Glycosylated, Lipid-Binding, CDR-Like Domains of SARS-CoV-2 ORF8 Indicate Unique Sites of Immune Regulation.

The outbreak of the novel coronavirus SARS-CoV-2 has posed a significant threat to human health and the global economy since the end of 2019. Unfortunately, due to the virus's rapid evolution, preventingand controlling the epidemic remains challenging. The ORF8 protein is a unique accessory protein in SARS-CoV-2 that plays a crucial role in immune regulation, but its molecular details are still largely unknown. In this study, we successfully expressed SARS-CoV-2 ORF8 in mammalian cells and determined its structure using X-ray crystallography at a resolution of 2.3 Å. Our findings reveal several novel features of ORF8. We found that four pairs of disulfide bonds and glycosylation at residue N78 are essential for stabilizing ORF8's protein structure. Additionally, we identified a lipid-binding pocket and three functional loops that tend to form CDR-like domains that may interact with immune-related proteins to regulate the host immune system. On cellular experiments also demonstrated that glycosylation at N78 regulats of ORF8's ability to bind to monocytes cells. These novel features of ORF8 provide structural insights to into its immune-related function and may serve as new targets for developing ORF8-mediated immune regulation inhibitors. IMPORTANCE COVID-19, caused by the novel coronavirus SARS-CoV-2 virus, has triggered a global outbreak. The virus's continuous mutation increases its infectivity and may be directly related to the immune escape response of viral proteins. In this study, we used X-ray crystallography to determine the structure of SARS-CoV-2 ORF8 protein, a unique accessory protein expressed in mammalian cells, at a resolution of 2.3 Å. Our novel structure reveals important structure details that shed light on ORF8's involvement in immune regulation, including conservation disulfide bonds, a glycosylation site at N78, a lipid-binding pocket, and three functional loops that tend to form CDR-like domains that may interact with immune-related proteins to modulate the host immune system. We also conducted preliminary validation experiments on immune cells. These new insights into ORF8's structure and function provide potential targets for developing inhibitors to block the ORF8-mediated immune regulation between viral protein and host, ultimately contributing to the development of novel therapeutics for COVID-19.

The journey of prochloraz pesticide in Citrus sinensis: Residual distribution, impact on transcriptomic profiling and reduction by plasma-activated water.

Prochloraz (PTIC) is a hazardous fungicide used worldwide on agricultural produce despite concerns about potential impacts on human health and environmental pollution. The residue of PTIC and its metabolite 2,4,6-trichlorophenol (2,4,6-TCP) in fresh produce has largely not been clarified. Herein, we address this research gap by examining residues of PTIC and 2,4,6-TCP in fruit of Citrus sinensis through a typical storage period. PTIC residue in the exocarp and mesocarp peaked on days 7 and 14, respectively, while 2,4,6-TCP residue gradually increased throughout storage period. Based upon gas chromatography-mass spectrometry and RNA-sequencing analysis, we reported the potential impact of residual PTIC on endogenous terpene production, and identified 11 DEGs encoding enzymes involved in terpene biosynthesis in Citrus sinensis. Additionally, we investigated both the reduction efficacy (max: 58.93%) of plasma-activated water in citrus exocarp and the minimal impact on quality attributes of citrus mesocarp. The present study not only sheds light on the residual distribution of PTIC and its impact on endogenous metabolism in Citrus sinensis, but also further provides theoretical basis for potential approaches for efficiently reducing or eliminating pesticide residues.

An intramolecular DNAzyme-based amplification for miRNA analysis with improving reaction kinetics and high sensitivity.

Sensitive, specific and rapid methods for detecting microRNAs (miRNAs) play critical roles in disease diagnosis and therapy. Enzyme-free amplification techniques based on DNAzyme assembly have recently been developed for the highly specific miRNA analysis. However, traditional DNAzyme-based assembly (free DNAzyme) amplifiers is mainly dependent on the target-induced split DNAzyme fragments to assemble into activated DNAzyme structures, which have made a compromise between the sensitivity and specificity due to the random diffusion of dissociative probes in a bulk solution with poor kinetics. Herein, based on a rationally designed DNA probe, we developed an intramolecular DNAzyme assembly (intra-DNAzyme) method to overcome these challenges. The miR-373 is used as model analyte for our current proof-of-concept experiments. Compared with the free-DNAzyme method, our method showed significantly improved analytical performance in terms of dynamic range, assay sensitivity and speed. This method can detect miR-373 specifically with a detection limit as low as 4.3 fM, which is about 83.7 times lower than the previous free-DNAzyme method. This intra-DNAzyme strategy would be of great value in both basic research and clinical diagnosis.

Global patterns and trends in stomach cancer incidence: Age, period and birth cohort analysis.

The cases of stomach cancer (SC) incidence are increasing per year and the SC burden has remained very high in some countries. We aimed to evaluate the global geographical variation in SC incidence and temporal trends from 1978 to 2007, with an emphasis on the effect of birth cohort. Joinpoint regression and age-period-cohort model were applied. From 2003 to 2007, male rate were 1.5- to 3-fold higher than female in all countries. Rates were highest in Eastern Asian and South American countries. Except for Uganda, all countries showed favorable trends. Pronounced cohort-specific increases in risk for recent birth cohorts were seen in Brazil, Colombia, Iceland, New Zealand, Norway, Uganda and US white people for males and in Australia, Brazil, Colombia, Costa Rica, Czech Republic, Ecuador, Iceland, India, Malta, New Zealand, Norway, Switzerland, United Kingdom, Uganda, US black and white people for females. The cohort-specific ratio for male significantly decreased in Japan, Malta and Spain for cohorts born since 1950 and in Austria, China, Croatia, Ecuador, Russia, Switzerland and Thailand for cohorts born since 1960 and for female in Japan for cohorts born since 1950 and in Canada, China, Croatia, Latvia, Russia and Thailand for cohorts born since 1960. Disparities in incidence and carcinogenic risk persist worldwide. The favorable trends may be due to changes in environmental exposure and lifestyle, including decreased Helicobacter pylori prevalence, increased intake of fresh fruits and vegetables, the availability of refrigeration and decreased intake of salted and preserved food and smoking prevalence.

Risk of Stroke/Transient Ischemic Attack or Myocardial Infarction with Herpes Zoster: A Systematic Review and Meta-Analysis.

BACKGROUND: Accumulating evidence indicates that herpes zoster (HZ) may increase the risk of stroke/transient ischemic attack (TIA) or myocardial infarction (MI), but the results are inconsistent. We aim to explore the relationship between HZ and risk of stroke/TIA or MI and between herpes zoster ophthalmicus (HZO) and stroke. METHODS: We estimated the relative risk (RR) and 95% confidence intervals (CIs) with the meta-analysis. Cochran's Q test and Higgins I2 statistic were used to check for heterogeneity. RESULTS: HZ infection was significantly associated with increased risk of stroke/TIA (RR = 1.30, 95% CI: 1.17-1.46) or MI (RR = 1.18, 95% CI: 1.07-1.30). The risk of stroke after HZO was 1.91 (95% CI 1.32-2.76), higher than that after HZ. Subgroup analyses revealed increased risk of ischemic stroke after HZ infection but not hemorrhagic stroke. The risk of stroke was increased more at 1 month after HZ infection than at 1-3 months, with a gradual reduced risk with time. The risk of stroke after HZ infection was greater with age less than 40 years than 40-59 years and more than 60 years. Risk of stroke with HZ infection was greater without treatment than with treatment and was greater in Asia than Europe and America but did not differ by sex. CONCLUSIONS: Our study indicated that HZ infection was associated with increased risk of stroke/TIA or MI, and HZO infection was the most marked risk factor for stroke. Further studies are needed to explore whether zoster vaccination could reduce the risk of stoke/TIA or MI.

Versatile polyvinylidene fluoride hybrid ultrafiltration membranes with superior antifouling, antibacterial and self-cleaning properties for water treatment.

Novel ultrafiltration membranes with both superior antibacterial and self-cleaning properties were fabricated. By using a non-solvent induced phase separation method (NIPS), N-halamine epoxide and siloxane were grafted onto the multi-walled carbon nanotubes (N-Si-MWNTs) to fabricate polyvinylidene fluoride (PVDF) hybrid membranes. The membrane morphology was observed under a field emission scanning electron microscopy. The results demonstrated that the PVDF hybrid membranes had an asymmetrical structure, and their hydraulic permeability was evidently enhanced with the addition of modified MWNTs. When compared with the primitive PVDF membrane, the hybrid membranes presented improved surface hydrophilicity. After three ultrafiltration-regeneration cycles with bovine serum albumin as model biofoulant and pure water as detergent, the PVDF hybrid membranes exhibited a high flux recovery ratio (FRR). Furthermore, when compared with other membranes, the membrane containing N-Si-MWNTs displayed the highest FRR value of above 96.5% after the entire fouling and cleaning experiment. The fabricated PVDF/N-Si-MWNTs hybrid membranes had excellent antibacterial efficacy, presenting maximum antibacterial efficacy of 98.0% and 95.6% against Staphylococcus aureus and Escherichia coli, respectively. Thus, the PVDF/N-Si-MWNTs membranes fabricated in this study are environment-friendly with both benign antibacterial and self-cleaning properties.

Correction: Changes in Prevalence of HIV or Syphilis among Male Sex Workers and Non-Commercial Men Who Have Sex with Men in Shenzhen, China: Results of a Second Survey.

[This corrects the article DOI: 10.1371/journal.pone.0167619.].

Efficacy and safety of chronomodulated chemotherapy for patients with metastatic colorectal cancer: a systematic review and meta-analysis.

AIM: Chronomodulated chemotherapy has been reported to be superior to conventional chemotherapy, but the results from randomized controlled trials (RCTs) are inconsistent. We performed a meta-analysis to summarize the efficacy and safety of chronomodulated chemotherapy for patients with metastatic colorectal cancer. METHODS: A literature search for relevant RCTs comparing the efficacy and safety of chronomodulated chemotherapy and conventional chemotherapy was performed. The main outcomes were overall survival (OS), objective response rate (ORR) and toxicity (grade 3/4), which included vomiting and nausea, diarrhea, mucositis, neutropenia and peripheral sensory neuropathy. Pooled relative risks (RRs) and hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were estimated. RESULTS: Six RCTs involving 1347 patients were included. Chronomodulated chemotherapy showed no advantages for OS (HR = 0.95; 95% CI, 0.84-1.08; P = 0.463) or ORR (RR = 1.06; 95% CI, 0.81-1.39; P = 0.499). The two groups were similar in terms of grade 3/4 vomiting and nausea (RR = 1.02; 95% CI, 0.78-1.35; P = 0.872), diarrhea (RR = 1.44; 95% CI, 0.87-2.36; P = 0.149) or peripheral sensory neuropathy (RR = 0.86; 95% CI, 0.56-1.34; P = 0.512), whereas decreased risks of mucositis (RR = 0.31; 95% CI, 0.14-0.66; P = 0.000) and neutropenia (RR = 0.40; 95% CI, 0.27-0.57; P = 0.000) were observed in chronomodulated chemotherapy. CONCLUSION: Chronomodulated chemotherapy may be favorable to reduce the risks of certain side effects, but there is no current evidence for improvement in OS or ORR. Our analysis suggests that the available data does not support the use of chronomodulated chemotherapy.

A systematic review and network meta-analysis of neoadjuvant therapy combined with surgery for patients with resectable esophageal squamous cell carcinoma.

BACKGROUND: The role of neoadjuvant therapy combined with surgery for treating esophageal squamous cell carcinoma (ESCC) remains controversial. We performed a network meta-analysis to synthesize direct and indirect evidence to identify the optimal therapeutic method for ESCC. METHODS: We identified 15 randomized controlled trials that compared any of the following 4 therapeutic measures: surgery alone (S), preoperative chemotherapy followed by surgery (CTS), preoperative radiotherapy followed by surgery (RTS), and preoperative chemoradiotherapy followed by surgery (CRTS). The main outcomes were 5-year survival, rate of radical resection, operative mortality and postoperative complications. RESULTS: Network meta-analysis showed that CRTS was associated with improved survival as compared with S (OR = 1.50 [95% CI 1.21 to 1.97]) and decreased occurrence of complications as compared with RTS (OR = 0.50 [95% CI 0.22 to 0.99]). Direct evidence revealed CRTS associated with improved survival (OR = 1.61 [95% CI 1.01 to 2.57]) and radical resection (OR = 4.01 [95% CI 1.66 to 9.69]) as compared with S. In terms of radical resection, CTS was more effective than S (OR = 1.73 [95% CI 1.09 to 2.76]). Findings for CTS and RTS did not differ for 5-year survival, operative mortality and postoperative complications. CONCLUSIONS: Overall, CRTS might be the best choice for resectable ESCC because it could increase the radical resection rate and lower the occurrence of complications, thereby prolonging survival time.

Changes in Prevalence of HIV or Syphilis among Male Sex Workers and Non-Commercial Men Who Have Sex with Men in Shenzhen, China: Results of a Second Survey.

BACKGROUND: A previous time-location sampling survey (TLS) was performed in 2008 to evaluate the HIV or syphilis infection rate among male sex workers (MSWs) and non-commercial men who have sex with men (ncMSM) in Shenzhen, China. This is a second TLS performed in 2014. This article describes the findings and changes in the prevalence of HIV and syphilis. METHODS: TLS was used to collect information as a second cross-sectional survey to an earlier TLS assessment. Data on behavior (e.g., sexual history and sexual behavior) were analyzed. Blood specimens were drawn for HIV and syphilis testing. To determine the changes in the prevalence of HIV and syphilis, we analyzed these results and compared them to the results of our first survey. RESULTS: A total of 965 participants were recruited, including 489 MSWs and 476 ncMSM. Overall, the prevalence of HIV was 9.7%: 2.9% for MSWs and 16.8% for ncMSM (P<0.001). 10.9% of the 965 participants tested positive for syphilis: 4.5% among MSWs and 17.4% among ncMSM (P<0.001). The HIV prevalence in MSWs decreased from 4.5% in 2008 to 2.9% in 2014 (P = 0.143) but increased in ncMSM (7.0% in 2008 vs 16.8% in 2014, P<0.001). Decreased syphilis rates were observed in both MSWs (12.9% in 2008 vs 4.5% in 2014, P<0.001) and ncMSM (20.2% in 2008 vs 17.4% in 2014, P = 0.221). CONCLUSIONS: Overall, there was a decline in the prevalence of HIV and syphilis in MSWs but not in ncMSM. The study indicated the need for continued efforts to improve public health, particularly to counter the rising rate of HIV in ncMSM.

Efficacy and Safety of Laser Surgery and Transurethral Resection of the Prostate for Treating Benign Prostate Hyperplasia: a Network Meta-analysis.

BACKGROUND: Traditional meta-analyses or systematic reviews of randomized controlled trials (RCTs) have been used to compare laser surgeries and transurethral resection of the prostate (TURP) for benign prostate hyperplasia (BHP), but they cannot provide a hierarchy regarding efficacy and safety of treatment. OBJECTIVE: We therefore performed a network meta-analysis (NMA) to compare and create hierarchies for efficacy and safety of TUPR and laser surgeries for BPH. MATERIALS AND METHODS: We searched for reports of RCTs published up to April 25, 2015. After methodological quality assessment and data extraction, we performed an NMA to compare TURP and laser surgeries for BPH. RESULTS: We ranked the treatments of TURP and laser surgeries for BPH. For IPSS at 6 months, holmium laser resection of the prostate (HoLRP) ranked the first-best and at 12 months, holmium laser enucleation of the prostate (HoLEP). For Qmax at 6 and 12 months, HoLEP ranked the first-best; for operative time it was TURP; for cathedral removal time, diode laser enucleation of the prostate (DiLEP) ranked the first-best. CONCLUSIONS: Although TURP is considered the gold standard for treating BPH, it is not better in terms of efficacy and safety compared with the laser surgery. Our NMA created hierarchies for the 9 types of surgery in terms of efficacy and safety, which should help clinicians choose the best approach for the individual patient.

Risk of colorectal cancer with hysterectomy and oophorectomy: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the second most commonly diagnosed cancer worldwide in females. Sex hormones may play a protective effect in CRC pathogenesis. Ovarian sex steroid levels are reduced in premenopausal women after hysterectomy. Prospective studies have revealed an 80% decrease in serum oestradiol levels after bilateral oophorectomy in premenopausal women. We aimed to elucidate the relationship between hysterectomy or oophorectomy and risk of CRC. METHODS: We estimated relative risk (RR) and 95% confidence intervals (95% CIs) with the meta-analysis. Cochran's Q test and Higgins I2 statistic were used to check for heterogeneity. Subgroup and sensitivity analyses were performed as were Egger's and Begg's tests and the "trim-and-fill" method for publication bias analysis. RESULTS: Risk of CRC was increased 30% for women undergoing oophorectomy relative to the general population and 24% with hysterectomy relative to no surgery. The risk was increased 22% with hysterectomy with bilateral salpingoo-ophorectomy as compared with simple hysterectomy. On subgroup analysis, risk of rectal cancer was increased 28% and colon cancer 19% with hysterectomy. Europeans seem to be sensitive to the risk of CRC, with 27% increased risk after hysterectomy. The risk of CRC after oophorectomy gradually increased with age at oophorectomy. The risk was greater with bilateral oophorectomy, with 36% increased risk, than unilateral oophorectomy, with 20% increased risk. Risk was increased 66% with time since oophorectomy 1-4 years as compared with 5-9 and ≥ 10 years. CONCLUSIONS: Risk of CRC was increased for women undergoing hysterectomy or oophorectomy. Women with susceptibility genes for ovarian cancer or metrocarcinoma should choose oophorectomy or hysterectomy. For women not at high risk for these cancers, oophorectomy or hysterectomy should not be recommended for increasing the subsequent risk of CRC.

Combined effects of ramipril and angiotensin II receptor blocker TCV116 on rat congestive heart failure after myocardial infarction.

BACKGROUND: Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin converting-enzyme inhibitor (ACEI) is the cornerstone in its treatment. However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin II (Ang II) by alternative pathways. The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang II type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI). METHODS: Congestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery. The experiment protocol included sham-operated rats (Sham), MI-control rats (MI-control), MI rats treated with ramipril 3 mg/kg (MI-ramipril) or TCV116 2 mg/kg (MI-TCV116) per day, half dosage (MI-1/2R&T) or full dosage (MI-R&T) combination of the two. At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as beta myosin heavy chain (betaMHC), B-type natriuretic peptide (BNP), transforming growth factor-beta1 (TGF-beta1), collagen I and III were quantified with reverse transcription polymerase chain reaction (RT-PCR) in the surviving septum myocardium, and survival rates were calculated. RESULTS: There were no significant differences in MI sizes (%) among each MI related experimental groups (33 +/- 13, 34 +/- 14, 33 +/- 13, 35 +/- 13 and 33 +/- 14 for MI-control, MI-ramipril, MI-TCV116, MI-1/2R&T and MI-R&T, respectively, no statistical significance for all). Compared with sham-operated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P < 0.01); while their hemodynamic parameters were significantly impaired (P < 0.01), and in terms of spontaneous deaths survival rate shortened (P < 0.05). Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P < 0.01); while their hemodynamic parameters were significantly improved (P < 0.05 or P < 0.01), and in terms of spontaneous deaths survival rate prolonged (P < 0.05). Both half and full dosage combined treatments exerted more powerful effects on improvement of cardiac phenotypic changes and on attenuation of betaMHC, BNP mRNA expressions (P < 0.05 vs monotherapy); while LVEDP was further lowered (P < 0.05 vs monotherapy). However, the total death in MI rats with full dosage combined treatment was more though there were no significant differences when compared with other treatments. CONCLUSIONS: The results suggest that treatment with appropriate dosage combination of a chronic ACEI and a chronic ARB may further improve cardiac remodeling and cardiac function after MI.

[Effects of tumor necrosis factor alpha on expression of phospholamban and intracellular calcium in cardiomyocytes].

OBJECTIVE: To explore the effects of tumor necrosis factor alpha (TNFalpha) on the expression of phospholamban (PLB) and sarco (endo) plasmic reticulum Ca(2+)-ATPase (SERCA2a) and concentration of intracellular free calcium in myocardiocytes. METHODS: The neonatal rat myocardiocytes were randomly divided into 6 groups: treatment with different concentrations of TNFalpha (1,10,30,50,and 70 microg/L, respectively) and without TNFalpha (control). The mRNA and protein expression of PLB and SERCA2a were detected with one-step reverse transcription-polymerase chain reaction and Western blotting. The changes of intracellular free calcium concentration ([Ca2+]i) in cultured single neonatal rat cardiomyocyte were determined with Fluo-3/AM loading by laser scanning confocal microscopy. RESULTS TNFalpha significantly increased the expression of PLB mRNA and protein in a dose-dependent fashion. The ratio of PLB/beta-actin mRNA in myocardiocytes incubated with 10,30,50, and 70 microg/L TNFalpha significantly increased by 66%, 106%, 141%, and 189% compared with control (P < 0.05), and protein levels significantly increased by 30%, 48%, 73%, and 114% respectively compared with control (P < 0.001), but there was no significant difference in PLB mRNA expression between the group treated with 1 microg/L TNFalpha and control group. TNFalpha had no effect on the expression of mRNA and protein of SERCA2a. TNFalpha (50 microg/L) incubated with cell for 24 hours diminished delta[Ca2+]i of single neonatal rat cardiomyocyte about 33% stimulated by isoproterenol (P < 0.01), but had no effect on delta [Ca2+]i of cardiomyocyte without isoproterenol stimulation. CONCLUSION: TNFalpha can increase the expression of PLB and decrease delta[Ca2+]i in cardiomyocytes, which may be related with its negative inotropic effects on cardiomyocytes.

Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction.

OBJECTIVE: Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined. The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. METHODS: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. RESULTS: The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r = 0.920, P < 0.0001), left ventricular ejection fraction (r = -0.868, P < 0.0001) and left ventricular end diastolic pressure (r = 0.835, P < 0.0004). Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r = -0.913, P < 0.0001) and left ventricular end diastolic pressure (r = 0.893, P < 0.0001). CONCLUSION: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.

[Effect of tongxinluo capsule on function of vascular endothelium in patients with unstable angina pectoris].

OBJECTIVE: To evaluate the effect of Tongxinluo (TXL) Capsule on function of vascular endothelium in patients with unstable angina pectoris (UAP). METHODS: Forty-six UAP patients were randomly divided into two group, the 28 patients in the treated group treated by conventional therapy plus TXL and the 18 patients in the control group treated by conventional therapy alone. Changes of blood levels of endothelin (ET), nitric oxide (NO), Von Willebrand factor (vWF), soluble vascular cell adhesive molecule-1 (sVCAM-1) and soluble intracellular adhesive molecule-1 (sICAM-1) from before treatment to after two months of treatment were observed, and the flow-mediated dilatation (FMD) in brachial artery was detected at the same time using ultrasonography. RESULTS: After treatment, the blood level of vWF and ET obviously decreased (P < 0.01), levels of NO and FMD increased (P < 0.05 or P < 0.01) in both groups. Levels of sVCAM-1 and sICAM-1 significantly decreased in the treated group (P < 0.01), while in the control group, no marked change was found in sVCAM-1 and sICAM-1 (P > 0.05). Compared with the control group after treatment, the levels of vWF, ET, sVCAM-1 and sICAM-1 in the treated group were lower (P < 0.01), and levels of NO and FMD were higher (P < 0.01). CONCLUSION: TXL might protect vascular endothelium, improve clinical therapeutic effect by path of decreasing blood levels of ET, vWF and partial cellular adhesive factor, and increasing the level of NO.

[Protective effect of trimetazidine on rabbit myocardium during ischemia- reperfusion].

OBJECTIVE: To investigate the protective effects of trimetazidine on rabbit myocardium in ischemia and reperfusion. METHODS: Fourty rabbits were divided into five groups randomly: normal control group, ischemia control group, ischemia and drug intervention group, reperfusion control group, reperfusion and drug intervention group. Ischemia lasted for 30 minutes and reperfusion was given for 30 minutes. Serum CPK, SOD activities and MDA concentrations were measured in each group and ischemia tissue ATP concentrations were also measured. Heart tissue was examined with electron microscope in each group. RESULTS: (1) Serum concentrations of MDA in ischemia and drug intervention group were significantly different from those in ischemia control group [(4.09+/-0.40 vs 4.79+/-0.92)nmol/ml, P<0.01], serum activities of CPK [(1322+/-1148 vs 1498+/-190) NU/ml], SOD[(324+/-71 vs 288+/-54)NU/ml] were not significantly different between ischemia and drug intervene group and ischemic control group (PP>0.05,respectively). (2) Serum activities of CPK [(1512+/-226 vs 1904+/-203) NU/ml], SOD[(213+/-71 vs 119+/-55) NU/ml], concentrations of MDA [(6.09+/-0.69 vs 7.43+/-0.20)nmol/ml] and concentrations of ATP[(1.401+/-0.248 vs 0.629+/-0.175) micromol/g] in ischemia heart tissue of reperfusion and drug intervention group were significantly different from those in reperfusion control group (P<0.001 - 0.01 respectively). (3) There were significant differences in electron microscopic observation between intervention group and control group. CONCLUSION: Trimetazidine can improve cardiac mitochondrial metabolism and scavenge oxygen free radicals. Trimetazidine has cardioprotective function during ischemia and reperfusion.

[Experimental study on the relationship between insulin and hypertension].

OBJECTIVE: To investigate the association between insulin and hypertension. METHODS: Twenty spontaneously hypertension rats(SHR) and twenty Wistar-Kyoto rats(WKY) were randomly divided into two groups control group and insulin injection group. Systolic blood pressure(SBP),pulse rate(P), fasting blood sugar(FBS), fasting serum insulin(FINS) and insulin sensitivity index(ISI) were observed or calculated before and at the 60th day of the experiment. RESULTS: (SBP 165.5+/-5.8 compared with 108.2+/-4.7mmHg,P<0.01), P(405.8+/-19.6 compared with 336.6+/-9.6 /min P<0.01), FINS (6.89+/-0.99 compared with 5.78+/-0.91mU/L,P<0.05)of SHR were higher than those of WKY before experiment, but there was a lower ISI of SHR -3.397+/-0.191 compared with -3.085+/-0.132,P<0.01 . There were increases of SBP(210.0+/-8.5 compared with 184.3+/-8.0 mmHg,P<0.01),P(452.2+/-13.9 compared with 406.0+/-22.7/min P<0.01) and FINS (28.37+/-3.86 compared with 7.32+/-0.87 mU/L,P<0.01) in insulin injection group of SHR than those in controls,but ISI -4.119+/-0.260 compared with -3.604+/-0.174 P<0.01 decreased in insulin injection group; The same changes were observed in WKY rats after insulin injection (131.6+/-6.7 compared with 110.4+/-5.1 mmHg, 378.2+/-13.2 compared with 347.1+/-14.9/min 22.64+/-2.13 compared with 5.55+/-0.77 mU/L,-3.474+/-0.214 compared with 3.094+/-0.191 P<0.01 respectively). CONCLUSION: Insulin resistance and hyperinsulinemia exist in SHR,chronic hyperinsulinemia may increase SBP and P,decrease ISI of WKY and SHR.

[intercellular adhesion molecule-1 and CD11a/CD18 expression in coronary heart disease]

OBJECTIVE: To investigate the expression of soluble intercellular adhesion molecule-1(sICAM-1) and CD11a/CD18 in coronary heart disease(CHD). METHODS: The sICAM-1 and CD11a/CD18 levels were measured by ELISA and flow cytlemetry in 76 CHD patients and 65 healthy subjects. RESULTS: The level of sICAM-1 and CD11a/CD18 were significantly higher in CHD patients than healthy subjects [SICAM-1(g/L):263.5 +/-66.2 compared with 205.9 +/-57.2, P<0.01; CD11a/CD18 (%):33.7 +/-6.4 compared with 19.3 +/-8.1, P<0.001]. They were also significantly higher in acute myocardial infarct and unstable angina than that of stable angina patients. There was correlation between sICAM-1 and CD11a/CD18(r=0.436, P<0.01). CONCLUSION: Elevated levels of sICAM-1 and CD11a/CD18 associated with unstable angina and myocardial infarction may indicate their significant role in the pathogenesis of acute coronary events.

[Angiotensin II increases the expression of lectin-like oxidize low-density lipoprotein receptor- 1 in cultured human umbilical vein endothlial cells]

OBJECTIVE: To observe whether angiotensin II (AngII) influences expression of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) in cultured human umbilical vein endothlial cells(HUVECs). METHODS: Cultured HUVECs were incubated with 10(-5)mol/L approximate, equals 10(-10) mol/L AngII for 24 h or with 10(-6) mol/L AngII for various time up to 48 h. Then HUVECs LOX-1 protein expression was measured by endothlial cell enzyme linked immunosorbent assay, and mRNA level of LOX-1 was detected by quantitative competitive reverse transcription-polymerase chain reaction. RESULTS: Incubation of HUVECs with AngII for 24 h significantly increased LOX-1 protein expression (P<0.001). The increase was dependent on AngII concentration (10(-5)mol/L approximate, equals 10(-9)mol/L). LOX-1mRNA expression was also induced by AngII, and after 24 h incubation of AngII(10(-5)mol/L approximate, equals 10(-8)mol/L), LOX-1mRNA expression increased 4.43, 4.25, 2.71, 1.84 times, respectively. After treatment with 10(-6) mol/L AngII for 3 h, LOX-1 expression (protein and mRNA) was elevated (P<0.001) in HUVECs, reaching its maxium at 24 approximate, equals 36 h. CONCLUSION: AngII upregulates LOX-1 expression concentration-dependently and time-dependently in HUVECs.