OBJECTIVE To explore the potential of Aconiti Kusnezoffii Radix in affecting diabetes mellitus type 2(T2DM) and the potential mechanism for T2DM related symptoms based on systematic pharmacology, bioinformatics, molecular docking and in vitro and in vivo experiments. METHODS The database was used to search the related chemical components of Aconiti Kusnezoffii Radix, predict the potential targets and intervene related diseases. The differential genes of T2DM relative healthy people were retrieved from GEO database, mapped with the action target of Aconiti Kusnezoffii Radix, and placed in DAVID database for biological function enrichment. The sensitivity of the target gene to T2DM was analyzed by one-way ANOVA, binary logistic regression analysis and ROC curve. The binding position and interaction force between chemical compounds of Aconiti Kusnezoffii Radix and target proteins were analyzed by molecular docking technology. The effect of Aconiti Kusnezoffii Radix and its chemical compounds on the expression of target protein was verified by T2DM model in vivo and in vitro. RESULTS Through database retrieval and analysis, 304 kinds of target related diseases(P value<0.05, FDR<0.05) were obtained, and T2DM with the highest degree value(Degree=59) was selected and analyzed. The 43 target genes were obtained from the intersection of differential genes in T2DM relatively healthy people and potential action targets of Aconiti Kusnezoffii Radix. A total of 9 genes with significant differences were obtained by one-way ANOVA, 5 meaningful genes were obtained by binary logistic regression analysis, and 3 genes with area under ROC curve AUC>0.5 were obtained. By molecular docking (+)-Isoboldine binds to proteins APEX1, CASP1 and CBFB, Napelline binds to proteins CBX1 and EHMT2 through different forces such as hydrogen bond interaction, ligand interaction, hydrophobic interaction, ionizability and electrostatic interaction, so as to increase the ability of ligands to target proteins. After 2 weeks of treatment with Aconiti Kusnezoffii Radix aqueous extract, Aconiti Kusnezoffii Radix may alleviated the symptoms of T2DM by improving peripheral neuropathy. Moreover, Aconiti Kusnezoffii Radix could affect the protein expression of APEX1, CASP1, CBFB, CBX1 and EHMT2 in rat liver tissue. The effect of (+)-Isoboldine and Napelline chemical compounds in Aconiti Kusnezoffii Radix on the target protein of the model in vitro was consistent with that in vivo. CONCLUSION It is preliminarily revealed that Aconiti Kusnezoffii Radix can be used as a potential therapeutic drug to improve T2DM peripheral neuropathy, which lays a theoretical foundation for the research and development of Chinese Mongolian medicine and the excavation of new target drugs for the treatment of T2DM.

Objective To explore the expression of serum microRNA(miR)-126 and miR-132 in patients with sepsis complicated with acute respiratory distress syndrome(ARDS)and their relationship with disease outcome.Methods A total of 106 patients with sepsis complicated with ARDS admitted to a hospital from January 2021 to July 2023 were selected as the study group,another 110 patients with simple sepsis in the hos-pital in the same period were selected as the control group.Real-time fluorescence quantitative PCR was used to detect the relative expression levels of miR-126 and miR-132 in serum of all subjects.106 patients with sep-sis complicated with ARDS were divided into survival group(n=65)and death group(n=41)according to the prognosis of the disease after 28 days'treatment.The relative expression levels of miR-126 and miR-132 in serum of all groups were compared.Receiver operating characteristic curve was drawn to analyze the prognos-tic value of serum miR-126 and miR-132 in patients with sepsis complicated with ARDS.Multivariate Logistic stepwise regression was used to analyze the risk factors of disease outcome in patients with sepsis complicated with ARDS.Results The relative expression levels of miR-126 and miR-132 in the study group were lower than those in the control group,and the difference was statistically significant(P＜0.05).The relative expres-sion levels of serum miR-126 and miR-132 in the death group were lower than those in the survival group,and the difference was statistically significant(P＜0.05).The area under the curve(AUC)of serum miR-126 and miR-132 to predict the disease outcome of patients with sepsis complicated with ARDS were 0.749(95％CI:0.705-0.818)and 0.825(95％CI:0.782-0.875)respectively,and the combined forecast AUC was 0.908(95％CI:0.859-0.954).Multivariate Logistic stepwise regression showed that multiple organ failure(OR=3.494,95％CI:1.519-8.037),miR-126＜0.75(OR=4.707,95％CI:1.834-12.083),miR-132＜7.73(OR=5.307,95％CI:2.104-13.385)were risk factors for disease outcome in patients with sepsis complicated with ARDS(P＜0.05).Conclusion The decreased expression of serum miR-126 and miR-132 in sepsis complicated with ARDS is related to the adverse disease outcome,and the two may be used as biological indicators to eval-uate the prognosis of sepsis complicated with ARDS.

To reveal the effects of N-carbamylglutamic(NCG)on growth performance,blood pa-rameters and meat quality of meat rabbits,192 Hyla rabbits at 35 days of age were assigned to four groups randomly with 0.00％,0.05％,0.10％,and 0.20％NCG added to the basal diet,with six replicates of eight rabbits in each group and one replicate of eight rabbits.The results indicated that:compared to the control group,the body weight of the 0.20％NCG group at d 35(P＜0.01),the BW at d 14 and the average daily gain(ADG)from d 1 to 14 in the 0.05％NCG group(P＜0.05)were significantly elevated;the ADG of the control group from d 1 to 35 was significantly lower than the 0.10％and 0.20％NCG groups(P＜0.05).The levels of total superoxide dismutase(T-SOD)in the 0.10％NCG group(P＜0.01),total antioxidant capacity(T-AOC)and urea nitro-gen(BUN)in the 0.20％NCG group(P＜0.05)were significantly higher compared to the control group;the levels of T-SOD in the 0.10％NCG group were significantly elevated compared to the 0.05％NCG group(P＜0.05).NCG significantly increased polyunsaturated fatty acids(PUFA)and PUFA/SFA(P＜0.05).The cooked meat rate of the longissimus lumborum in the 0.20％NCG group was significantly increased compared to the control group(P＜0.01),while the water holding rate of the longissimus lumborum increased significantly in the 0.10％NCG groups(P＜0.01)and the control group(P＜0.05)and 0.05％NCG group(P＜0.05)than the 0.20％NCG group.NCG significantly reduced the crypts depth(P＜0.01)and had the tendency to in-crease the V/C value(P=0.067),while the villi height of jejunal in the 0.20％NCG group was significantly elevated compared to the control group(P＜0.05).In conclusion,NCG could promote the growth performance,enhance the antioxidant capacity,and improve the intestinal morphology and meat quality of meat rabbits.The appropriate amount of NCG added to meat rabbit diet is 0.10％.

BACKGROUND: Cancer patterns in China are becoming similar to those in the United States (US). Comparing the recent cancer profiles, trends, and determinants in China and the US can provide useful reference data. METHODS: This study used open-source data. We used GLOBOCAN 2022 cancer estimates and United Nations population estimates to calculate cancer cases and deaths in both countries during 2024. Data on cancer incidence and mortality trends were obtained from the Surveillance, Epidemiology, and End Results (SEER) program and National Centre for Health Statistics in the US and cancer registry reports of the National Cancer Center (NCC) of China. Data from the Global Burden of Disease study (GBD) and a decomposition approach were used to estimate the contributions of four determinants to the change in cancer deaths. RESULTS: In 2024, there are an estimated 3,246,625 and 2,510,597 new cancer cases and 1,699,066 and 640,038 cancer deaths in China and the US, respectively. The highest estimated cancer cases are lung cancer in China and breast cancer in the US. The age-standardized incidence rates of lung and colorectal cancer in the US, and stomach, liver, and esophageal cancer in China have decreased, but the incidence rates of liver cancer in the US and colorectal cancer, prostate cancer in men, and cervical cancer in women in China have increased. Increases in the adult population size and population aging are main reasons for the increase in cancer deaths; case fatality rates are a main reason for the decrease in cancer deaths in both countries. CONCLUSIONS China has made progress in cancer control but lags the US. Considering the transformation in China's pattern of cancers epidemiology, it is imperative to develop stronger policies by adopting the cancer prevention and control strategies used in the US to address population aging and curb growing cancer trends.
Humans ; China/epidemiology* ; United States/epidemiology* ; Male ; Neoplasms/mortality* ; Female ; Incidence ; SEER Program ; Middle Aged ; Adult ; Aged ; Lung Neoplasms/mortality*

Objective:To analyze the occurrence of early hypotony after the intravitreal injection of anti-vascular endothelial growth factor (VEGF) and its risk factors.Methods:A case-control study was performed.One hundred and twenty-seven eyes of 127 patients with fundus vascular disease who received intravitreal injections of anti-VEGF drugs were enrolled in Henan Provincial People's Hospital from January 2020 to January 2022.Of the 127 patients, there were 71 males and 56 females, with an average age of (61.85±11.53) years and a mean intraocular pressure of (15.28±3.71)mmHg (1 mmHg=0.133 kPa). All subjects were intravitreally injected with 0.05 ml of anti-VEGF drugs, including 56 cases receiving ranibizumab, 38 cases receiving conbercept and 33 cases receiving aflibercept.The intraocular pressure was measured with a non-contact tonometer at 30 minutes, 1 hour and 2 hours after the injection.The cases were grouped as hypotony group or non-hypotony group according to the intraocular pressure of subjects was less than 10 mmHg or not.The differences in sex, age, distribution of left eye and right eye, disease type, intraocular pressure before injection, injection frequency, lens status, drug type, injection timing, injection site, with or without high myopia, with or without a history of glaucoma or ocular hypertension, and with or without a history of vitreoretinal surgery were analyzed to investigate the factors with a P-value <0.05, which were used as the independent variable and the occurrence of hypotony as the dependent variable in logistic regression analysis to explore the risk factors for hypotony.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2022-42). Results:Hopotony occurred in 8 eyes within 2 hours after the injection.There were significant differences in intraocular pressure at different time points before and after injection between the hypotony and non-hypotony groups ( Fgroup=62.177, P<0.001; Ftime=25.128, P<0.001). The intraocular pressure of the hypotony group at 30 minutes, 1 hour and 2 hours after injection were lower than before injection, and the intraocular pressure of the non-hypotony group was higher at 30 minutes after injection than before injection (all at P<0.05). The average reduction of intraocular pressure of the hypotony group was 7.88, 7.63 and 7.23 mmHg at 30 minutes, 1 hour and 2 hours after the injection, and the intraocular pressure returned to baseline level at 1 day after injection.There was no significant difference in sex, distribution of left and right eyes, disease type, pre-injection intraocular pressure, injection frequency, lens status, drug type, injection timing, injection site, with or without a history of high myopia and with or without a history of glaucoma or ocular hypertension between the two groups.There were significant differences in age and with or without a history of vitreoretinal surgery between the two groups ( t=8.265, P<0.001; χ2=6.907, P=0.035). Multivariate logistic regression analysis showed younger patients and having a history of vitreoretinal surgery were the risk factors for early hypotony after anti-VEGF intravitreal injection (odds ratio=88.563, P<0.001; odds ratio=20.991, P=0.009). Conclusions:Patients with younger age and having a history of vitreoretinal surgery are susceptible to early hypotony after anti-VEGF intravitreal injection.

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.
Humans ; Autism Spectrum Disorder/metabolism* ; Autistic Disorder ; Exome Sequencing ; DNA Copy Number Variations ; East Asian People ; Brain/metabolism* ; Mutation/genetics* ; Genetic Predisposition to Disease/genetics*

OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

The back-propagating action potential (bpAP) is crucial for neuronal signal integration and synaptic plasticity in dendritic trees. Its properties (velocity and amplitude) can be affected by dendritic morphology. Due to limited spatial resolution, it has been difficult to explore the specific propagation process of bpAPs along dendrites and examine the influence of dendritic morphology, such as the dendrite diameter and branching pattern, using patch-clamp recording. By taking advantage of Optopatch, an all-optical electrophysiological method, we made detailed recordings of the real-time propagation of bpAPs in dendritic trees. We found that the velocity of bpAPs was not uniform in a single dendrite, and the bpAP velocity differed among distinct dendrites of the same neuron. The velocity of a bpAP was positively correlated with the diameter of the dendrite on which it propagated. In addition, when bpAPs passed through a dendritic branch point, their velocity decreased significantly. Similar to velocity, the amplitude of bpAPs was also positively correlated with dendritic diameter, and the attenuation patterns of bpAPs differed among different dendrites. Simulation results from neuron models with different dendritic morphology corresponded well with the experimental results. These findings indicate that the dendritic diameter and branching pattern significantly influence the properties of bpAPs. The diversity among the bpAPs recorded in different neurons was mainly due to differences in dendritic morphology. These results may inspire the construction of neuronal models to predict the propagation of bpAPs in dendrites with enormous variation in morphology, to further illuminate the role of bpAPs in neuronal communication.
Action Potentials/physiology* ; Dendrites/physiology* ; Neurons/physiology* ; Neuronal Plasticity ; Pyramidal Cells/physiology*

Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-