AIM To investigate the renal protective effects of Shiwei Ruxiang Powder on gouty nephritis in rats based on mitophagy.METHODS Rats were randomly divided into the blank group,the model group,the low-dose,medium-dose,and high-dose Shiwei Ruxiang Powder groups(200,400,800 mg/kg)and allopurinol group(10 mg/kg).The rat model of gouty nephropathy was established by gavage of potassium oxyzinate(750 mg/kg)and uric acid(300 mg/kg).The rats had their levels of UA,SCr,BUN,XOD,SOD,MDA,ROS measured by automatic biochemical analyzer,ELISA and chemical fluorescence method;their renal pathological changes observed by HE staining;their apoptosis of renal tissue cells observed by TUNEL staining;and their mRNA and protein expressions of IL-1β,TNF-α,Bax,Bcl-2,caspase-3,caspase-9,PINK1,Parkin and LC3-Ⅱ detected by RT-qPCR and Western blot.RESULTS Compared with the model group,Shiwei Ruxiang Powder groups displayed dose-dependently decreased serum levels of UA,BUN and SCr,renal deposition of urate crystal and apoptosis(P<0.05);decreased renal levels of ROS and inflammatory factors IL-1β and TNF-α(P<0.05);and increased renal expressions of mitochondrial autophagy-related proteins PINK1,Parkin and LC3-Ⅱ(P<0.01).CONCLUSION Shiwei Ruxiang Powder may relieve gouty kidney injury in rats by reducing the uric acid level,the renal oxidative stress and inflammatory response,and activating mitophagy pathway as well.

Objectives: It is unclear whether G protein-coupled receptor 61 (GPR61) affecting body weight, plays a role in the association between birth weight and weather. This study aimed to assess the effects of prenatal weather and GPR61 on birth weight. Methods: A total of 567 mother-newborn pairs were recruited in Houzhai Center Hospital during 2011-2012. We detected the maternal and neonatal GPR61 promoter methylation levels, and obtained meteorological and air pollution data. Results: A positive association was observed between maternal and neonatal GPR61 methylation levels, and both of them were affected by precipitation, relative humidity (RH) and daily temperature range (DTR). Birth weight was associated negatively with RH and positively with DTR ( P < 0.05). A significant association was observed between birth weight and neonatal GPR61 methylation. We observed that maternal GPR61 methylation seemed to modify associations between weather and birth weight ( P _interaction < 0.10), while neonatal GPR61 methylation mediated the effects of RH and DTR on birth weight ( P < 0.05). Conclusions Our findings revealed the significant associations among prenatal weather, GPR61 methylation and birth weight. Maternal GPR61 methylation may modify the susceptibility of birth weight to prenatal weather conditions, while neonatal GPR61 methylation may be a bridge of the effects of prenatal RH and DTR on birth weight.
Air Pollution/analysis* ; Birth Weight ; Female ; Humans ; Infant, Newborn ; Nerve Tissue Proteins ; Pregnancy ; Receptors, G-Protein-Coupled/metabolism* ; Temperature ; Weather

OBJECTIVE: To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways. METHODS: Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot. RESULTS: Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05). CONCLUSIONS Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.

OBJECTIVE: To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture (MA). METHOD: A three-step study was conducted, the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli (ST 36), including 12 Wistar rats which were divided into control, control+MA1, and control+MA7 groups. In the experiment 2, the paw withdrawal latency (PWL), immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B (NFκB) p65 (p-p65), phospho-NFκB p50 (p-p50) at ST 36 were performed on rats of saline, saline+MA, and complete Freund's adjuvant (CFA)+MA groups (n=6). In experiment 3, 24 rats were divided into saline+DMSO, CFA+DMSO, CFA+DMSO+MA, and CFA+BAY 11-7082+MA groups, the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted. RESULT: (1) The gene: inhibitor of NFκB (Nfkbia), interleukin-1β (Il1b), interleukin-6 (Il6), chemokine c-x-c motif ligand 1 (Cxcl1), monocyte chemoattractant protein-1 (MCP-1/Ccl2) expressions in the control+MA7 group were significantly increased (P<0.05 or P<0.01), and the expression of NFκB p65 (Rela), NFκB p50 (Nfkb1) were increased in the control+MA7 group (P<0.05). (2) CFA+MA groups showed increased PWL from day 1 to 7 (P<0.01 vs. CFA), and the Western blot results were consistent with immunohistochemistry, the expression of NFκB p-p65 and NFκB p-p50 were significantly increased in the MA-related groups compared with control and CFA groups (P<0.05). (3) Compared with the CFA+DMSO+MA group, the PWL of the CFA+ BAY 11-7082+MA group decreased significantly and continued until day 5 and 7 (P<0.05 and P<0.01, respectively), and the NFκB p65 expression of CFA+BAY 11-7082+MA was significantly reduced compared with CFA+DMSO+MA (P<0.01). CONCLUSION Local NFκB signaling cascade in acupoint caused by MA is an important step in initiating the analgesic effect, which would provide new evidence for the initiation of MA-effect and improve the understanding of the scientific basis of acupuncture analgesia.
Acupuncture Analgesia ; Acupuncture Points ; Animals ; Electroacupuncture ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Signal Transduction

OBJECTIVE The present study was aimed to investigate the role of Wnt/β-catenin sig-naling in spinal VGLUT2 regulation and neuropathic pain. METHODS To elucidate the association be-tween VGLUT2 and neuropathic pain,we determined the expression and distribution characteristics of VGLUT2 in mice subjected to spared nerve injury(SNI),and then observed the effects of two VGLUT2 targeting shRNAs on mechanical allodynia and glutamate release.The effects of Wnt/β-catenin signal-ing on VGLUT2 expression and pain behavior were investigated by using Wnt agonist,Wnt1,and Wnt/β-catenin pathway inhibitor XAV939 in SNI mice.RESULTS SNI surgery induced significant up-regula-tion of VGLUT2 on postoperative days 7,14,and 21.Double immunofluorescence labeling of VGLUT2 with NeuN,MAP2,Iba-1,or GFAP showed that VGLUT2 was mainly expressed in neurons in the dor-sal horn of the spinal cord after SNI(NeuN,MAP2).Intrathecal administration of VGLUT2 shRNAs be-fore or after SNI surgery significantly decreased mechanical allodynia and glutamate release. Mean-while,Wnt1/β-catenin signaling increased significantly after SNI surgery.Over-expression of β-catenin in PC12 cells increased VGLUT2 protein level,intrathecal administration of Wnt agonist or Wnt1 signifi-cantly increased VGLUT2 protein expression in spinal cord, while Wnt/β-catenin pathway inhibitor XAV939 decreased VGLUT2 expression in PC12 cells and spinal cord.Additionally,intrathecal admin-istration of XAV939 7 days after SNI significantly attenuated mechanical allodynia in mice, which was in accordance with down-regulation of VGLUT2 protein levels.VGLUT2 shRNAs significantly attenuat-ed Wnt agonist or Wnt1 induced mechanical allodynia. CONCLUSION Wnt1/β-catenin signaling path-way up-regu-lates the spinal VGLUT2 expression,and this regulation is involved in neuropathic pain behavior.

Objective: To observe the short- and long-term clinical outcomes of fraction flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients with SYNTAX score≥33 unsuitable for coronary artery bypass grafting (CABG). Methods: A total of 117 CAD patients admitted in our hospital from 2012-01 to 2015-06 were enrolled. Since SYNTAX score≥33, EuroSCORE>6, the patients were unsuitable for CABG and treated in 2 groups: Medication group, n=20 and PCI group, during FFR-guided PCI procedure, patients received ROTA or IVUS according to physician's experience, n=97. All patients were followed-up for at least 12 months. Meanwhile, taking "coronary stent and bypass", "CABG and PCI" as key words, we searched relevant documents in VIP Chinese science and technology journal full-text database, WanFang medical database, ChinaNet and Chinese biomedical literature database from 2012-01-01 to 2015-12-31, patients' outcomes were compared with the above references to explore the clinical benefit. Results: ① PCI group and Medication group had similar SYNTAX score and EuroSCORE, P>0.05. The common pathogenesis was LAD involvement, chronic occlusion was 31.3% (5/16) in patients with partial revascularization.②PCI group had 18.6% (18/97) incidence of major adverse cardiac and cerebral events (MACCE), 2 patients died during follow-up period and 9 received revascularization; Medication group had 60% (12/20) incidence of MACCE, 3 patients died during follow-up period; the difference between 2 groups showed statistical meaning, P<0.05.③There were 22 relevant documents retrieved as comparison; in our research, PCI group had similar incidence of MACCE to the documents, P>0.05; Medication group had increased incidence of MACCE than the documents, P<0.05. Conclusion: FFR-guided PCI could bring clinical benefit in CAD patients with SYNTAX score≥33 unsuitable for CABG.

OBJECTIVE: To investigate the effects of Radix Angelicae Sinensis (RASI) and hydrocortisone combination on the murine asthma model and the mechanism. METHODS: BALB/c mice were randomly divided into control group, blood stasis model group, asthma model group, HSS group, RASI group and RASI+HSS group (=12). Ovalbumin (OVA) was used to replicate mice asthma model and hydrocortisone sodium succinate (HSS) to copy blood stasis model. Effects of RASI, HSS and their combination on hemorheology, anti-asthma (asthmatic behaviors, lung function, lung index and water content in lung tissue) were observed. and anti-asthma mechanisms The expression of relative cytokines, high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) was detected by ELISA and immunohistochemistry respectively. RESULTS: Eight g/kg RASI, 0.05 g/kg HSS and their combination could significantly relieve asthma behavioral indicators, improve lung function, reduce lung index and water content in lung tissue, decrease the levels of TNF-α, IL-1β and IL-6 in broncho-alveolar lavage fluid (BALF), and inhibit the high expression of HMGB1, TLR4 and NF-κB in lung tissue. The improvement of lung function and the decrease in level of relative cytokines (TNF-α、IL-1βIL-6) were better in RASI+HSS group than those in RASI group and HSS group, and the inhibition of protein expression of TLR4 and NF-κB was also too. Combined administration of RASI and hydrocortisone could decrease serum thromboxane B2 (TXB2) content and blood viscosity, which were increased induced by hydrocortisone. CONCLUSIONS Combined administration of RASI and hydrocortisone have obvious anti-asthma effects and one of the mechanisms is to inhibit protein synthetization of HMGB1, TLR4 and NF-κB.The combined administration of RASI and hydrocortisone has stronger improvement of lung function than that of RASI and hydrocortisone alone, and it may be related to the inhibition of TLR4 and NF-κB synthetization. The combined administration of RASI can alleviate abnormal changes of hemorheology induced by hydrocortisone in treatment of asthma.
Animals ; Anti-Asthmatic Agents ; Asthma ; Bronchoalveolar Lavage Fluid ; Cytokines ; Hydrocortisone ; Lung ; Mice ; Mice, Inbred BALB C ; NF-kappa B

BACKGROUNDThe optimal timing of surgical revascularization for patients presenting with ST-segment elevation myocardial infarction (STEMI) and impaired left ventricular function is not well established. This study aimed to examine the timing of surgical revascularization after STEMI in patients with ischemic heart disease and left ventricular dysfunction (LVD) by comparing early and late results.

METHODSFrom January 2003 to December 2013, there were 2276 patients undergoing isolated coronary artery bypass grafting (CABG) in our institution. Two hundred and sixty-four (223 male, 41 females) patients with a history of STEMI and LVD were divided into early revascularization (ER, <3 weeks), mid-term revascularization (MR, 3 weeks to 3 months), and late revascularization (LR, >3 months) groups according to the time interval from STEMI to CABG. Mortality and complication rates were compared among the groups by Fisher's exact test. Cox regression analyses were performed to examine the effect of the time interval of surgery on long-term survival.

RESULTSNo significant differences in 30-day mortality, long-term survival, freedom from all-cause death, and rehospitalization for heart failure existed among the groups (P > 0.05). More patients in the ER group (12.90%) had low cardiac output syndrome than those in the MR (2.89%) and LR (3.05%) groups (P = 0.035). The mean follow-up times were 46.72 ± 30.65, 48.70 ± 32.74, and 43.75 ± 32.43 months, respectively (P = 0.716). Cox regression analyses showed a severe preoperative condition (odds ratio = 7.13, 95% confidence interval 2.05-24.74, P = 0.002) rather than the time interval of CABG (P > 0.05) after myocardial infarction was a risk factor of long-term survival.

CONCLUSIONSSurgical revascularization for patients with STEMI and LVD can be performed at different times after STEMI with comparable operative mortality and long-term survival. However, ER (<3 weeks) has a higher incidence of postoperative low cardiac output syndrome. A severe preoperative condition rather than the time interval of CABG after STEMI is a risk factor of long-term survival.

Aged ; Coronary Artery Bypass ; methods ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; mortality ; surgery ; Myocardial Ischemia ; mortality ; surgery ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Ventricular Dysfunction, Left ; mortality ; surgery

OBJECTIVETo study the effect of diallyl thiosulfinate (DATS) on the proliferation of side population (SP) cells in multiple myeloma (MM) and its mechanism.

METHODSRPMI-8226 and NCI-H929 cells were cultured, and the level of SP cells was detected by Hoechst33342 staining. The SP cells were cultured and treated with 10 µg/ml DATS, the CCK8 assay was carried out to examine the effect of DATS on the proliferation ability in SP cells, and plate colony-forming test was used to examine the colony-forming ability, the flow cytometry assay was carried out to examine the cell cycle, Western blot assay was used to examine the expression of cyclin D1, cyclin E, CDK2 and CDK4.

RESULTSSP cells were detected in RPMI-8226 and NCI-H929 cells with a proportion of 3.17±0.98 and 2.65±0.61, respectively. DATS treatment could significantly inhibit the SP cells survival in a time-dependent manner, and also could significantly inhibit the colony forming. In addition, DATS treatment could significantly induce the G/S arrest and suppress the expression of cyclin D1, cyclin E, CDK2 and CDK4.

CONCLUSIONDATS can inhibit the proliferation and colony-forming of SP cells in multiple myeloma, and induce the G/S arrest that may be carried out via suppressing the expression of cyclin D1, cyclin E, CDK2 and CDK4.

Obiective Tend to explore the correlation between thyroid function and the severity of coronary artery lesions in chinese coronary heart disease(CHD)patients. Methods A total of 558 patients who underwent coronary angiography at the cardiology department of Peking University First Hospital from January 2013 to June 2015 were enrolled in this retrospective study. All patients were divided into coronary heart disease group and non-coronary heart disease group. Thyroid hormone levels were tested in all patients before angiography,and clinical characteristics,lipid profiles and SYNTAX scores were also obtained. Results Of the 558 patients,409 were diagnosed of CHD(73.3％),and among them,5 patients were hyperthyroid/subclinical hyperthyroid(1.2％),13 patients were hypothyroid/subclinical hypothyroid(3.2％),14 patients had euthyroid sicknesssyndrome(ESS)(3.2％),377 patients were euthyroid(92.2％). Among the 149 non-CHD patients(26.7％),3 patients were subclinical hyperthyroid(2.0％),8 patients were hypothyroid/subclinical hypothyroid(5.4％),2 patients were ESS(1.3％),172 patients were euthyroid(91.3％). The proportion of patients with ESS in the CHD group was significantly higher than that of the non-CHD group (3.4％ vs. 1.3％,P=0.018). Except for the patients with ESS,FT3 level was significantly lower the in CHD group than that in the non-CHD group[(4.52±0.57)pmol/L vs.(4.65±0.63)pmol/L,P=0.015]. There were no significant differences in FT4,T3,T4 levels between the two groups(P>0.05). In the CHD group,there was an association between the SYNTAX score groups and free triiodothyronine(FT3)levels(F=6.260,P=0.002). A significant correlation was also observed between the FT3 level and the number of coronary artery lesions(F=5.691, P=0.004). There was no correlation between the SYNTAX score groups or number of coronary artery lesions and thyroid hormone levels,respectively. There were no correlations between lipid profiles and thyroid function. Patients were further divided into three subgroups according to their serum TSH levels. The prevalence of CHD is significantly higher in the subgroup with elevated TSH(85.7％)than in the subgroup with normal TSH(68.6％, P=0.022). Conclusions FT3 level is weakly associated with the severity of CHD. Higher TSH level may be a risk factor of CHD.