Quercetin Attenuates Atherosclerosis via Modulating Apelin Signaling Pathway Based on Plasma Metabolomics / 中国结合医学杂志

OBJECTIVE@#To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS).@*METHODS@#Fourteen apolipoprotein E-deficient (ApoE-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot.@*RESULTS@#Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05).@*CONCLUSION@#Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.

The status and trend of child growth failure (CGF) burden in children aged < 5 years in China / 公共卫生与预防医学

Objective To analyze the status and trend for the mortality and DALY rates of child growth failure (CGF) in children aged < 5 years in China from 1990 to 2019, so as to provide a scientific basis for CGF prevention and control. Methods The mortality and DALY rates of CGF in children aged < 5 years from 1990 to 2019 were obtained from GBD 2019. The changes of these indicators with the years in China , the United States, Japan, Russia, India and the global were compared and analyzed. Results In 2019, the mortality of child wasting, child stunting and child underweight in children aged < 5 years in China were 9.62/100 000, 1.23/100 000, and 1.29/100 000 respectively, the mortality rates were 867.50/100 000 , 129.23/100 000 , and 112.87/100 000 rescpectively, higher than those of the United States, Japan, and Russia, and far lower than those of India and the global. The disease burden of three types of CGF were all higher in males than females, and higher in children aged < 1 years than children aged 1-4 years. From 1990 to 2019, the mortality and DALY rates of CGF in children aged < 5 years in China decreased from 300.41/100 000 and 26 445.38/100 000 to 10.49/100 000 and 943.57/100 000, respectively. China had the largest drop rate compared with all analyzed countries. As for children aged < 5 years in China, the DALY rate of lower respiratory infection ranked first in all the diseases caused by CGF. Conclusion From 1990 to 2019, the disease burden of CGF in children aged < 5 years has shown a significant decrease in China , but it is still far behind the developed countries. In the future, more attention should be paid to the problems of child growth in hope of reducing the mortality and DALY rates of CGF.

Kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during hot-air drying / 中国中药杂志

The present study explored the kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during the hot-air drying process to obtain the optimal process parameters under multiple goals such as drying efficiency and drying quality. The dry basis moisture content and drying rate curves along with the change of drying time of Atractylodis Macrocephalae Rhizoma were investigated at five levels of drying air temperatures(30, 40, 50, 60, and 70 ℃). The relationship between moisture ratio and time in the drying process of Atractylodis Macrocephalae Rhizoma was fitted and verified by Midilli model, Page model, Overhults model, Modified Page model, Logaritmic model, Two terms Exponential model, and Newton model. Meanwhile, the effective diffusion coefficient of moisture(D_(eff)) and activation energy(E_a) in Atractylodis Macrocephalae Rhizoma were calculated under different drying air temperatures. GC-MS was used to determine the volatile components and content changes of the fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures. The dry basis moisture content and drying rate of Atractylodis Macrocephalae Rhizoma were closely related to the temperature of the drying medium, and the moisture of the Atractylodis Macrocephalae Rhizoma decreased with the prolonged drying time. As revealed by the drying rate curve, the drying rate increased with the increase in hot air temperature, and the migration of moisture was accelerated. The comparison of the correlation coefficient(R~2), chi-square(χ~2), and root mean standard error(RMSE) of each model indicated that the parameter average of the Midilli model had the highest degree of fit, with R~2=0.999 2, χ~2=8.78×10~(-5), and RMSE=8.20×10~(-3). Besides, the D_(eff) at 30-70 ℃ was in the range of 1.04×10~(-9)-6.28×10~(-9) m~2·s~(-1), and E_a was 37.47 kJ·mol~(-1). The volatile components of fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures were determined by GC-MS, and 18, 18, 18, 17, 17, and 18 compounds were identified respectively, which accounted for more than 84.76% of the volatile components. In conclusion, the hot-air drying of Atractylodis Macrocephalae Rhizoma can be model-fitted and verified and the variation law of the moisture and volatile components of Atractylodis Macrocephalae Rhizoma with temperature is obtained. This study is expected to provide new ideas for exploring the drying characteristics and quality of aromatic Chinese medicine.

Suprapubic lipectomy with a "Ω" incision for buried penis in obese adult men / 中华男科学杂志

Objective@#To investigate the application of suprapubic lipectomy with a "Ω" incision to removal of the prepubic fat pad for the management of buried penis in obese adult patients.@*METHODS@#We retrospectively analyzed the clinical data on 20 obese adult patients with buried penis treated by suprapubic lipectomy via a "Ω" incision between August 2016 and September 2019.@*RESULTS@#The operations were successfully completed in all the cases, with a mean operation time of 3.7 ± 0.6 hours and an average hospital stay of 8.3 ± 3.3 days. There were no such severe surgery-related complications as hematoma, urethral injury, or fat embolism in any of the cases. Fat liquefaction-related superficial wound infection developed in 1 patient postoperatively, which was cured by combined topical and systemic antibiotic therapy. A 3-month follow-up showed a 95% satisfaction of the patients with the postoperative appearance of the penis and suprapubic incision, but no complications such as ED, abnormal penile sensation, or penile retraction.@*CONCLUSIONS@#Suprapubic lipectomy with a "Ω" incision to remove the prepubic fat pad is an effective surgical approach to the management of buried penis in obese adult males, which is an anatomy-based surgical correction and has the advantages of slight injury, rapid recovery and few complications./.

Research Progress of Intervention in Autoimmune Thyroid Diseases Based on Th17/ Treg Signal Axis with Traditional Chinese Medicine / 中国实验方剂学杂志

Autoimmune thyroid disease （AITD） is a complex organ-specific autoimmune disease， associated with many factors such as genetic susceptibility， environmental factors， immune system disorders， and intestinal microbiota imbalance， which seriously affect the quality of life. At present， oral medicine， iodine 131 treatment and surgical treatment are mainly adopted in clinical parctice of western medicine. Although they can exert a certain curative effect， they still have surgical risks and side effect. Modern research shows that， traditional Chinese medicine（TCM） has the characteristics of stable curative effect， multi-targeted regulation and less side effect. It has definite efficacy and unique advantages in the prevention and treatment of AITD. Helper T lymphocyte cell 17 （Th17） mediate inflammation to induce immune promotion， while regulatory T lymphocyte cell （Treg） mediate immunosuppression， Th17 and Treg cooperate to maintain the balance of the immune microenvironment. During AITD progress， Inflammatory Th17 can be high， and the levels of mediated immunosuppressive Treg are relatively decreased. The restoration of balance between the two plays a key role in the inflammatory and immune processes of AITD. In recent years， based on Th17/Treg cell axis， a large number of clinical and experimental studies on the intervention of TCM on Th17/Treg balance in AITD have been carried out in the field of TCM， and some results have been achieved. Studies have shown that intervention in the Th17/Treg signaling axis is an important mechanism for the treatment of autoimmune thyroid diseases. This paper summarizes and analyzes the previous studies on the intervention effect of Chinese medicine monomer， Chinese medicine composition and Chinese medicine compound on Th17/Treg cell axis in AITD， mainly from the aspects of intervention related inflammatory factor secretion， regulation of antibody titer and the expression of related genes of related genes. These studies will help people to understand the mechanism of TCM in interfering with the Th17/Treg balance in AITD more accurately and comprehensively， and provide references for the rational application of TCM in the prevention and treatment of autoimmune thyroid diseases in clinical practice.

Analysis on the status and trend of TB burden in China from the global views / 中华疾病控制杂志

@#Objective To analyze the status and trends for the prevalence，morbidity，mortality， and DALY of tuberculosis ( TB) in China from 1990 to 2017，so as to provide scientific basis for TB pre- vention and control． Methods From 1990 to 2017 in China，the United States，India，Japan，and the global，the TB ( standardized) prevalence，( standardized) morbidity，( standardized) mortality，and ( standardized) DALY rates were obtained from Institute for Health Metrics and Evaluation ( IHME) web- site，and comparative analysis of changes in these indicators with years were carried out． Ｒesults In 2017， the prevalence，morbidity，mortality，and DALY rate of TB in China were higher in the high-age group than in the low-age group． The prevalence，morbidity，mortality，and DALY rates were all higher for males than females． The prevalence was 29 641. 59/100 000 and 28 803. 26/100 000 for male and female，respectively． The male and female mortality rates were 72. 23/100 000 and 44. 85/100 000． The male and female mortali- ty rates were 3. 85/100 000 and 1. 67/100 000，and the DALY rate of male and female were 156. 95/100 000 and 84. 73/100 000． From 1990 to 2017，the prevalence of TB decreased from 32 178. 39/100 000 in 1990 to 29 231. 80/100 000 in 2017，the morbidity rate of TB decreased from 141. 83/100 000 in 1990 to 58. 83/100 000 in 2017，the mortality rate of TB decreased from 13. 82/100 000 in1990 to 2. 78/100 000 in 2017，and the DALY rate of TB decreased from 582. 87/100 000 in 1990 to 121. 60/100 000 in 2017． Conclusions The burden of TB in China declined markedly from 1990 to 2017． Although some progress has been made in the prevention and treatment of TB in China，but there is still a certain gap compared with de- veloped countries． It is still necessary to further reduce the morbidity rate and mortality rate of TB．

Current therapeutic condition of chronic obstructive pulmonary disease associated pulmonary arterial hypertension／ / 心血管康复医学杂志

Chronic obstructive pulmonary disease (COPD)‐associated pulmonary arterial hypertension (PAH) is one of the most frequent types of PAH .In recent years , with the aging aggravates in China , total number of patients with COPD‐associated PAH gradually rise .It has become a focus of attention to fully understand current therapeutic condition of COPD‐associated PAH and select reasonable therapeutic program .

Vascular protective effects of aqueous extracts of Tribulus terrestris on hypertensive endothelial injury / 中国天然药物

Angiotensin II (Ang II) is involved in endothelium injury during the development of hypertension. Tribulus terrestris (TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats (SHRs) and its protective effects against Ang II-induced injury in human umbilical vein endothelial cells (HUVECs). SHRs were administered intragastrically with TT (17.2 or 8.6 g·kg·d) for 6 weeks, using valsartan (13.5 mg·kg·d) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang II, endothelin-1 (ET-1), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10 mol·L Ang II. Cell Apoptosisapoptosis, intracellular reactive oxygen species (ROS) was assessed. Endothelial nitric oxide synthase (eNOS), ET-1, SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang II, ET-1, NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang II-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mRNA expression of Akt1, JAK2, PI3Kα, Erk2, FAK, and NF-κB p65 and protein expression of Erk2, FAK, and NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating Erk2, FAK and NF-κB p65.

Liraglutide protects pressure-overload rat heart from failure / 中国比较医学杂志

Objective To explore the effect of liraglutide on pressure?overload chronic heart failure in rats and related mechanisms. Methods Totally 30 SD rats were randomly divided into sham operation group, heart failure group and liraglutide group. The animals were anaesthetized and a Millar pressure volume conductance catheter SPR?838 ) was inserted through right carotid artery into LV to measure pressure?volume ( P?V ) loop. Body and organ weight were measured. After the end of intervention, the rats were anesthetized, and abdominal aortic blood taken from the upper serum after centrifugation. Kit method was used to measure superoxide dismutase (SOD), brain natriuretic peptide (BNP), malondialdehyde ( MDA) . Results Compared with those of the sham operation group, there was a increase in absolute heart weight and (P < 0?05). During the P?V loop analyses, We found that left ventricular (LV) end?systolic volume, end?diastolic volume, end?systolic pressure, end?diastolic pressure and maximum pressure were all remarkablely lower in liraglutide group than HF group in rats ( P < 0?05 ) . Peak rate of pressure rise ( dP/dt max ) , peak rate of pressure decline ( -dP/dt min) , ejection fraction and Maximum Power were increased in liraglutide group comparable by HF group (P < 0?05). SOD activity was significantly increased and BNP concentration was significantly decreased in liraglutide group compared to HF group (P < 0?05). Conclusions These results show that liraglutide protects pressure?overload rat heart from failure possibly through reducing oxidation.

Aqueous extracts of Tribulus terrestris protects against oxidized low-density lipoprotein-induced endothelial dysfunction / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the role of aqueous extracts of Tribulus terrestris (TT) against oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) dysfunction in vitro.</p><p><b>METHODS</b>HUVECs were pre-incubated for 60 min with TT (30 and 3 μg/mL respectively) or 10(-5) mol/L valsartan (as positive controls) and then the injured endothelium model was established by applying 100 μg/mL ox-LDL for 24 h. Cell viability of HUVECs was observed by real-time cell electronic sensing assay and apoptosis rate by Annexin V/PI staining. The cell migration assay was performed with a transwell insert system. Cytoskeleton remodeling was observed by immunofluorescence assay. The content of endothelial nitric oxide synthase (eNOS) was measured by enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) generation was assessed by immunofluorescence and flow cytometer. Key genes associated with the metabolism of ox-LDL were chosen for quantitative real-time polymerase chain reaction to explore the possible mechanism of TT against oxidized LDL-induced endothelial dysfunction.</p><p><b>RESULTS</b>TT suppressed ox-LDL-induced HUVEC proliferation and apoptosis rates significantly (41.1% and 43.5% after treatment for 3 and 38 h, respectively; P<0.05). It also prolonged the HUVEC survival time and postponed the cell's decaying stage (from the 69th h to over 100 h). According to the immunofluorescence and transwell insert system assay, TT improved the endothelial cytoskeletal network, and vinculin expression and increased cell migration. Additionally, TT regulated of the synthesis of endothelial nitric oxide synthase and generation of intracellular reactive oxygen species (P<0.05). Both 30 and 3 μg/mL TT demonstrated similar efficacy to valsartan. TT normalized the increased mRNA expression of PI3Kα and Socs3. It also decreased mRNA expression of Akt1, AMPKα1, JAK2, LepR and STAT3 induced by ox-LDL. The most notable changes were JAK2, LepR, PI3Kα, Socs3 and STAT3.</p><p><b>CONCLUSIONS</b>TT demonstrated potential lowering lipid benefits, anti-hypertension and endothelial protective effects. It also suggested that the JAK2/STAT3 and/or PI3K/AKT pathway might be a very important pathway which was involved in the pharmacological mechanism of TT as the vascular protective agent.</p>

Establishment and Evaluation of Hypertensive Rat Model with Excessive Accumulation of Phlegm-dampness Syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe mainfestations of syndrome and biochemical indices of hypertensive model rats with excessive accumulation of phlegm-dampness syndrome (EAPDS), and to explore its possible pathological mechanism.</p><p><b>METHODS</b>EAPDS rat model was prepared in 50 Wistar rats by feeding with high fat forage. Meanwhile, a normal control group consisting of 10 Wistar rats was set up by feeding with normal forage. After 25-week continuous feeding, 22 rats with body weight (BW) and blood pressure (BP) exceeding 25% those of the control group were selected as a model group. BW, BP, blood lipids, and related serological indicators were detected in all rats. Morphological changes of target organs were observed. mRNA expression levels of leptin receptor (LepR), Janus kinase2 (Jak2), signal transducer and activator of transcription 3 (Stat3), suppressor of cytokine signaling-3 (Socs3), angiotensin II receptor type 1 (AT1), angiotensin II receptor type 2 (AT2), phosphatidylinositol 3 kinase (P13K), serine threonine kinase (Akt), nuclear factor of kappa B (NF-κBp65), inhibitor of nuclear factor kappa-B kinase α (IKKα), NF-kappa-B inhibitor β (lKKβ), NF-kappa-B inhibitor α (IKBα), and AMP-activated protein kinase (AMPK) were detected by quantitative real-time PCR (qPCR). Expression levels of AT1 and LepR in aorta were detected by immunohistochemical assay and Western blot respectively.</p><p><b>RESULTS</b>Compared with the control group, BW, BP, and blood lipids increased; serum levels of leptin (Lep) , Ang II, Hcy, ET-1, TNF-α, IL-6, and p2-MG increased, but NO decreased in the model group (P < 0.05, P < 0.01). Aortal endothelial injury and smooth muscle cell proliferation occurred in the model group, accompanied with heart and renal injury. Compared with the control group, mRNA expression levels of LepR, Jak2, Stat3, Socs3, AT1 , PI3K, Akt, NF-κB p65, IKKβ, IKBα, and AMPK in aorta were up-regulated significantly (P < 0.05), while the expression of IKKa decreased (P < 0.05). Immunohistochem- ical staining showed, brownish yellow deposit of AT1 and LepR was obviously increased, with more extensively positive distribution. Western blot results showed, as compared with the control group, protein expression levels of AT1 and LepR obviously increased in the model group (P < 0.05).</p><p><b>CONCLUSIONS</b>Model rats exhibited typical syndromes of EAPDS. They put up weight with fat abdomen, gloomy hair, poor appetite, hypersomnia, lowered activities , reduced food intake, loose stool, dark red tongue, white tongue with white, thick, greasy fur. Lep could be taken as one of objective indicators for evaluating hypertension rat model with EAPDS.</p>

Can Ashi points stimulation have specific effects on shoulder pain? A systematic review of randomized controlled trials / 中国结合医学杂志

<p><b>OBJECTIVE</b>To provide an evidence-based overview regarding the efficacy of Ashi points stimulation for the treatment of shoulder pain.</p><p><b>METHODS</b>A comprehensive search [PubMed, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), Chongqing Weipu Database for Chinese Technical Periodicals (VIP) and Wanfang Database] was conducted to identify randomized or quasi-randomized controlled trials that evaluated the effectiveness of Ashi points stimulation for shoulder pain compared with conventional treatment. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. RevMan 5.0 was used for data synthesis.</p><p><b>RESULTS</b>Nine trials were included. Seven studies assessed the effectiveness of Ashi points stimulation on response rate compared with conventional acupuncture. Their results suggested significant effect in favour of Ashi points stimulation [odds ratio (OR): 5.89, 95% confidence interval (CI): 2.97 to 11.67, P<0.01, heterogeneity: χ(2) =3.81, P=0.70, I (2) =0% ]. One trial compared Ashi points stimulation with drug therapy. The result showed there was a significantly greater recovery rate in group of Ashi points stimulation (OR: 9.58, 95% CI: 2.69 to 34.12). One trial compared comprehensive treatment on the myofascial trigger points (MTrPs) with no treatment and the result was in favor of MTrPs.</p><p><b>CONCLUSIONS</b>Ashi points stimulation might be superior to conventional acupuncture, drug therapy and no treatment for shoulder pain. However, due to the low methodological quality of included studies, a firm conclusion could not be reached until further studies of high quality are available.</p>

Characteristics of electrocardiography in pressure-overload chronicity heart failure rats / 中国比较医学杂志

Objective To analyze the electrocardiography ( ECG ) data of pressure overload ?induced chronic heart failure rats. Methods Totally 20 SD rats were randomly divided into sham operation group and heart failure group. Heart failure rats were induced by abdominal aorta constriction. Echocardiogram measurement demonstrated the occurrence of cardiac function. Two lead ECG parameters of limb a was measured and statistically analyzed. Results Ten weeks after operation, there was a increase in heart rate, P amplitude, P duration and R amplitude comparing by those of the sham operation group (P < 0?05). ECG showed a significant and ubiquitous J point elevation (P < 0?05), with ST segment notable depression ( P < 0?05 ) . Conclusions ECG in pressure?overload chronicity heart failure rats exhibits obviously characteristic features. ECG is an useful tool for objective and accurate assessment of cardiac function in rats.

Evaluation and Estimation of the Provincial Infant Mortality Rate in China's Sixth Census / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To assess the data quality and estimate the provincial infant mortality rate (1q0) from China's sixth census.</p><p><b>METHODS</b>A log-quadratic model is applied to under-fifteen data. We analyze and compare the average relative errors (AREs) for 1q0 between the estimated and reported values using the leave-one-out cross-validation method.</p><p><b>RESULTS</b>For the sixth census, the AREs are more than 100% for almost all provinces. The estimated average 1q0 level for 31 provinces is 12.3‰ for males and 10.7‰ for females.</p><p><b>CONCLUSION</b>The data for the provincial 1q0 from China's sixth census have a serious data quality problem. The actual levels of 1q0 for each province are significantly higher than the reported values.</p>

Distribution and antimicrobial resistance of the clinical strains isolated f rom the cervical secretions of parturient women / 中国感染与化疗杂志

Objective To investigate the distribution and antimicrobial resistance of clinical bacterial strains isolated from the cervical secretions of parturient women .Methods A total of 239 bacterial strains were isolated from 1 519 cervical specimens of parturient women .These strains were identified and tested by Kirby‐Bauer method for their susceptibility to antimicrobial agents .Results Escherichia coli was the most frequently isolated bacteria ,accounting for 34 .3% .The bacterial strains were more or less resistant to commonly used antimicrobial agents .Conclusions Various bacterial species are identified in the cervical secretions of parturient women ,primarily Escherichia coli and Staphylococcus aureus .Bacterial culture and antimicrobial susceptibility testing are important for clinicians to take appropriate measures to reduce the incidence of mother‐to‐child infections .

Tanshinone II a protects against lipopolysaccharides-induced endothelial cell injury via Rho/Rho kinase pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To test whether tanshinone II A (Tan II A), a highly valued herb derivative to treat vascular diseases in Chinese medicine, could protect endothelial cells from bacterial endotoxin (lipopolysaccharides, LPS)-induced endothelial injury.</p><p><b>METHODS</b>Endothelial cell injury was induced by treating human umbilical vein endothelial cells (HUVECs) with 0.2 μg/mL LPS for 24 h. Y27632 and valsartan were used as positive controls. The effects of tanshinone II A on the LPS-induced cell viability and apoptosis rate of HUVECs were tested by flow cytometry, cell migration by transwell, adhesion by a 96-well plate pre-coated with vitronectin and cytoskeleton reorganization by immunofluorescence assay. Rho/Rho kinase (ROCK) pathway-associated gene and protein expression were examined by microarray assay; quantitative real-time polymerase chain reaction and Western blotting were used to confirm the changes observed by microarray.</p><p><b>RESULTS</b>Tan II A improved cell viability, suppressed apoptosis and protected cells from LPS-induced reductions in cell migration and adhesion at a comparable magnitude to that of Y27632 and valsartan. Tan II A, Y27632 and valsartan also normalized LPS-induced actomyosin contraction and vinculin protein aggregation. A microarray assay revealed increased levels of fibronectin, integrin A5 (ITG A5), Ras homolog gene family member A (RhoA), myosin light chain phosphatase, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K, or PIP2 in Western blotting), focal adhesion kinase, vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in the damaged HUVECs, which were attenuated to different degrees by Tan II A, Y27632 and valsartan.</p><p><b>CONCLUSION</b>Tan II A exerted a strong protective effect on HUVECs, and the mechanism was caused, at least in part, by a blockade in the Rho/ROCK pathway, presumably through the down-regulation of ITG A5.</p>

Effect of Guizhi Decoction (symbols; see text) on heart rate variability and regulation of cardiac autonomic nervous imbalance in diabetes mellitus rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe abnormalities in heart rate variability (HRV) in diabetic rats and to explore the effects of treatment with Guizhi Decoction ([symbols; see text]) on cardiac autonomic nervous (CAN) imbalance.</p><p><b>METHODS</b>A radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures: standard deviation of all RR intervals in 24 h (SDNN), root mean square of successive differences (RMSSD), percentage of differences between adjacent RR intervals greater than 50 ms (PNN50), and standard deviation of the averages of RR intervals (SDANN); frequency domain measures: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin (STZ)-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 (GAP-43), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) levels using an enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>(1) STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. (2) Compared with the model group, only RMSSD and TP increased in the methycobal group significantly (P<0.05); SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased (P<0.05), and SDANN just showed a decreasing trend in the Guizhi Decoction group (P>0.05). TH increased, CHAT decreased, and TH/CHAT increased in the myocardial homogenate of the model group (P<0.05). Compared with the model group, left ventricular TH reduced in the methycobal group; and in the Guizhi Decoction group CHAT increased, while TH and TH/CHAT decreased (P<0.05). Compared with the model group, CNTF in the interventricular septum increased in the methycobal group (P<0.05); GAP-43 increased, NGF decreased, and CNTF increased (P<0.05) in the Guizhi Decoction group. There were significant differences in the reduction of NGF and elevation of CNTF between the Guizhi Decoction group and the methycobal group (P<0.05). (3) Immunohistochemical results showed that TH expression significantly increased and CHAT expression significantly decreased in the myocardia of the model group, whereas TH expression decreased and CHAT expression increased in the Guizhi Decoction group (P<0.05).</p><p><b>CONCLUSION</b>Guizhi Decoction was effective in improving the function of the vagus nerve, and it could alleviate autonomic nerve damage.</p>

MiR-124 suppresses the proliferation of human prostate cancer PC3 cells by targeting PKM2 / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the mechanism of miR-124 inhibiting the proliferative activity of prostate cancer PC3 cells.</p><p><b>METHODS</b>Luciferase reporter gene assay was used to examine the specific binding ability of miR-124 to PKM2 mRNA 3'-UTR. After miR-124 was transfected mimic to PC3 cells, the expression levels of PKM2 mRNA and protein were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot, respectively. The effects of miR-124 mimic and PKM2 siRNA on the proliferative activity of the PC3 cells were determined by MTT assay.</p><p><b>RESULTS</b>The expressions of PKM2 mRNA and protein were upregulated (5.12 +/- 0.35) times and (4.05 +/- 0.20) times respectively in the PC3 cells as compared with those in the RWPE-1 cells (P < 0.05). Luciferase reporter gene assay demonstrated that miR-124 targeted PKM2 3'-UTR. At 24 hours after transfection with miR-124 mimic, the PKM2 protein expression in the PC3 cells was downregulated (0.16 +/- 0.04) times (P < 0.05), while the PKM2 mRNA level was not changed significantly (P > 0.05), as compared with the control group. MTT assay showed that both miRNA-124 mimic and PKM2 siRNA could inhibit the proliferation of the PC3 cells, but the former exhibited a greater inhibitory effect than the latter. After transfection with miR-124 mimic and PKM2 siRNA, the cell growth rates were (66.20 +/- 5.10)% vs (82.10 +/- 6.35)% at 24 hours (P < 0.05) and (49.34 +/- 2.37)% vs (70.10 +/- 5.80)% at 48 hours (P < 0.05).</p><p><b>CONCLUSION</b>miR-124 can suppress the proliferation of PC3 cells by regulating the PKM2 gene.</p>

Analysis of procalcitonin,C-reactive protein concentration and WBC count in patients infected by different bacteria / 国际检验医学杂志

Objective To investigate the concentration of procalcitonin,C-reactive protein and WBC count for patients with dif-ferent kind of bacterial infection.Methods 49 blood samples and 81 other samples were collected form different patients for bacteri-al culture.Meanwhile,procalcitonin,C-reactive protein concentration and WBC count of those patients were determined to find whether these indicators exhibited any difference between Gram-positive and Gram-negative bacteria infected patients.Results For bloodstream infection,PCT levels in patients with Gram-nagetive bacterial infection were obviously higher than those with Gram-positive infection(P 0.05).Conclusion PCT concentration is valuable in the differential diagnosis of blood stream infection caused by Gram-negative and Gram-positive bacteria,but not in local infection infection.

Correlation analysis between abundance of K-ras mutation in plasma free DNA and its correlation with clinical outcome and prognosis in patients with metastatic colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect K-ras gene mutations in plasma free DNA by peptide nucleic acid clamp PCR assay (PNA-PCR) and nested primer PCR, and to analyze the correlation between K-ras mutations and prognosis in patients with metastatic colorectal cancer (mCRC).</p><p><b>METHODS</b>Peripheral blood was collected and free DNA was extracted from plasma in 106 patients with mCRC. Nested primer PCR and PNA-PCR were used to detect K-ras gene mutation in the plasma free DNA. The patients were divided into three groups by K-ras status: wild-type group (wild-type determined by both methods), low mutation group (mutation by PNA-PCR method, wild-type by nested primer PCR method) and high mutation group (mutation by two methods). The correlation between K-ras mutations and prognosis was analyzed.</p><p><b>RESULTS</b>The mutation rate of K-ras in tumor tissues of the 106 patients was 40.6%. The Mutation rate of K-ras in plasma free DNA detected by PNA-PCR was 31.1%, significantly higher than that of 15.1% detected by nested primer PCR (P = 0.006). The consistent rate of the K-ras status in plasma free DNA detected by PNA-PCR and that in tumor tissue detected by traditional method was up to 83.0%. The median overall survival (OS) of patients of the wild type, low mutation and high mutation groups was 23.5 months, 17.3 months and 13.9 months, respectively (P = 0.002). The median progression-free survival (PFS) of the K-ras wild-type, low mutation and high mutation groups with first-line chemotherapy was 6.8 months, 6.1 months and 3.2 months, respectively (P = 0.002), and the median OS of them were 23.0 months, 15.5 months and 13.9 months, respectively (P = 0.036). The overall response rate (ORR) was improved in the K-ras wide-type patients who received cetuximab combined with chemotherapy as first-line therapy (75.0% vs. 23.4%, P = 0.058). Cetuximab combined with in second-line therapy chemotherapy led to a significant improvement in disease control rate (DCR) ( 100% vs. 35.7%, P < 0.001) as compared with those of chemotherapy alone. COX regression model showed that K-ras status detected by PNA-PCR, ECOG PS, number of surgery and initially metastatic site were independent factors for prognosis.</p><p><b>CONCLUSIONS</b>PNA-PCR for the detection of K-ras mutation in plasma free DNA can be used to substitute the traditional method for detection of K-ras mutation in tumor tissues. The abundance of K-ras mutation in plasma free DNA is an independent prognostic factor for patients with metastatic colorectal cancer.</p>