Treatment of Sepsis with Chinese Medicine： A Review Based on NF-κB Signaling Pathway / 中国实验方剂学杂志

Sepsis， a common critical disease in the intensive care unit（ICU）， features high morbidity and mortality. At present， it is mainly tackled with western medicine， which may trigger a series of problems like antibiotic resistance， adverse hormonal reactions， and high cost after a long-term use. Therefore， exploring new efficient， safe， and cheap drugs and treatment modes has become the focus of our research at this stage. By virtue of unique advantages including "the concept of holism and individualized treatment based on syndrome differentiation"， Chinese medicine has accumulated quite rich experience in the prevention and treatment of sepsis. In recent years， research on the regulation of Chinese medicine on nuclear transcription factor-κB（NF-κB） signaling pathway in sepsis has kept emerging. On this basis， this paper reviewed the etiology and pathogenesis of sepsis， syndrome differentiation and treatment， NF-κB signaling pathway， and its intervention with Chinese medicine. It has been found that some single Chinese herbs and their extracts， Chinese herbal compounds， and Chinese herbal injections effectively inhibit the expression of such inflammatory factors as NF-κB-mediated tumor necrosis factor-α（TNF-α）， interleukin-1（IL-1）， and IL-6 as well as the related proteins， reduce the systemic inflammatory response and organ injury， and improve the prognosis by regulating the activation of NF-κB signaling pathway and the immune function of macrophages. However， due to the limitations of objective conditions， some studies also have the problems of fuzzy pro-inflammatory anti-inflammatory balance mechanism， unclear pharmacokinetics and low drug safety evaluation， which need to be further studied and explored in order to provide a new theoretical basis and diagnosis and treatment thinking for the treatment of sepsis with traditional Chinese medicine.

Research status and evolution of health management in China from 2011 to 2020 / 中华健康管理学杂志

Objective:To analyze research status and development trends in the field of health management in China from 2011 to 2020.Methods:“CNKI” was chosen as the data source, and “health management（precise）” was used as the search term, and a total of 13, 686 valid data were finally obtained. Frequency counts were used to tabulate the number of articles published in the field of health management from 2011 to 2020. CiteSpace software was used to analyze the cooperation of institutions, and to explore the research hotspots and development trends in the field of health management by institutions co-occurrence, keyword co-occurrence and clustering timeline map. Bicomb software and SPSS 26.0 software were used for multi-dimensional scale analysis of keywords to comprehensively reflect the core degree and maturity of research topics.Results:The amount of domestic health management research literature had shown an increasing trend from 2011 (804) to 2020 (2 044). The top 5 keywords in terms of frequency were “hypertension（611）” “diabetes（577）” “health education（485）” “community（460）” and “chronic diseases（457）”. “Elderly” “Traditional Chinese Medicine（TCM health management）” and “Health management model” were the hot keywords and research trends of health management. There were 7 themes in the field of health management, namely “Construction and application of chronic diseases health management model” “Community health service and health management” “Health management in essential public health service” “Health management of the elderly” “Health management of Traditional Chinese Medicine” “Health examination and health management organization” “Health management based on big data and modern information technology”.Conclusions:A relatively close network of cooperation has been formed in the field of health management research and the number of articles has increased. The elderly, chronic disease and Traditional Chinese Medicine health management are the research trend. The construction and implementation of health management models, the integration of artificial intelligence and health management are the development trends in this field.

Expression and Clinical Significance of Serum Long Chain Non-encoded RNA ANRIL in Chronic Heart Failure Patients / 中国循环杂志

Objective: To explore the expression and clinical significance of serum long chain non-encoded RNAANRIL (LncRNA ANRIL) in chronic heart failure (CHF) patients. Methods: Our research included in 2 groups: CHF group, n=120 patients treated in our hospital and Control group, n=28 healthy subjects at the same period of time. Based on NYHA classification, CHF patients were further divided into 4 subgroups: NYHAⅠ subgroup, n=28, NYHA Ⅱ subgroup, n=34, NYHA Ⅲ subgroup, n=35 and NYHA Ⅳ subgroup, n=23. Expressions of serum ANRIL and cystatin C were examined by real time fluorescence quantitative PCR (QRT-PCR) and compared between 2 groups; the relationship between ANRIL, cystatin C and cardiac function were studied. Results: Compared with Control group, CHF group had increased serum levels of ANRIL and cystatin C, P<0.05. ANRIL expression was gradually increasing by cardiac function decreasing in CHF I to CHF Ⅳ subgroups, P<0.05. Correlation analysis found that serum level of ANRIL was positively related to cystatin C (r=0.873, P<0.001). ANRIL was elevated by increased left ventricular end diastolic diameter and decreased ejection fraction, both P<0.05. Conclusion: Serum ANRIL level has been related to CHF at certain degree which may indirectly reflect the severity of HF in relevant patients.

Study on the association between catechol-O-methyltransferase gene polymorphisms and type 2 diabetes mellitus / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the association between the two single nucleotide polymorphisms located in catechol-O-methyltransferase (COMT) gene and type 2 diabetes mellitus (T2DM)in Han population in Guangdong province.</p><p><b>METHODS</b>Two tagSNPs (rs4646312 and rs4680) were picked out from COMT gene. Using the SNPscan(TM) Kit, SNP genotyping was then performed, in two cohorts, including 595 cases and 725 controls. Finally, Chi-square test, logistic regression model and other methods were employed for statistical analysis.</p><p><b>RESULTS</b>The frequencies of TT, CT and CC of rs4646312 appeared to be 304(51.1%), 234(39.3%)and 57 (8.6%) in cases, 323 (44.6%), 319 (44.0%) and 83(11.4%)in controls, respectively. The frequencies of GG,GA and AA of rs4680 were 311(52.4%), 236 (39.8%) and 46(7.8%)in cases, 417(57.7%), 265 (36.6%) and 41 (5.7%) in controls, respectively.</p><p><b>RESULTS</b>showed that SNP rs4646312 was significantly associated with T2DM both in allelic association analysis (P = 0.020,OR = 1.26, 95%CI:1.04-1.53)and in recessive model (P = 0.022, OR = 1.35, 95% CI:1.05-1.74)after adjustment for sex,BMI and TG. The association between rs4680 and T2DM was not significant, but BMI was remarkably different among the three genotypes of rs4680 after controlling for other factors.</p><p><b>CONCLUSION</b>SNP rs4646312 of COMT gene was associated with the increased risk of T2DM in Han population in Guangdong province. However, rs4680 was not significantly associated with T2DM.</p>

Variation of lipid profile in patients with acute myocardial infarction of different age groups / 中华全科医师杂志

Objective To investigate the variation of lipid profile in patients with acute myocardial infarction (AMI) of different age groups.Methods Total 1214 patients of AMI were admitted to our hospital from May 2007 to July 2011.The age of patients ranged 40-89 years,and patients were divided into 5 age groups with 10-years step.Differences in lipid levels were observed by using pair-wise comparison among different age groups.Results Pair-wise comparisons among different age groups indicated that TC levels were higher in 40-69 years age groups [(4.71 ± 1.08),(4.80 ± 1.30),(4.69 ± 1.03) mmol/L,respectively] than those in the 70-89 age groups [(4.41 ± 0.96),(4.38 ± 1.03) mmol/L],all P ＜ 0.05(t values were 2.381,2.323,4.382,3.965,3.317,3.096).TG levels among three age groups ＜ 59 years had no significant difference,which were higher than those in groups over 60 years.Among 50-89 years age groups,TG gradually reduced with increase of age.HDL levels were lower in 40-59 years age groups [(1.03 ± 0.23),(1.05 ± 0.26) mmol/L,respectively] than those in 60-89 years age groups [(1.11 ±0.28),(1.11±0.28),(1.16±0.34) mmol/L,respectively],allP＜0.05 (t values were-2.777,-2.789,-3.731,-2.543,-2.566,-3.644).Total cholesterol (TC) (r =-0.123,P ＜0.01),lowdensity lipoprotein cholesterol (LDL) (r =-0.139,P ＜ 0.01) and triglyceride (TG) (r =-0.287,P ＜0.01) were negatively but high-density lipoprotein cholesterol (HDL) (r =0.125,P ＜ 0.01) was positively correlated with age of patients.TC levels in female patients were higher than those in male patients in 50-89 years age groups; LDL levels in female patients were higher than those in male patients in 50-69 years age groups and HDL levels in female patients were higher than those in male patients in 40-79 years age groups (all P ＜ 0.05,t values were-2.878,-3.007,-3.352,-3.333).Conclusions Results show that the non-elderly AMI patients (＜60 years) have higher levels of TC,LDL and TG,and lower level of HDL than the elderly patients; the TC,LDL and HDL levels are higher in female AMI patients than those in male patients at the same age groups.

Effects of curcumin on syndecan-4 protein and p44/42 mitogen-activated protein kinase expression in tumor necrosis factor-α-induced rat vascular smooth muscle cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of curcumin on the expression of syndecan-4 protein and p44/42 mitogen- activated protein kinase(MAPK) phosphorylation in rat vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-α (TNF-α) in vitro.</p><p><b>METHODS</b>Rat VSMCs cultured in vitro were stimulated for 24 h by 20 ng/ml TNF-α, 20 µmol/L curcumin, or 20 ng/ml TNF-α plus 20 µmol/lL curcumin. /assay was adopted to evaluate the proliferation of the VSMCs, and the expression of syndecan-4 protein and phosphorylated p44/42 MAPK were determined by Western blotting.</p><p><b>RESULTS</b>Compared with the normal control cells, VSMCs exposed to TNF-α showed significantly enhanced proliferation (P/0.01). Curcumin treatment did not obviously affect the growth of otherwise untreated VSMCs(P>0.05), but could significantly suppress TNF-α-induced proliferation of VSMCs (P/0.01). TNF-α treatment also significantly increased the expression of syndecan-4 protein and phosphorylated p44/42 MAPK (P<0.01), which was markedly lowered by treatment with curcumin (P/0.01). Curcumin alone did not produce any obvious effects on the expression of syndecan-4 protein or phosphorylated p44/42 MAPK (P>0.05).</p><p><b>CONCLUSION</b>Curcumin can suppress the proliferation of rat VSMCs and lower the expression of syndecan-4 protein and phosphorylated p44/42 MAPK in TNF-α-induced VSMCs.</p>

High inferior vena cava thrombosis in a 16-year-old postpartum patient: A case report / 华中科技大学学报（医学）（英德文版）

Postpartum inferior vena cava (IVC) thrombosis is a rare, but potentially life-threatening disorder. Here we reported one case of the youngest woman to date who presented with massive IVC thrombus extending from deep veins of the right leg to the level of the 11th thoracic vertebra, associated with asymptomatic pulmonary embolism.

Multiple hemodynamic effects of endogenous hydrogen sulfide on central nervous system in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endogenous hydrogen sulfide is a new neuromodulator which takes part in the regulation of central nervous system physiology and diseases. Whether endogenous hydrogen sulfide in the central nervous system regulates cardiovascular activity is not known. In the present study, we observed the hemodynamic changes of hydrogen sulfide or its precursor by intracerebroventricular injection, and investigate the possible roles of endogenous digitalis like factors and sympathetic activity in the regulation.</p><p><b>METHODS</b>Ninety-four Sprague-Dawley rats underwent a right cerebroventricular puncture, then the hydrogen sulfide saturation buffer or its precursor injected by intrcerebroventricular catheter. A heperin-filled catheter was inserted into the right femoral artery or into the left ventricle, and changes of blood pressure or cardiac function recorded by a Powerlab/4S instrument. Phentolamine or metoprolol were pre-injected to observe the possible role in autonomic nerve activity. After rats were sacrificed, plasma was collected and endogenous digitalis-like factors were measured with a commercial radioimmunoassay kit. The aortic, cardiac sarcolemmal vesicles were isolated and the activity of Na(+)-K(+)-ATPase was measured as ouabain-sensitive ATP hydrolysis under maximal velocity conditions by measuring the release of inorganic phosphate from ATP. Unpaired Student's t test for two groups or analysis of variances (ANOVA) for multiple groups were used to compare the differences of the changes.</p><p><b>RESULTS</b>Intracerebroventricular injection of hydrogen sulfide induced a transient hypotension, then dramatic hypertenive effects in a dose-dependent manner. Bolus injection of L-cysteine or beta- mercaptopyruvate also increased mean arterial pressure (P < 0.01), whereas hydroxylamine-a cystathionine beta synthase inhibitor decreased the arterial pressure (P < 0.01). Hydrogen sulfide and L-cysteine increased mean arterial pressure, left ventricular develop pressure and left-ventricle maximal rate of systolic and diastolic pressure; these functions were decreased by hydroxylamine (P < 0.01). Glibenclamide (a K(ATP) channel blocker) blocked the transient hypotensive effect, phentolamine (an alpha-adrenergic receptor blocker) blocked the hypertensive effect, and metoprolol (a selective beta 1 receptor blocker) blocked the positive inoptropic effect of central nervous system hydrogen sulfide. The endogenous digitalis-like factors in plasma were elevated (P < 0.01) after treatment with L-cysteine, association with decreasing Na(+)-K(+)-ATPase activity in cardiac or aortic sarcolemmal vesicles (P < 0.01). Hydroxylamine injection reduced the endogenous digitalis-like factors level in plasma association with increasing Na(+)-K(+)-ATPase activity in cardiac and aortic sarcolemmal vesicles.</p><p><b>CONCLUSION</b>Central nervous system endogenous hydrogen sulfide upregulated mean arterial pressure and cardiac systolic function by activation of sympathetic nerves or release of endogenous digitalis-like factors.</p>

Pravastatin inhibits the expression of syndecan-4 protein in tumor necrosis factor-alpha-induced rat vascular smooth muscle cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of pravastatin on the proliferation of rat vascular smooth muscle cells (VSMCs) and expression of syndecan-4 protein induced by tumor necrosis factor-alpha (TNF-alpha).</p><p><b>METHODS</b>VSMCs cultured in vitro were exposed to 20 ng/ml TNF-alpha, 10 micromol/ml pravastatin, 20 micromol/ml pravastatin, 10 micromol/ml pravastatin with 20 ng/ml TNF-alpha, or 20 micromol/ml pravastatin with 20 ng/ml TNF-alpha for 24 h. The proliferation of the VSMCs was determined by non-radioactive MTS/PMS assay and the expression of syndecan-4 protein was detected by Western blotting using anti-syndecan-4 antibody.</p><p><b>RESULTS</b>Compared to the control group, TNF-alpha at 20 ng/ml significantly stimulated the proliferation of rat VSMCs (P<0.05). Pravastatin alone produced no obvious effect on VSMCs growth (P>0.05), but significantly inhibited TNF-alpha-induced VSMC proliferation (P<0.05). The expression of syndecan-4 protein in the VSMCs was significantly enhanced by 20 ng/ml TNF-alpha (P<0.01). Pravastatin alone did not affect the expression of syndecan-4 protein (P>0.05), but significantly inhibited TNF-alpha-induced enhancement of syndecan-4 protein expression (P<0.01).</p><p><b>CONCLUSION</b>Pravastatin can inhibit the proliferation and syndean-4 protein expression in rat VSMCs induced by TNF-alpha in vitro.</p>

Tumor necrosis factor-alpha regulates the proliferation and syndecan-4 expression of human umbilical vein endothelial-like cells cultured in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of tumor necrosis factor-alpha(TNF-alpha) on syndecan-4 protein expression and proliferation of cultured human umbilical vein endothelial-like cells (HUVECs) in vitro.</p><p><b>METHODS</b>HUVECs exposed to different concentrations of TNF-alpha(100, 20, 10, and 1 ng/ml) were cultured for 24 h and 36 h to observe their proliferation in comparison with the control group. The cell proliferation rate was determined by non-radioactive MTS/PES assay. The expression of syndecan-4 protein was evaluated by immunoblotting technique using anti-syndecan-4 antibody. Results The proliferation rate of the endothelial-like cells was 1.956-/+0.214 in the control group, and 2.154-/+0.250, 2.260-/+0.151, 2.118-/+0.205 and 2.106-/+0.136 in TNF-alpha-treated groups corresponding to TNF-alpha concentrations of 100, 20, 10 and 1 ng/ml at 24 h, respectively. It was shown that TNF-alpha significantly stimulated cell proliferation at the concentration above 1 ng/ml (P<0.05) as compared with the control group (P<0.05). The proliferation rate of the endothelial-like cell was 1.915-/+0.236 in the control group, and 2.067-/+0.328, 2.207-/+0.150, 2.052-/+0.126 and 2.051-/+0.180 in TNF-alpha-treated groups corresponding to TNF-alphaconcentrations of 100, 20, 10 and 1 ng/ml at 36 h, respectively. The expression of syndecan-4 protein was significantly enhanced by TNF-alpha.</p><p><b>CONCLUSIONS</b>TNF-alpha can stimulate HUVEC proliferation, and expression of syndean-4 may represent an additional component of the pro-inflammatory, growth-stimulating pathways that are activated in response to changes in the vascular wall.</p>

Protective effect of tert-butylhydroquinone on bone marrow cells in rats from cytotoxicity induced by benzene in vitro / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of tert-butylhydroquinone on bone marrow cells in rats from cytotoxicity induced by benzene in vitro.</p><p><b>METHODS</b>The bone marrow cells in rats were divided into two groups randomizedly. Cells of the control group were stimulated by 0, 5, 10, 15, 20 mmol/L benzene for 2, 4, 6 hours respectively. Cells of the tBHQ-pretreated group were treated by 100 micromol/L tBHQ for 12 hours followed by the same conditions as the control group. The DNA damage was detected by single cell gel electrophoresis assay (SCGE) and cell apoptosis was examined by flow cytometry. The activities of NAD (P) H: quinone oxidoreductase (NQO1) in bone marrow cells of rats were also measured before benzene treatment in two groups.</p><p><b>RESULTS</b>In control group, the DNA damage and the apoptosis of bone marrow cells was increased with the growing concentration and time of benzene treatment. The DNA migration and the lengths of DNA migration of the bone marrow cells in the rats under 5, 10, 15, 20 mmol/L benzene treatment in the tBHQ-pretreated group were significantly lower than those in control group at the same time point (P < 0.05). The apoptosis of the bone marrow cells in the rats stimulated by 15, 20 mmol/L benzene for 2 hours and 10, 15, 20 mmol/L benzene for 4 hours as well as 5, 10, 15, 20 mmol/L benzene for 6 hours were also significantly lower than those in control group (P < 0.05). The activities of NQO1 in the bone marrow cells in the rats were increased after tBHQ treatment (P < 0.01) (1.62 +/- 0.16 min(-1).mg(-1) vs. the control group: 0.95 +/- 0.08 min(-1).mg(-1)).</p><p><b>CONCLUSION</b>The benzene can induce the DNA damage and the apoptosis of bone marrow cells in rats in a time dependent and dose dependent manner to some extent. The tBHQ can protect the bone marrow cells in rats from the cytotoxicity induced by benzene, which can be partly explained by the increase of the NQO1 activity induced by tBHQ.</p>

Variation analysis of the severe acute respiratory syndrome coronavirus putative non-structural protein 2 gene and construction of three-dimensional model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The rapid transmission and high mortality rate made severe acute respiratory syndrome (SARS) a global threat for which no efficacious therapy is available now. Without sufficient knowledge about the SARS coronavirus (SARS-CoV), it is impossible to define the candidate for the anti-SARS targets. The putative non-structural protein 2 (nsp2) (3CL(pro), following the nomenclature by Gao et al, also known as nsp5 in Snidjer et al) of SARS-CoV plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development, so we carried on this study to have an insight into putative polymerase nsp2 of SARS-CoV Guangdong (GD) strain.</p><p><b>METHODS</b>The SARS-CoV strain was isolated from a SARS patient in Guangdong, China, and cultured in Vero E6 cells. The nsp2 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into eukaryotic expression vector pCI-neo (pCI-neo/nsp2). Then the recombinant eukaryotic expression vector pCI-neo/nsp2 was transfected into COS-7 cells using lipofectin reagent to express the nsp2 protein. The expressive protein of SARS-CoV nsp2 was analyzed by 7% sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The nucleotide sequence and protein sequence of GD nsp2 were compared with that of other SARS-CoV strains by nucleotide-nucleotide basic local alignment search tool (BLASTN) and protein-protein basic local alignment search tool (BLASTP) to investigate its variance trend during the transmission. The secondary structure of GD strain and that of other strains were predicted by Garnier-Osguthorpe-Robson (GOR) Secondary Structure Prediction. Three-dimensional-PSSM Protein Fold Recognition (Threading) Server was employed to construct the three-dimensional model of the nsp2 protein.</p><p><b>RESULTS</b>The putative polymerase nsp2 gene of GD strain was amplified by RT-PCR. The eukaryotic expression vector (pCI-neo/nsp2) was constructed and expressed the protein in COS-7 cells successfully. The result of sequencing and sequence comparison with other SARS-CoV strains showed that nsp2 gene was relatively conservative during the transmission and total five base sites mutated in about 100 strains investigated, three of which in the early and middle phases caused synonymous mutation, and another two base sites variation in the late phase resulted in the amino acid substitutions and secondary structure changes. The three-dimensional structure of the nsp2 protein was successfully constructed.</p><p><b>CONCLUSIONS</b>The results suggest that polymerase nsp2 is relatively stable during the phase of epidemic. The amino acid and secondary structure change may be important for viral infection. The fact that majority of single nucleotide variations (SNVs) are predicted to cause synonymous, as well as the result of low mutation rate of nsp2 gene in the epidemic variations, indicates that the nsp2 is conservative and could be a target for anti-SARS drugs. The three-dimensional structure result indicates that the nsp2 protein of GD strain is high homologous with 3CL(pro) of SARS-CoV urbani strain, 3CL(pro) of transmissible gastroenteritis virus and 3CL(pro) of human coronavirus 229E strain, which further suggests that nsp2 protein of GD strain possesses the activity of 3CL(pro).</p>

Changes of myocardial fibrotic indices and its mechanism in patients with ischemic cardiomyopathy / 中南大学学报(医学版)

OBJECTIVE@#To investigate the myocardial fibrotic indices in patients with ischemic cardiomyopathy (ICM), and explore the mechanism of myocardial fibrosis.@*METHODS@#The concentration of serum procollagen type III aminoterminal peptide (P III P), procollagen type IV aminoterminal peptide (P IV P), lamnin (LN), and hyaluronic acid (HA), as well as plasma angiotension II (AngII), aldosterone (ALD), and transforming growth factor beta 1 (TGFbeta1) in 46 ICM patients and 37 normal controls were measured by radioimmunoassay (RIA). The correlations between the plasma levels of AngII, ADL, TGFbeta1, and serum levels of P III P, P IV P, LN, and HA were analyzed.@*RESULTS@#Compared with normal controls, the concentrations of serum P III P, P IV P, LN, HA, and plasma AngII, ADL, and TGfbeta1, significantly increased in ICM patients. AngII, ALD, and TGFbeta1 levels were positively correlated with the indices of myocardial fibrosis.@*CONCLUSION@#The myocardial fibrosis exists in ICM patients and the serum concentrations of P III P, P IV P, LN, and HA may be an indirect index of myocardial fibrosis. AngII, ADL, and TGFbeta1 levels play important roles in myocardial fibrosis.

Changes of VASP in shear stress induced cytoskeleton reorganization in endothelial cells / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of different level of laminar shear stresses on the vasodilator-stimulated phosphoprotein (VASP) location and expression changes associated with actin reorganization and it's mechanism.</p><p><b>METHODS</b>A parallel-plate flow chamber device was used to create laminar shear stress in vitro on cultured human umbilical endothelial cells (HUVECs). The distribution of VASP and microfilament were observed by double immunofluorescence staining. RT-PCR was used to test VASP mRNA level, while VASP parameters were analyzed quantitatively with Western blot.</p><p><b>RESULTS</b>After exposure to a flow of 10 dyn/cm2 flow for 24 h, HUVECs were elongated and oriented gradually to the direction of the flow. The microfilaments were recruited and oriented to the direction of flow with thicker VASP, specially targeted to the ends of stress fibres. RT-PCR result indicated shear could induce VASP mRNA increase. Western blotting data showed a dynamic reversible phosphorylation of VASP during 24 h, and total VASP expression increased rapidly, peaked at 2 h, then recovered at 8h followed by a slow increase again. H89, a cAMP inhibitor could inhibit shear induced VASP expression increase and phosphorylation.</p><p><b>CONCLUSION</b>VASP is an potential important component which participates in the regulation of cell cytoskeleton reorganization and morphology modification induced by shear flow via a cAMP/cAK pathway.</p>

Effect of thyroid hormone on protein kinase C signal pathway in cardiac myocytes and fibroblasts of rats in vitro / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of thyroid hormone on protein kinase C activity and isoprotein expressions in cardiac myocytes and fibroblasts of rats in vitro.</p><p><b>METHODS</b>Cardiac myocytes and fibroblasts were cultured according to the method of Simpson. Cells were pretreated with 1% newborn calf serum (NCS) or Angiotensin II (Ang II) for 24 hours, then Triiodothyronine (T3) was added to the culture medium and the culture was kept for another 48 hours. The protein kinase C activation were measured by PepTaga non-radioactive PKC assay, and the expressions of PKC alpha and PKC epsilon were detected by Western blot method.</p><p><b>RESULTS</b>At the condition of 1% NCS culture medium, T3 could inhibit PKC activity and PKC epsilon expression in cardiac myocytes significantly, but the expression of PKC alpha in cardiac myocytes was not influenced by T3. In cardiac fibroblasts, neither PKC activity nor PKC alpha and PKC epsilon expressions was influenced by T3. When cells were pretreated with Ang II for 24 hours, PKC activities in cardiac myocytes and fibroblasts were increased significantly, and PKC epsilon expressions in cardiac myocytes were also markedly increased. Following a T3 treatment, PKC activity and PKC epsilon expression in cardiac myocytes were markedly decreased, but PKC activity in cardiac fibroblasts was not changed.</p><p><b>CONCLUSION</b>Whether at the condition of 1% NCS medium or in a pretreatment with Ang II, thyroid hormone could inhibit the PKC activity and PKC epsilon expression in cardiac myocytes. The influence of thyroid hormone on the PKC signal pathway in cardiac myocyte may be involved in many pathophysiological progress of myocardium.</p>

Mechanism of improving effect of losartan on insulin sensitivity of non-insulin-dependent diabetes mellitus rats / 生理学报

The specific inhibition of angiotensin II action at AT(1) receptors by losartan has been shown to decrease peripheral insulin resistance in type 2 diabetic patients and animal models. We examined the effect of losartan on the expression of insulin receptor substrate 1 (IRS-1), protein kinase B (PKB) and glucose transporter 4 (GLUT4), as well as the phosphorylation status of IRS-1 and the association between IRS-1 and phosphatidylinositol (PI) 3-kinase in skeletal muscle from fat-fed and-streptozotocin (STZ)-treated rats, an animal model of type 2 diabetes mellitus. In addition, the effects of losartan on GLUT4 translocation in muscle cells and on insulin sensitivity were also evaluated. Muscle tissues were isolated from male losartan-treated and untreated normal or non-insulin-dependent diabetes mellitus (NIDDM) rats with a dose of 4 mg/kg per day for 6 weeks. Oral administration of losartan improved insulin sensitivity, which was determined by an oral glucose tolerance test (OGTT). In skeletal muscles, the protein levels of IRS-1, PKB and GLUT4 in NIDDM rats were not significantly different from those of the control rats, and they were not affected by losartan. The levels of IRS-1 tyrosine phosphorylation, PI 3-kinase activity associated with IRS-1 and PKB activation after stimulation with insulin in muscle tissue of NIDDM rats were significantly decreased (P<0.01) compared with those in the control rats, while they were not increased by losartan. Losartan had a major effect on GLUT4 translocation in myocytes, as it significantly increased (P<0.05) the insulin-induced amounts of GLUT4 in plasma membrane (PM) and T-tubules (TT) in myocytes from NIDDM rats. Consistent with these results, the plasma glucose level in losartan-treated NIDDM rats was decreased (P<0.05) compared with that in untreated NIDDM rats. Our results suggest that losartan may exert beneficial effects on insulin resistance by increasing the translocation of GLUT4 in muscle tissue, which is probably associated with a non-PI 3-kinase-dependent mechanism.

Fermentative production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) by recombinant Aeromonas hydrophila 4AK4 (pTG01) / 生物工程学报

Copolyesters consisting of 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HHx) (PHBHHx), a new type of biodegradable material, are receiving considerable attentions recently. The material properties are strongly related to the 3HHx fraction of PHBHHx. As the 3HHx fraction increase, crystallinity and melting point of PHBHHx decrease, flexibility and tractility increase. PHBHHx of different 3HHx fraction can meet different demands of commercial application and research. Aeromonas are the best studied PHBHHx-producing strains. Recent studies have been focused on optimizations of fermentative culture media and culture conditions for low-cost and efficient fermentative production. Aliphatic substrates such as long-chain fatty acid and soybean oil were used in the PHBHHx fermentation as the sole carbon source and energy source. Two-stage fermentation method was also developed for more efficient PHBHHx production. While studies on Aeromonas hydrophila revealed that the monomer composition of PHBHHx could not easily be regulated by fermentative process engineering methods such as changing substrates and fermentative conditions because precursors involved in the PHBHHx synthesis were all from the beta-oxidation pathway. In this study, phbA gene encoding beta-ketothiolase and phbB gene encoding acetoacetyl-CoA reductase were introduced into a PHBHHx-producing strain Aeromonas hydrophila 4AK4 so as to provide a new 3HB precursors synthesis way. phbA gene encodes beta-ketothiolase which can catalyze two acetyl-CoA to form acetoacetyl-CoA; phbB gene encodes acetoacetyl-CoA reductase catalyzing acetoacetly-CoA into 3HB-CoA which is the precursor of 3HB. The introduced novel 3-hydroxybutyrate precursor synthesis pathway allowed the recombinant strain to use unrelated carbon source such as gluconate to provide 3HB precursors for PHBHHx synthesis. Shake-flask experiments were carried out to produce PHBHHx of controllable monomer composition and fermentations in 5 L fermentor were also proceeded for confirmation of these result in large-scale culture. In flask culture, it was possible to reduce the 3HHx mol fraction in PHBHHx from 15 % in the wild type to 3% - 12% in the recombinant by simply changing the ratio of gluconate to lauric acid in the culture media. When lauric acid was used as the sole carbon source, 51.5 g/L Cell Dry Weight (CDW) containing 62 % PHBHHx with 9.7 % 3HHx mol fraction was obtained in 56 hours of fermentation in a 5 liter fermentor. When co-substrates of sodium gluconate and lauric acid (1:1) were used as carbon sources, 32.8 g/L CDW containing 52 % PHBHHx with 6.7% 3HHx mol fraction was obtained in 48 hours of fermentation. These results showed the possibility for fermentative production of PHBHHx with controllable monomer composition.

Recombinant human interleukin-10 inhibits proliferation of vascular smooth muscle cells stimulated by advanced glycation end products and neointima hyperplasia after carotid injury in the rat / 生理学报

The purposes of this study was to determine the effects of recombinant human interleukin-10 (rhIL-10) on proliferation of vascular smooth muscle cells (VSMCs) stimulated by advanced glycation end products (AGE) and neointima hyperplasia after rat carotid arterial injury. Rat aortic VSMCs were cultured and treated with rhIL-10 or AGE respectively, and then co-treated with rhIL-10 and AGE. Proliferation of VSMCs was quantified by colormetric assay. Cell cycle analysis was performed by flow cytomertry. Sprague-Dawley rats were treated with recombinant human IL-10 (rhIL-10) for 3 d after carotid arteries injury. The ratio of neointima to media area at the site of arterial injury was measured 28 d after balloon injury. The p44/42 MAPK activity was evaluated by the immunoblotting technique using anti-p44/42 phospho-MAPK antibody. Compared to control, AGE stimulated VSMCs proliferation. rhIL-10 alone had no effect on VSMCs growth. With AGE stimulation, rhIL-10, at dose as low as 10 ng/ml, inhibited VSMCs growth (P<0.05). The cell number in G(0)/G(1) phase of AGE and rhIL-10 co-treatment group was higher than that of AGE treatment alone (P<0.01) by flow cytometry analysis. Compared with the control group of neointima hyperplasia in rats, the ratio of neointima to media area of recombinant human IL-10 group was reduced by 45% (P<0.01). The p44/42 MAPK activity was significantly enhanced by AGE. The AGE effects were opposed by rhIL-10. The anti-inflammatory cytokine rhIL-10 inhibits AGE-induced VSMCs proliferation. Recombinant human IL-10 also inhibited neointima hyperplasia after carotid artery injury in rats. The results suggest the possibility that recombinant human IL-10, as a potential therapeutic approach, prevents neointimal hyperplasia.

The neurophysiological features of shoulder-hand syndrome after stroke / 中华物理医学与康复杂志

Objective T_O analyze the electrophysiological features of shoulder-hand syndrome(SHS)fol- lowing stroke and investigate the relationships between peripheral nerve damage and the factors causing SHS.Meth- ods Fifty-eight stroke patients were divided into an SHS group(39 patients with shoulder-hand syndrome)and a model group(19 patients without shoulder-hand syndrome).Standard sensory and motor nerve conduction studies were performed with 58 of the patients,including sensory nerve conduction velocity(SCV),amplitude of the sensory nerve action potential(SNAP),distal motor latency(DMI)and the amplitude of the compound muscle action poten- tial(CMAP)of the median nerve.A needle electromyogram(EMG)test was performed on the abductor pollicis of the affected side with both groups.Results The needle EMG showed abnormal insertion potential,fibrillation po- tential and positive sharp waves in all 39 cases of the SHS group,which was significantly higher than in the model group.The amplitude of the sensory nerve action potential(7.77?4.34 mV)and the amplitude of the compound muscle action potential(10.13?3.15 mV)were significantly lower than those of the model group.Abnormal ampli- tude was more severe in sensory nerves than in motor nerves.Conclusion Peripheral nerve damage was found in the shoulder-hand syndrome patients,and this damage was mainly the dystrophy of axonal neuropathy.The damage severity was more in sensory nerves than in motor nerves.The study could offer an useful clue of prevention and treat- ment of shoulder-hand syndrome.

Recombinant human interleukin-10 inhibits vascular smooth muscle cell proliferation induced by TNF-alpha / 生理学报

Vessel injury provokes a release in proinflammatory cytokines that influence vascular smooth muscle cell (VSMC) proliferation. The purposes of this study was to determine the effects of recombinant human interleukin-10 (rhIL-10) on rat vascular smooth muscle cell proliferation and the activity of p44/p42 mitogen-activated protein kinase (MAPK) promoted by tumor necrosis factor-alpha (TNF-alpha). Rat aortic VSMCs were cultured and treated with rhIL-10 or TNF-alpha respectively, and then cotreated with rhIL-10 and TNF-alpha. The proliferation of VSMCs was quantified by colormetric assay. Cell cycle analysis was performed by flow cytometry. The p44/42 MAPK activity was evaluated by the immunoblotting technique using anti-p44/42 phospho-MAPK antibody. Compared to control group, TNF-alpha stimulated significantly VSMC proliferation in TNF-alpha group. rhIL-10 alone had no effect on VSMC growth, but significantly inhibited VSMC proliferation induced by TNF-alpha at a dose of 10 ng/ml. The cell number in G(0)/G(1) phase of TNF-alpha and rhIL-10 co-treatment group was higher than that of TNF- alpha group (P<0.01) by flow cytometry analysis. The p44/42 MAPK activity was significantly enhanced by TNF-alpha and the TNF-alpha effect was opposed by rhIL-10. It is suggested that rhIL-10 can inhibit TNF-alpha induced VSMC proliferation and phosphorylation of p44/42 MAPK.