Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.
Humans ; Metformin/pharmacokinetics* ; Diabetes Mellitus, Type 2/metabolism* ; Hypoglycemic Agents/pharmacology* ; AMP-Activated Protein Kinases/metabolism* ; Aging

ObjectiveA rapid method for identification of chemical constituents in Puerariae Lobatae Radix dispensing granules was established in order to clarify the material basis. MethodThe chemical constituents of Puerariae Lobatae Radix dispensing granules was qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） under positive and negative ion modes， and the chromatographic conditions were on an ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） as mobile phase for gradient elution（0-4 min， 5%-10%B； 4-10 min， 10%-15%B； 10-20 min， 15%-16%B； 20-27 min， 16%-31%B； 27-33 min， 31%-59%B； 33-42 min， 59%-95%B； 42-42.1 min， 95%-5%B； 42.1-45 min， 5%B）， the flow rate was 0.35 mL·min^-1， the column temperature was 40 ℃， the injection volume was 5 μL， and electrospray ionization（ESI） was selected. Then these chemical constituents were comprehensively identified based on PeakView 1.2， PubChem， ChemicalBook， ChemSpider， comparative control profiles and literature information. ResultA total of 128 chemical constituents were identified from the dispensing granules， including 60 flavonoids， 26 organic acids， 7 glycosides， 6 coumarins， 3 nucleosides and 26 other compounds. By focusing on the cleavage patterns of flavonoids， organic acids， glycosides， coumarins， nucleosides and other compounds， 12 compounds that have not been reported in Puerariae Lobatae Radix species were identified from the dispensing granules. ConclusionThe established method can systematically and rapidly identify the chemical constituents in Puerariae Lobatae Radix dispensing granules， and cleared it composition is mainly flavonoids and organic acids. Laying a foundation for the study of the material basis， mechanism of action and clinical application of the dispensing granules.

Objective To investigate the effect of salidroside on intestinal mucosal immune status in rats under compound stress of hypoxia and training (HTCS) and the mechanism. Methods SD rats were randomly divided into HTCS model group (model), placebo group (placebo) and salidroside group (salidro). Model group received no intervention, and placebo and salidro group received intraperitoneal injection of normal saline and salidroside, respectively. Then, ileum tissue of rats were collected and the intestinal damage was assayed by HE staining and Chiu scores. Intestinal permeability indices, including serum D-diamine oxidase (DAO), D-lactic acid (DLA) and endotoxin (END) and secretory immunoglobulin A (sIgA) of intestinal tissue were detected by ELISA. T lymphocyte subsets of intestinal tissue were detected by flow cytometry. Expression of tight junction molecules, including ZO-1, Claudin-3, occluding, were detected by PCR and western blot. Activation of TLR4/NF-κB signaling pathway was detected by Western blot analysis. Results Compared with model group and placebo group, salidro group had the decreased intestinal mucosal injury and low Chiu score, and the level of intestinal permeability indices including serum DAO, DLA and END fell off. CD4⁺ T cell percentage, CD4⁺/CD8⁺ ratio and sIgA level were went up, while CD8⁺ T cell percentage was went down. mRNA and the level of protein expressions of ZO-1, claudin-3 and occludin increased, while activation of TLR4/NF-κB signaling pathway was inhibited. Conclusion Salidroside can alleviate the intestinal barrier injury and improve intestinal mucosal immune status of rats under compound stress of hypoxia and training via inhibiting TLR4/NF-κB signalling pathway.
Animals ; Rats ; Rats, Sprague-Dawley ; NF-kappa B ; Toll-Like Receptor 4/genetics* ; Claudin-3 ; Hypoxia ; Immunoglobulin A, Secretory ; Signal Transduction

Objective:To automatically and rapidly detect mild cognitive impairment (MCI) in an objective manner using natural language processing (NLP).Methods:A total of 215 participants (half female) aged 50 to 80 were recruited for the study′s normal cognition and MCI groups. Speech tasks and the mini mental state examination (MMSE-2) were used to collect audio data and quantify cognitive functioning. Altogether 162 acoustic features were extracted including the speaking speed, syllable number, syllable duration, number of pauses, duration of pauses, the standard deviation of formant frequency and sound pressure variation. They were compared between the two groups and genders. Multiple regression analysis was used to formulate a model predicting MCI. The sensitivity, specificity and accuracy of its predictions were used to evaluate its predictive power.Results:There were significant differences between the two groups in 50 acoustic features including their pronunciation rhythm and pronunciation accuracy. Univariate correlation analysis revealed that the pronunciation rhythm was significantly associated with cognitive functioning. The sensitivity, specificity and accuracy of the model were 0.54, 0.80 and 0.69 for males and 0.00, 0.86 and 0.63 for females.Conclusion:MCI greatly affects pronunciation rhythm. Acoustic analysis based on NLP can detect MCI rapidly and objectively.

Objective:To investigate the expression of ras-related C3 botulinum toxin substrate 3 (RAC3) in glioma tissues and its effect on the migration and invasion of glioma cells.Methods:The expression of RAC3 in 57 glioma patients and their adjacent tissues from the First People’s Hospital of Shangqiu was detected by immunohistochemical assay. According to the experimental requirements, brain glioma cells U87MG were divided into experimental group and control group. The experimental group U87MG cells were transfected with RAC3-siRNA plasmid, and the control group U87MG cells were transfected with MOCK-siRNA plasmid. RAC3 mRNA in each group was detected by fluorescence quantitative PCR. The expressions of RAC3 and MMP2 in each group were detected by Western blot. Transwell was used to detect the migration and invasion ability of cells in each group.Results:The positive rate of RAC3 in glioma patients was 89.47% (51/57 cases) , and the expression rate in paracancer tissues was 14.04% (8/57 cases) . The expression rate of RAC3 in glioma tissues was significantly higher than that in paracancer tissues, with statistical significance ( P<0.01) . After siRNA transfection, mRNA expression of RAC3 in experimental group and control group was 1.23±0.20 and 0.43±0.12, and protein expression of RAC3 was 1.19±0.11 and 0.23±0.08, respectively. The expression of MMP2 protein was 1.19±0.11 and 0.23±0.08, respectively. The expression of MMP2 in experimental group was significantly decreased ( P<0.05) . Transwell assay showed that the number of invasive cells in experimental group and control group U87MG cells was (22±5) and (45±8) , and the number of migratory cells was (34±6) and (90±11) , respectively. In experimental group, U87MG cell migration and invasion ability decreased significantly (both P<0.05) . Conclusion:The high expression of RAC3 in glioma tissues may be related to the malignant degree of development, and affect the migration and invasion ability of glioma cells by regulating the expression of MMP2.

Background and purpose:The Shanghai Municipal Center for Disease Control and Prevention provides annual updates on cancer occurrence and trends in Shanghai.This study aimed to investigate the cancer incidence and mortality in 201 7 and their trends from 2002 to 2017 in Shanghai. Methods:Data of new cancer diagnoses and deaths from 2002 to 2017 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.Cancer incidence and mortality stratified by year of diagnosis or death,gender and age group were analyzed.Number,proportion,crude rate,age-specific rate,age-standardized rate and others were calculated.The number,proportion and rates of common cancers in different groups were also calculated.Trends in age-standardized rate of incidence and death rates for all cancers combined and for the common cancer types by gender were estimated by joinpoint analysis and characterized by the annual percent change(APC)and average annual percent change(AAPC).Segi's 1960 world standard population was used for calculating age-standardized incidence and mortality. Results:The new cancer cases and deaths were 79 378 and 37 186 in Shanghai in 2017.The crude rate of incidence was 546.55/105,and the age-standardized rate was 246.31/105.The age-standardized rate of incidence was higher among females than among males.The crude rate of mortality was 256.04/1 05,and the age-standardized rate was 88.41/105.The age-standardized rate of mortality was higher among males than among females.The age-specific numbers and rates of incidence and mortality increased with age.The age-specific number and rate of incidence reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among males reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among females reached the peak at the age groups of older than 85 years,respectively.The sites of top 10 common cancer types sorted by the number of incidence cases among males were lung,colorectum,stomach,prostate,liver,thyroid,pancreas,bladder,kidney and oesophagus,and among females were lung,breast,thyroid,colorectum,stomach,pancreas,liver,brain,central nervous system(CNS),cervix uteri and gallbladder,the sites of those sorted by the number of deaths among males were lung,stomach,colorectum,liver,pancreas,prostate,oesophagus,bladder,lymphoma and gallbladder,among females were lung,colorectum,breast,stomach,pancreas,liver,gallbladder,brain,CNS,ovary and lymphoma.The top 10 common cancer types stratified by gender and the top 5 common cancer types stratified by common age groups merged of incidence and mortality had wide variations.Overall,the age-standardized rates of incidence were stable from 2002 to 2009,and increased 2.88％on average per year from 2009 to 201 7.The age-standardized rates of mortality were stable from 2002 to 2011,and decreased 2.66％on average per year from 2011 to 201 7.The trends differed by gender and cancer type. Conclusion:Lung cancer,colorectal cancer,pancreatic cancer,thyroid cancer,female breast cancer,cervical cancer and male prostate cancer are the most common cancers in Shanghai,the appropriate screening technical scheme should be formulated according to the current situation of malignant tumors in Shanghai,promote cancer opportunistic screening,promote appropriate technologies for intervention and management of cancer patients in the community,reduce the disease burden of malignant tumors.

Objective:To investigate the survival of cancer cases diagnosed during 2002-2013 in Shanghai. Methods:Data on new cancer cases with dead and follow-up information were obtained from the population-based cancer registry and vital statistics system of Shanghai Municipal Center for Disease Control and Prevention.Survival indicators stratified by year of diagnosis,gender,site and age were analyzed.Number of cases and proportion were calculated.The observed survival rates were calculated based on the life table.The probabilities of surviving from 0 to 99 years old were estimated according to the Elandt-Johnson model,and then the cumulative expected survival rates were calculated according to the Ederer Ⅱ method.Finally,the relative survival rates and average annual percent changes of their trends were calculated.The age-standardized relative survival rates adjusted by International Cancer Survival Standard weights were calculated. Results:Total 644 520 new cancer cases were diagnosed during 2002-2013 in Shanghai,accounting for 643 545(99.85％)cases included in the observed cohort for survival analysis.The 5-year observed survival rate increased from 37.61％to 46.47％.The 5-year relative survival rate increased from 42.1 8％to 51.11％.The 5-year age-standardized relative survival rate increased from 40.57％to 49.80％.Among the 5-year relative survival rates of cases diagnosed during 2011 to 2013,99.43％of thyroid cancer was the highest,followed by female breast cancer(88.35％)and corpus uteri cancer(85.56％);5.87％of pancreas cancer was the lowest,followed by gallbladder cancer(13.64％)and oesophagus cancer(17.72％).the rate of lung cancer with the largest number of cases was 23.59％,followed by colorectal cancer(59.82％)and stomach cancer(38.65％).The 5-year relative survival rate of total cases of all sites increased from 40.55％in 2002 to 52.77％in 2013,with an average annual percent change of 2.40％.13 cancer types showed increasing trends,such as liver cancer and lung cancer,while the trends of other cancer types were not statistically significant,such as pancreatic cancer and gallbladder cancer. Conclusion:The diagnostic levels and survival rates of cancer cases have been improved continuously in Shanghai.The trends of different cancer types were varied.

Objective:To analyze the incidence and mortality of prostate cancer in Shanghai in 2016 and trends during 2002-201 6,and to provide a basis for prostate cancer prevention and treatment. Methods:The data of prostate cancer incidence and mortality in Shanghai from 2002-2016 were obtained from the Population-Based Cancer Registry and Vital Statistics of Shanghai Municipal Center for Disease Control and Prevention.The incidence,mortality,proportion,crude rate,age-specific rate and age standardized rate of prostate cancer were calculated.Age-standardized incidence and mortality were calculated using Segi's 1960 world standard population.Trends of prostate cancer incidence,mortality,age-standardized rate and age-specific rate were estimated by Joinpoint 4.9.1.0 software. Results:In 2016,there were 3 226 cases of newly diagnosed prostate cancer and 1 067 deaths in Shanghai,crude rate of incidence was 44.91/105,crude rate of mortality was 14.85/105,age-standardized incidence and mortality were 15.47/105 and 4.34/105.Age-specific incidence and mortality increased with age,and reached the highest level in the 80-84 year-old group and 85-year-old group.Urban incidence was higher than suburb in the 50-54 year-old group,75-79 year-old group,and 80-84 year-old group,with no statistical difference in mortality.Between 2002 and 2016,incidence and mortality increased gradually,the rise of age-standardized incidence slowed down after 2012,and the age-standardized mortality in urban area declined after 2012.The age-standardized incidence in suburb increased faster than that in urban area,and the incidence rate increased faster in the younger age groups. Conclusion:The incidence and mortality of prostate cancer in Shanghai were lower than the world level but higher than the national level,and the incidence increased gradually between 2002 and 2016.Incidence and mortality were higher in urban area than in suburb,but increased faster in suburb,and the incidence increased more rapidly in younger age groups,but the proportion of early stages at diagnosis was still low,suggesting that appropriate screening strategies should be considered.

Objective:To describe the epidemiological features and temporal trends of colorectal cancer in urban Shanghai from 1973 to 2017. Methods:Data on colorectal cancer in urban Shanghai was obtained through Shanghai Cancer Registry and Vital Statistics System.Joinpoint analysis was used to describe the temporal trends and annual percent change(APC)and age-period-cohort analysis was used to estimate the association between age,period and birth cohort and colorectal cancer. Results:A total of 105 847 cases and 60 447 deaths of colorectal cancer were diagnosed in urban Shanghai over the 45-year study period.Both the number of new cases and the number of deaths showed an increasing trend.In the same period,the age-standardized incidence of colorectal cancer in urban areas of Shanghai increased significantly from 14.1/100 000 in 1973 to 27.7/100 000 in 2017,while the age-standardized mortality rate increased from 8.2/100 000 to 10.7/100 000.The overall average annual age-standardized incidence and mortality rates were 20.4/100 000 and 11.0/100 000,respectively.With the increase of age,the age-standardized morbidity and mortality of colorectal cancer showed an obvious upward trend.Taking 1993-1997 as reference,the risk of colorectal cancer in Shanghai reached the highest in 2013-2017,and the corresponding relative risk was 1.2(95％confidence interval:1.2-1.3),while the lowest was 0.9(95％confidence interval:0.8-1.0)during 1973-1977.Mortality risk,on the contrary,decreased with the increase of time.Before 1953-1957,the risk of colorectal cancer in urban Shanghai increased with the increase of birth cohort time,and then showed a downward trend.There was a corresponding decline in the risk of colorectal cancer death among people born after 1957. Conclusion:The incidence and mortality of colorectal cancer in Shanghai showed an increasing trend from 1973 to 2017,but the prevalence trend of colorectal cancer is still different among different populations.

ObjectiveTo explore the factors affecting neurobehavioral development of 18-month-old infants with low birth weight （LBW）， and to provide scientific basis for early identification of neurobehavioral abnormalities. MethodsThe information of LBW infants who required follow-up in maternal and child health care institutions of 16 districts in Shanghai from January to October 2018 was collected. The subjects who met the inclusion and exclusion criteria were investigated by questionnaire， physical growth measurement and Gesell development diagnosis evaluation. ResultsA total of 885 qualified subjects were included in this study， including 400 boys （45.2%）， 485 girls （54.8%）， 32 cases with birth weight <1 500 g （3.6%）， and 853 cases with birth weight ranging from 1 500 g to 2 500 g （96.4%）. The percentage of abnormalities in the LBW infants at 18 months was 3.3% for gross-motor， 10.3% for fine-motor， 15.7% for adaptive behaviors， 22.1% and 14% for language and personal-social behaviors （DQ≤85）， respectively. Multivariate analysis， with gender， birth weight and gestational age adjusted as confounding factors， showed the following risk factors： male for LBW fine-motor dysplasia （OR=1.86， 95%CI： 1.19‒2.90） and personal-social behavior dysplasia （OR=1.69， 95%CI： 1.14‒2.50）； gestational age less than 32 weeks for personal-social behavior dysplasia （OR=4.95， 95%CI： 2.08‒11.79）； stress during pregnancy for gross- motor dysplasia （OR=3.3， 95%CI： 1.33‒8.21）， language dysplasia （OR=1.72， 95%CI： 1.03‒2.88） and personal-social behavior dysplasia （OR=2.72， 95%CI： 1.56‒4.72）； cigarette smoke exposure during pregnancy for fine-motor dysplasia （OR=5.52， 95%CI： 2.07‒14.70） and adaptive behavior dysplasia （OR=2.88， 95%CI： 1.12‒7.43）； gestational diabetes for language dysplasia （OR=2.22， 95%CI： 1.12‒4.42）； pregnancy induced hypertension （PIH） for abnormal personal-social behavior development （OR=3.57， 95%CI： 1.86‒6.83）； and small head circumference （HCZ<-2） for gross-motor dysplasia （OR=16.15， 95%CI： 3.05‒85.69）， fine-motor dysplasia （OR=11.17， 95%CI： 1.15‒108.83） and language dysplasia （OR=7.86， 95%CI： 1.45‒42.57）. ConclusionThe neurobehavioral development of LBW infants is related to gender， gestational age， mood during pregnancy， cigarette smoke exposure during pregnancy， diseases during pregnancy and head circumference development. Thus， avoiding adverse environmental exposure during pregnancy， actively preventing complications during pregnancy， paying attention to head circumference follow-up and prevention of preterm delivery are of protective significance to the neurobehavioral development of low birth weight infants.