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Insulin resistance (IR) is an important pathological and physiological mechanism of type 2 diabetes (T2DM), and the treatment of IR has become the key to the prevention and treatment of T2DM. IR is a state of insensitivity or reduced sensitivity of insulin-stimulated tissue cells to glucose, resulting in cells that are unable to efficiently take up glucose in the bloodstream and thus causing hyperglycemia. Adenosine monophosphate-activated protein kinase (AMPK) is an energy-sensing enzyme that can regulate multiple metabolic pathways and maintain the stability of adenosine triphosphate (ATP) in the cell. In recent years, traditional Chinese medicine (TCM) has played an increasingly important role in the prevention and treatment of T2DM. The research on exploring the AMPK signaling pathway of TCM intervention in the progress of T2DM has gradually increased. Many pharmacological studies have shown that TCM has advantages such as safety and high efficiency in the prevention and treatment of T2DM. AMPK signaling pathway is one of the key pathways for the active ingredients of TCM and TCM extracts to improve IR. Active ingredients such as phenols, flavonoids, polysaccharides, alkaloids, and saponins, as well as other herbal extracts can improve IR by activating the AMPK signaling pathway cascade response, thereby improving IR by regulating glucolipid metabolism, inhibiting inflammatory response, anti-oxidative stress and maintaining mitochondrial homeostasis. Based on this, this paper reviews the pharmacological and experimental research results of TCM intervening the AMPK signaling pathway to improve IR in recent years, expecting to provide reference for further research, development and application of TCM in intervening IR and treating T2DM.
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ObjectiveTo retrospectively analyze the clinical efficacy of Xibining Ⅱ prescription in the treatment of knee osteoarthritis with cold-dampness blockage syndrome by oral medication and to explore the influencing factors of endpoint events. MethodA real-world retrospective cohort design was adopted, and medical records of knee osteoarthritis patients with cold-dampness blockage syndrome treated with oral medication from the orthopedics outpatient department of Jiangsu Province Hospital of Chinese Medicine were collected. All patients received conventional Western medicine treatment and were divided into non-exposure group (573 cases) and exposure group (427 cases) according to whether or not they received treatment with Xibining Ⅱ prescription. Descriptive analysis of the baseline data of the 1 000 screened cases was performed using IBM SPSS 27.0. According to the baseline data, 334 pairs were matched using the propensity score matching method, resulting in a total of 668 cases in both groups. The changes in visual analogous scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, Japanese Knee Osteoarthritis Measure (JKOM) score, and traditional Chinese medicine (TCM) syndrome score before treatment and at 2, 6, 12 weeks after treatment, as well as the incidence of adverse reactions, were compared between the two groups. A multivariate logistic regression analysis was conducted to analyze the influencing factors of endpoint events, with clinical cure judged based on the improvement rate of WOMAC total score before and after treatment. ResultAfter 12 weeks of treatment, compared to the results before treatment, the VAS, WOMAC total score, JKOM score, and TCM syndrome score of patients in both groups significantly decreased (P<0.01). Compared to the non-exposure group, the exposure group showed a more significant reduction in VAS, WOMAC total score, JKOM score, and TCM syndrome score (P<0.01). After 12 weeks of treatment, the clinical cure rate and significant efficiency were higher in the exposure group than in the non-exposure group (P<0.05). Compared to the results before treatment within each group, VAS, WOMAC pain, stiffness, function scores, JKOM score, and TCM syndrome score significantly decreased at 2, 6, 12 weeks after treatment in both groups (P<0.01). Compared to the non-exposure group at the same time points, the exposure group showed a reduction in VAS at 2, 12 weeks, WOMAC pain at 6, 12 weeks, and function scores at 12 weeks (P<0.05, P<0.01). The JKOM score decreased at 6, 12 weeks, and the TCM syndrome score significantly decreased at 2, 6, 12 weeks in the exposure group (P<0.05, P<0.01). Multivariate logistic regression analysis at 12 weeks showed that factors affecting clinical cure included the course of disease, history of alcohol consumption, hypertension, coronary heart disease, and the use of Xibining Ⅱ prescription (P<0.05, P<0.01). Compared to the non-exposure group at the same time points, the incidence of epigastric discomfort in the exposure group was lower at 2, 12 weeks (P<0.01), the incidence of diarrhea and vomiting was slightly higher than that in the non-exposure group, but the difference was not statistically significant. ConclusionThe clinical application of Xibining Ⅱ prescription combined with conventional Western medicine treatment in the treatment of knee osteoarthritis with cold-dampness blockage syndrome is more effective than conventional Western medicine treatment alone. It can significantly reduce VAS, WOMAC total score, JKOM score, and TCM syndrome score, with more pronounced long-term effects and a low incidence of adverse reactions.
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BACKGROUND@#Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US.@*METHODS@#The deaths, and mortality rates of asthma in China and the US during 1990-2019 were obtained from the Global Burden of Disease Study 2019. The age-period-cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated.@*RESULTS@#In 1990-2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively.@*CONCLUSIONS@#In 1990-2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.
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Adult , Humans , Male , Female , Aged , Young Adult , United States/epidemiology , Asthma/epidemiology , Risk Factors , Smoking , China/epidemiologyABSTRACT
Diabetic nephropathy (DN) is a serious complication of diabetes, a major risk factor for chronic renal failure and end-stage renal disease, a major cause of deaths of diabetic patients, and a major cause of noncommunicable disease-associated deaths in the world. Pyroptosis and inflammasome activation are closely associated with the occurrence and development of DN. They can mediate a variety of pathological changes such as the loss and fusion of podocytes, up-regulated expression of inflammatory cytokines, macrophage infiltration, glomerular mesangial matrix expansion, and increased urinary albumin-to-creatinine ratio, eventually leading to nephron loss and kidney injury. The available studies have reported that the active ingredients in Chinese medicinal herbs or classical prescriptions play a role in the treatment of DN by lowering blood glucose and lipid levels, mitigating insulin resistance, reducing inflammation, alleviating oxidative stress, and regulating immunity. Moreover, the active ingredients can inhibit the activation of inflammasomes and the pyroptosis of renal cells, repair the inflammation-induced damage, improve renal function, and slow the progression of DN, demonstrating definite therapeutic effect. Chinese medicines can treat DN in a multi-target, multi-pathway, and multi-system manner, possessing broad prospects in the prevention and treatment of DN. Despite the extensive studies about the traditional Chinese medicine (TCM) intervention of DN in vivo and in vitro, a comprehensive summary of experimental studies on the TCM intervention of DN model remains to be carried out. This paper reviews the research progress in pyroptosis, inflammasomes, roles of pyroptosis and inflammasomes in DN, and TCM intervention of DN, aiming to provide ideas and reference for the research and development of drugs for this disease.
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Objective:To investigate the effects and mechanisms of curcumin on insulin resistance in streptozocin-induced diabetic rats.Methods:Diabetic rats were induced by intraperitoneal injection of STZ, then all the rats were randomly divided into diabetes (DM), diabetes+ curcumin (DM+ Cur), and diabetes + buffer control (DM+ NC) groups. Normal SD rats were used as control group (NC). The DM+ Cur group was treated with curcumin, while the DM+ NC group was treated with equal-volume buffer. The test lasted 12 weeks. The blood glucose was detected, and hyperinsulinemic-euglycemic clamp test was performed to estimate peripheral insulin resistance. At the end of the experiments, rats were killed and the total protein and cell membrane protein were extracted from skeletal muscle. The levels of phosphorylated PI3K, phosphorylated AKT, total PI3K, and total AKT were measured by Western blot. The levels of total GLUT4 and GLUT4 of cell membrane were also detected by Western blot, GLUT4 levels in skeletal muscle cell membranes were detected by immunofluorescence.Results:Blood glucose levels of DM+ Cur group were lower than those of DM group [(18.67±1.99 vs 24.38±2.88) mmol/L, P<0.05], and insulin resistance was also improved[the average GIR(14.69±0.29 vs 10.25±0.30) mg·kg -1·min -1, P<0.01]. The phosphorylation levels of PI3K and AKT were increased, and GLUT4 translocation to the cell membrane was increased. Conclusion:By activating the PI3K/AKT pathway, curcumin promotes GLUT4 translocation, increases skeletal muscle glucose uptake, and finally improves insulin resistance.
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Objective:To investigate the changes of proopiomelanocortin(POMC) expression in hypothalamus and corresponding metabolism in miR-21 knockout mice.Methods:miR-21 knockout or wild-type C57BL/6J mice were divided into diabetic group and control group, respectively. Diabetic mice model were forged with high-fat diet and low-dose streptozotocin. The changes of body weight and blood glucose in each group were monitored. By the end of the experiment, mice were sacrificed, and POMC protein expression and STAT3 mRNA expression in hypothalamus were detected.Results:There were no significant differences in body weight and blood glucose levels among all groups at baseline( P>0.05). The differences of body weight and blood glucose levels among various groups were compared at 3, 6, 9 and 12 weeks after the model was established. The results showed that body weight of mice in the diabetes group or miR-21 knockout+ diabetes group was higher than that in the control group at each time point( P<0.05). Moreover, there were significant difference in body weight between diabetes group and miR-21 knockout+ diabetes group at 3 and 12 weeks( P<0.05). The blood glucose levels in diabetes group were significantly higher than those in other groups at each time point( P<0.05). The blood glucose level in miR-21 knockout+ diabetes group was lower than that in diabetes group and higher than control group( P<0.05). POMC protein and STAT3 mRNA levels in diabetes group were significantly lower than those in control group, while those in the miR-21 knockout+ diabetes group were higher than those in the diabetes group. Conclusions:The expression of POMC in hypothalamus of miR-21 knockout mice is higher than that of wild-type diabetic mice. miR-21 knockout can decrease blood glucose level and body weight, and improve energy metabolism of diabetic mice.
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OBJECTIVE:To discuss the mechanism of synovitis of knee osteoarthritis (KOA)relieved by “Sanse powder ” volatile oil based on the activation of Nod-like receptor family 3(NLRP3)inflammasome. METHODS :“Sanse powder ”volatile oil was extracted by distillation- condensation process and the components of it were analyzed by GC-MS. Fibroblast-like synovial cells(FLS)were extracted from the knee joint of male SD rats. The effects of 10,25,50,100,250,500,1 000 μg/mL“Sanse powder”volatile oil on the viability of FLS were examined by CCK-8 assay. KOA inflammatory cell model was induced by lipopolysaccharide for 12 h. The effects of 10,250 μg/mL“Sanse powder ”volatile oil on the protein and mRNA expression of NLRP3,caspase-1 and apoptosis-associated speck-like protein (ASC)were detected. The levels of IL- 1β and IL-18 in supernatants of FLS were determined . RESULTS :Totally 0.51-0.61 g volatile oil with yellow clear and unique aromatic odor were extracted from“Sanse powder ”,and the extraction rate was 0.33%-0.41%(n=9). A total of 41 chemical components were isolated ,and 30 of them were identified and their peak area accounted for 90.073 6% of the total peak area. The components with high relative content were gingerol flavonoids (17.573 9%),δ-junionene(15.434 5%),gingerol(11.509 5%),etc. When the concentration of volatile oil was 10-250 μg/mL,there was no significant effect on survival rate of FLS (P>0.05). Compared with blank group ,the relative protein and mRNA expression of NLRP 3,caspase-1 and ASC and the levels of IL- 1β and IL-18 in supernatant were significantly increased in model group (P<0.05). Compared with model group ,relative expression or levels of above indexes were all decreased significantly in FLS and supernatant of “Sanse powder ”volatile oil 10 and 250 μg/mL groups(P<0.05). CONCLUSIONS:“Sanse powder ”volatile oil can inhibit NLRP 3 inflammasome activation in FLS and reduce the downstream inflammatory cascade response ,thus exerting its efficacy in ameliorating synovial inflammation of KOA.
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BackgroundSuper-spreading events were associated with the outbreaks of SARS and MERS, but their association with the outbreak of COVID-19 remains unknown. Here, we report a super-spreading transmission chain of SARS-CoV-2 involving an index patient, seven cancer patients, 40 health care workers and four family members. MethodsWe conducted a retrospective study to identify the index patient and the exposed individuals linked to a chain of transmission associated with COVID-19. We collected and analyzed the data on demographic features, exposure history, clinical presentation, laboratory investigation, radiological examination, and disease outcome of these patients. ResultsWe identified the index patient and another presumptive "super-spreader", who initiated and amplified a super-spreading transmission chain associated with COVID-19, respectively. There were 31 female and 21 male patients in this cohort, and the median age was 37 years (range: 22-79 years). Each of them had an exposure history with the index patient or his close contacts. Approximately 87% (45/52) of the patients had fever or other symptoms, 96% (50/52) had abnormal chest CT-scan findings, 86% of the tested patients (39/45) were positive for SARS-CoV-2 in the nasopharyngeal or throat swab specimen, 85% of the tested patients (29/34) were positive for SARS-CoV-2-specific IgM and/or IgG, 15% of the RT-PCR positive patients were tested negative for the specific IgM and/or IgG at the convalescent phase, and 15% of the RT-PCR negative patients were tested positive for the specific IgM and/or IgG. The severe patients experienced a significant decrease in oximetry saturation, lymphocyte, and platelet counts, along with a significant increase in C-reactive protein, D-dimer, and lactate dehydrogenase. All six fatal cases had comorbidities and five of the seven cancer patients (71%) died within 2-20 days of the disease onset. ConclusionsThe super-spreading events were associated with the outbreak of COVID-19 in Wuhan and its impact on disease transmission warrants further investigation. Cancer patients appeared highly vulnerable to COVID-19. The finding that a significant portion of SARS-CoV-2 infected patients were tested negative for the serum specific IgM and IgG at the convalescent phase should be addressed by additional studies.
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Objective To analyze the correlation between urinary albumin/creatinine ratio (ACR) and 24-hour urinary microalbumin (UMA) and evaluate the predictive value of ARC for early diabetic nephropathy.Methods A total of 368 patients with type 2 diabetes mellitus were retrospectively collected.Early diabetic nephropathy was defined as 24h UMA 30~<300 mg/24h.The correlation between ACR and 24hUMA,and the area under the receiver operating characteristic (ROC) curve of ACR in diagnosis of early diabetic nephropathy were calculated.Gender,age,course of disease,fasting venous blood glucose,glycosylated hemoglobin,blood pressure,triglyceride and total cholesterol were used as adjusting variables to establish univariate and multivariate logistic models of ACR for early diabetic nephropathy,respectively.A regression model was used to evaluate the diagnostic value of ACR for early diabetic nephropathy.Results The correlation between ACR and 24h UMA was 0.658.The area under ROC curve of ACR for early diabetic nephropathy was 0.907 before and 0.933 after adjustments of gender,age,course of disease,fasting venous blood glucose,glycosylated hemoglobin,blood pressure,triglyceride and total cholesterol,respectively.The OR value of ACR of diabetic nephropathy was 2.016 before and 2.762 after same adjustments.The calibration of Hosmer-Lemeshow chi-square test evaluation model was 19.362 before (P=0.13) and 14.928 after adjustments (P=0.061).Conclusion ACR is a better predictor for early diabetic nephropathy although its value is influenced by gender,age,course of disease,blood sugar,lipid,and blood pressure.
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Objective To assess the correlation of serum 25-hydroxyvitamin D (25-OHD) levels with vitamin D-binding protein (the group-specific component,GC) gene polymorphism in chronic obstructive pulmonary disease (COPD).Methods In a cross-sectional case-control study,250participants,including 116 COPD patients with smoking history and 134 healthy smokers,were investigated.A questionnaire about smoking history,vitamin D intake and comorbidities was collected.General pulmonary function was done by routine.Serum 25-OHD levels were detected by ELISA.The genetic variants (rs4588and rs7041) were genotyped by real time fluorescence polymerase chain reaction (RT-PCR) with TaqMan probe technology.Results The COPD patients had lower serum vitamin D level than the smoker subjects (36.58 nmol/L vs 43.80 nmol/L,P <0.001).In the COPD patients,vitamin D level was 39.43 nmol/L in those with percentage of predicted forced expiratory volume in 1 second (FEV1 % pred) greater than or equal to 80%.In other groups with FEV1 % pred 50%-80%,30%-50% and lower than 30%,vitamin D levels were 35.32 nmol/L,32.21 nmol/L,26.25 nmol/L respectively (P < 0.01).Moreover,there was a significant relevance of 25-OHD levels with FEV1 % pred in both COPD patients and healthy smokers (r2 =1.911; P <0.000 1).The mean 25-OHD concentration had a negative correlation with Global Initiative for Obstructive Lung Disease (GOLD) stages.Homozygous carriers of vitamin D-binding protein gene rs7041 T allele were independently related to 25-OHD levels and susceptibility of COPD (P < 0.01 ; OR =2.140,95% CI 1.157-3.959,P =0.015 respectively).Conclusions Patients with COPD are at high risk of vitamin D deficiency and the severity of COPD is inversely correlated with vitamin D levels.Furthermore,homozygous carrier of rs7041 T allele influences 25-OHD serum levels and is related to susceptibility of COPD,which may be a potential candidate gene for screening COPD.
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Objective:To explore a new method of the cultivation of adoptive immunotherapy cells.Methods: Mononuclear cells was isoplated by density gradient centrifugation and then proliferated by using CD 40-agonist monoclonal antibody 5C11、cytokine of IFN-αand IL-7(CD40 group)in vitro.During the culturing procedure ,the cell morphology was obersved by optical microscope.The percentage of T-lymphocytes, NK-T cells, Treg cells and the cell proliferation, which were compared with CIK group CD3mAb activated,was detected on the 9th day.Results:There was no significant difference of CD 4+/CD8+T cells percentage between the two groups.But the Treg cells percentage of CIK group was far higher than that of CD 40 group,while the percentage of CD3+CD56+NK-T cells was lower than that of CD 40 group.And a group of Mo-NK-DC cells were observed in the CD 40 group.Conclusion: The new method of adoptive immunity therapy has been established in this study could increase the percentage of NK -T cells which had the ability to kill tumor cells.Simultaneously ,it is reduced the amount of Treg cells significantly.