Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation， and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis， uptake， secretion， and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important， and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis， 3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism， the degradation and regulatory mechanisms of HMGCR， and the application of inhibitors， as well as the role of HMGCR in liver diseases， in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

Objective To investigate the relationship between omentin-1,aquaporin 4(AQP4),and visinin-like protein 1(VILIP-1)levels and vascular recanalization after emergency endovascular treatment in patients with acute large vessel occlusion stroke(ALVOS)and their combined predictive efficacy.Methods In total,110 patients with ALVOS undergoing emergency endovascular treatment were categorized into a non-reopening group(23 patients)and a reopening group(87 patients)based on whether the blood vessels were re-opened after surgery.Clinical data and omentin-1,AQP4,and VILIP-1 levels were compared between the two groups.Factors influencing postoperative blood vessel reopening were analyzed,and nomograms were drawn to evaluate their predictive performance and calibration.Results Significant differences were observed in the proportion of patients with hypertension;preoperative NIHSS scores;emergency blood glucose;AQP4,VILIP-1,omentin-1,and platelet levels;time from onset to endovascular treatment;preoperative ASPECTS;and proportion of patients undergoing intravenous thrombolysis between the two groups(P＜0.05).Preoperative ASPECTS and omentin-1 levels were independent protective factors associated with postoperative vascular recanalization,whereas the time from onset to endovas-cular treatment,preoperative NIHSS scores,and AQP4 and VILIP-1 levels were independent risk factors associated with postoperative vascular recanalization(P＜0.05).The C-index of the nomogram for predicting postoperative vascular recanalization was 0.994,and the AUC of the nomogram for predicting postoperative vascular recanalization was 0.994,with a calibration degree of 0.975.Conclusion Omentin-1,AQP4,and VILIP-1 levels are important factors affecting vascular recanalization in patients with ALVOS after emergency endovascular treatment.Clinically,monitoring these levels may help to predict and evaluate early vascular recanalization fol-lowing treatment.

Objective To investigate the modulatory effect of Yulian Pills(composed of Coptidis Rhizoma and Euodiae Fructus)on splenic memory follicular T helper cell(mTfh)in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods Forty BALB/c mice were randomly divided into normal group,model group,Yulian Pills group(0.5 g·kg-1)and Mesalazine group(0.3 g·kg-1),10 mice in each group.The mouse model of ulcerative colitis was induced by ad libitum drinking 3%DSS solution for 7 days.During the experiment,the mental state,faecal characteristics,blood in stool and body mass of the mice were recorded daily,and the length and mass of the colon were measured and the colon mass index was calculated;HE staining was used to observe the pathological and morphological changes of the colon tissue;ELISA was used to determine the expression levels of interleukin(IL)-6 and IL-15 in the colon tissues;flow cytometry was used to determine the mTfh cell subpopulation in the spleen tissue expression;Western Blot was used to determine the protein expression levels of Roquin-1,AMPK-α,p-AMPK-α in colon tissues.Results Compared with the normal group,the mice in the model group showed a significant decrease in body mass(P＜0.01),a significant shortening of colon length(P＜0.01),significant increase in colon mass(P＜0.05)and colon mass index(P＜0.01),and severe pathological damage to colon tissues;the expression levels of the pro-inflammatory cytokines IL-6 and IL-15 in the colon tissues were significantly increased(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+ GL7+,CD4+CCR7-CXCR5+GL7+ were significantly increased in spleen tissues(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly decreased(P＜0.01);and protein expression levels of Roquin-1,AMPK-α,p-AMPK-α were significantly reduced in the colonic tissues(P＜0.05).Compared with the model group,mice in the Yulian Pills group and Mesalazine group showed a significant increase in body mass(P＜0.05),a significant extension of colon length(P＜0.01),a significant reduction in colon mass(P＜0.05),a significant decrease in the colon mass index(P＜0.01),and a more obvious improvement in pathological damage of the colon tissues;a significant decrease in the expression levels of IL-6 and IL-15 in the colon tissues(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+GL7+,CD4+CCR7-CXCR5+GL7+ in splenic tissues was significantly reduced(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly increased(P＜0.01);the protein expression levels of Roquin-1,AMPK-α,and p-AMPK-α were significantly increased in colon tissues(P＜0.05,P＜0.01).Conclusion The therapeutic effect of Yulian Pills on DSS-induced ulcerative colitis mice can ameliorate the histopathological damage of colon,which may be related to the activation of the Roquin-1/MPK-α signalling pathway,the down-regulation of the expressions of inflammatory cytokines IL-6 and IL-15,and the modulation of the homeostasis of the mTfh cell subpopulation.

Objectives:To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China.Methods:The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR) and relative risk ( RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results:From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions:The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

Objectives:To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China.Methods:The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR) and relative risk ( RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results:From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions:The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

Objective:To explore the characteristics of delay discounting and non-systematic response data in intertemporal choice of adults with attention deficit hyperactivity disorder(ADHD),and to explore the best data processing strategy for delay discounting task.Methods:Totally 108 adults with ADHD meeting the diagnostic cri-teria of the Diagnostic and Statistical Manual of Mental Health Disorder,Fifth Edition(DSM-5)and 87 gender matched normal controls were enrolled.ADHD symptoms were assessed using the ADHD Symptom Rating Scale,the delay discounting task was used to measure the delay discounting rate,and a model-free algorithm was used to i-dentify non-systematic response data.Results:There was no significant difference in the proportion of non-systemat-ic response data between ADHD group and normal control group(P＞0.05).In the data sets using different data screening strategies,the delay discounting rates were higher in the ADHD group than in the normal control group(Ps＜0.05).The delay discounting rates were positively correlated with the hyperactive impulse scores(r=0.24,P=0.001),the inattention scores(r=0.20,P＜0.01)and the total scores of ADHD symptom Rating Scale(r=0.22,P＜0.01).Conclusion:Adults with ADHD prefer to obtain immediate small rewards in intertemporal choice.The immediate preference of intertemporal choice may be mainly related to hyperactive impulsive symp-toms.Exclusion strategy of non-systematic response data may be more applicable to delay discount task research.

Acute liver failure(ALF)is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people.Due to its high morbidity and mortality rates,unclear pathogenesis,and limited treatment methods,ALF has become a major problem that needs to be solved urgently in the field of liver diseases.In recent years,more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF,and the IRE1α/TRAF2/JNK pathway,as a part of endoplasmic reticulum stress signaling,plays a role in amplifying inflammatory response,promoting hepatocyte apoptosis,and inhibiting liver regeneration ability during the progression of diseases.As a traditional treasure of China,traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs.This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway,such as salidroside,Fructus Broussonetiae,Fructus Psoraleae+Schisandra chinensis,baicalein,genipin,kaempferol,resveratrol,sea buckthorn polysaccharide extract,and luteol,in order to provide a reference for further research and clinical practice of ALF.

To analyze the differences in cerebral blood flow (CBF) characteristics among children with different subtypes of attention deficit and hyperactivity disorder (ADHD) and their relationship with executive function using arterial spin labeling (ASL) technology.

Objective: Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder with significant gender differences. The sexual dimorphism of ADHD may be associated with estrogen acting through estrogen receptors (ESR). This study investigates the impact of ESR gene polymorphism and its interactions with neurodevelopmental genes on ADHD susceptibility. Methods: The study compared genotyping data of single nucleotide polymorphisms in ESR1 and ESR2 in 1,035 ADHD cases and 962 controls. The gene-gene interactions between ESR genes and three neurodevelopmental genes (brain-derived neurotrophic factor [BDNF], synaptosomal-associated protein of 25 kDa gene [SNAP25], and cadherin-13 [CDH13]) in ADHD were investigated using generalized multifactor dimensionality reduction and verified by logistic regression analysis. Results: The G allele of rs960070/ESR2 (empirical p=0.0076) and the A allele of rs8017441/ESR2 (empirical p=0.0426) were found significantly higher in ADHD cases than in the controls but not in male or female subgroups. Though no difference was found in all subjects or females, the A allele of rs9340817/ESR1 (empirical p=0.0344) was found significantly higher in ADHD cases than controls in males. We also found genetic interaction models between ESR2 gene, neurodevelopmental genes and ADHD susceptibility in males (ESR2 rs960070/BDNF rs6265/BDNF rs2049046/SNAP25 rs362987/CDH13 rs6565113) and females (ESR2 rs960070/BDNF rs6265/BDNF rs2049046) separately, though it was negative in overall subjects. Conclusion The ESR gene polymorphism associates with ADHD among Chinese Han children, with interactions between ESR genes and neurodevelopmental genes potentially influencing the susceptibility of ADHD.

Objective:To analyze changes in nutritional status and immune function of elderly men receiving regular physical examinations, and to investigate the effects of aging on the nutritional status and immune function among elderly men.Methods:A total of 209 elderly men aged 60-101(72.9±11.5)years and receiving regular physical check-ups were enrolled.All research subjects were subjected to nutritional risk screening(NRS2002)and monitoring of nutrition and immune-related indicators, including routine blood work, blood biochemistry, immunoglobulin and T lymphocyte subsets.Results:Body weight, body mass index, hemoglobin, total protein, albumin and serum iron of elderly men decreased with age( F=21.754, 6.257, 47.528, 12.285, 18.397, 18.667, all P<0.001), with those aged 80 and above showing more significant decline and a greater proportion with malnutrition( χ2=77.134, P<0.001). The B lymphocyte counts of elderly men aged 80 and above were significantly lower( P<0.05)while serum IgA and IgG levels were significantly higher( F=3.110, 3.866, P=0.047, 0.022)than those of the 70-79 year old group.In addition, the B lymphocyte count and B lymphocyte ratio in malnourished elderly men were significantly lower( t=2.512, 2.874, P=0.013, 0.005), and IgA was significantly increased( t=2.513, P=0.017), compared with those with normal nutrition. Conclusions:The risk of malnutrition and reduced immune function among elderly men aged 80 years and above is significantly increased, and assessment and screening of the risk of malnutrition in the elderly should be stressed.