BACKGROUND:Agomelatine is a clinically proven treatment for neuropsychiatric symptoms,such as anxiety and depression.Furthermore,our previous study has demonstrated that agomelatine ameliorates cognitive behaviors,hippocampal synaptic plasticity,and brain pathology in a mouse model of Alzheimer's disease.However,it remains unclear whether agomelatine can improve anxiety and depression-like behaviors in Alzheimer's disease model mice. OBJECTIVE:To investigate the improving effects of agomelatine on anxiety-and depression-like behaviors in APP/PS1 transgenic mice and its underlying molecular mechanisms. METHODS:(1)Eighteen APP/PS1 transgenic mice were randomly divided into model control group(n=9)and model intervention group(n=9).Another wild-type mice were randomized into control group(n=9)and intervention group(n=9).Model intervention group and intervention group were intraperitoneally injected with 10 mg/kg agomelatine per day for 31 continuous days.Behavioral experiments,including the elevated cross maze and forced swimming tests,and mRNA sequencing of the hippocampus were then performed.(2)Mouse hippocampal neuronal cell lines(HT22)and brain microvascular endothelial cell lines(bEnd.3)were cultured and divided into four groups:blank group without any drug,drug group with 20 μmol/L agomelatine,model group with 10 μmol/L β-amyloid 1-42,and experimental group with 10 μmol/L β-amyloid 1-42+20 μmol/L agomelatine.After 24 hours of incubation,protein expression of S416p-tau and S9p-GSK3β in HT22 cells was detected by immunoblotting,and protein expression of low-density lipoprotein receptor-related protein 1 and glycosylation end-product receptor in bEnd.3 cells was detected by immunoblotting. RESULTS AND CONCLUSION:In the elevated plus maze test,the time spent in the open arms(P＜0.01)and the entries into open arms(P＜0.05)in the mice of model control group were evidently lower than those in the control group,whereas those were obviously increased in the model intervention group compared with the model control group(P＜0.05).Forced swimming test results showed that the immobile time exhibited a marked increase in the model control group compared with the control group(P＜0.05),but it was significantly decreased in the model intervention group compared with the model control group(P＜0.05).Hippocampal tissue mRNA sequencing showed that agomelatine enhanced the expression of low-density lipoprotein receptor-related protein 1 in the hippocampus of APP/PS1 mice.Western blot analysis revealed that the level of S416p-tau in HT22 cells was higher in the model group than the blank group(P＜0.05),while it was markedly decreased in the experimental group compared with the model group(P＜0.05);the level of S9p-GSK3β in HT22 cells was higher in the drug group than the blank group(P＜0.05)as well as higher in the experimental group than the model group(P＜0.05).Moreover,the expression of low-density lipoprotein receptor-related protein 1 in bEnd.3 cells was higher in the experimental group than the model group(P＜0.05).To conclude,agomelatine can alleviate anxiety-and depression-like behaviors in Alzheimer's disease mice by promoting the clearance of β-amyloid and phosphorylated tau.

BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Objective:To explore the genetic etiology and clinical phenotype of Feingold syndrome due to chromosome 2p24.3p24.2 microdeletion.Methods:The clinical data of a child admitted to Henan Provincial People′s Hospital in November 2021 and diagnosed as Feingold syndrome type 1 (FGLDS1) associated with chromosome 2p24.3p24.2 microdeletion were collected. The clinical and genetic variation characteristics of the patient were summarized, and 10 patients with chromosome 2p microdeletion reported until November 2022 were reviewed.Results:The boy was 12 years and 5 months old. He presented with backward physical development, motor development retardation, low intelligence, special body and facial appearance, finger developmental deformity and other manifestations, accompanied by hyperactivity and aggressive behavior, impulsive irritability, self-injury and other behavior problems. The proband showed normal chromosome karyotype; the genome-wide copy number variant sequencing and trio-whole exome sequencing revealed a 2.61 Mb deletion at chromosome 2p24.3p24.2 region, and 10 genes including MYCN gene (exons 1 to 3) in the deleted region.The same deletion was not found in either of his parents. The genetic features of 11 cases (including this case) with chromosome 2p microdeletion were summarized, all of whom had insufficient haploid dosage of the MYCN gene due to chromosome 2p microdeletion, and the clinical manifestations of these 11 patients matched the clinical diagnosis of FGLDS1. Conclusion:The proband is consistent with the clinical presentation of the typical Feingold syndrome, and the haploinsufficiency of the MYCN gene due to the microdeletion of chromosome 2 is the genetic etiology of the proband.

Objective:To observe the effects of acupuncture and moxibustion at Feishu(BL13)on inflammatory responses and intestinal short-chain fatty acids(SCFAs)in rats with asthma. Methods:Fifty-six Sprague-Dawley rats were randomly divided into a normal group(16 rats)and a modeling group(40 rats).Rats in the modeling group were subjected to establishing asthma models using ovalbumin(OVA).Model evaluation was conducted using 4 rats from each group.The remaining rats that successfully developed asthma were then randomly divided into a model group,an acupuncture group,and a moxibustion group,with 12 rats in each group.Rats in the acupuncture group received acupuncture treatments,and those in the moxibustion group received moxibustion treatments,both at Feishu(BL13)for 30 min.Following the treatments,the rats were exposed to atomization excitation with a 1%OVA solution for 20 min daily for 14 consecutive days.At the end of the experiment,inflammatory markers in the rats'peripheral blood were analyzed using a biochemical method.In addition,inflammatory cells in the bronchoalveolar lavage fluid(BALF)were counted using Wright-Giemsa staining.The lung tissue of rats was examined under a light microscope after staining with hematoxylin-eosin to observe morphological or pathological changes.Furthermore,real-time fluorescence quantitative polymerase chain reaction was utilized to measure the mRNA expression of inflammatory factors in the lung tissue.Lastly,the concentration of SCFAs in the rat's feces was determined using gas chromatography-hydrogen flame ionization. Results:The levels of eosinophils(Eos),neutrophils(Neu),and lymphocytes(Lym)in the peripheral blood,as well as Eos and Neu in the BALF,and the expression of interleukin(IL)-4,IL-5,IL-13,IL-33,and thymic stromal lymphopoietin(TSLP)mRNAs in the lung tissue were all found to be significantly increased(P<0.05 or P<0.01);the lung tissue structure displayed severe injuries;the levels of acetic acid,propionic acid,isobutyric acid,butyric acid,and valeric acid in the feces decreased significantly in the model group(P<0.05 or P<0.01).Compared with the model group,the peripheral blood levels of Eos,Neu,and Lym,as well as Eos in the BALF,and the mRNA expression levels of IL-4 and IL-5 in the lung tissue decreased significantly in both the acupuncture group and the moxibustion group(P<0.05 or P<0.01).This reduction was accompanied by alleviated pathological damage in the lung tissue.Additionally,there were significant increases in the levels of acetic acid,propionic acid,isobutyric acid,and butyric acid in the feces in both the acupuncture group and the moxibustion group(P<0.05 or P<0.01).In the acupuncture group,the expression levels of Lym in the BALF and IL-13 mRNA in the lung tissue decreased significantly(P<0.05 or P<0.01).In the moxibustion group,the mRNA expression levels of IL-33 and TSLP in the lung tissue also reduced significantly(P<0.05 or P<0.01).Furthermore,the level of valeric acid in the feces increased notably in the moxibustion group(P<0.01).Compared with the acupuncture group,it was found that the mRNA levels of IL-5 and IL-13 in the lung tissue,as well as the acetic acid level in the feces,were significantly higher in the moxibustion group(P<0.05 or P<0.01). Conclusion:Both acupuncture and moxibustion were effective in reducing abnormal inflammation and regulating intestinal SCFAs in asthma model rats.Acupuncture demonstrated superiority in inhibiting pro-inflammatory factors,particularly IL-5 and IL-13,while moxibustion exhibited better regulation on intestinal metabolites SCFAs,especially acetic acid.

Objective: To evaluate the effectiveness for the construction of "mosquito-free village" in Xuejia Village, Pujiang County, Zhejiang Province, so as to provide the guidance for the construction of "mosquito-free village" in other rural areas. Methods: Density of adult mosquitoes in Xuejia Village was investigated using light trap method and density of larval mosquitoes was investigated using larval straw method from April to November each year. Totally 30 households of villagers were randomly selected, and their awareness rates of mosquito control knowledge, mosquito control behavior forming rates and satisfaction rates were surveyed through questionnaires. Investment during construction (from August 2016 to December 2018) and maintenance period (from 2019 to 2023) of "mosquito-free village" were investigated through data review and interviews. Long-term effects of "mosquito-free village" construction in Xuejia Village were evaluated in terms of mosquito density from 2016 to 2023, effectiveness of health education for villagers, satisfaction and investment. Results: Compared with the year 2016, the densities of adult and larval mosquitoes in Xuejia Village were significantly decreased from 2017 to 2023. The average monthly density of adult mosquitoes in 2023 decreased by 98.34%, and the average monthly 100 household index of larval mosquitoes decreased by 98.45% compared to 2016. The average monthly density of adult mosquitoes from 2019 to 2023 was less than or equal to one mosquito per light trap in a night, and the average monthly 100 household index of larval mosquitoes was less than or equal to five places per 100 households. The awareness rate of mosquito control knowledge was 93.33%, the behavior forming rate was 86.67%, and the satisfaction rate was 90.00%. By December 2023, the total investment during construction and maintenance period was 450 thousand Yuan, with an average annual investment of 60.7 thousand Yuan and average annual investment of 206.61 Yuan per household. The average annual investment during maintenance period was 36.2 thousand Yuan, and the average annual investment per household was 109.70 Yuan. Conclusion The mosquito density, effectiveness of health education for villagers and satisfaction of "mosquito-free village" in Xuejia Village all meet the evaluation criteria of "mosquito-free village", and the investment is reasonable, making it suitable for promotion to other rural areas.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective Preliminary exploration of the effects of modified electroconvulsive therapy(MECT)on cognitive function and gender differences in middle-aged and young patients with depressive episodes.Methods A group of middle-aged and young patients with depressive episodes,who were admitted to Beijing Anding Hospital affiliated to Capital Medical University,completed 6 rounds of MECT.The 17-item Hamilton depression scale(HAMD-17),Hamilton anxiety scale(HAMA),and repetitive battery for the assessment of neuropsychological status(RBANS)were used to score depressive symptoms,anxiety symptoms,and cognitive function at baseline,after the 3rd MECT,and after the 6th MECT,respectively.Gender differences were compared between the young and middle-aged groups.Results A total of 122 patients with depressive episodes were included,with 83 cases in the youth group and 39 cases in the middle-aged group.There was no gender difference in baseline HAMD and HAMA scores,as well as the HAMD reduction rates after MECT between the two groups(P>0.05).Repeated measures ANOVA showed that in the youth group,the time effects of RBANS total score,visual breadth factor score,and attention factor score were significant(P<0.05),and increased after treatment compared to baseline.There was no significance in gender group effects or interaction effects(P>0.05).In the middle-aged group,the time and gender interaction effect of RBANS total score and visual breadth factor score was significant(P<0.05).Female patients showed an increase in RBANS total score,visual breadth factor score,and attention factor score after the 6th MECT compared to baseline(P<0.05),while there was no significance in time effect and gender group effect(P>0.05).Conclusion Middle-aged and young depressed patients showed overall improvement in cognitive function after MECT,while there were gender differences in cognitive function changes among middle-aged patients.It is necessary to optimize the MECT program based on the patient's gender and age characteristics to reduce cognitive impairment.

Objective To compare the effect of glycopyrrolate or atropine in combination with neostigmine on adverse cardiovascular events(ACEs)after operation in elderly patients undergoing laparo-scopic surgery.Methods A total of 142 patients scheduled for elective laparoscopic surgery were enrolled,69 males and 73 females,aged 65-80 years,BMI 18-28 kg/m2,ASA physical status Ⅰ or Ⅱ.The pa-tients were randomly divided into two groups:the glycopyrrolate group(group G)and the atropine group(group A),71 patients in each group.After the last administration of muscle relaxants for more than 30 mi-nutes,antagonizing residual neuromuscular blockade was performed.Glycopyrrolate 4 μg/kg and neostigmine 20 μg/kg were given intravenously in group G,atropine 10 μg/kg and neostigmine 20 μg/kg were given intravenously in group A.The incidence of ACEs and severe ACEs during operation and 72 hours after operation were recorded.Recovery situation in PACU such as NRS scores at rest and coughing,Rich-mond agitation-sedation scale(RASS)score,and modified Aldrete score 15 and 30 minutes after extubation were recorded.Emergence agitation,dry mouth,nausea,vomiting,and delirium 24 hours after operation were recorded.Results Compared with group A,the total incidence of ACEs,tachycardia,and myocardial ischemia after operation were significantly decreased in group G(P＜0.05),the incidence of dry mouth 24 hours postoperatively was significantly increased in group G(P＜0.05).There was no severe ACEs oc-curred in the two groups 72 hours after operation.Conclusion Compared with atropine,glycopyrrolate combined with neostigmine in elderly patients undergoing laparoscopic surgery can reduce the incidence of cardiac tachycardia,myocardial ischemia,and total ACEs after operation,and there was no severe ACEs occurred.However,it can increase the incidence of dry mouth 24 hours after operation.

Objective:To analyze the epidemiological characteristics of rabies in China from 2007 to 2023, and to provide reference evidence for tailoring strategies to facilitate the elimination of rabies in the country.Methods:Case data from 2007 to 2023 were obtained from China′s National Notifiable Infectious Disease Reporting Information System, and the spatial, temporal, and demographic features of cases were analyzed.Results:From 2007 to 2023, a total of 18 751 human rabies cases were reported in China, with an average annual incidence rate of 0.08 per 100 000. The average annual percentage change (AAPC) in incidence rate was -18.58% (95% CI: -21.32% to -15.75%, P<0.05), with three significant turning points in 2011, 2018, and 2021. Based on the trend of the epidemic, Chinese provinces can be roughly divided into five categories. The geographical range affected by rabies has decreased from 23 provinces and 984 counties (districts) in 2007 to 17 provinces and 101 counties (districts) in 2023. Since 2019, the high-incidence counties (districts) have been mainly concentrated in the southwestern part of Hunan, the southern part of Henan, and the western part of Anhui. Fourteen provinces have reported no cases for at least two consecutive years. Males (70.24%) and farmers (72.18%) were the main affected groups, and the proportion of cases aged 65 and above increased from 17.43% in 2007 to 36.07% in 2023. Conclusions:The incidence of rabies in China has changed from endemic in many areas to sporadic, with the remaining endemic regions mainly located in parts of the middle and lower reaches of the Yangtze River. The main vulnerable groups are middle-aged and elderly farmers. The current prevention and control measures can effectively curb the transmission of rabies, but the decline of cases has slowed down recently.