AIM:To study whether the pulmonary infection of Escherichia coli (E.coli) interferes the glu-colipid metabolism in high-fat diet-induced obese mice.METHODS:High-fat diet-induced obese mice (n=48) and nor-mal chow-fed control mice ( n=48) were intranasally infused with 40 μL fluid containing 4 ×109 CFUs E.coli.The ser-um, periepididymal adipose tissue and liver were obtained at 0 d, 1 d, 2 d, 3 d and 4 d after infection.The body mass, periepididymal adipose tissue and liver were weighed , and the levels of fasting blood glucose (FBG), fasting blood insulin ( FINS) , free fatty acid ( FFA) and very-low-density lipoprotein ( VLDL) were measured by ELISA .The serum total cho-lesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol ( LDL-C) , and hepatic TG contents were detected , and the hepatic steatosis was observed under microscope with oil red O staining.RESULTS:Compared with day 0, the body mass, fat mass and fat index were decreased significantly from day 1 to day 4 after infection (P<0.05).The levels of FBG, FINS and HOMA-IR were apparently raised from day 2 to day 4 af-ter infection (P<0.05).The contents of serum FFA, TG and VLDL were increased markedly from day 1 to day 4 after in-fection (P<0.05).However, the concentrations of serum TC, LDL-C and HDL-C were decreased obviously from day 1 to day 3 ( P<0.05 ) .The liver mass , liver index and TG content were significantly increased from day 1 to day 4 ( P<0.05 ) .Consistently , the lipid droplet accumulation in the liver cells was increased obviously at day 2 and day 4 after infec-tion.Compared with control group , except the levels of serum TC , LDL-C and HDL-C in obese group substantially de-creased, the other indexes were increased by different degrees during the whole experiment period (P<0.05).CONCLU-SION:Pulmonary infection of Escherichia coli exacerbates the disorder of glucose and lipid metabolism in high-fat diet-in-duced obese mice , which contributes the development of insulin resistance and hepatic steatosis .

OBJECTIVETo investigate the prevalence of esophageal and gastric cardia cancer and various precancerous lesions in high-risk rural areas.

METHODSRandom cluster sampling method was used to select people aged 40-69 years of some natural villages as screening objects in Feicheng, Shangdong province, from 2006 to 2012. The screening program was conducted by endoscopy with iodine staining and indicative biopsy followed by pathological examination.

RESULTSA total of 24 759 subjects were screened during 2006-2012 years. The positive detection rates of esophagus and gastric cardia cancers were 1.37% and 0.42%, respectively, the early diagnosis rates were 84.71% and 65.05%, and the treatment rates were 92.65% and 92.23%, respectively. The detection rates of all lesions in males were significantly higher than those in females (P < 0.05), and were gradually increased with age (P < 0.05). The time trend analysis showed that detection rates of all lesions in the two sites showed no significant changes during this period, and the detection rates of esophageal lesions were higher than those of gastric cardia.

CONCLUSIONSThere are considerable numbers of patients with precancerous lesions in the general population from the high risk areas. Men and the elderly are the key populations calling for cancer control programs. Endoscopy using iodine staining is an effective method to increase the detection rate of precancerous lesions and cancers. The root of mucosal fold in gastric cardia must be carefully observed so as to increase the detection rate of early gastric cardia lesions.

Adult ; Aged ; Biopsy ; Carcinoma, Squamous Cell ; Cardia ; Coloring Agents ; Early Detection of Cancer ; statistics & numerical data ; Esophageal Neoplasms ; diagnosis ; epidemiology ; Esophagoscopy ; Female ; Gastroscopy ; Humans ; Iodine ; Male ; Middle Aged ; Precancerous Conditions ; diagnosis ; epidemiology ; Prevalence ; Rural Population ; statistics & numerical data ; Sex Distribution ; Stomach Neoplasms ; diagnosis ; epidemiology

Objective To understand the application and research progress of Mendelian randomization (MR) studies related to gastric cancer and provide a scientific basis for gastric cancer prevention. Methods Published studies on risk factors of gastric cancer based on MR methods were searched in PubMed, Web of Science, EMBASE, CNKI, and WANFANG DATA from the establishment of each database to November 1^9th, 2022. Two researchers examined the eligibility of studies, extracted key information, and assessed the research quality independently. Results A total of 30 publications published from 2016 to 2022 were included in the study, and 20 were judged to be of high quality. These studies examined the relationship between behaviors and lifestyle factors, anthropometric characteristics, indicators of biological exposure, and other pathological conditions and gastric cancer, and the results suggest potential causal associations between smoking and other factors and the risk of gastric cancer. Conclusion Previous MR studies extensively investigated the causal association between internal and external exposures or traits and gastric cancer and provided positive evidence of gastric cancer etiology. However, MR studies may be subject to methodological limitations. Interpretation of results needs to be approached with caution, which necessitates the integration with biological plausibility and evidence from observation studies.

Objective:To evaluate the efficacy of low-dose radiotherapy in patients with advanced hypopharyngeal cancer without high-risk factors.Methods:Clinical data of 235 patients diagnosed with advanced hypopharyngeal cancer treated in Department of Head and Neck Surgery of Shandong Provincial ENT Hospital from December 2013 to August 2018 were retrospectively analyzed. All patients were divided into two groups: low-dose radiotherapy group (50 Gy, n=158) and high-dose radiotherapy group (>60 Gy, n=77). Clinical baseline characteristics, treatment, follow-up and survival of patients were collected. Survival curve was delineated using the Kaplan-Meier method, and the differences in survival between two groups were calculated using the log-rank test. Clinical baseline characteristics between two groups were compared by χ2 test. Univariate and multivariate analyses of prognostic factors were conducted by logistic regression model. Results:The median follow-up time was 45 months (5-94 months). The 3-year overall survival (OS) rate of the whole group was 68.5%, and 70.3% and 64.9% in the low-dose and high-dose groups, respectively ( P=0.356). The 3-year progression-free survival (PFS) rate of the whole group was 64.3%, and 65.8% and 61.0% in the low-dose and high-dose groups, respectively ( P=0.361). Univariate analysis showed that T stage, N stage, lesion location and degree of pathological differentiation significantly affected clinical prognosis (all P<0.05), whereas there was no significant relationship between age, sex, radiotherapy dose, interval between surgery and radiotherapy and survival. Multivariate analysis showed that T stage, N stage and the degree of pathological differentiation were the independent prognostic factors (all P<0.05) of the 3-year OS and PFS. Sex, radiotherapy dose and interval between surgery and radiotherapy were not correlated with OS and PFS. Conclusion:This study showed that for hypopharyngeal cancer patients without positive surgical margins and extracapsular extension, postoperative radiotherapy at a dose of 50 Gy given to tumor bed and selective lymph node drainage area does not compromise local disease control and OS.

Objective To explore the intrinsic relationship between circadian clock and cell cycle in osteoarthritis(OA)chondrocytes,especially the regulation of cell cycle-related genes by the clock gene Bmal1.Methods The chondroid ATDC5 cells induced by insulin-transfering-selenium(ITS)were divided into control group,OA group and LV-Bmal1 group.The cell viability of each group was detected by CCK8 method.The expression of Bmal1,Per1,Wee1,Cdk1,Ccnb1 and Mmp13 mRNA in each group was detected by RT-qPCR.The expression of BMAL1,PER1,WEE1,CDK1,CCNB1 and MMP13 protein in each group was detected by Western blot.The effects of Bmal1 on different stages of cell cycle and apoptosis was analyzed by flow cytometry.The regulation of Bmal1 on Per1,Wee1,Cdk1,Ccnb1 and Mmp13 and their roles in OA were analyzed.Results Compared with the normal group,the cell viability of the OA group was increased,the relative mRNA expression of Bmal1 and Wee1 in the OA group decreased,and the relative mRNA expression of Per1,Cdk1,Ccnb1 and Mmp13 increased signif-icantly.The cell viability of LV-Bmal1 group decreased,the relative expression of Bmal1 and Wee1 mRNA in-creased,and the relative expression of Per1,Cdk1,Ccnb1 and Mmp13 mRNA decreased(P＜0.05).Correlation analysis showed that Bmal1 was positively correlated with Wee1 and they were negatively correlated with Per1,Cdk1,Ccnb1 or Mmp13.The results of Western blot showed that protein expression in different groups were con-sistent with the trend of PCR.The results of cell cycle and apoptosis showed that compared with the normal group,the S phase and G2/M phase of the OA group were shortened,the proportion of cells decreased significantly,and the proportion of early and late apoptosis increased.The S phase and G2/M phase of the LV-Bmal1 group were prolonged,the proportion of cells was increased,and the proportion of early and late apoptosis was decreased.Conclusions Circadian clock gene Bmal1 in inflammatory chondrocytes might regulate the expression of cell cycle-related genes.

In this study, apoptosis was induced by new type gosling viral enteritis virus (NGVEV) in experimentally infected goslings is reported in detail for the first time. After 3-day-old goslings were orally inoculated with a NGVEV-CN strain suspension, the time course of NGVEV effects on apoptotic morphological changes of the internal tissues was evaluated. These changes were observed by histological analysis with light microscopy and ultrastructural analysis with transmission electron microscopy. DNA fragmentation was assessed with a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and DNA ladder analysis. A series of characteristic apoptotic morphological changes including chromatin condensation and margination, cytoplasmic shrinkage, plasma membrane blebbing, and formation of apoptotic bodies were noted. Apoptosis was readily observed in the lymphoid and gastrointestinal organs, and sporadically occurred in other organs after 3 days post-infection (PI). The presence and quantity of TUNEL-positive cells increased with infection time until 9 days PI. DNA extracted from the NGVEV-infected gosling cells displayed characteristic 180~200 bp ladders. Apoptotic cells were ubiquitously distributed, especially among lymphocytes, macrophages, monocytes, and epithelial and intestinal cells. Necrosis was subsequently detected during the late NGVEV-infection phase, which was characterized by cell swelling, plasma membrane collapse, and rapidly lysis. Our results suggested that apoptosis may play an important role in the pathogenesis of NGVE disease.
*Adenoviridae/classification/pathogenicity ; Adenoviridae Infections/pathology/*veterinary/virology ; Animals ; *Anseriformes ; *Apoptosis ; Bird Diseases/*virology ; DNA Fragmentation ; Enteritis/*veterinary/virology ; Epithelial Cells/cytology/virology ; In Situ Nick-End Labeling ; Intestines/cytology/virology ; Leukocytes/cytology/virology ; Lymphoid Tissue/cytology/virology ; Macrophages ; Microscopy, Electron, Transmission

Objective:To analyze the mutation sites and characteristics of phospholipase CE1( PLCE1) gene in children with primary nephrotic syndrome(PNS) in Zhuang, Guangxi, China, so as to explore the expression status of PLCE1 protein in peripheral blood of PNS patients. Methods:(1)Blood samples of 154 Zhuang children with PNS and 98 healthy children of Zhuang nationality from July 2015 to September 2017 in Affiliated Hospital of Youjiang Medical College for Nationalities were collected to sequence PLCE1 gene with FastTarget target gene capture method in the combination with next generation sequencing.Based on the comparison between mutation results and information from the database, the pathogenicity, phenotype and distribution characteristics of these mutation sites were discovered and appraised.(2)The concentration of PLCE1 protein in serum samples were measured by enzyme-linked immuno sorbent assay, then the data of PNS group and healthy control group were compared and analyzed statistically with SPSS 25.0. Results:(1)A total of 18 low-frequency mutations of PLCE1 were observed, 5 of them(c.670C>T, c.578T>C, c.923G>T, c.4916C>T, and c. 5927_5929del) were found only in the PNS group, and 3 of them occurred in both PNS group and healthy control group: c.176C>T, c.389T>C, and c. 4304C>T.Five newly discovered mutations (c.923G>T, c.958T>A, c.1151C>T, c.2341A>G, and c. 3592G>C)were discovered and only c. 923 G>T is pathogenic mutation of PLCE1.(2)The concentration of PLCE1 protein in healthy control group was 414.65 (231.20, 729.81) ng/L and the level of PLCE1 in PNS group was 237.84 (116.14, 535.85) ng/L, ( Z=-3.212, P<0.001), and the value of PNS group was lower than that in the healthy control group. Conclusions:(1)As a new pathogenic mutation of PLCE1, c.923G>T was found.(2)The phenotype of PLCE1 gene mutation in Zhuang children with PNS was diverse, and they may differ by race and region.(3) PLCE1 protein of serum may act as a protective protein to guarantee various life activities of cells by participating in multiple signal transduction pathways.

Objective To systematically review the worldwide simulation model studies on the natural history of breast cancer and to summarize related parameters.Methods A structured literature search was conducted in PubMed and the Cochrane Library to identify articles during 1980-2015.Articles were screened independently by two researchers.Health states in the natural history and relevant parameters were extracted.Results A total of 36 studies were included for analysis,within the earliest one was published in 1990.Most studies were from Europe and America countries,and 2 studies from China.Markov model was mostly applied to evaluating breast cancer screening programs (n=32).Reported health status included “healthy” (n=36),ductal carcinoma in situ (DCIS,n=17),invasive breast cancer (IBC,n=36),and death (n=27).There were two definite classifications for IBC,tumor size (n=9) and TNM staging (n=9,3 studies reported transition rates).The median (range) of annual transition rates from DCIS to stage-I IBC,I to Ⅱ,Ⅱ to Ⅲ,Ⅲ to Ⅳ were 0.279 (0.259-0.299),0.150 (0.069-0.430),0.100 (0.060-0.128) and 0.210 (0.010-0.625),respectively.A total of 15 studies reported the mean duration from predinical to clinical stage for IBC was 1.95-4.70 years,which gradually increased with age,and 7 studies reported that for DCIS.Conclusions Despite closer attention was paid to breast cancer natural history models,in recent years atypical hyperplasia has been neglected.Data on the mean duration of DCIS requires reasonable conversion.Various classifications for IBC exist whereas transition rates are limited.Current findings would be valuable references but challenging for the Chinese-population specific natural history model,development.

Objective: To analyze the related factors of esophageal squamous cell carcinoma and precancerous lesions among residents aged 40-69 years old in rural areas of Shandong Province. Methods: In October 2018, 300 villages in 13 counties of the Shandong upper gastrointestinal cancerearly diagnosis and treatment projectin 2017 were selected as research areas, and 30 400 residents aged 40-69 were recruited in this study. The demographic characteristics, health status and lifestyle information were collected through the questionnaire survey, and endoscope iodine staining and indicative biopsy methods were used for cancer screening among eligible people.The multivariate logistic regression model was used to analyze the risk factors for esophageal cancer and precancerous lesions. Results: The subjects in this study were (56.42±7.24) years old, including 13 193 males (43.40%).There were 936 cases of esophageal cancer and precancerous lesions (3.08%), including 521 males and 415 females.Compared with women, 40-49 years old, high level education, drinking tap water, regular intake of meat, eggs and milk, and family average annual income more than 30 000 RMB, men (OR=1.90, 95%CI: 1.65-2.19), 60-69 years old (OR=5.28, 95%CI: 4.11-7.30), primary school education or below (OR=1.50, 95%CI: 1.20-1.89), drinking groundwater (OR=1.71, 95%CI: 1.38-2.13), never eating meat, eggs and milk (OR=1.48, 95%CI: 1.22-1.80), and family average annual income less than 30 000 RMB (OR=1.41, 95%CI: 1.16-1.70) would increase the risk of esophageal cancer and precancerous lesions. Conclusion The gender, age, educational level, annual household income, drinking water source, the frequency of eating meat, egg and milk were related to the occurrence of esophageal cancer and precancerous lesions among 40-69 years old residents in rural areas of Shandong Province.

Objective: To parameterize the 1-year transition probabilities between different health status of the natural history of breast cancer based on the data of randomized controlled trial of X-ray mammography screening worldwide. Methods: Based on the breast cancer screening randomized controlled trials defined by a mammography screening review from the Cochrane 2013 and the International Agency for Research on Cancer, a systematic review was initiated in PubMed by searching names of the key investigators of the trials, combined with the diseases, screening intervention and outcome indicators. If applicable, all the original cumulative incidence rates were converted into one-year transition rate, using the life-table approach considering time length of follow-up. Results: A total of 23 reports from 9 RCTs were included. The data on transition rate between the healthy status to precancerous lesions was absent. The 1-year transition rate from health to carcinoma in situ was 17.78 to 50.21 per 100 000 persons in the intervention group and 9.16 to 26.84 per 100 000 persons in the control group. Correspondingly, the 1-year transition rate from health to breast cancer (including carcinoma in situ and invasive cancer) were estimated as 143.75 to 316.97 per 100 000 persons in the intervention group, and 141.45 to 288.84 per 100 000 persons in the control group. Furthermore, the transition rate from the healthy status to invasive breast cancer was 159.79 to 264.60 per 100 000 persons in intervention group and 170.12 to 255.33 per 100 000 persons in control group. The transition rate from carcinoma in situ to invasive breast cancer varied among different pathological types. Conclusions The most common natural history states of reported by the included trials involved the full healthy status, carcinoma in situ and invasive breast cancer. The findings of transition rates between different health statuses will be informative for future model development of natural history studies of breast cancer. Information in relation to breast precancerous lesions still limited and needs to be further addressed.