Metformin (MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension. This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus (PVN). Salt-sensitive rats received a high-salt (HS) diet to induce hypertension, or a normal-salt (NS) diet as control. At the same time, they received intracerebroventricular (ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure (MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity, reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in salt-sensitive hypertension via attenuating oxidative stress, inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.
Animals ; Antioxidants ; therapeutic use ; Arterial Pressure ; drug effects ; Hypertension ; chemically induced ; drug therapy ; Infusions, Intraventricular ; Male ; Metformin ; administration & dosage ; pharmacology ; Neurotransmitter Agents ; metabolism ; Oxidative Stress ; drug effects ; Paraventricular Hypothalamic Nucleus ; drug effects ; Rats ; Reactive Oxygen Species ; metabolism ; Sodium Chloride, Dietary ; pharmacology

Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.
Angiotensin I ; antagonists & inhibitors ; metabolism ; Animals ; Antioxidants ; pharmacology ; Blood Pressure ; drug effects ; Hypertension ; chemically induced ; drug therapy ; Male ; Oxidative Stress ; drug effects ; Paraventricular Hypothalamic Nucleus ; drug effects ; Peptide Fragments ; antagonists & inhibitors ; metabolism ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Sodium Chloride, Dietary ; pharmacology

Alterations of mitochondrial structure and function in tumor cells allow cell survival and proliferation under hypoxic and acidic microenvironment. The effect of normal mitochondria on tumor initiation and development remains unknown. In this study, mice were euthanized by rapid cervical dislocation for isolation of hepatic mitochondria, which were injected intravenously to melanoma-bearing mice. This animal experiment had been approved by Southwest University Experiment Animal Ethics Review Committee. The results showed that exogenous mitochondria can significantly inhibit the growth of melanoma. Mitochondria isolated from the liver of young mice had more potent anti-melanoma effect than those isolated from aging mice. The average volume of tumors decreased significantly from 1.35 cm³ to 0.34 cm³, and the average mass of tumors decreased significantly from 0.63 g to 0.22 g. This anti-tumor mechanism might be associated with induction of mitophagy and cell necrosis after the exogenous mitochondria entering the melanoma cells. As mitotherapy can clinically improve somatic cell survival for treatment of pediatric patients with myocardial ischemia, the observed anti-tumor effect of exogenous mitochondria provides a hope for selective tumor treatment.

Objective:To explore the molecular mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma (FLRSM) in the treatment of retinitis pigmentosa (RP) based on network pharmacology and bioinformatics. Method:Possible intake active components and targets of FLRSM were screened out and predicted by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP). Gene targets related to RP were mined through disease gene databases. Protein-protein interaction (PPI) network of component-targets and disease-targets were mapped by functional protein association networks (STRING), and the intersection of the two networks was obtained. The gene ontology and kyoto encyclopedia of genes and genomes(KEGG) pathway of the intersection network were analyzed by the database for annotation, visualization and integrated discovery(DAVID). CytoHubba analysis was used to screen out the key targets. Result:A total of 390 active ingredients related to FLRSM were retrieved from TCMSP. According to pharmacokinetic parameters, 110 active ingredients were screened out, 19 active ingredients were further screened out, and 208 targets related to these constituents were retrieved. Totally 206 genes directly related to RP were obtained from the disease gene databases. And 79 genes were obtained from the intersection of PPI networks of component targets and disease targets. These genes mainly involved in biological processes, such as protein autophosphorylation, transcriptional regulation and cell proliferation, and the molecular functions mainly involved adenosine triphosphate binding, transcription factor activity, core promoter binding, and were enriched in nuclear, transcription factor complex, nucleus, cytoplasm and other regions. It was mainly related to neurotrophin signaling pathway, cell cycle related pathway and Wnt signaling pathway. And 8 key gene targets for FLRSM treatment of RP were identified by further screening. Conclusion:The material basis of pharmacodynamic action of FLRSM involves 19 active ingredients, such as porous sterol and tanshinone Ⅱ_A. The key targets of FLRSM in the treatment of RP include 8 genes, such as E2F transcription factor 1(E2F1) and retinoblastoma gene1(RB1).The main mechanism is related to the regulation of neurotrophin signaling pathways, cell cycle related pathways and other signaling networks.

OBJECTIVETo compare clinical results of Sanders II-IV fractures of calcaneus treated by self-setting calcium phosphate cement and allograft with locking reconstruction bone plate internal fixation.

METHODSFrom March 2012 to December 2015, 48 patients with Sanders II-IV fractures of calcaneus were treated by open reduction and internal fixation through L-shape incision, bone grafting were performed on reserved bone defect of calcaneal fracture. The patients were divided into self-setting calcium phosphate cement and allograft group according to different materials. Twenty-eight patients in self-setting calcium phosphate cement group, including 23 males and 5 females aged from 22 to 52 years old with an average of (34.46±7.33) years old; 8 cases were type II, 11 cases were type III and 7 cases were type IV according to Sanders classification. Twenty patients in allograft group, including 17 males and 3 females aged from 24 to 55 years old with an average of(36.40±7.93) years old; 6 cases were type II, 7 cases were type III and 9 cases were type IV according to Sanders classification. Postoperative wound complications, Böhler angle before and after operation and 12 months, Maryland functional score were evaluated.

RESULTSAll patients obtained bone union, and were followed up from 12 to 42 months with an average of 25 months. There were no statistical significance in Böhler angle and Manyland score before and after operation and 12 months between two groups. Five patients occurred wound complications in allograft group and 2 cases occurred wound complications in self-setting calcium phosphate cement and allograft group.

CONCLUSIONSBoth of open reduction bone grafting and reconstructive plate internal fixation have good effective results for calcaneal fracture. Compared with allograft, self-setting calcium phosphate cement, which has no rejection response and less complications, has equal effects for calcaneal fracture and deserves to be popularized.

Objective:To observe the effect of Zhen'ai needling method in Nei Jing (Classic of Internal Medicine) on quality of life in patients with allergic rhinitis (AR).Methods:A total of 99 patients with AR who met the inclusion criteria were randomized into a conventional needling group (51 cases) and a Zhen'ai needling group (48 cases).The conventional needling group was treated with acupuncture at Zusanli (ST 36),Hegu (LI 4),Juliao (ST 3),Yingxiang (LI 20),Yintang (GV 29),Shangxing (GV 23) and Baihui (GV 20).The Zhen'ai needling group added acupoints of Zhen'ai needling method {Lieque (LU 7),Shanglianquan [Extra,located at 1 cun above Lianquan (CV 23)] and Tianrong (SI 17)} in addition to points in the conventional needling group.The needles were retained for 30 min.The treatment was performed twice a week.All patients were assessed by total nasal symptom score (TNSS),total ocular symptom score (TOSS) and sino-nasal outcome test-20 (SNOT-20) before and after 15 treatments to evaluate the quality of life.The clinical efficacy was evaluated after 15 treatments.Results:During the treatment,8 cases dropped out in the conventional needling group and 7 cases in the Zhen'ai needling group.There were no significant differences in TNSS,TOSS and SNOT-20 scores between the two groups before treatment (all P＞0.05).After treatment,the total effective rate of the Zhen'ai needling group was 92.7％,versus 88.4％ in the conventional needling group.There was no significant difference between the two groups (P＞0.05).After treatment,there were no significant differences between the two groups in TNSS and TOSS scores (both P＞0.05).The SNOT-20 score of the Zhen'ai needling group was lower than that of the conventional needling group,and the difference was statistically significant (P＜0.05).There were statistical differences between the two groups in the scores of cough and nasal reflux (to the throat) of the NOT-20 scale (both P＜0.05).Conclusion:Both Zhen'ai needling method and conventional acupuncture are effective in the treatment of AR.Zhen'ai needling method has a better effect than conventional acupuncture in improving cough and nasal reflux (to the throat) in AR patients.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

OBJECTIVE: To study the promoting-apoptosis effect of HDAC6 on the human leukemia cells and its mechanism. METHODS: The siRNA interference technology was used to inhibit the expression of HDAC6 gene, the RT-PCR and Western blot were used to detect the expression of HDAC6 and related signal pathway proteins respectively, the flow cytometry and Hoechest staining were used to detect the apoptosis and morphology changes of K562 cells. RESULTS: Compared with the periphal blood monocyte and bone marrow stromal cells of healthy volunteers, the expression level of HDAC6 in leukemia cell lines was up-regulated significantly(P<0.05); the flow cytometry and Hoechest staining showed that after interference of HDAC6 gene, the apoptosis of K562 cells increased, moreover the cell morphology was changed; the Western blot detection showed that the interfering HDAC6 increased BAX/BCL-2 ratio and cleaved caspase 3 expression, and activated the MAPK, ATK, ERK signaling pathway. CONCLUSION The interferance of HDAC6 can promote the K562 cell apoptosis, its mechanism may relate with activation of MAPK signaling pathway.
Apoptosis ; Cell Proliferation ; Down-Regulation ; Histone Deacetylase 6 ; Humans ; K562 Cells ; Leukemia ; RNA, Small Interfering

OBJECTIVETo investigate the hemostatic effect of spleen-invigorating, qi-replenishing and blood-containing formula on simvastatin-induced zebrafish hemorrhage model, and to compare with the effect of clearing heat and cooling blood formula.

METHODSZebrafishes from breed A B line were treated with 0.5 µmol/L simvastatin for 24 hours to establish zebrafishes hemorrhage model. Under strict blinded experimental conditions, the above mentioned zebrafishes were then treated with experimental drug of different concentrations at the maximum non-lethal dose. The intervention effect of spleen-invigorating, qi-replenishing and blood-containing formula was comprehensively assessed by examining the main observational parameters, such as bleeding reduction rate and hemostasis rate while referring to additional parameters, such as blood flow, improvement rate of blood flow, velocity of movement, improvement rate of motion, which are characteristics of spleen qi deficiency.

RESULTSWhen the hemostatic effect of experimental drug B1 at the concentrations of 500 and 1 000 µg/ml, zebrafish bleeding rates were 30% and 15%, the hemostatic rate was 60% and 80%, respectively; when the experimental drug B2 at concentration of 500 and 1 000 µg/ml, Zebrafish bleeding rates were 45% and 40%, the hemostatic rate was 40% and 47%, respectively, showing that experimental drug B1 was superior to B2 in terms of decreasing bleeding rate and improving hemostatic effect in zebrafish. In the equal concentration, the experimental drug B1 was superior to B2 in terms of increasing and improving the blood flow of hemorrhagic zebrafish. Promotion and improvement of motion: in equal concentration, experimental drug B1 was superior to B2 in terms of promoting the motion velocity and increasing the improving rate of motion in zebrafish.

CONCLUSIONThe spleen-invigorating, qi-replenishing and blood-containing formula displays a good hemostatic effect on simvastatin-induced hemorrhage of zebrafish. It also boosts the blood flow and motion velocity in hemorrhagic zebrafish, therefore, providing an experimental basis for the treatment of syndrome of spleen failing to control blood by spleen-invigorating, qi-replenishing and blood-containing formula.

BACKGROUNDA large proportion of the patients with papillary thyroid microcarcinoma are young women. Therefore, minimally invasive endoscopic thyroidectomy with central neck dissection (CND) emerged and showed well-accepted results with improved cosmetic outcome, accelerated healing, and comforting the patients. This study aimed to evaluate the safety and effectiveness of robotic total thyroidectomy with CND via bilateral axillo-breast approach (BABA), compared with conventional open procedure in papillary thyroid microcarcinoma.

METHODSOne-hundred patients with papillary thyroid microcarcinoma from March 2014 to January 2015 in Jinan Military General Hospital of People's Liberation Army (PLA) were randomly assigned to robotic group or conventional open approach group (n = 50 in each group). The total operative time, estimated intraoperative blood loss, numbers of lymph node removed, visual analog scale (VAS), postoperative hospital stay time, complications, and numerical scoring system (NSS, used to assess cosmetic effect) were analyzed.

RESULTSThe robotic total thyroidectomy with CND via BABA was successfully performed in robotic group. There were no conversion from the robotic surgeries to open or endoscopic surgery. The subclinical central lymph node metastasis rate was 35%. The mean operative time of the robotic group was longer than that of the conventional open approach group (118.8 ± 16.5 min vs. 90.7 ± 10.3 min, P < 0.05). The study showed significant differences between the two groups in terms of the VASs (2.1 ± 1.0 vs. 3.8 ± 1.2, P < 0.05) and NSS (8.9 ± 0.8 vs. 4.8 ± 1.7, P < 0.05). The differences between the two groups in the estimated intraoperative blood loss, postoperative hospital stay time, numbers of lymph node removed, postoperative thyroglobulin levels, and complications were not statistically significant (all P > 0.05). Neither iatrogenic implantation nor metastasis occurred in punctured porous channel or chest wall in both groups. Postoperative cosmetic results were very satisfactory in the robotic group.

CONCLUSIONSRobotic total thyroidectomy with CND via BABA is safe and effective for Chinese patients with papillary thyroid microcarcinoma who worry about the neck scars.

Adult ; Carcinoma, Papillary ; blood ; surgery ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Neck Dissection ; Operative Time ; Postoperative Period ; Robotic Surgical Procedures ; methods ; Thyroglobulin ; blood ; Thyroid Neoplasms ; blood ; surgery ; Thyroidectomy ; methods