The present study was to investigate the role of TRPC6 in pulmonary artery smooth muscle cells (PASMCs) proliferation and apoptosis under hypoxia and hypercapnia. PASMCs were isolated from chloral hydrate-anesthetized male Sprague-Dawley (SD) rats. Cellular purity was assessed by immunofluorescence staining for smooth muscle α-actin under fluorescence microscopy. Passage 4-6 PASMCs were starved for 24 h in serum-free DMEM and divided into 5 groups randomly: normoxia, hypoxia and hypercapnia, DMSO, TRPC6 inhibitor SKF-96365 and TRPC6 activator OAG groups. The normoxic group was incubated under normoxia (5% CO, 21% O, 37 °C) for 24 h, and the others were incubated with corresponding drugs under hypoxic and hypercapnic (6% CO, 5% O, 37 °C) atmosphere for 24 h. TRPC6 mRNA was detected by reverse transcription-PCR. TRPC6 protein was detected by Western blotting. The proliferation of PASMCs was performed by CCK-8 kit. Apoptosis of the PASMCs was detected using TUNEL assay. The [Ca]in the PASMCs was measured using Fura 2-AM fluorescence. The results showed that the expressions of TRPC6 mRNA and protein, and [Ca]were upregulated under hypoxic and hypercapnic conditions. Hypoxia and hypercapnia promoted cellular proliferation and inhibited apoptosis in the PASMCs. OAG enhanced the above-mentioned effects of hypoxia and hypercapnia, whereas SKF-96365 reversed these effects. These results suggest that TRPC6 may play a role in PASMCs proliferation and apoptosis under hypoxia and hypercapnia by regulating [Ca].
Actins ; Animals ; Apoptosis ; Calcium ; metabolism ; Cell Hypoxia ; Cell Proliferation ; Cells, Cultured ; Hypercapnia ; physiopathology ; Imidazoles ; Male ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; metabolism ; Pulmonary Artery ; cytology ; Rats ; Rats, Sprague-Dawley ; TRPC Cation Channels ; metabolism

Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development.
Animals ; Antibodies, Viral/blood ; Antigens, Viral/genetics/*immunology ; Body Weight ; Cross Protection/*immunology ; Disease Models, Animal ; Epitopes, T-Lymphocyte/genetics/immunology ; Female ; Influenza A Virus, H3N2 Subtype/genetics/*immunology ; Influenza Vaccines/*immunology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections/*immunology/mortality/pathology/prevention & control ; Peptides/genetics/*immunology ; Random Allocation ; Survival Analysis ; Vaccines, Synthetic/immunology ; Virus Replication

According to different toxicities of various aqueous extracts of Polygonum multiflorum on hepatocyte, the impacts of chemical composition on the safety of P. multiforum was studied. In this study, 8 main chemical compositions in aqueous extracts of P. multiflorum were determined by the established HPLC method; at the same time, the inhibition ratios of different aqueous extracts of P. multiflorum on L02 cell were determined. Afterwards, the potential compounds related to the toxicity of P. multiforum were tentatively found through a multiple correlation analysis. The results showed that P. multiforum with different chemical compositions exhibited great differences in dissolution. The hepatocyte toxicity of P. multiflorum powder was much greater than P. multiflorum lumps. In addition, three constituents closely related to toxicity of P. multiflorum were found by multiple correlation analysis. The study revealed that chemical composition of P. multiflorum is closely related to the hepatotoxicity, and the hepatotoxicity of P. multiflorum powder is greater than that of other dosage forms. This study indicates that P. multiflorum with different chemical compositions show varying toxicity, which therefore shall be given high attention.

Salvia miltiorrhiza is one of the most common traditional Chinese medicines. It has rich resources in China. According to modern studies, phenolic acids are the main effective components in S. miltiorrhiza. These components have cardiovascular and cerebrovascular protective effect, and anti-tumor, antioxidant, anti-inflammatory, and antifibrotic activities, etc. It has been widely used for the treatment of cardiovascular and cerebrovascular diseases and others. In this paper, the chemicals and pharmacological effects of phenolic acids from S. miltiorrhiza were summarized in the last decade. Its researches and development prospects were also analyzed for further studying and comprehensive utilization of these phenolic acids.

OBJECTIVETo investigate the protective effects of high-dose ulinastatin on the vital organs in patients undergoing total arch replacement for type A aortic dissection.

METHODSBetween September 2014 and March 2016, 66 patients with type A aortic dissection underwent total arch replacement at our center. Thirty-six of the patients received ulinastatin treatment at 300 000 U/8 h from admission to 3 days postoperatively and at 300 000 U/2 h during cardiopulmonary bypass surgery (UTI group), and the other 30 patients did not receive perioperative ulinastatin treatment (control group). The surgical data and blood biochemistry profiles on days 1, 3, and 5 postoperatively were compared between the two groups, and the postoperative ICU stay, re-operation for bleeding, ventilation for over 7 days, ultrafiltration for postoperative renal failure, tracheotomy, incidences of pulmonary and neurological complications and hospital death were also compared.

RESULTSs The operating time, cardiopulmonary bypass time, ACP time, cardiac arrest time, the lowest rectal temperature and frequency of bilateral and unilateral antegrade selective cerebral perfusion were similar between the two groups (P>0.05). Compared with those in the control group, patients in UTI group had lower lactate, S-100 and neuron specific enolase levels on the first postoperative day and higher OI on the 1st, 3rd, and 5th postoperative days (P<0.05), but serum creatinine, blood urea nitrogen, total bilirubin, and alanine aminotransferase levels were comparable between the two groups (P>0.05). No significant differences were found in the frequency of re-operation for bleeding, ultrafiltration for renal failure, tracheotomy, neurological complications or hospital death after the operation between the two groups, but the patients in UTI group had a shorter ICU time, a less frequent long-term ventilation and a lower incidence of pulmonary infection (P<0.05).

CONCLUSIONHigh-dose ulinastatin offers protection on pulmonary function and lowers the specific brain injury markers in patients with type A aortic dissection after total arch replacement, but its protective effects on brain is uncertain.

Aneurysm, Dissecting ; surgery ; Aorta, Thoracic ; surgery ; Aortic Aneurysm, Thoracic ; surgery ; Body Temperature ; Brain ; drug effects ; Cardiopulmonary Bypass ; Cerebrovascular Circulation ; Glycoproteins ; therapeutic use ; Humans ; Incidence ; Lactic Acid ; blood ; Lung ; drug effects ; Perfusion ; Phosphopyruvate Hydratase ; blood ; Postoperative Period ; Protective Agents ; therapeutic use ; S100 Proteins ; blood ; Time Factors

BACKGROUNDThe efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.

METHODSIt is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.

RESULTSThe effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.

CONCLUSIONSTelmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.

TRIAL REGISTRATIONchictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.

Adolescent ; Adult ; Benzimidazoles ; adverse effects ; therapeutic use ; Benzoates ; adverse effects ; therapeutic use ; Blood Pressure ; drug effects ; China ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; drug effects ; Glomerulonephritis, IGA ; blood ; drug therapy ; Humans ; Isoxazoles ; adverse effects ; therapeutic use ; Kidney Function Tests ; Male ; Middle Aged ; Prospective Studies ; Ticlopidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Uric Acid ; blood ; Young Adult

OBJECTIVETo establish the diagnostic quantitative criteria for fire-heat syndrome (FHS) of Chinese medicine (CM) based on the receiver operating characteristic (ROC) curve and principal component analysis (PCA).

METHODSThe symptoms and signs of FHS cases and healthy subjects from Guangzhou, Henan and Hunan of China were collected through questionnaire, and the diagnostic quantitative score tables were established for the three regions, respectively, with the method of maximum likelihood analysis. The homogeneity test was then performed on the diagnostic score tables for the three regions with ROC curve, and the diagnostic efficiency of diagnostic score tables for the three regions was compared with the prospective test and retrospective test. The method of PCA was adopted to obtain the analysis matrix for classifying the tapes of FHS.

RESULTSTwenty-seven elements of FHS were confirmed through Chi-square test, and the diagnostic score tables for the three regions were established with the method of maximum likelihood analysis on the basis of the collected case data. According to the ROC curve test, the areas under ROC curve of Guangzhou diagnostic score table assessment with candidates in Guangzhou, Henan and Hunan were 0.998, 0.961 and 0.956, respectively. It showed that the diagnostic efficiency of Guangzhou diagnostic score tables was the highest one. With the prospective test, the area under ROC of Guangzhou diagnostic score table was 0.949, and more than any other diagnostic score table. By PCA, FHS was classified into excess fire and deficiency fire, and then classified into syndrome of flaring up of Heart (Xin) fire, syndrome of Lung (Fei)-Stomach (Wei) excess fire, syndrome of deficiency of Liver (Gan)-yin and Kidney (Shen)-yin, and syndrome of deficiency of Lung-yin from the view of viscera. In the retrospective test, the consistency with clinicians' diagnosis was 69.4%, and in the prospective test, it was 70.1%.

CONCLUSIONSThe Guangzhou diagnostic score table could be used as the recommended criteria for the diagnosis of FHS. The classification of FHS was basically in conformity with the clinical situation.

Adult ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Principal Component Analysis ; Prospective Studies ; ROC Curve ; Retrospective Studies ; Syndrome

OBJECTIVETo study the relationship between the levels of erythropoietin (EPO) in serum and brain injury in preterm infants.

METHODSThree hundred and four preterm infants (gestational age: 28-34 weeks) born between October 2014 and September 2015 were enrolled in this study. Brain injury was diagnosed using cerebral ultrasound and MRI. The levels of EPO, S100 protein, neuron-specific enolase (NSE) and myelin basic protein (MBP) in serum were detected using ELISA. To compare the incidence of brain injury in different serum EPO levels in preterm infants, and the relationship between brain injury and serum EPO levels was analyzed.

RESULTSThe incidence rate of brain injury in preterm infants was 41.1% (125/304). The incidence rate of brain injury in the low EPO level group was significantly higher than that in the middle-high EPO level groups (P<0.01). The serum levels of S100 protein, NSE, and MBP in the brain injury groups were significantly higher than in the control group (P<0.01). The serum EPO levels were negatively correlated with serum S100 protein concentration and NSE levels (P<0.05). According to the multiple logistic regression analysis, low gestational age, low birth weight, asphyxia, prolonged mechanical ventilation, anemia and low serum EPO levels were the risk factor for brain injury in preterm infants.

CONCLUSIONSThere is a higher incidence rate of brain injury in preterm infants with lower serum EPO levels. The serum EPO levels may be correlated with brain injury in preterm infants.

Brain Injuries ; blood ; epidemiology ; Erythropoietin ; blood ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; blood ; Male ; Myelin Basic Protein ; blood

OBJECTIVETo study the rehabilitation effects ergometry on COPD patients.

METHODSThirty COPD out-patients in our Hospital were randomly divided into 2 groups. Rehabilitation group, 15 patients, performed leg ergometry exercise of 80% peak Watt x 30min/d x 3d/w x 12w. Another 15 patients were control group without exercise. All patients received conventional therapy. Pulmonary function testing (PFT), cardiopulmonary exercise testing (CPET), arterial blood gas analysis (ABG), Borg and CAT sores were done at both baseline and 12 w.

RESULTSThere was no statistically difference in lung function testing, blood gas analysis and cardiopulmonary exercise test when pre- exercises between 2 sub-groups. The IC, peak VO2 and peak, W of rehabilitation group significantly increased (P < 0.05); and Borg and CAT.scores significantly decreased (P < 0.05) from baseline; and other PFT and ABG did not change (P > 0.05). While there was no difference in control group (P > 0.05).

CONCLUSIONLeg submaximal ergometry rehabilitation improves health condition and ameliorate dyspnea symptoms in COPD patients.

Blood Gas Analysis ; Dyspnea ; therapy ; Exercise Test ; Exercise Therapy ; Humans ; Pulmonary Disease, Chronic Obstructive ; therapy ; Respiratory Function Tests

OBJECTIVETo improve the diagnosis and treatment of testicular teratoma in children by analysis of clinical data.

METHODSWe retrospectively analyzed the clinical data about 64 cases of testicular teratoma treated in the Children's Hospital of Chongqing Medical University from 1995 to 2014.

RESULTSSixty-one of the cases presented painless scrotal mass with a sense of bearing down and the other 3 cases were confirmed because of empty scrotum diagnosed as cryptorchidism. The level of serum alpha fetal protein ( AFP) was obviously increased in 46 cases but normal in the other 18 preoperatively. Ultrasonography manifested abnormal inhomogeneous echo zones with calcification or necrosis. X-ray examination presented patchy or curvilinear high-density shadows in 28 cases. Forty-one of the patients underwent testis-sparing surgery (TSS) , 20 received high inguinal orchiectomy, and 3 refused surgical treatment. Pathological examination revealed 3 mature germinal layers in the 49 cases of mature teratoma and immature germinal tissue, including the original neural tube, and 11 cases of immature teratoma. The mature cases were exempted from chemotherapy, while the immature cases received the combination of cisplatin, etoposide, and bleomycin (PEB). The patients were followed up for 2 years postoperatively, which revealed no recurrence or metastasis.

CONCLUSIONMost children with testicular teratoma presented painless scrotal mass with a sense of bearing down and with abnormal serum AFP in most cases. Ultrasonography and plain radiography of the scrotum contribute to the diagnosis of the tumor. TSS is the main treatment option and intraoperative frozen-section can help the surgeons decide on the surgical mode. Postoperative chemotherapy is necessitated for immature teratoma but not for mature cases.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; administration & dosage ; Child ; Cisplatin ; administration & dosage ; Cryptorchidism ; diagnosis ; Etoposide ; administration & dosage ; Gonadal Dysgenesis, 46,XY ; diagnosis ; Humans ; Male ; Orchiectomy ; methods ; Retrospective Studies ; Scrotum ; Teratoma ; blood ; diagnosis ; pathology ; therapy ; Testicular Neoplasms ; blood ; diagnosis ; pathology ; therapy ; Testis ; abnormalities ; alpha-Fetoproteins ; analysis