OBJECTIVE To compare the efficacy and safety of chemotherapy combined with tislelizumab or sintilimab in patients with advanced non-small cell lung cancer （NSCLC）， and to analyze the influential factors of prognostic. METHODS A retrospective study was conducted on 163 patients with advanced NSCLC who received chemotherapy combined with tislelizumab or sintilimab at the First People’s Hospital of Yunnan Province from September 1， 2021 to November 30， 2024. Among them， there were 90 patients in the tislelizumab group and 73 patients in the sintilimab group. The objective response rate （ORR）， disease control rate （DCR）， progression free survival （PFS）， and overall survival （OS） of two groups were observed， and the occurrence of adverse drug reactions in patients was evaluated. Kaplan-Meier method was used to plot PFS and OS survival curves， Log-rank test was applied for univariate analysis， and Cox regression model was used to evaluate the independent prognostic factors of PFS and OS. RESULTS The median PFS of patients in the tislelizumab group and the sintilimab group were 14.14 months （95%CI of 10.95-17.33） and 10.95 months （95%CI of 8.75-13.15）， respectively. The median OS was 25.89 months （95%CI of 22.67-29.11） and 24.25 months （95%CI of 19.34-29.16）， with ORR of 45.56% and 49.32%， DCR of 94.44% and 90.41%， and the incidence of adverse drug reactions of 84.44% and 79.45%， respectively， the differences were not statistically significant （P＞0.05）. Age ≥60 years （HR＝1.542， 95%CI of 1.044-2.278， P＝0.029） and systemic immune inflammatory nutritional index （SIINI）＞ 116.58 （HR＝1.541， 95%CI of 1.058-2.245， P＝0.024） were risk factors for PFS in NSCLC patients receiving immune checkpoint inhibitor therapy； the use of antibiotics may affect the overall survival of patients （P＝0.001）. CONCLUSIONS The efficacy and safety of chemotherapy combined with tislelizumab or sintilimab for advanced NSCLC are comparable； age≥60 years and SIINI ＞116.58 are risk factors for PFS in NSCLC patients， and the use of antibiotics may affect the patients’ OS.

Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective To compare the efficacy and safety of osimertinib and aumolertinib in the treatment of advanced non-small cell lung carcinoma(NSCLC)with epidermal growth factor receptor(EGFR)mutation.Methods A total of 139 patients with EGFR-mutated advanced NSCLC treated in the First People's Hospital of Yunnan Province from January,2019 to December,2022 were retrospectively collected.After screening by that row of criteria,104 patients were included in this study.According to the treatment drugs,they were divided into osimertinib group and aumolertinib group,with 52 cases in each group.The osimertinib group received osimertinib mesylate tablets 80 mg once daily,and the aumolertinib group received aumolertinib mesylate tablets 110 mg once daily.The disease control rate(DCR),objective remission rate(ORR)and progression-free survival(PFS)of the two groups were observed.PFS and overall survival(OS)were evaluated.The Cox regression model was used to analyze the key factors affecting patient survival.Results The ORR of aumolertinib group was significantly higher than that of osimertinib group.The median progression-free survival(mPFS)of aumolertinib group was significantly longer than that of osimertinib group(P=0.045).Cox regression model showed that clinical stage Ⅲ(HR=2.25,95%Cl 1.28～3.95,P=0.005),no brain metastasis(HR=0.59,95%Cl 0.35～0.98,P=0.040),third generation TKI type aumolertinib(HR=1.82,95%CI 1.15～2.87,P=0.011).Conclusion Aumolertinib and osimertinib have similar clinical efficacy in the treatment of advanced NSCLC patients with EGFR mutation.However,in terms of long-term efficacy,aumolertinib has significantly better median PFS and overall OS,and higher safety than osimertinib.

Objective:To evaluate the role and molecular mechanism of laminin β1(LAMB1)in cortical neurons in regulation of glutamate receptors.Methods:Recombinant lentivirus(LV-shLamb1)-mediated knockdown of LAMB1 expression in mouse primary cortical neurons was performed,followed by immunofluorescence staining and Western blot to detect changes in F-actin,glutamate receptor subtypes(AMPA receptors GluR1/GluR2,NMDA receptors NR1/NR2A),and ERK-related protein expression in cortical neurons.Results:LV-shLamb1 significantly inhibited LAMB1 expression in mouse cortical neurons.Concurrently,LV-shLamb1 markedly increased F-actin polymerization,as well as the expression of AMPA receptor subunits GluR1 and GluR2,and NMDA receptor subunits NR1 and NR2A.Further,Western blot detection showed that the phosphorylation level of ERK was significantly increased after LV-shLamb1 infec-tion.Conclusion:LAMB1 is expressed in cortical neurons.Suppression of LAMB1 expression in mouse cortical neu-rons activates the ERK pathway,which in turn promotes the polymerization of the cytoskeletal protein F-actin and the expression of glutamate receptors.This suggests that LAMB1 may regulate F-actin homeostasis and glutamate receptor levels through the ERK pathway,thereby playing a potentially important role in neuronal function.

Objective:To evaluate the role and molecular mechanism of laminin β1(LAMB1)in cortical neurons in regulation of glutamate receptors.Methods:Recombinant lentivirus(LV-shLamb1)-mediated knockdown of LAMB1 expression in mouse primary cortical neurons was performed,followed by immunofluorescence staining and Western blot to detect changes in F-actin,glutamate receptor subtypes(AMPA receptors GluR1/GluR2,NMDA receptors NR1/NR2A),and ERK-related protein expression in cortical neurons.Results:LV-shLamb1 significantly inhibited LAMB1 expression in mouse cortical neurons.Concurrently,LV-shLamb1 markedly increased F-actin polymerization,as well as the expression of AMPA receptor subunits GluR1 and GluR2,and NMDA receptor subunits NR1 and NR2A.Further,Western blot detection showed that the phosphorylation level of ERK was significantly increased after LV-shLamb1 infec-tion.Conclusion:LAMB1 is expressed in cortical neurons.Suppression of LAMB1 expression in mouse cortical neu-rons activates the ERK pathway,which in turn promotes the polymerization of the cytoskeletal protein F-actin and the expression of glutamate receptors.This suggests that LAMB1 may regulate F-actin homeostasis and glutamate receptor levels through the ERK pathway,thereby playing a potentially important role in neuronal function.

As an important part of the enteric nervous system(ENS),enteric glial cells(EGCs)play an important role in regulating intestinal homeostasis and maintaining intestinal health in hu-mans and animals.This review focuses on the role of EGCs in maintaining intestinal barrier homeo-stasis,maintaining gastrointestinal transit and motor function,regulating the niche of intestinal cells,and the role in the occurrence and development of intestinal diseases,hoping to provide new ideas for further research on the function and mechanism of EGCs in the intestine and the occur-rence,development and treatment of related intestinal diseases.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

Objective:To investigate the correlation between time within the glucose target range(TIR) and hyperuricemia(HUA) in patients with type 2 diabetes mellitus(T2DM).Methods:A total of 215 patients with T2DM in the First Affiliated Hospital of Bengbu Medical College from June 2021 to May 2022 were selected and divided into HUA group and non-HUA group according to serum uric acid level. The clinical characteristics and biochemical indicators of the patients were collected. The association of 72 h glucose monitoring system(FGMS) related indicators TIR, mean blood glucose fluctuation range(MAGE), blood glucose variability(CV), blood glucose standard deviation(SDBG), and mean blood glucose(MBG) with serum uric acid level was analyzed. The influencing factors of T2DM combined with HUA were analyzed with binary logistic regression, and receiver operating characteristic(ROC) curve was drawn to evaluate their predictive values.Results:TIR of HUA group was significantly decreased compared with non-HUA group, while HbA 1C, MAGE, CV, SDBG, and MBG were increased( P<0.001). Spearman correlation analysis showed that serum uric acid levels were negatively correlated with TIR, but positively correlated with MAGE, CV, SDBG, and MBG( P<0.001). After dichotomous logistic regression analysis, TIR was found to be an independent protective factor for T2DM with HUA. The ROC curve results showed that the area under the curve(AUC) of TIR for predicting HUA in T2DM was 0.856(95% CI 0.803-0.909, P<0.001), with the best cut-off value being 64.5%, the sensitivity being 76.8%, and the specificity being 90.3%. Conclusion:TIR in patients with T2DM combined with HUA was significantly decreased. TIR is an independent protective factor for T2DM combined with HUA, and TIR shows a certain predictive value for T2DM combined with HUA.