This study was aimed to evaluate effect of Qinghua Granules (QHG) on glycometabolism, pancreatic islet function and oxidative stress in type-2 diabetics with heat syndrome. A total of 60 cases of type-2 diabetics with heat syndrome (according to the Syndrome Element Syndrome Differentiation) were enrolled in the clinic of the Department of Endocrinology and Metabolism, Shuguang Hospital Affiliated to Shanghai University of Tradi-tional Chinese Medicine. The average age of enrolled cases was (57.9 ± 6.9) years. Enrolled cases were randomly divided into the treatment group and the control group. The original hypoglycemic plan was continued to use. In the treatment group, QHG was administrated. And in the control group, placebo was given. The administration dosage in both groups was one package per day. The treatment course was 12 weeks. The fasting and postpran-dial (120 min after standard meal) blood samples before and after medication were collected. The main evalua-tion indexes were fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and hemoglobin A1c (HbA1c). The secondary evaluation indexes were homeostasis model assessment (HOMA2-%B, HOMA2-%S, HOMA2%-IR), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), maleic dialdehyde (MDA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). The anal-ysis of variance was used in the comparison of efficacy between two groups . The results showed that HbA1c in the treatment group was obviously reduced, and HOMA2-%B was obviously increased. There was no significant changes in the control group ( P = 0 . 044 , P = 0 . 016 ) . In the treatment group , SOD increased obviously , MDA reduced obviously. There was no significant change in the control group. There was difference b etween two groups (P = 0.011, P = 0.049). There was no change on blood lipids or other evaluation indexes. It was conclud-ed that QHG is effective in the improvement of glycometabolism, islet β-cell functions and oxidative stress in type-2 diabetics with heat syndrome .

OBJECTIVETo explore the effects of principal-subordinate acupoints combination on improving myocardial ischemia, and the gene regulatory pathways for the protection of myocardial ischemia.

METHODSAccording to the random number table method, 70 SPF Wistar male rats were divided into a normal group, a model group, a LY294002 group, an insulin-like growth factors-1(IGF-1) group, a Neiguan group, an acupoint combination group and an acupoint combination + LY294002 group, 10 rats in each one. Rats in the normal group were injected with 0.9% NaCl solution, while rats in the remaining groups were treated with abdominal subcutaneous injection of isoroterenol hydrochloride to establish the rat model of myocardial ischemia. Rats in the LY294002 group and IGF-1 group were treated with injection of LY294002 solution and IGF-1 solution for 14 days. Rats in the Neiguan group were treated with electroacupuncture (EA) at "Neiguan" (PC 6) by using Han-200 EA apparatus for 10 min per treatment. Rats in the acupoint combination group were treated with EA at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) by using Han-200 EA apparatus for 10 min per treatment. Rats in the acupoint combination + LY294002 group were treated with LY294002 solution for 14 days, and EA at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) was given before model establishment, once a day for 21 days. EA pretreatment was given before model establishment in all acupuncture groups. The heart rate (HR) and ST segment voltage were detected before and after treatment; the myocardial pathological morphology was observed by HE staining; the expressions of P13K mRNA and Akt mRNA were tested.

RESULTSAfter modeling, HR and ST segment voltage in all intervention groups were higher than those in the normal group (all P < 0.01); after the intervention, the HR and the ST segment voltage in the acupoint combination group, IGF-1 group and IGF-1 group were improved (P < 0.01, P < 0.05), which was more significant in the acupoint combination group and Neiguan group (all P < 0.01). As for the myocardial pathological morphology, obvious myocardial ischemia was observed in the model group, and that in the LY294002 group was the most serious, and that in the acupoint combination+ LY294002 group was moderate. After intervention, the myocardial pathological damage in the IGF-1 group, Neiguan group and acupoint combination group was significant improved, which was more significant in the IGF-1 group and acupoint combination group. As for the expression of PI3K mRNA and Akt mRNA, compared with normal group, the expression of PI3K mRNA was increased in the remaining groups after modeling (P < 0.01, P < 0.05), which was more significant in the IGF-1 group and acupoint combination group (all P < 0. 01). The expression of Akt mRNA in the LY294002 group and acupoint combination + LY294002 group was reduced (P < 0. 01, P < 0.05), while that in the remaining groups was increased (P < 0.01, P < 0.05), which was more significant in the IGF-1 group and acupoint combination group (all P < 0.01).

CONCLUSIONThe principal-subordinate acupoints combination could improve heart rate and ST segment voltage in rats with chronic myocardial ischemia, reduce myocardial pathological damage, which is superior to single selection of "Neiguan" (PC 6). The PI3K/Akt signaling pathway may be involved in the regulation mechanism of principal-subordinate acupoints combination for the protection of chronic myocardial ischemia.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Chronic Disease ; therapy ; Electroacupuncture ; Electrocardiography ; Heart Rate ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Male ; Myocardial Ischemia ; enzymology ; pathology ; physiopathology ; therapy ; Myocardium ; pathology ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Rats ; Rats, Wistar

Objective To systematically evaluate the effect of metformin on the prognosis of patients with breast cancer. Methods The databases including PubMed, Embase, Cochrane Library, ClinicalTrials, ScineceDirect, CBM, CNKI, Wanfang database and VIP were electronically searched from their inception to April 18, 2018 to collect the studies about the effect of metformin on the prognosis of patients with breast cancer. According to the inclusion and exclusion criteria, two reviewers screened the literatures independently, extracted data and assessed methodological quality. The meta-analysis was performed by using Review Manager 5.1 software. Results A total of 2 randomized controlled trials and 17 cohort studies involving 8929 patients were included. The meta-analysis showed that compared with control group, the metformin group marked increase in pathologic complete remission (pCR) rate (RR=2.97, 95％CI 1.80-4.90, P<0.01) and cancer-specific survival (CSS) time was prolong significantly (RR= 0.70, 95％CI 0.57-0.87, P= 0.001). Subgroup analysis of the overall survival (OS) time according to different areas showed that the metformin group's OS time was prolong significantly (Europe and America studies subgroup: RR=0.75, 95％CI 0.65-0.86, P<0.01; Asian studies subgroup:RR=0.48, 95％CI 0.37-0.61, P<0.001). Conclusion The use of metformin is positive for the prognosis of patients with breast cancer, it may improve the pCR rate, CSS and OS time of patients.

w biomarker to predict the presence of vulnerable plaque.

AIM: To explore the expressive role of lipoprotein-associated phospholipase A_2, high sensitive C-reactive protein and matrix metalloproteinase-9 in vulnerable atherosclerotic plaques in a rabbit model. METHODS: Forty eight New Zealand white male rabbits were randomly divided into 4 groups (12 rabbits each): control group, stable plaque group, p53 group, and p53+drug group. Rabbits in control group were fed with a regular diet and underwent sham operation. Rabbits in stable plaque group, p53 group and p53+drug group underwent balloon induced arterial wall injury and then were fed on a diet with 1% cholesterol. The animals were all fed for 3 months, then the rabbits in p53 group and p53+drug group underwent Ad5-CMV p53 transfection at 10th week. Before killed, the animals in p53+drug group underwent pharmacological triggering with Russell's viper venom (RVV) and histamine to induce the rupture of the atherosclerotic plaques. At the 1st day and before sacrifice, the serum was collected for measuring Lp-PLA_2, hs-CRP, MMP-9, HDL, LDL and VLDL. The expressions of Lp-PLA_2, hs-CRP and MMP-9 in tissues were determined by the methods of hybridization and immunohistochemistry. RESULTS: At the end of 12th week, the serum and tissue levels of Lp-PLA_2 and MMP-9 in stable plaque group, p53 group and p53+drug group were significant different from those in control group and in each group at the first day (P<0.05). The serum levels of Lp-PLA_2 and hs-CRP in p53 group and p53+drug group were significantly higher than those in control group and stable group (P<0.05). The serum levels of Lp-PLA_2, hs-CRP and MMP-9 were all significantly different between p53 group and p53+drug group (P<0.05). At the end of 12th week, pathological results showed that 4 groups were normal artery, stable plaque, vulnerable plaque and rupture plaque, respectively. The fabric cap was thicker in plaque groups than that in normal group (P<0.05). The rupture and formation of thrombus were more significant in p53+drug group than those in p53 group. The serum level of Lp-PLA_2 had negative interrelated relationship with fabric cap in plaque groups (r=-0.710, P<0.01), and hs-CRP, MMP-9 had no interrelated relationships with fabric cap in plaque groups. CONCLUSION: Base on the successful establishment of the atherosclerotic plaque animal model, serum Lp-PLA_2 shows better interrelated relationships to plaques stability. Combination with hs-CRP and MMP-9, we can exactly evaluate the nature of plaques.

Objective:To investigate the value of cystatin C (Cys-C) in the early diagnosis of acute kidney injury (AKI) after radical nephrectomy and the predictive value for the prognosis of Cys-C based estimated glomerular filtration rate (eGFR Cys-C) after surgery. Methods:The clinical data of 118 patients who underwent unilateral radical nephrectomy in our hospital from January 2019 to December 2020 were retrospectively analyzed. According to the diagnostic criteria of AKI, they were divided into AKI group of 75 cases and no-AKI group of 43 cases. AKI group was (62.7±10.7) years old, with 49 males and 26 females. The no-AKI group was (62.3±12.8) years old, with 21 males and 22 females. The urea nitrogen was (4.9±1.3) mmol/L, creatinine (75.7±14.5)μmol/L, Cys-C (0.85±0.22) mg/L, eGFR Cr(76.3±11.2)ml/(min·1.73m 2), and eGFR Cys-C(101.4±17.4)ml/(min·1.73m 2)in AKI group before operation.In no-AKI group, preoperative urea nitrogen was (4.9±1.5) mmol/L, creatinine (74.5±13.1)μmol/L, Cys-C (0.81±0.29) mg/L, eGFR Cr(78.6±12.5)ml/(min·1.73m 2), and eGFR Cys-C(99.3±18.8)ml/(min·1.73m 2), and there were no significant differences in the values of urea nitrogen, creatinine, Cys-C and eGFR between the two groups before surgery ( P>0.05). ROC curve was used to analyze the diagnostic value of urea nitrogen, creatinine, Cys-C, eGFR calculated based on creatinine and Cys-C at 48h after surgery, and binary Logistic regression was used to analyze the risk factors for AKI. The creatinine status of patients diagnosed with SPS was evaluated 6 months after surgery, based on the definition of Cys-C based eGFR being less than 70% of creatinine-based eGFR(SPS=eGFR Cys-C/ eGFR Cr≤0.7). Results:In AKI group, creatinine was(115.2±22.1)μumol/L, Cys-C (1.8±0.27) mg/L, eGFR Cr (51.6±9.6)ml/(min·1.73m 2), and eGFR Cys-C(43.4±8.5)ml/(min·1.73m 2)48 h after operation. The creatinine was(92.7±13.3)μmol/L, Cys-C(1.3±0.23) mg/L, eGFR Cr(62.2±11.3)ml/(min·1.73m 2), and eGFR Cys-C(61.5±9.5)ml/(min·1.73m 2) in no-AKI group, and difference were statistically significant between the two groups ( P<0.01). ROC curve was used to analyze the diagnosis of AKI. Creatinine, Cys-C, eGFR Cr and eGFR Cys-Cwere all of diagnostic value for AKI (all P<0.01), and AUC(Area under curve) were 0.809, 0.889, 0.761 and 0.925 respectively. The sensitivity, specificity and area under the curve of eGFR Cys-C were 93.3%, 74.4% and 92.5% respectively. Binary Logistic regression analysis showed that creatinine( OR=10.851, 95% CI 2.322-50.688, P=0.004), Cys-C( OR=10.016, 95% CI 2.306-43.362, P=0.001), eGFR Cr( OR=17.923, 95%CI 3.216-53.172, P=0.001) and eGFR Cys-C( OR=19.817, 95% CI 3.367-55.263, P=0.001)were all independent risk factors for AKI. The predictive accuracy of eGFR Cys-C, creatinine, Cys-C, eGFR Cr were 91.6%, 85.7%, 90.2%, 88.5%, respectively. There were 15 cases were confirmed SPS in the AKI group, and only 2 cases were confirmed SPS in the no-AKI group, indicating patients in the AKI group developed more SPS than those in the no-AKI group, with statistically significant difference(Kappa value was 5.22, P=0.02). The 6-month follow-up showed that the creatinine of confirmed SPS was (103.8±23.4)μmol/L and the creatinine of unconfirmed SPS was (86.8±27.2)μmol/L, with statistically significant difference ( P<0.01). Conclusions:eGFR Cys-C calculated based on Cys-C has high sensitivity in diagnosing AKI and has early diagnostic value. Patients diagnosed with SPS based on eGFR Cys-C had higher creatinine 6 months after surgery.

Objective To evaluate the relationship between the hippocampal neuron-protective mechanism of hydrogen in a rat model of oxygen-glucose deprivation and restoration(OGD/R)and mito-chondrial autophagy.Methods Hippocampal neurons isolated from healthy Sprague-Dawley rats(24 h af-ter birth)were cultured in vitro,seeded in polylysine-coated 6-well plates at a density of 7×105 cells/well and then divided into 5 groups(n＝30 each)using a random number table method: control group(C group),OGD/R group,OGD/R+H2 group,OGD/R plus 3-methyladenine(3-MA)group(OGD/R+3-MA group),and OGD/R plus H2 plus 3-MA group(OGD/R+H2+3-MA group).The cells were cultured for 24 h in normal culture atmosphere(75％N2-20％O2-5％CO2)in group C,and cells were subjected to oxygen-glucose deprivation for 2 h followed by O2-glucose supply for 24 h to establish the model of OGD/R injury in OGD/R,OGD/R+H2,OGD/R+3-MA and OGD/R+H2+3-MA groups.The cells were cultured for 24 h in a hydrogen-rich incubator(60％H2-10％O2-5％CO2-25％N2)after establishing the model in group OGD/R+H2.Autophagy inhibitor 3-MA 10 mmol/L was added,and then cultured for 24 h in normal culture atmosphere after establishing the model in group OGD/R+3-MA.Autophagy inhibitor 3-MA 10 mmol/L was added,and then cultured for 24 h in hydrogen-rich incubator after establishing the model in group OGD/R+H2+3-MA.The cell survival rate was measured using MTT assay.DCFH-DA fluorescent probe was applied for determination of reactive oxygen species(ROS)activity.The mitochondrial membrane potential was measured using a JC-10 assay kit.The neuronal apoptosis was detected by flow cytometry,and apoptosis rate was calculated.The expression of mitophagy-related protein microtubule-associated protein 1 light chain 3(LC3),PINK1 and Parkin was determined by Western blot,and LC3Ⅱ/LC3Ⅰ ratio was calculated.Results Compared with group C,the cell survival rate and MMP were significantly decreased,the apop-tosis rate and ROS activity were increased,and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰrati-o were increased in OGD/R and OGD/R+H2 groups(P＜0.05).Compared with group OGD/R,the cell survival rate and MMP were significantly increased,the apoptosis rate and ROS activity were decreased,and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were increased in group OGD/R+H2(P＜0.05),and the cell survival rate and MMP were significantly decreased,the apoptosis rate and ROS activ-ity were increased,and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were decreased in group OGD/R+3-MA(P＜0.05).Compared with group OGD/R+H2,the cell survival rate and MMP were significantly decreased,the apoptosis rate and ROS activity were increased,and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were decreased in OGD/R+3-MA and OGD/R+H2+3-MA groups(P＜0.05).Conclusion Hippocampal neuron-protective mechanism of hydrogen against OGDR injury is relat-ed to promoting mitochondrial autophagy in rats.

Objective: To evaluate the relationship between the hippocampal neuron-protective mechanism of hydrogen in a rat model of oxygen-glucose deprivation and restoration (OGD/R) and mitochondrial autophagy. Methods: Hippocampal neurons isolated from healthy Sprague-Dawley rats (24 h after birth) were cultured in vitro, seeded in polylysine-coated 6-well plates at a density of 7×10⁵ cells/well and then divided into 5 groups (n=30 each) using a random number table method: control group (C group), OGD/R group, OGD/R+ H₂ group, OGD/R plus 3-methyladenine (3-MA) group (OGD/R+ 3-MA group), and OGD/R plus H₂ plus 3-MA group (OGD/R+ H₂+ 3-MA group). The cells were cultured for 24 h in normal culture atmosphere (75%N₂-20%O₂-5%CO₂) in group C, and cells were subjected to oxygen-glucose deprivation for 2 h followed by O₂-glucose supply for 24 h to establish the model of OGD/R injury in OGD/R, OGD/R+ H₂, OGD/R+ 3-MA and OGD/R+ H₂+ 3-MA groups.The cells were cultured for 24 h in a hydrogen-rich incubator (60% H₂-10% O₂-5% CO₂-25% N₂) after establishing the model in group OGD/R+ H₂.Autophagy inhibitor 3-MA 10 mmol/L was added, and then cultured for 24 h in normal culture atmosphere after establishing the model in group OGD/R+ 3-MA.Autophagy inhibitor 3-MA 10 mmol/L was added, and then cultured for 24 h in hydrogen-rich incubator after establishing the model in group OGD/R+ H₂+ 3-MA.The cell survival rate was measured using MTT assay.DCFH-DA fluorescent probe was applied for determination of reactive oxygen species (ROS) activity.The mitochondrial membrane potential was measured using a JC-10 assay kit.The neuronal apoptosis was detected by flow cytometry, and apoptosis rate was calculated.The expression of mitophagy-related protein microtubule-associated protein 1 light chain 3 (LC3), PINK1 and Parkin was determined by Western blot, and LC3Ⅱ/LC3Ⅰ ratio was calculated. Results: Compared with group C, the cell survival rate and MMP were significantly decreased, the apoptosis rate and ROS activity were increased, and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were increased in OGD/R and OGD/R+ H₂ groups (P<0.05). Compared with group OGD/R, the cell survival rate and MMP were significantly increased, the apoptosis rate and ROS activity were decreased, and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were increased in group OGD/R+ H₂(P<0.05), and the cell survival rate and MMP were significantly decreased, the apoptosis rate and ROS activity were increased, and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were decreased in group OGD/R+ 3-MA (P<0.05). Compared with group OGD/R+ H₂, the cell survival rate and MMP were significantly decreased, the apoptosis rate and ROS activity were increased, and the expression of PINK1 and Parkin and LC3Ⅱ/LC3Ⅰ ratio were decreased in OGD/R+ 3-MA and OGD/R+ H₂+ 3-MA groups (P<0.05). Conclusion Hippocampal neuron-protective mechanism of hydrogen against OGDR injury is related to promoting mitochondrial autophagy in rats.