1. Paraventricular Nucleus P2X7 Receptors Aggravate Acute Myocardial Infarction Injury via ROS-Induced Vasopressin-V1b Activation in Rats
Wenjing CHENG ; Kokwin OOI ; Chunmei XIA ; Danian ZHU ; Yinggang SUN ; Qin WU ; Yi FENG
Neuroscience Bulletin 2021;37(5):641-656
The present study was designed to investigate the mechanisms by which P2X7 receptors (P2X7Rs) mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus (PVN) of the hypothalamus of rats with acute myocardial ischemia (AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG (brilliant blue G, a P2X7R antagonist), nelivaptan (a vasopressin V1b receptor antagonist), or diphenyleneiodonium (DPI) [an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species (ROS) and NADPH oxidase 2 (NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes. Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine (AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron-V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.
2.Microglia-Derived NLRP3 Activation Mediates the Pressor Effect of Prorenin in the Rostral Ventrolateral Medulla of Stress-Induced Hypertensive Rats.
Li HU ; Shutian ZHANG ; Kokwin OOI ; Xuehai WU ; Jiaxiang WU ; Jian CAI ; Yinggang SUN ; Jijiang WANG ; Danian ZHU ; Fuxue CHEN ; Chunmei XIA
Neuroscience Bulletin 2020;36(5):475-492
Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.
3.Effect of oral nutritional supplementation on nutritional status and quality of life in patients with gastric cancer after operation(23 cases RCT observations)
Hongyuan CUI ; Xin YANG ; Danian TANG ; Xinping ZHOU ; Runyu DING ; Mingwei ZHU ; Junmin WEI
Chinese Journal of Clinical Nutrition 2017;25(3):183-188
Objective To investigate the effect of oral nutritional supplementation on the nutritional status and quality of life in patients with gastric cancer after operation.Methods In this prospective,single blind,randomized,controlled clinical study,25 postoperative patients with gastric cancer received neoadjuvant chemotherapy in outpatient clinic were enrolled.All patients received dietary guidance.In the intervention group,in addition to standard diet,oral nutritional supplements with 2 090 kJ/d of Intacted Protein Enteral Nutrition Powder were added,which lasted 90 days.The changes of body mass,body mass index(BMI),hemoglobin,prealbumin,albumin,gastrointestinal function score,and life quality score 30,60,and 90 days after discharge were recorded.Patients on standard diets were used as the control group.Results In the intervention group,the body mass increased by(0.66 ±1.47)kg 60 d after discharge and(-0.90±1.82)kg on 90 d after discharge,which were [60 d:(-5.13±1.79)kg,90 d:(-9.56±2.44)kg] in the control group,and the difference was statistically significant(P=0.027,P=0.015).The BMI of intervention group increased by(0.20 ±0.55)kg/m2 on 60 d and(-0.32±0.55)kg/m2 on 90 d after discharge,which were(-2.06±0.67)kg/m2 on 60d and(-3.21± 0.73)kg/m2 on 90 d in the control group(P=0.014,P=0.003).There was no significant difference in terms of serum albumin,prealbumin and other laboratory indicators.Intestinal functional status and quality of life also showed no significant difference between these two groups.ConclusionOral nutrition supplementation can reduce the body mass loss and improve the nutritional status in patients with gastric cancer during chemotherapy after operation.
4.A bioequivalence evaluation of long-chain triacylglycerol/medium-chain triacylglycerol emulsion in beagle dogs
Mingwei ZHU ; Zhuming JIANG ; Jingsheng LIU ; Dakui LI ; Wei LIU ; Danian TANG ; Dan MEI ; Xiaoxiao LI ; Suodi ZHAI ; Fang FANG ; Junmin WEI ; Jinduo CAO
Chinese Journal of Clinical Nutrition 2017;25(6):329-334
Objective Long-chain triacylglycerol (LCT) by three producers,each mixed with the same medium-chain triacylglycerol (MCT),were compared with the brand MCT/LCT in causing focal necrosis of hepatocytes in beagle dogs (a bioequivalence evaluation).Methods 21 beagle dogs (male,0.7-1.5 years old,10-15 kg) were used in this study.According to the sources of the LCT,the animals were divided into Group A (LCT made in China),Group B (LCT made in Japan),Group C (LCT made in Germany),and the control group (the brand 10% MCT/LCT).Central venous port was placed via the lumber vein of the animals under general anesthesia.After 2 weeks of rehabilitation,MCT/LCT was administered through this port for 28 days at 9 g/ (kg · d) [while the routine dose used clinically was 1 g/ (kg · d)].The laboratory indexes and the pathomorphism of the liver and kidney were studied single blindly.Results Laboratory tests,including liver and kidney function,blood coagulation function and lipid metabolism,did not identify differences among emulsions with different sources of LCT.Liver biopsy at day 28 showed no focal necrosis in Group C and the control group;there was minor damage in Group B;and Group A had obvious liver necrosis.and the pathological findings of other organs are similar.No significant difference was observed in biopsies of other organs.Conclusions Emulsions with different sources of LCT varied in their damage to the liver.Generics with LCT of higher quality were equivalent to the brand MCT/LCT in terms of safety.
5.Preparation of 131I-Anti-EGFRv Ⅲ and its imaging distribution in malignant glioma-loading nude mice
Lei AN ; Danian WEI ; Kai HUANG ; Guanhua ZHANG ; Yonghui ZHU ; Tiejian LIU ; Chengyong LIU
Chinese Journal of Neuromedicine 2016;15(9):878-883
Objective To explore the experimental methods and conditions of 131I-labeled anti-epidermal growth factor receptor (EGFR) vⅢ preparation,and to evaluate the targeting distribution of 131I-Anti-EGFRvⅢ in malignant glioma-loading nude mice.Methods The 131I labeling on anti-EGFRvⅢ was performed by Iodogen method.The labeling rate was determined after separation and purification and paper chromatography was used for the determination of radioactive chemical purity.Twenty-eight U87-EGFRvⅢ malignant glioma-loading nude mice with glioma average diameter of 10-15 mm were chosen and randomly divided into group of 131I-Anti-EGFRvⅢ intravenous injection,group of Na131I intravenous injection,group of 131I-Anti-EGFRvⅢ intratumor injection and group of Na131I intratumor injection;7.5 MBq/0.1 mL labeled products with 131I-Anti-EGFRvⅢ or Na131I were injected in the veins or the tumors to observe the changes of the radioactivity distribution of malignant glioma-loading nude mice with SPECT imaging.Results The rate of 131I-labeled anti-EGFRvⅢ was (68.12±6.19)%,and the immediate rate of radiochemieal purity was (95.12±0.59)%,and (87.78 ±5.35)% in room temperature and (85.12±3.58)% in 37 ℃ serum placed for 24 h.SPECT scan showed that the tumor site had significantly stronger imaging than the thyroid gland with the labeled products either by intravenous or intratumor injection.Conclusions It is applicable to the 131I-labeled Anti-EGFRvⅢ with Iodogen method.131I-Anti-EGFRvⅢ has good radiation chemical purity and stability in vitro and in vivo,and could be combined with tumor tissue specificity.
6.Liver transplantation in an adult patient with situs inversus
Jiangchun QIAO ; Danian TANG ; Yannan LIU ; Mingwei ZHU ; Xiuwen HE ; Hongyuan CUI ; Junmin WEI
Chinese Journal of Hepatobiliary Surgery 2012;18(5):334-336
ObjectiveTo study the feasibility and technique in liver transplantation (LT) in an adult with situs inversus (SI) and reviewed the medical literature on this subject.MethodsA 45-year-old male with complete SI,suffered from progressive hepatic failure secondary to hepatolithiasis,obstructive jaundice,portal hypertension and liver cirrhosis.He underwent liver transplantation in July 2004.His anatomy was studied by preoperative CT scan and three-dimensional liver reconstruction imaging and angiography.LT was performed using the modified piggyback technique.The donor right liver was rotated 45 degree to the left,making the donor left liver pointing to the left paracolic sulcus and the donor right liver was in the recipient hepatic fossa.The donor suprahepatic vena cava was anastomosed end-to-side to the recipient vena cava,and the infrahepatic vena cava was closed by oversewing.ResultThe patient recovered uneventfully.His liver function was stable during a follow-up of 75 months.ConclusionLT in patients with SI is safe and feasible.Exact determination of the anatomy,comprehensive preoperative planning,and good technique in liver transplantation play important roles in LT for patients with SI.
7.Prevalence of nutritional risk and malnutrition among hospitalized elderly abdominal surgical patients with malignant tumors
Guodong YE ; Mingwei ZHU ; Hongyuan CUI ; Danian TANG ; Qi AN ; Jifang MEN ; Junmin WEI
Chinese Journal of Clinical Nutrition 2011;19(6):364-367
ObjectiveTo investigate the prevalence of nutritional risk and malnutrition among hospitalized elderly abdominal surgical patients with malignant tumors.MethodsTotally 269 elderly patents ( ≥ 65 years) with malignant tumor who were hospitalized in our department of abdominal surgery from December 2009 to November 2010 were consecutively enrolled.Nutritional Risk Screening 2002 ( NRS 2002 ) was performed on the next morning after admission.Body mass index (BMI) lower than 18.5 kg/m2 was considered as malnutrition.Results The NRS 2002 was completed in all the 269 enrolled patients.The overall prevalence of malnutrition was 30.1% (81/269) ; more specifically,37.5% (21/56) among geriatric patients ( ≥80 years) and 17.6% (43/245) among the other age groups (P =0.001 ).The overall rate of nutrition risk was 38.3% (103/269) ; more specifically,57.1% (32/56) among the geriatric patients and 29.3% (72/245) among the other age groups (P <0.001 ).The rate of nutrition risk in patients with pancreas cancer was 58.3%,which was higher than other elderly patients; on the contrary,and the rate of nutrition risk in the patients with colorectal cancer was relatively lower.ConclusionThe rates of nutrition risk and malnutrition in hospitalized elderly abdominal surgical patients ( ≥ 65years) with malignant tumor are relatively higher than other age groups,especially among the geriatric patients.
8.Clinical outcome of the combined nutritional support for colorectal cancer patients at nutritional risk: a retrospective study of 60 cases
Danian TANG ; Mingwei ZHU ; Jianhua SUN ; Qi AN ; Hongyuan CUI ; Jifang MEN ; Junmin WEI
Chinese Journal of Clinical Nutrition 2011;19(6):355-359
ObjectiveTo explore the clinical outcome of the combined nutrition support for colorectal cancer patients.MethodsTwo research arms were obtained using a cohort sampling method.Ann A ( the study group): from 2009 to 2010,30 colorectal cancer patients were enrolled.They received nutritional risk screening (NRS) 2002 after admission.Nutritional risk was defined as NRS 2002 score ≥3 three days before operation.Patients with nutritional risk received enteral nutrition (EN) for bowel preparation without laxative drug and enema.After operation,they received EN combined with parenteral nutrition (PN) supports provided.Arm B (control group): 30 cases with historically confirmed colorectal cancer were enrolled from 2007 to 2008.They received routine bowel preparation (diet control,laxative drug,and enema) and PN supports after operation.Nutritional parameters,the rate of infectious complications,the rate of systemic inflammatory response syndrome,and the duration of hospital stay were analyzed.ResultsThere were no significant difference in body weight and plasma albumin between these two arms ( P > 0.05 ). The incidence of systemic inflammatory response syndrome (13.3 % ),infectious complications (10.0% ),and the duration of hospital stay [ (12.3 ± 6.5 ) d ] in arm A were significantly lowerthan those in arm B [33%,30%,and (15.0 ±7.2) d,respectively] (P =0.038,P =0.042,P =0.045).Conclusion For the colorectal cancer patients,nutritional risk screening on admission,bowel preparation with eneral nutrition before operation,and combined nutritional support after operation can improve the clinical outcome.
9.Prevalence of nutritional risk and malnutrition and nutrition support in elderly hospitalized patients
Danian TANG ; Junmin WEI ; Mingwei ZHU ; Zhe LI ; Qi AN ; Jianhua SUN
Chinese Journal of Geriatrics 2011;30(11):974-976
ObjectiveTo investigate the prevalence of nutritional risk and malnutrition,and nutritional support in elderly hospitalized patients.Methods2386 elderly hospitalized patents (aged ≥65 years) in Beijing Hospital from April 2007 to June 2009 were consecutively enrolled.Nutritional Risk Screening 2002 (NRS 2002) was performed on the next morning after admission.Body mass index (BMI)lower than 18.5 kg/m2 or serum albumin lower than 35 g/L was diagnosed as malnutrition.Results Among 2517 enrolled patients,NRS 2002 was completed by 94.8%,including 466 cases in Department of Respiratory,580 cases in Department of General surgery,549 cases in Department of Neurology,180 cases in Department of Nephrology,301 cases in Department of Gastroenterology and 310 cases in Department of Thoracic Surgery in Beijing Hospital.The prevalence of nutrition risk was 28.2% (673/2 386),and the ratioes of nutrition risk in Department of Respiratory,General Surgery,Neurology,Nephrology,Gastroenterology and Thoracic Surgery were 27.5%,30.3%,28.5%,29.4%,25.9% and 25.4%,respectively.The prevalence of malnutrition was 26.4%,and the ratios of malnutrition in Department of Respiratory,General surgery,Neurology,Nephrology,Gastroenterology and Thoracic Surgery were 26.2%,29.8%,26.9 %,28.3%,22.3% and 22.9%,respectively.Among 48.1% of patients with nutrition risk who received nutritional support,the proportions of nutritional support in Department of Respiratory,General Surgery,Neurology,Nephrology,Gastroenterology and Thoracic Surgery were 30.1%,85.2%,26.1%,18.2% 73.8% and 64.9%,respectively.Among 15.1% of patients without nutrition risk (NRS<3) who received nutritional support,the proportions of nutritional support in Department of Respiratory,General Surgery,Neurology,Nephrology,Gastroenterology and Thoracic Surgery were 10.6%,25.2%,6.3%,3.8 %,34.2% and 17.4 %,respectively.The ratio of parenteral nutrition (PN) over enteral nutrition(EN) was more than 4:1.ConclusionsA large proportion of elderly hospitalized patients are at nutrition risk and malnutrition.And nutritional support is somehow inappropriately applied.Evidence-based guideline of PN or EN is needed to improve this situation.
10.Effect of a carbohydrate-electrolyte solution on glycometabolism and inflammatory response in elderly patients after abdominal operation: a double-blind randomized controlled trial
Donghui XIE ; Mingwei ZHU ; Hongyuan CUI ; Qi AN ; Puxian TANG ; Guodong YE ; Danian TANG ; Xinping ZHOU ; Junmin WEI
Chinese Journal of Geriatrics 2011;30(1):20-23
Objective To evaluate the effects of a carbohydrate-electrolyte solution on serum glucose, pancreas islet function and inflammatory response in elderly patients after abdominal operation.Methods It was a prospective, randomized, double-blinded and controlled trial. Totally 40 elderly patients after abdominal operation who met the defined criteria were enrolled. The subjects in study group were administered with 1000 ml carbohydrate-electrolyte solution intravenously in consecutive three days since 1st or 2nd postoperative day. Control group was administered with 1000 ml of 10% glucose on the same method. The changes of serum glucose, insulin, C-peptide and inflammatory response cytokine (IL-6, TNF-α, CRP) were detected before and after injection.Systemic inflammatory response syndrome (SIRS) was observed.Results All the 40 patients completed the study according to the study protocol. The incremental rate of serum glucose was significantly lower in study group than in control group on the 2nd and 3rd day after administration [(4.40±2.58) mmol/L vs. (14.97±3.44) mmol/L, t=2.984, P=0.008; (2.70± 1.55) mmol/L vs. (8.11± 2.60) mmol/L, t= 5.659, P= 0.000]. The changes of insulin and C-peptide of two group were similar before and after operation. The levels of IL-6 and TNF-α were significantly lower in study group than in control group on the 3rd day after administration[IL-6: (21.76±10.40) ng/Lvs. (50.17±35.24) ng/L, t=-2.447, P=0.034; TNF-α:(23.92±14.89) ng/L vs. (51.48±42.81) ng/L, t=-2.268, P=0.043]. In study group, 6 cases experienced SIRS and 4 cases had infective complications, but in control group the numbers were 8 and 6 respectively.Conclusions Appropriate application of carbohydrate-electrolyte solution intravenously has relatively mild effects on serum glucose and inflammatory response cytokine in elderly patients after abdominal operation, it decreases incidence of SIRS and maybe decrease infective complications.

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