molecular mechanisms underlying follicle development, particularly apoptosis regulation in ovary, remain elusive. Here, we generated sox3 knockout zebrafish lines using CRISPR/Cas9. sox3 knockout led to follicle development retardation and a reduced fecundity in females. Comparative analysis of transcriptome between sox3 and wild-type ovaries revealed that Sox3 was involved in pathways of ovarian steroidogenesis and apoptosis. Knockout of sox3 promoted follicle apoptosis and obvious apoptosis signals were detected in somatic cells of stages III and IV follicles of sox3 ovaries. Moreover, Sox3 can bind to and activate the promoter of cyp19a1a. Up-regulation of Cyp19a1a expression promoted 17β-estradiol synthesis, which inhibited apoptosis in follicle development. Thus, Sox3 functions as a regulator of Cyp19a1a expression, via 17β-E2 linking apoptosis suppression, which is implicated in improving female fecundity.