Glucose Transport Proteins, Facilitative ; deficiency ; Humans ; Syndrome

Objective:Phthalates （PAEs） are common environmental endocrine disruptors. In this study， the effects of oxidative stress on liver and nutrient metabolism were determined in male diabetic rats exposed to di-2-ethylhexyl phthalate （DEHP）， and the mechanism of DEHP toxicity was explored. Methods:Thirty-two SPF male Wistar rats aged five weeks， weighing 150-170 g， were fed adaptively for one week to establish the model of type 2 diabetes. The model was established by intraperitoneal injection of streptozotocin （STZ） （25 mg/kg） after feeding with high sugar and high fat diet for four weeks. Second STZ injection was given two days later. The model was considered to be established successfully when the random blood glucose level was found to be higher than 16.7 mmol/L in two separate tests. Twenty diabetic rats were then randomly divided into four groups， including control group （corn oil）， 100， 300 and 900 mg/kg DEHP groups. The rats were treated with DEHP by gavage （5 mL/kg） once a day for 30 days. They were fed with normal diet during the treatment period. Caudal venous blood was collected on the 1st， 14th， and 28th days to measure the random blood glucose level. The changes of glucose tolerance were determined by oral glucose tolerance test on the 29th day. Fasting blood glucose （FPG） was measured on the next day of the last exposure. After the rats were anesthetized with pentobarbital and killed， the liver was weighed， the liver coefficient was calculated and the liver pathological section was made. Blood was taken from the abdominal aorta. The levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， triacylglycerol （TG） and albumin （ALB） in serum were measured by spectrophotometry， and the levels of insulin， glutathione （GSH）， H₂O₂， malondialdehyde （MDA） and superoxide dismutase （SOD） in fasting serum were measured by radioimmunoassay. Results:There was no significant difference in body weight and random blood glucose in the type 2 diabetic rats exposed to different concentrations of DEHP （all P>0.05）. At each time point of the glucose tolerance curve， the blood glucose value of the exposure groups was higher than that of the control group. A "false plateau period" appeared after the blood glucose value reached or exceeded the upper limit at 15 minutes， and the blood glucose level in each group was higher than that of the control group at 120 minutes. The liver organ coefficient of 300 and 900 mg/kg DEHP groups was higher than that of the control group （both P<0.01）， and the liver organ coefficient was positively correlated with the exposure concentration of DEHP （r=0.80，P<0.000 1）. Under the microscope， the liver cells in diabetic rats were swollen， the cytoplasm was light stained， and there were vacuoles in the cells. The serum ALP level in diabetic rats of 900 mg/kg DEHP group was significantly higher than that in the control group （P<0.01）. The serum ALP level was positively correlated with the concentration of DEHP （r=0.75， P<0.01）. The serum MDA level in diabetic rats of 300 mg/kg and 900 mg/kg DEHP groups was significantly higher than that of the control group （both P<0.01）， and the serum MDA level was positively correlated with the concentration of DEHP （r=0.84， P<0.000 1）. The serum SOD level of 900 mg/kg DEHP group was significantly higher than that of control group （P<0.01）. Conclusion:DEHP exposure could lead to liver damage， abnormal glycolipid metabolism， and increase the level of oxidative stress and antioxidant level in male diabetic rats， but did not show a significant effect on insulin resistance.

Aim To investigate the effect of the aryl hydrocarbon receptor (AhR) on the expression of inflammatory factors in macrophages RAW264. 7 induced by pyocyanin (PCN) and the regulatory mechanism of its signaling pathway. Methods RAW264. 7 cells were treated with different concentrations of PCN for 24 h, respectively, and the effect of PCN on cell activity was detected by CCK8 assay to determine the optimal PCN concentration for manufacturing infection models. The cells were divided into the control group (given 0. 1% dimethyl sulfoxide DMSO), PCN group, PCN + AhR inhibitor (CH223191) group, and PCN + AhR agonist (FICZ) group, and the expression of AhR was detected by immunofluorescence. The expression levels of inflammatory factors (IL-6, IL-1β, and TNF-α) were detected by ELISA. The protein expression of AhR, pp38 MAPK and p-p65NF-κB, was detected by Western blotting. Results PCN induced a significant quantitative effect on AhR expression in RAW264. 7 cells. CH223191 increased PCN-induced inflammatory factor secretion and enhanced the phosphorylation of p38MAPK and p65NF-κB compared with the control group. FICZ decreased PCN-induced inflammatory factor production and reduced the phosphorylation of p38MAPK and p65NF-κB phosphorylation capacity. Conclusions AhR can regulate PCN-induced inflammatory factor expression in RAW264. 7 cells, and the p38MAPK/p65NF-κB signaling pathway may be an essential pathway for the involvement of AhR in immune regulation.

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in diabetic nephropathy(DN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with DN was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from database inception to October 2022. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 software and RevMan 5.4.1 were used to analyze the data of the literature that met the quality standards. Finally, 53 RCTs were included, involving 6 Chinese patent medicines. The total sample size was 4 891 cases, including 2 449 cases in the test group and 2 442 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Jinshuibao Capsules + conventional western medicine, and Niaoduqing Granules + conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Shenshuaining Capsules/Granules/Tablets + conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Bailing Capsules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(4) In terms of reducing UAER, the top 3 optimal interventions according to SUCRA were Shenshuaining Capsules/Granules/Tablets + conventional western medicine, Huangkui Capsules + conventional western medicine, and Jinshuibao Capsules + conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granules + conventional wes-tern medicine, and Tripterygium Glycosides Tablets + conventional western medicine.(6) In terms of reducing BUN, the first 3 optimal interventions according to SUCRA were Niaoduqing Granules + conventional western medicine, Tripterygium Glycosides Tablets + conventional western medicine, and Huangkui Capsules + conventional western medicine.(7) In terms of improving the clinical total effective rate, the first 3 optimal interventions according to SUCRA were Jinshuibao Capsules + conventional western medicine, Niaoduqing Granu-les + conventional western medicine, and Huangkui Capsules + conventional western medicine. The results showed that the combination of western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of western medicine and Chinese patent medicine was superior to western medicine alone in reducing Scr, BUN, and UAER, and improving the total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.
Humans ; Tumor Necrosis Factor-alpha ; Network Meta-Analysis ; Nonprescription Drugs ; Diabetic Nephropathies/drug therapy* ; C-Reactive Protein ; Capsules ; Interleukin-6 ; Drugs, Chinese Herbal/therapeutic use* ; Glycosides ; Tablets ; Diabetes Mellitus/drug therapy*

Objective: To investigate the association between metabolically healthy obesity and the incident risk of stroke in people aged ≥40 years from rural areas of Henan Province. Methods: During 2007 to 2008, 20 194 residents aged ≥18 years were selected for baseline examination by random cluster sampling and 17 265 participants were followed up during 2013 to 2014. According to the aim of current study, a total of 11 864 eligible subjects were included in this post-hoc analysis. Depending on body mass index and metabolic status, subjects were divided into four groups: metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity. Multivariate logistic regression model was used to analyze the relationship between metabolically healthy obesity and the risk of stroke. Results: The median (Q₁, Q₃) age of study participants was 54(46, 61) years, and 4 526 participants were men. During the mean follow-up of 6 years, the cumulative incidence of stroke was 7.16%. The incidence of stroke in metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight, and metabolically abnormal obesity were 3.73%, 4.61%, 8.99% and 9.38%, respectively (χ²=117.458, P<0.001). After adjusting possible confounding factors, compared with metabolically healthy normal weight, the risk of stroke was significantly increased in the metabolically healthy obesity group, metabolically abnormal normal weight group and metabolically abnormal obesity group with the odds ratio (OR) and 95% confidence interval (CI) of 1.52(1.10-2.12), 2.11(1.61-2.77) and 2.78(2.18-3.55), respectively. Stratified analysis showed that the risk of stroke was significantly higher in metabolically healthy obesity people aged 40-59 years compared with metabolically healthy normal weight group (OR=2.12, 95%CI: 1.36-3.30). Conclusion: Metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity are positively associated with the risk of stroke.
Adolescent ; Adult ; Body Mass Index ; Humans ; Male ; Middle Aged ; Obesity/complications* ; Obesity, Metabolically Benign/epidemiology* ; Risk Factors ; Stroke/epidemiology*

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.
Antineoplastic Agents ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Neoplasms/therapy* ; Precision Medicine ; Syndrome