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

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

Objective·To investigate the potential causal relationship between type l diabetes and colorectal cancer by using Mendelian randomization(MR).Methods·Two-sample bidirectional MR was used to investigate the causal relationship between type 1 diabetes and colorectal cancer.All research data were collected from the IEU Open GWAS Project database.The dataset of type l diabetes included 9 266 cases and 15 574 controls,with correlation analysis in 12 783 129 single nucleotide polymorphisms(SNPs);the dataset of colorectal cancer included 5 657 cases and 372 016 controls,with correlation analysis in 29 999 696 SNPs.The instrumental variables SNPs were screened.The results derived from the inverse-variance weighted(IVW)method were used as the main indicator of effect.The results derived from other four methods,namely MR-Egger regression,weighted median,simple mode,and weighted mode,were used as reference.Sensitivity was analyzed with the leave-one-out method.Heterogeneity was analyzed with Cochran's Q test by using both IVW and MR-Egger methods.Pleiotropy was analyzed with MR-pleiotropy function,and Steiger test was used for directional research.The colocation analysis was used to find out whether the causal relationship between type 1 diabetes and colorectal cancer was caused by the same SNP.The genetic correlation between 2 diseases was analyzed by using the linkage disequilibrium score regression(LDSC).All tests were analyzed by using R language software(version 4.3.1).Results·After being screened,a total of 33 instrumental variables(SNPs)were used.The heterogeneity test results showed that there was heterogeneity among the SNPs(IVW and MR-Egger:P＜0.05),so the effect evaluation was based on the results of the random effect model.MR analysis showed that type 1 diabetes had a significant causal effect on colorectal cancer(P＜0.05)by using IVW,MR-Egger,weighted median and weighted mode.Sensitivity analysis showed that the results were stable.Pleiotropy was not detected in pleiotropy test(P＞0.05).Steiger test showed that the effect of type l diabetes on colorectal cancer was not interfered with by the reverse effect.Reverse MR analysis showed no causal effect of colorectal cancer on type l diabetes(P＞0.05).The results of colocalization analysis showed that the probability of H4 hypothesis was 45.7％,and the causal relationship between the 2 diseases was not caused by the same SNP in the gene sequences.LDSC analysis demonstrated that there was no genetic correlation between the two diseases.Conclusion·Type 1 diabetes may promote colorectal cancer,but colorectal cancer has no effect on type 1 diabetes.

Objective To assess the effects of low-dose esketamine on the median effective dose(ED50)of ciprofol for anesthesia induction in painless gastrointestinal endoscopy.Methods Fifty-nine pa-tients underwent elective painless gastrointestinal endoscopy,26 males and 33 females,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups by random number table method:esketamine combined with ciprofol group(group EC,n = 29)and ciprofol group(group C,n = 30).Group EC received intravenous injection of esketamine 0.3 mg/kg and group C received the same amount of normal saline 2 minutes before administration of ciprofol.The initial anesthesia induction dose of ciprofol was 0.4 mg/kg.If a positive reaction occurs during the examination,the next patient will receive an increase dose of propofol 0.04 mg/kg,otherwise will decrease by propofol 0.04 mg/kg.The positive reaction was defined that the patient's BIS can not be decreased to 60 2 minutes after anesthesia induction,or the cough or body movement reaction occur at level 2 or above when entering the mirror.The dosage of ciprofol,recovery time,discharge time,the occurrence of intraoperative and postoperative adverse reactions were recorded.The ED50,95%effective dose(ED95)and 95%confidence interval(CI)of the two groups were calculated by Probit probability regression analysis.Results Compared with group C,the dosage of ciprofol,the incidence of hypotension and frequency of administration of vasoactive drugs during the exami-nation process in group EC were significantly reduced(P＜0.05).The ED50 of ciprofol for anesthesia in-duction in painless gastrointestinal endoscopy in group EC was 0.21 mg/kg(95%CI 0.12-0.25 mg/kg)and the ED95 was 0.32 mg/kg(95%CI 0.26-0.39 mg/kg).The ED50 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group C was 0.37 mg/kg(95%CI 0.32-0.40 mg/kg)and the ED95 was 0.48 mg/kg(95%CI 0.43-0.54 mg/kg).The ED50 and ED95 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group EC was significantly lower than that in group C(P＜0.05).There was no significant difference in other frequency of adverse events between the two groups.Conclusion Esketamine 0.3 mg/kg can reduce the ED50 of ciprofol in painless gastrointestinal endoscopy and reduce the dosage of ciprofol during the examination process,which is safe for painless gastrointestinal endoscopy with stable intraoperative circulation.

Ischemic stroke is an acute cerebro-vascular disease with high disability and mortality,is the most common cause of death in China.De-spite years of research,there are still no biomark-ers for stroke,and the molecular mechanisms re-main largely unknown.In the past decade,single-cell sequencing technology,as a rapidly developing emerging technology,can conduct high-throughput sequencing of multiple omics including genome,transcriptome,epigenome and proteome at the level of a single cell,providing a new way to discov-er biomarkers and analyze pathological mecha-nisms.In this paper,the progress of single-cell multi-omics sequencing technology and its applica-tion in the discovery of biomarkers,pathological mechanisms and drug development of ischemic stroke are introduced in detail,in order to provide valuable reference for precision medicine of isch-emic stroke.

Objective:To investigate the correlation between psychological resilience and the risk of all-cause mortality in disabled older individuals.Methods:A total of 8, 089 disabled older adults were selected from the Chinese Longitudinal Healthy Longevity Survey(1998-2018)after screening with the Katz index.Psychological resilience was assessed at baseline using a seven-item self-rating scale.Participants were followed up until 2018, with survival data being recorded.Restricted cubic spline regression and Cox proportional hazard models were employed to analyze the association between psychological resilience and all-cause mortality, as well as to explore the potential interaction between psychological resilience and levels of disability.Results:After adjusting for potential confounding factors, a linearly negative relationship was found between levels of psychological resilience and mortality risk( P-nonlinear 0.781).Stratified analyses by degree of disability revealed that for older adults with mild disability, a 1 standard deviation increase in psychological resilience was associated with a 12% decrease in mortality risk( HR=0.88, 95% CI: 0.83-0.94).However, no significant association was observed between psychological resilience and mortality risk in severely disabled participants.A significant interaction was noted between resilience levels and degree of disability( P-interaction=0.026). Conclusions:This study offers observational evidence supporting the importance of maintaining psychological resilience in reducing mortality risk among disabled older individuals, particularly those with mild disability.The findings highlight the potential benefits of psychological interventions for older adults with varying levels of functional decline.

The unfolded protein response is triggered by the presence of unfolded or misfolded proteins in the endoplasmic reticulum and mitochondria, aiming to regulate and maintain cellular homeostasis under stress stimuli. Recent studies have shown that unfolded protein response plays a crucial role in the pathogenesis of female reproductive-related diseases. This article delves into the specific signaling pathways of unfolded protein response in the endoplasmic reticulum and mitochondria and summarizes its impact on the physiological functions and common diseases of the female reproduction, trying to provide novel potential therapeutic targets for the diagnosis and treatment of reproductive disorder related diseases.