OBJECTIVE To investigate the improvement effects and mechanism of Zhichi suanzaoren decoction （ZSD） on hippocampal oxidative stress injury in hippocampal neurons of mice with perimenopausal insomnia. METHODS The potential targets of active ingredients in ZSD were predicted using TCMSP and TCMIP databases； the targets related to insomnia were searched through GeneCards， OMIM and DisGeNET databases； protein-protein interaction network of intersecting targets of ZSD ingredients and insomnia was constructed； Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted on key targets. Sixty mice were divided into sham operation group， model group， ZSD low-， medium-， and high-dose groups （11， 22， and 33 g/kg）， and eszopiclone group （positive control， 1 mg/kg）. Except for sham operation group， the perimenopausal insomnia model was constructed by ovariectomy （OVX） in the other groups. After successful modeling， mice in each group were gavaged with normal saline or the corresponding drug solution， once a day， for three consecutive weeks. The sleep status of mice was evaluated through the pentobarbital sodium sleep synergy experiment， and the pathological changes of hippocampal neurons and the expressions of related genes and proteins in mice were observed by HE staining， immunohistochemistry staining， immunofluorescence staining， transcriptome sequencing technology and Western blot. RESULTS The results of network pharmacology showed that there were 296 intersection targets between ZSD and perimenopausal insomnia. Protein kinase B1 （Akt1） was a key target for treating insomnia with ZSD. After administration of ZSD， the sleep latency of mice was shortened， the sleep duration was prolonged significantly， and the mean optical density value of neuron-specific nuclear protein in the hippocampal CA1 region was significantly increased （P＜0.01）. Additionally， hippocampal neuron damage in OVX mice was significantly alleviated. The results of transcriptome sequencing showed that ZSD significantly upregulated the transcriptional levels of Nfe2l2 gene in hippocampal tissue of OVX mice （P＜0.05）. After administration of ZSD， protein expressions of nuclear factor E2 related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in hippocampal tissue of OVX mice， as well as the phosphorylated Akt level， were increased significantly （P＜0.01）. CONCLUSIONS ZSD can ameliorate hippocampal oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice by activating the Akt/Nrf2/HO-1 signaling pathway.

Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency， it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat， spleen and stomach damp-heat， and spleen deficiency is divided into deficiency of spleen yin， deficiency of spleen qi ， and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories，i.e. stomach-heat and spleen yin-deficiency， stomach-heat and spleen qi-deficiency， and stomach-heat and spleen yang-deficiency， and the main treatment methods are clearing and draining heat， nourishing yin and moistening intestine， clearing dampness and heat， strengthening spleen and qi， clearing dampness and heat， strengthening spleen and warming yang， respectively， with prescriptions as Maziren Pills （麻子仁丸）， Qinlian Pingwei Powder （芩连平胃散）， and Jiawei Lianli Decoction （加味连理汤） accordingly.

Objective:To study the prognosis of congenital bile duct cysts following cyst resection, and to analyze the risk factors associated with the development of postoperative biliary calculus.Methods:Clinical data of 149 patients with congenital bile duct cysts undergoing surgery in the First Affiliated Hospital of Nanjing Medical University from May 2004 to January 2022 were retrospectively analyzed, including 59 males and 90 females, with a median age of 32 (21, 47) years old. Patients were divided into two groups: the stone group ( n=51, biliary calculus occurred during the follow-ups after surgery) and non-stone group ( n=98). Clinical data such as gender, age, medical history, cyst type, biliary calculus, anastomotic stenosis and occurrence of cancer were compared. All patients were followed up via telephone consultations. A logistic regression analysis was used to identify the risk factors associated with the occurrence of biliary calculus after surgery. Results:The duration of the follow-ups was 120 (24, 211) months. The observed incidence of postoperative biliary calculus, anastomotic stricture, and cancer in the patients were 34.2% (51/149), 8.7% (13/149), and 4.7% (7/149), respectively. The logistic regression analysis indicated that incomplete cyst resection ( OR=3.332, 95% CI: 1.221-9.094) and postoperative anastomotic stenosis ( OR=13.300, 95% CI: 2.586-68.401) were associated with a higher risk of biliary calculus formation after cystectomy (all P<0.05). Conclusion:Patients with congenital bile duct cysts suffer a high risk of biliary calculus formation after cystectomy. The residual cyst and postoperative anastomotic stenosis are independent risk factors for biliary calculus after surgery.

Objective:To examine the correlation between serum Klotho levels and frailty in elderly people.Methods:In this cross-sectional study, 150 community-dwelling elderly people aged 65 years and over were enrolled.Subjects were divided into a frail(n=50, 33.3%), a pre-frail(n=47, 31.3%)and a non-frail(n=53, 35.3%)group based on the Fried phenotype.General participant data, routine laboratory test results, short physical performance battery(SPPB)results and human body composition data were collected.Serum Klotho protein levels were measured by an enzyme-linked immunosorbent assay.The relationship between serum Klotho protein levels and frailty was analyzed by using Spearmen's correlation analysis and Logistic regression analysis.Results:Klotho protein levels were lower in the frail group than in the non-frail group( P=0.001), whereas differences between the frail group and the pre-frail group and between the pre-frail group and the non-frail group were not statistically significant(all P>0.05).When Klotho protein levels were classified into four quartiles, i.e., Q 1, Q 2, Q 3, and Q 4, using three cut-off vales(2.28, 3.52, and 5.09 mg/L), the prevalences of frailty were 51.4%(19/37), 39.5%(15/38), 24.3%(9/37)and 18.4%(7/38), respectively.The prevalence of frailty decreased with increasing Klotho protein levels( χ2=11.204, P=0.011).Spearman correlation analysis showed that the Klotho protein level was negatively correlated with frailty( r=-0.310, P<0.001).Multivariate Logistic regression analysis results showed that age( OR=1.109, 95% CI: 1.011-1.217, P=0.028)and sarcopenia( OR=6.511, 95% CI: 1.279-33.147, P=0.024)were risk factors for frailty, while walking( OR=0.104, 95% CI: 0.033-0.326, P<0.001), a high SPPB score( OR=0.780, 95% CI: 0.627-0.970, P=0.026), and a high Klotho protein level( OR=0.752, 95% CI: 0.581-0.974, P=0.031)were protective factors against frailty. Conclusions:The serum Klotho protein level may be used as a parameter for the assessment of frailty.It is negatively correlated with frailty, suggesting that elderly people with low serum Klotho protein levels are at high risk of developing frailty.

Children with rare disease belong to a vulnerable group. When China’s current medical security system cannot provide comprehensive health care, they not only face physical and mental torture, but also have a higher risk of children participating in clinical trials than adults. So, adequate protection of children’s safety and rights is the key to ethical review. This paper analyzed the current status of drugs clinical trials for rare disease in children, including trial difficulties and guarantee system; explained the ethical principles that should be followed in clinical trials, such as the principle of informed consent and the principle of no harm; and discussed the path of protecting children’s safety and rights, so as to raise awareness and attention of the importance of ethical review of clinical trials.

Alzheimer disease(AD),commonly known as senile dementia,is the most common type of dementia,resulting in progressive impairment of cognitive function,and is often accompanied by a variety of psychiatric symptoms,such as agitation.Agitated symptoms in AD patients often cause an increasing burden on caregivers,and current psychiatric medications may exacerbate adverse effects such as cognitive impairment and motor retardation in patients.Therefore,non-drug intervention is a very important adjuvant treatment option.This article reviews the clinical manifestations,possible mechanisms,drug therapy and non-drug intervention measures of agitation in order to provide reference for more effective treatment of AD.

Objective To investigate the regulatory effects of LINC00467 on proliferation and metastasis of lung adenocarcinoma cells and the involvement of autophagy in its regulatory mechanism.Methods LINC00467 expression levels in lung adenocarcinoma tissues and their correlation with the patients'survival outcomes were analyzed using data from TCGA database.LINC00467 expression was also examined using qRT-PCR in human bronchial epithelial cells 16HBE and lung adenocarcinoma cell lines A549 and H1299.In A549 and H1299 cells transfected with a short hairpin RNA targeting LINC00467(shLINC00467),the effects of 3-methyladenine(3-MA,an autophagy inhibitor)and BML-275(an AMPK inhibitor)treatment on cell proliferation,migration,and expressions of LC3 and the AMPK/mTOR pathway proteins were tested using colony formation assay,wound-healing and Transwell assays,immunofluorescence staining and Western blotting.GSEA enrichment analysis was conducted to analyze the correlation between LINC00467 and the autophagy pathway.Results The expression level of LINC00467 was significantly higher in lung adenocarcinoma tissues than in the adjacent tissues(P<0.001)and increased progressively with the clinical stage(P<0.05),and its high expression was associated with a poor overall survival(P=0.049)and a high first progression rate(P=0.026)of the patients.LINC00467 expression was also significantly higher in A549 and H1299 cells than in 16HBE cells.In A549 and H1299 cells,LINC00467 knockdown significantly decreased colony-forming,migration and invasion abilities of the cells,lowered p-mTOR/mTOR and p62 expressions,and increased p-AMPK/AMPK expressions and LC3Ⅱ/Ⅰ ratio,and these effects were strongly attenuated by application of either 3-MA or BML-275.GSEA analysis suggested an inhibitory effect on LINC00467 on the autophagy pathway(|NES|>1,P<0.05,FDR<0.25).Conclusion High expressions of LINC00467 promote proliferation and metastasis of lung adenocarcinoma cells possibly by inhibiting cell autophagy mediated by the AMPK/mTOR signaling pathway.

Pancreatogenic diabetes is a type of diabetes mellitus secondary to exocrine pancreatic disease,and it was officially proposed by the American Diabetes Association in 2014,with chronic pancreatitis as the most common etiology,followed by pancreatic cancer.At present,the misdiagnosis rate of this disease is extremely high,and patients with pancreatogenic diabetes have a higher risk of death and readmission than patients with type 2 diabetes.Therefore,it is of great significance to fully understand,correctly identify,and diagnose pancreatogenic diabetes in the early state,so as to reduce the disability rate and mortality rate of this disease.This article reviews the advances in the possible pathogenesis,diagnosis,treatment,and management of pancreatic diabetes secondary to pancreatitis and pancreatic cancer.

Objective To investigate the regulatory effects of LINC00467 on proliferation and metastasis of lung adenocarcinoma cells and the involvement of autophagy in its regulatory mechanism.Methods LINC00467 expression levels in lung adenocarcinoma tissues and their correlation with the patients'survival outcomes were analyzed using data from TCGA database.LINC00467 expression was also examined using qRT-PCR in human bronchial epithelial cells 16HBE and lung adenocarcinoma cell lines A549 and H1299.In A549 and H1299 cells transfected with a short hairpin RNA targeting LINC00467(shLINC00467),the effects of 3-methyladenine(3-MA,an autophagy inhibitor)and BML-275(an AMPK inhibitor)treatment on cell proliferation,migration,and expressions of LC3 and the AMPK/mTOR pathway proteins were tested using colony formation assay,wound-healing and Transwell assays,immunofluorescence staining and Western blotting.GSEA enrichment analysis was conducted to analyze the correlation between LINC00467 and the autophagy pathway.Results The expression level of LINC00467 was significantly higher in lung adenocarcinoma tissues than in the adjacent tissues(P<0.001)and increased progressively with the clinical stage(P<0.05),and its high expression was associated with a poor overall survival(P=0.049)and a high first progression rate(P=0.026)of the patients.LINC00467 expression was also significantly higher in A549 and H1299 cells than in 16HBE cells.In A549 and H1299 cells,LINC00467 knockdown significantly decreased colony-forming,migration and invasion abilities of the cells,lowered p-mTOR/mTOR and p62 expressions,and increased p-AMPK/AMPK expressions and LC3Ⅱ/Ⅰ ratio,and these effects were strongly attenuated by application of either 3-MA or BML-275.GSEA analysis suggested an inhibitory effect on LINC00467 on the autophagy pathway(|NES|>1,P<0.05,FDR<0.25).Conclusion High expressions of LINC00467 promote proliferation and metastasis of lung adenocarcinoma cells possibly by inhibiting cell autophagy mediated by the AMPK/mTOR signaling pathway.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.