OBJECTIVE To investigate the potential mechanism of berberine improving diabetes mellitus type 2 （T2DM） combined with metabolic-associated fatty liver disease （MAFLD） by regulating ceramide. METHODS Thirty-two db/db mice with blood glucose levels＞11.1 mmol/L （T2DM model） were divided into four groups： model group， berberine low- and high-dose groups [100， 200 mg/（kg·d）] and metformin group [300 mg/（kg·d）]， with 8 mice in each group. Additionally， 8 wt/wt mice were selected as the normal control group. Mice in each group were administered the corresponding drug solution or water by gavage once daily for a continuous period of 6 weeks. During the experiment， the body weight of the mice was monitored， and the differences in final body weight were analyzed. After the last administration， the body shape of the mice in each group was observed， and their fasting blood glucose （FBG） and the lipid indicators [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] were measured. Fasting serum insulin （FINS） levels were also measured， and the insulin resistance index HOMA-IR） and insulin sensitivity index （ISI） were calculated. Liver weight， liver index and serum liver function indicators [alanine transaminase （ALT）， aspartate transaminase（AST）] were assessed， and hepatic histopathological changes were observed. Additionally， the expression of fatty acid synthesis-related proteins [sterol regulatory element-binding protein 1 （SREBP1）， fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）] in liver tissue was examined. Serum samples from the normal control group， model group， and berberine high-dose group were collected for non-targeted lipidomics analysis and validation. RESULTS Compared with the model group， the pathological changes， including disordered liver tissue cell arrangement and lipid vacuoles， were significantly improved in the berberine low- and high-dose groups. The significant decreases or down-regulations were observed in body weight in the last week， as well as FBG， TC， TG， and LDL-C levels， HOMA-IR （except for the berberine low-dose group）， liver weight， liver index， AST and ALT levels， and protein expressions of SREBP1， FASN and ACC1. Additionally， HDL-C levels， FINS （except for the berberine high-dose group）， and ISI （except for the berberine low-dose group） were significantly increased （P＜0.05）. A total of 21 potential differential metabolites， including multiple types of ceramides， were identified； these metabolites were primarily enriched in sphingolipid metabolism and glycerophospholipid metabolism pathways. Verification experiments confirmed that high-dose berberine significantly reduced the serum content of ceramide in model mice （P＜0.05）. CONCLUSIONS Berberine reduces insulin resistance， improves liver damage and lipid accumulation in the T2DM combined with MAFLD mice， and these effects may be related to the reduction of ceramide content.

Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P＜0.01).Insomnia was reported by 37.0％of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00％±2.38％vs.8.26％±1.73％,P＜0.01).Gastrointestinal symptoms were present in 57.5％of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26％±2.23％vs.8.43％±1.98％,P＜0.01).Furthermore,26.3％of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18％±2.44％vs.8.45％±1.86％,P＜0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P＜0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5％(P＜0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.

This paper discussed the clinical ideas and methods of treating diabetes by improving symptoms. Diabetes-related symptoms can affect the control of blood glucose and other metabolic indicators to varying degrees， and affect the quality of life of patients. In the clinical diagnosis and treatment of diabetes， “equal emphasis on both indicators” is suggested， meaning that quality of life indicators is as important as metabolic indicators. The patient's symptoms should be paied attention to， and the diagnosis and treatment should start from “symptom differentiation”， and emphasize the “key symptoms”. When there are many symptoms， it is advised to adopt the combined treatment mode of “syndrome cluster”， and take the principle of “treating both the root and accompanying symptoms in mild cases with multiple symptoms， and prescribing multiple formulas daily”. At the same time， the model of co-management of three disciplines of diabetes consisting of diabetes specialists， traditional Chinese medicine doctors， and health managers can help the management of diabetes symptoms.

Objective:To investigate the impacts and mechanisms of the GCH1-S81A mutants of the rate-limiting enzyme GTP cyclohydrolase 1 (GCH1) at key phosphorylation sites on the radiosensitivity of esophageal cancers during the de novo synthesis of tetrahydrobiopterin (BH4). Methods:The KYSE-150 cell lines of esophageal squamous cell carcinoma with stable GCH1 overexpression at different phosphorylation levels were constructed in this study. Based on GCH1′s phosphorylation levels and radiation doses, the experimental groups were divided into the blank control group, the empty virus group, the empty virus + irradiation group, the wild-type GCH1 group, the GCH1 phosphorylation group, the GCH1 dephosphorylation group, the GCH1 dephosphorylation + irradiation group, the validation group, and the validation + irradiation group. The Western blot and the CCK-8 assay were employed to detect the infection efficiency and the survival rates of tumor cells in various groups, respectively. The flow cytometry was applied to detect the changes in the apoptosis rate, reactive oxygen species (ROS) level, and lipid peroxide level of tumor cells in various groups. The colony formation assay was used to detect the changes in the radiosensitivity of tumor cells. Besides, the Western blot was performed to detect the changes in the expression of ferroptosis-related proteins.Results:The GCH1 dephosphorylation group showed a significantly decreased expression level of phosphorylated GCH1-S81 protein in the cells at 48 h after infection ( t=9.35, 16.57, P<0.05). Compared to the empty virus + irradiation group, the GCH1 dephosphorylation + irradiation group exhibited a significantly decreased cell survival rate 24 h after 10 Gy X-ray irradiation ( t=26.97, P<0.05). The ROS levels in KYSE-150 cells at 8 h after 10 Gy X-ray irradiation, and the apoptosis rates and lipid peroxide levels at 48 h after irradiation, all showed a significant increase ( t=17.89-131.1, P<0.05), which was further aggravated following the addition of GCH1-S81A mutants ( t=157.06-97.81, P<0.05). This phenomenon could be inhibited by complementing wild-type GCH1 ( t=66.38-23.08, P<0.05). Compared to the empty virus + irradiation group, the GCH1 dephosphorylation + irradiation group manifested decreased colony formation capacity under various X-ray doses (2, 4, 6 and 8 Gy, t=7.31-8.16, P<0.05). The GCH1-S81A mutation reduced the expression level of the ferroptosis-related protein GPX4 ( t=4.55, P<0.05), which was further decreased after 10 Gy X-ray irradiation ( t=12.98, P<0.05). Conclusions:The GCH1-S81A dephosphorylated mutants can inhibit the growth of esophageal carcinoma cells KYSE-150 and enhance their radiosensitivity, which may hold promise as a novel approach to improve the efficacy of radiotherapy for esophageal cancers.

Objective:To investigate the family management level of children with bronchiolitis obliterans and analyze its influencing factors, so as to provide reference for clinical medical staff to adopt targeted nursing and health education programs.Methods:This was a cross-sectional study. From January 1, 2019, to April 30, 2022, 201 families of bronchiolitis obliterans children hospitalized in Hunan Children's Hospital were selected as the research objects, and the General Data Questionnaire, Family Management Scale, Coping Style Scale of Parents, and Chronic Disease-Related Health Literacy Scale was used to investigate. Single-factor analysis and multiple regression analysis were used to analyze the influencing factors of bronchiolitis obliterans children's family management level.Results:The total score of bronchiolitis obliterans children's family management was (179.67 ± 9.92) points, the total score for parents' coping style was (177.14 ± 22.19) points, and the total score for health literacy was (102.95 ± 8.60) points. Multiple regression analysis showed that age, disease course, family residence, parents' education level, family monthly income, parents' coping style, and health literacy level were the influencing factors of family management level (all P<0.05). Conclusions:The family management ability of parents of children with bronchiolitis obliterans needs to be further improved. It is suggested that medical staff should formulate corresponding measures according to the age, course of the disease, family residence, parents' education level, etc., carry out targeted health education and home management training, improve the parents' health literacy level, and guide them to deal with diseases positively, to improve their family management level and promote the recovery of children's diseases.

Severe acute respiratory syndrome coronavirus（SARS-CoV-2）is highly infectious and people are generally susceptible to it. In this article,we reviewed current research into the epidemiological characteristics of coronavirus disease 2019（COVID-19）,introduced China's effective prevention and control experience,preliminarily summarized the phased Results of China's fight against the COVID-19,and reviewed the early measures taken by Singapore,Japan,Italy,Iran and South Korea. We recommended China’s prevention and control measures in response to COVID-19 to the world;appealed to pay attention to non-drug interventions,to strengthen the cooperation and sharing of COVID-19 epidemic data and research,to improve the global ability in respond to public health emergencies,and to reduce the impact of COVID-2019 on the sustainable development of economy and society.

AIM: To investigate the effects of astragalus injection combined with puerarin injection on endo-plasmic reticulum stress through PERK pathway in diabetic nephropathy mice .METHODS: Male KKAy mice were ran-domly divided into model group ( injected with normal saline ) and treatment group ( injected with astragalus and puerarin ) . The male C57BL/6J mice served as normal group .The mice were sacrificed 4 weeks after treatments for observing morpho-logical changes under electron microscope .The renal tissues were collected to determine the expression of protein kinase R-like endoplasmic reticulum kinase ( PERK ) , eukaryotic initiation factor 2α( eIF2α) and glucose-regulated protein 78 (GRP78) at mRNA and protein levels by real-time PCR and Western blot.RESULTS: Under electron microscope, the renal tubular epithelial cells in model group and treatment group showed the swelling of the nucleus , endoplasmic reticulum and mitochondria .The results of real-time PCR and Western blot showed that the expression of PERK , eIF2αand GRP78 at mRNA and protein levels in model group was higher than that in normal group (P<0.05), while that in treatment group was lower than that in model group .CONCLUSION: Astragalus injection combined with puerarin injection reduces the mRNA and protein expression of PERK , eIF2αand GRP78, thus inhibiting the endoplasmic reticulum stress in type 2 dia-betic mice to protect the kidney function .

OBJECTIVETo investigate the association between microRNA (miR)-146a gene polymorphisms and susceptibility to gastrointestinal cancer.

METHODSPubMed, Medline and Ovid full text databases, China Journal Full-text Database (CNKI), Articles Database and Chinese Biomedical Literature Database were researched to retrieved literatures about the association between miR-146a gene polymorphism and susceptibility to gastrointestinal cancer published from July 2010 to March 2014. Modified Jadad quality score was used to evaluate the quality of the literatures and Stata 11.0 software was used to analyze and calculate OR value of the following 5 different genotypes: allele (G vs. C), the dominant genetic model (GC+GG vs. CC), a recessive genetic model (GG vs. GC+CC) and homozygote (GG vs. CC) and heterozygote (GC vs. CC) to assess the association.

RESULTSA total of 16 studies were enrolled, including 7090 cancer patients and 9928 healthy controls. Meta-analysis showed that people with G allele was more susceptible to gastrointestinal cancer than those with C(gastric cancer: OR=1.1,95% CI:1.04-1.17, P=0.001, colorectal cancer: OR=1.09,95% CI:1.01-1.18, P=0.020); dominant model (GC+GG) was more susceptible to gastric cancer than CC (OR=1.12, 95% CI:1.02-1.22, P=0.016); recessive genetic model GG was more susceptible to gastrointestinal cancer than CC+GC (gastric cancer: OR=1.16, 95% CI:1.05-1.27, P=0.004, colorectal cancer: OR=1.13, 95%CI:1.00-1.28, P=0.047); GG homozygote was more susceptible to gastrointestinal cancer than CC (gastric cancer: OR=1.20, 95% CI:1.06-1.35, P=0.003, colorectal cancer: OR=1.19, 95% CI:1.01-1.41, P=0.042). Dominant genetic model GC+GG and CC in colorectal cancer as well as heterozygous GC and CC in gastrointestinal cancer were not significantly different(P>0.05).

CONCLUSIONmiR-146a cancer susceptibility gene polymorphism is closely associated with gastrointestinal cancers.

Alleles ; Asian Continental Ancestry Group ; China ; Gastrointestinal Neoplasms ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; MicroRNAs ; Polymorphism, Genetic

Objective To investigate the association between microRNA (miR)-146a gene polymorphisms and susceptibility to gastrointestinal cancer. Methods PubMed, Medline and Ovid full text databases, China Journal Full-text Database (CNKI), Articles Database and Chinese Biomedical Literature Database were researched to retrieved literatures about the association between miR-146a gene polymorphism and susceptibility to gastrointestinal cancer published from July 2010 to March 2014. Modified Jadad quality score was used to evaluate the quality of the literatures and Stata 11.0 software was used to analyze and calculate OR value of the following 5 different genotypes: allele(G vs. C), the dominant genetic model(GC+GG vs. CC), a recessive genetic model (GG vs. GC+CC) and homozygote (GG vs. CC) and heterozygote (GC vs. CC) to assess the association. Results A total of 16 studies were enrolled, including 7090 cancer patients and 9928 healthy controls. Meta-analysis showed that people with G allele was more susceptible to gastrointestinal cancer than those with C (gastric cancer:OR=1.1,95% CI:1.04-1.17, P=0.001, colorectal cancer: OR=1.09,95% CI:1.01-1.18, P=0.020)﹔dominant model (GC+GG) was more susceptible to gastric cancer than CC (OR=1.12, 95% CI:1.02-1.22, P=0.016)﹔ recessive genetic model GG was more susceptible to gastrointestinal cancer than CC+GC (gastric cancer: OR=1.16, 95% CI:1.05-1.27, P=0.004, colorectal cancer: OR=1.13, 95%CI:1.00-1.28, P=0.047)﹔ GG homozygote was more susceptible to gastrointestinal cancer than CC(gastric cancer: OR=1.20, 95% CI:1.06-1.35, P=0.003, colorectal cancer: OR=1.19, 95% CI:1.01-1.41, P=0.042). Dominant genetic model GC+GG and CC in colorectal cancer as well as heterozygous GC and CC in gastrointestinal cancer were not significantly different (P>0.05). Conclusion miR-146a cancer susceptibility gene polymorphism is closely associated with gastrointestinal cancers.

Objective To investigate the association between microRNA (miR)-146a gene polymorphisms and susceptibility to gastrointestinal cancer. Methods PubMed, Medline and Ovid full text databases, China Journal Full-text Database (CNKI), Articles Database and Chinese Biomedical Literature Database were researched to retrieved literatures about the association between miR-146a gene polymorphism and susceptibility to gastrointestinal cancer published from July 2010 to March 2014. Modified Jadad quality score was used to evaluate the quality of the literatures and Stata 11.0 software was used to analyze and calculate OR value of the following 5 different genotypes: allele(G vs. C), the dominant genetic model(GC+GG vs. CC), a recessive genetic model (GG vs. GC+CC) and homozygote (GG vs. CC) and heterozygote (GC vs. CC) to assess the association. Results A total of 16 studies were enrolled, including 7090 cancer patients and 9928 healthy controls. Meta-analysis showed that people with G allele was more susceptible to gastrointestinal cancer than those with C (gastric cancer:OR=1.1,95% CI:1.04-1.17, P=0.001, colorectal cancer: OR=1.09,95% CI:1.01-1.18, P=0.020)﹔dominant model (GC+GG) was more susceptible to gastric cancer than CC (OR=1.12, 95% CI:1.02-1.22, P=0.016)﹔ recessive genetic model GG was more susceptible to gastrointestinal cancer than CC+GC (gastric cancer: OR=1.16, 95% CI:1.05-1.27, P=0.004, colorectal cancer: OR=1.13, 95%CI:1.00-1.28, P=0.047)﹔ GG homozygote was more susceptible to gastrointestinal cancer than CC(gastric cancer: OR=1.20, 95% CI:1.06-1.35, P=0.003, colorectal cancer: OR=1.19, 95% CI:1.01-1.41, P=0.042). Dominant genetic model GC+GG and CC in colorectal cancer as well as heterozygous GC and CC in gastrointestinal cancer were not significantly different (P>0.05). Conclusion miR-146a cancer susceptibility gene polymorphism is closely associated with gastrointestinal cancers.