Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs.@*METHODS@#We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model.@*RESULTS@#Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE.@*CONCLUSIONS@#The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

Interactions between induced T regulatory cells and B cells in inflammatory milieu in mice with collagen-induced arthritis / 中国免疫学杂志

Objective:To investigate the interactions between induced T regulatory cells ( iTregs ) and B cells in the inflammatory milieu in mice with collagen-induced arthritis(CIA). Methods: CD19+ cells were isolated from the spleen cells of normal DBA1/J(N-B) mice and CIA mice(CIA-B) on the 35th day after the first immunization with established arthritis. These B cells were used as antigen-presenting cells to observe their effects on the induction of Tregs. Tregs were induced with the classic method and co-cultured with CIA-B cells. CIA-B cell effects on iTreg proliferation and the expression of CTLA-4 on iTregs were explored. iTregs′ influence on the expressions of co-stimulators(CD80,CD86) and MHCⅡon B cells was studied and its mechanism was determined by the Transwell experiments. Results: CIA-B could induce more Treg production and proliferation. CIA-B could also promote the CTLA-4 expression on iTreg cell surface which worked through a cell-contact pathway, while iTregs could increase the expressions of co-stimulators(CD80,CD86) and MHCⅡby the same way. Conclusion: iTregs could show their immune suppressive function through the interactions with CIA-B cells in the inflammatory milieu in mice with CIA. These interactions work by a cell-contact pathway.

Effects of CXCL4 on human dermal microvascular endothelial cells and secretion of vasomotion factors / 中国免疫学杂志

Objective:To identify the proliferation effect and angiogenic ability of CXCL4 on human dermal microvascular endothelial cells(HDMECs),and to explore the secretion of vasomotion factors.Methods:HDMECs were treated with gradient concentration to test the proliferation of HDMECs.CCK-8 was used to explicated the proliferation of HDMECs.The effect of CXCL4 on angiogenic ability of HDMECs was determined by tube formation assay.The mRNA levels of endothelin-1(ET-1),Fli-1,AngiotensinⅡtype 1 receptor(AT1R) and endothelin-1 type A receptor (ETAR) were detected by real-time quantitative polymerase chain reaction (Real-time PCR).Results:The specific receptor of CXCL4 was expressed on HDMECs.CXCL4 could inhibit the proliferation of HDMECs and the number of tube formation in a dose-depend manner.After CXCL4 intervention,the relative amplification multiples of ET-1,AT1R were significantly increased(P<0.05),Fli-1 was decreased(P<0.05),and ETAR had no change as compared with the control group.Furthermore,CXCL4 antagonist could reverse the effects of CXCL4 on HDMECs.Conclusion:CXCL4 inhibit the proliferation and angiogenesis of HDMECs and induce the secretion of ET-1 and AT1R,reduce the secretion of Fli-1 in a dose-dependent manner.

Comprehensive analysis on variation of cardiac enzyme and troponin induced by acute organophosphorous poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To discuss the diagnostic value of cardiac enzyme and troponin in acute organophosphorus pesticide poisoning (AOPP).</p><p><b>METHODS</b>A retrospective study was performed in the document published in domestic journals and PubMed from 1979 to 2010. The data of the cardiac enzyme and troponin were collected. Statistical analysis was conducted with one-way ANOVA and rank sum test. 2129 cases with AOPP were enrolled.</p><p><b>RESULTS</b>The levels of creatine kinase (CK), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) in milder, moderate and severe poisoning groups were significantly elevated compared by the healthy control group (P < 0.05). The differences were also dramatic among three patients groups (P < 0.05). The ratios of CK-MB to CK in both moderate and severe groups were significantly lower than in healthy controls (P < 0.05). The levels of CK, CK-MB and cTnI were higher especially in patients with intermediate myasthenic syndrome (IMS) than patients without IMS. Meanwhile, the levels of CK and CK-MB were elevated in patients with respiratory failure compared by non-failure ones, but decreased in the ratios of CK-MB to CK (P < 0.05).</p><p><b>CONCLUSIONS</b>The elevation of CK and CK-MB in serum could not be judged as the criteria of myocardial damage in AOPP, the ratio of CK-MB to CK were more valuable; the value of cTnI in myocardial damage was still in suspect. CK, CK-MB and cTnI could be used as auxiliary criteria of AOPP classification.</p>

Influence of MDR1 gene C3435T on peripheral white blood cell counts in workers exposed to benzene / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the effects of MDR1 C3435T on the peripheral white blood cell counts in workers exposed to benzene.</p><p><b>METHODS</b>One hundred and twenty-one benzene-exposed workers and 110 healthy controls without benzene exposure were enrolled in this study. White blood cell counts influenced by the polymorphism of MDR1 gene were analyzed.</p><p><b>RESULTS</b>The frequency of MDR1 3435 C/C, C/T, T/T in healthy controls was 37.27%, 46.36%, 16.37%, respectively, and it was 38.84%, 41.33%, 19.83% in the benzene-exposed workers, respectively. The frequency of the MDR1 gene was also not significantly different between benzene exposed workers and controls. Subjects exposed to benzene with MDR1 3435 mutation genotype (T/T) had the significantly lower WBC [(5.46 ± 1.51) × 10(9)/L] than those carrying wild type (C/C) and heterozygous (C/T), whose WBC were (6.08 ± 1.28) × 10(9)/L (P = 0.044).</p><p><b>CONCLUSION</b>P-glycoprotein encoded by MDR1 gene may be implicated into the hematotoxicity of benzene. Subjects carrying MDR1 3435 T/T genotype may have a higher risk of benzene poisoning.</p>

High-resolution melting: a analysis for genotyping of MDR1 C3435T in benzene-exposed workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>Using high resolution melting (HRM) to analysis MDR1 C3435T in people exposed to benzene.</p><p><b>METHODS</b>Restriction fragment length polymorphism (RFLP) was utilized to detect the polymorphism of MDR1 3435 in 121 benzene-exposed workers, and the results were compared with the HRM in 10% samples and were confirmed with direct sequencing for six people in them.</p><p><b>RESULTS</b>By direct sequencing, consistent results of benzene-exposed workers with RFLP or HRM were got. The new high resolution melting curve analysis is more efficient, more convenient, and cheaper than RFLP.</p><p><b>CONCLUSION</b>High-resolution melting analysis provides a valid approach to efficiently detect DNA genetic diagnosis, which is suitable for detect susceptible genes in occupational surveillance.</p>

Meta-analysis of the effectiveness of plasma exchange in treatment of severe and acute organophosphate poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To discuss the effectiveness of severe and acute organophosphate poisoning (AOPP) treated with plasma exchange in China.</p><p><b>METHODS</b>Researches about effectiveness of severe AOPP treated with plasma exchange were analyzed by Review Manager 4.2 and fixed effect model of meta-analysis method were used.</p><p><b>RESULTS</b>Six trials including 433 patients were identified. Treatment group including 211 patients adopted traditional physician therapy plus plasma exchange, and control group including 222 patients received physician therapy only. The case-fatality rate of the treatment group was lower than the control one [RR=0.30, 95%CI (0.19-0.49), P<0.01].</p><p><b>CONCLUSION</b>Plasma exchange can improve the cure rate of severe AOPP.</p>

Molecular analysis of a SNP in SCL2A9 and uric acid levels in Chinese male gout patients / 中华风湿病学杂志

ObjectiveSLC2A9 is a novel identified urate transporter that affects serum uric acid levels. The present study is aimed to investigate rs7442295 polymorphism in intron 6 of SLC2A9 in a population of Chinese male gout or hypemricaemia subjects. MethodsA total of 268 gout patients and 288 healthy male volunteers were included. Blood pressure, body mass index(BMI), serum uric acid, glucose, lipid,urea and creatine were detected. DNA was purified from peripheral blood and the rs7442295 polymorphism was evaluated using high resolution melting ( HRM ) analysis and direct sequencing. Data were analyzed with t test or chi-square test. Results A/A and A/G genotypes were unambiguously distinguished with HRM technology. The occurrence of the homozygous type (G/G) was completely absent among the study population.The prevalence of the A/A and A/G genotype was 96.2％ and 3.8％ respectively. However, no significant differences of genotype frequencies were found in gout patients and normal subjects(x2=0.003, P=0.82; x2=0.003, P=1.00). But the serum uric acid levels in individuals with the A/G genotype[(293±100) μmol/L]were significantly lower than those with the A/A genotype[(392±133) μmol/L](t=2.426, P＜0.01 ). The A/G genotype frequency was significantly higher in the low-uric acid group than in the high uric-acid group (x2=6.279, P=0.01 ). Genotyping based on HRM was fully concordant with sequencing. Conclusion The polymorphism rs7442295 in SLC2A9 may be a genetic marker to assess risk of hyperuricemia among Chinese male Hart population. HRM is a simple, fast, reliable and close-tube technology for genotyping.

Different therapeutic efficacy of pralidoxime chloride PAM-Cl on AChE against acute toxicity of methamidophos, dichlorvos and omethoate / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the treatments on the patients with acute methamidophos dichlorvos (DDV) and omethoate poisoning and provide the reliable basis for the rational treatments on these three organophosphorus pesticides poisoning.</p><p><b>METHODS</b>101 patients with AOPP in 7 hospitals were divided into three groups: Group A, 59 patients with acute methamidophos poisoning, Group B, 32 patients with acute DDV/dipterex (DEP) poisoning, Group C, 10 patients with acute omethoate/dimethoate poisoning. The levels of erythrocyte AChE and the therapeutic efficacies of pralidoxime chloride (PAM-Cl) were compared among the three groups.</p><p><b>RESULTS</b>The AChE activities of all the three groups were inhibited on level of (9.12 +/- 7.99) U/g Hb (group A), 7.32 +/- 4.62 U/g Hb (group B) and (12.01 +/- 9.53) U/g Hb (group C), among which no significant difference was found (P > 0.05). All the patients recovered from acute cholinergic excitation or crisis after the treatment of PAM-Cl. The erythrocyte AChE activities were obviously reactivated in group A three hours later after admission to hospital, each on level of (11.37 +/- 8.67) U/g Hb, (12.51 +/- 6.98) U/g Hb, (15.90 +/- 7.31) U/g Hb, (18.33 +/- 4.78) U/g Hb and (18.91 +/- 7.00) U/g Hb at the 12th, 24th, 48th, 72nd hour and discharge (P < 0.05), and the upgrade tendency was continuous. AChE activities in group B were also reactivated after treatment, each on level of (8.91 +/- 5.89) U/g Hb, (1.31 +/- 6.61) U/g Hb, (13.00 +/- 7.55) U/g Hb, (14.22 +/- 7.80) U/g Hb, (12.78 +/- 7.07) U/g Hb and (16.87 +/- 7.06) U/g Hb at the 3rd, 12th, 24th, 48th, 72nd hour and discharge, but the upgrade tendency turned slowly after 12 hours, the inhibited AChE activities were not reactivated in group C from the beginning to the end.</p><p><b>CONCLUSION</b>After the treatment of PAM-Cl, the AChE activities of the patients with acute methamidophos poisoning could be continuously reactivated, the AChE activities of the patients with acute DDV/DEP poisoning could also be reactivated in 12 hours, and then keep stable, but the AChE activities of the patients with acute omethoate/dimethoate poisoning could not be reactivated. However, PAM-Cl has therapeutic efficacy against acute toxicity of all the three organophosphorus pesticides. Oximes should be vigorously used in the treatment of AOPP, including acute omethoate/dimethoate poisoning.</p>

A case-control study of risk factors for myelodysplastic syndromes / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To determine the risk factors involved in myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>A 1:2 case-control study was conducted in 20 Shanghai' hospitals over a 3-year period, covering 266 "de novo" MDS cases corresponded to FAB criteria, and 532 age- and gender-matched controls from same hospitals with MDS cases. Subjects were all surveyed using the same standard questionnaire including histories of medications (Chloramphenicol, Sulfonamides, Meprobamate, Phenytoin, Colchicine, Cyclophosphamide, Propylthiouracil, Anti-TB medication, Tolbutamide, Primaquine and Chinese traditional herbs such as Bezoar, Angelica, Arsenic, Thunder cloud vine) at least 5 years prior to the onset of the disease, tumors, exposure to benzene, heavy metal, organic phosphates, pesticides, petrol/diesel, organic solvents, dye and hair dye products, radiation, house decorating, alcohol and smoking.</p><p><b>RESULTS</b>Occupational exposure to benzene increased significantly the risk of MDS (OR: 8.52, 95% CI: 2.30 - 31.10). Living near high voltage power lines (100 m) increased significantly the risk of MDS (OR: 1.60, 95% CI: 1.10 - 2.32). House decorating (one year prior to the onset of the disease) increased significantly the risk of MDS (OR: 2.40, 95% CI: 1.38 - 4.14). Other investigated occupational poisons did not increase significantly the risk of MDS. Hair dye products, alcohol and smoking did not increase significantly the risk of MDS.</p><p><b>CONCLUSION</b>Occupational exposure to benzene, living near high voltage power lines and house decorating are the risk factors of MDS.</p>

Genetic polymorphism of tumor necrosis factor-alpha in patients with chronic benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the relationship between genetic polymorphism of tumor necrosis factor-alpha (TNF-alpha, sites at -238 nt and -308 nt) and susceptibility to chronic benzene poisoning.</p><p><b>METHOD</b>The polymorphism of TNF-alpha gene were detected by nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique from 50 benzene poisoning patients and 60 control individuals exposed to benzene.</p><p><b>RESULTS</b>The frequency of the TNF-alpha-238G/G, A/G and A/A in controls (95%, 5% and 0%, respectively), were not significantly different from those in patients (92%, 6% and 2%, respectively, P > 0.05). The frequency of the TNF-alpha-308G/G, A/G and A/A in patients were 76%, 24% and 0% respectively, and that in control individuals were 93%, 7% and 0% respectively. Chi(2) test showed that frequency of TNF-alpha-308A/G in patients was significantly higher than that in controls (chi(2) = 6.22, P = 0.013). Logistic analysis showed that TNF-alpha-308A/G was the independent risk factor of benzene poisoning (OR = 5.3, P < 0.05).</p><p><b>CONCLUSION</b>Individuals with TNF-alpha-308A/G gene polymorphism are susceptible to benzene poisoning.</p>

The research of quantitative salivary gland scintigraphy in the diagnosis of Sjgren's syndrome / 中华风湿病学杂志

Objective The purpose of this study is to determine whether the quantitative parameters of salivary gland scintigraphy are useful in the diagnosis of Sjgren's syndrome(SS).Method Forty patients with SS and 29 control subjects underwent salivary gland scintigraphy.Two indices,uptake ratio and maximum se- cretion were mearsured.The optimal cut-points of both indices were derived from receiver operative character- istic curve(ROC).The diagnostic value of the indices was assessed by the area under ROC curve(AUC~(ROC)). Results The optimal cut-point of uptake ratio was 5.5～5.7.The optimal cut-point of maximum secretion was 0.20.The sensitivities of both indices were 86.2%～89.7%.The specificity of uptake ratio was 63.4%～65.9%. The specificity of maximum secretion was 82.9%～85.4%.The AUC\+\{RoC\} of uptake ratio was 0.780/0,776.The AUC\+\{ROC\} of maximum secretion was 0.905/0,899.Conclusion The quantitative parameters of salivary gland scintigraphy may be useful in the diagnosis of Sj(?)gren syndrome.