Molecular mechanism of the interaction between Megalocytivirus-induced virus-mock basement membrane (VMBM) and lymphatic endothelial cells.

IMPORTANCE: Viruses are able to mimic the physiological or pathological mechanism of the host to favor their infection and replication. Virus-mock basement membrane (VMBM) is a Megalocytivirus-induced extracellular structure formed on the surface of infected cells and structurally and functionally mimics the basement membrane of the host. VMBM provides specific support for lymphatic endothelial cells (LECs) rather than blood endothelial cells to adhere to the surface of infected cells, which constitutes a unique phenomenon of Megalocytivirus infection. Here, the structure of VMBM and the interactions between VMBM components and LECs have been analyzed at the molecular level. The regulatory effect of VMBM components on the proliferation and migration of LECs has also been explored. This study helps to understand the mechanism of LEC-specific attachment to VMBM and to address the issue of where the LECs come from in the context of Megalocytivirus infection.

Resveratrol reduces lactate production and modifies the ovarian cancer immune microenvironment.

Tumor cells show deregulated metabolism leading to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment has been reported to impair effector T cells. However, T-regulatory cells (Tregs) show metabolic advantages in lactate-rich TME that maintain a strong suppression of effector T cells, which leads to tumor immune evasion. Therefore, the glycolytic process of tumors could represent a therapeutic target, and agents that modify the energy metabolism of tumor cells have therapeutic potential. Resveratrol is a naturally occurring polyphenol that has been confirmed to suppress tumor cells' glycolytic metabolism. In this study, we show that resveratrol induces metabolic reprogramming in ovarian cancer cells. Resveratrol increases oxidative and decreases glycolysis, in association with decreased lactate production both in vitro and in vivo. Lactate reduction in TME weakens the suppressive function of Tregs, and subsequently restores anti-tumor immunity. Significantly, combined resveratrol and PD-1 blockade promote anti-tumor efficacy. These data suggest that resveratrol's anti-tumor actions in ovarian cancer could be explained, in part, through modification of the anti-tumor immunity, and indicate a novel treatment strategy for improving immune checkpoint blockade therapy using resveratrol.

Identification of infectious spleen and kidney necrosis virus (ISKNV)-encoded microRNAs.

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by complementary binding to target mRNAs. Virus-encoded miRNAs play important roles in virus life cycle and virus-host interactions. Viruses from the Megalocytivirus genus, family Iridoviridae, infect a wide range of fishes, bringing great challenges to aquaculture. Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus. In this study, using Illumina sequencing coupled with miRNA precursor prediction and stem-loop real-time PCR, 14 putative ISKNV-encoded miRNAs were preliminarily identified from ISKNV-infected mandarin fish MFF-1 cells. To initially study their functions, inhibitors of the 14 viral miRNAs were synthesized and transfected into MFF-1 cells, which were further infected with ISKNV. The results showed that these viral miRNAs could affect the virus titers in the supernatant of ISKNV-infected cells and the expression of major capsid protein (MCP). Moreover, we observed that inhibition of several ISKNV miRNAs had different effects on MCP expression and on titer of released virus, suggesting complex roles of viral miRNAs in ISKNV infection. The current study may provide a fundamental information for further identification and functional studies on miRNAs encoded by Megalocytivirus.

Transcriptional programs of infectious spleen and kidney necrosis virus (ISKNV) in vitro and in vivo.

Infectious spleen and kidney necrosis virus (ISKNV), causing serious infectious diseases to marine and freshwater fishes, is the type species of the genus Megalocytivirus, family Iridoviridae. In this study, the transcriptional programs of ISKNV in vitro (MFF-1 cells) and in vivo (spleens from mandarin fish) were investigated using real-time PCR. Transcription of all the putative open reading frames (ORFs) of ISKNV was verified. The temporal expression patterns of ISKNV ORFs in vitro and in vivo, including peak expression times (PETs) and relative maximal expression levels, were determined and compared. The K-means clustering with Spearman rank correlation was generated in heat maps constructed based on ISKNV ORF expression profiles in vivo and in vitro. The current study may provide a global picture of ISKNV infection at the transcription level and help better understand the molecular pathogenic mechanism of megalocytiviruses.

Elevated MYO10 Predicts Poor Prognosis and its Deletion Hampers Proliferation and Migration Potentials of Cells Through Rewiring PI3K/Akt Signaling in Cervical Cancer.

MYO10, recognized as an important regulator of cytoskeleton remodeling, has been reported to be associated with tumorigenesis. However, its functional implication in cervical cancer and potential mechanism still remain to be undetermined currently. MYO10 level in cervical cancer tissues was analyzed by using data retrieved from The Cancer Genome Atlas and ONCOMINE databases. Messenger RNA and protein expression levels were determined by quantitative real-time polymerase chain reaction and Western blotting. Small-interfering RNA and overexpressing plasmid were used for MYO10 silencing and overexpression, and cell proliferation was analyzed by CCK-8. Transwell assays were performed to investigate the ability of cell migration and invasion. MYO10 was upregulated in cervical cancer tissues and cells when compared to normal controls, and survival analysis showed patients with high MYO10 expression had worse overall survival. Moreover, knockdown/overexpression of MYO10 significantly inhibited/enhanced the proliferation, invasion, and migration capabilities of cervical cells transfected with siRNAs/overexpressing plasmid. Additionally, MYO10 silencing inhibited PI3K/Akt signaling pathway by decreasing the phosphorylation status of PI3K and AKT. Data from the present study indicated that MYO10 were overexpressed in patients with cervical cancer and positively linked with poor prognosis. Experimental results suggested that MYO10 induced a significant encouraging effect in cervical cancer cell proliferation, invasion, and migration, linked with involvement of PI3K/Akt signaling. Collectively, these results emphasize a novel role for MYO10 overexpression in cervical cancer and provide a potent therapeutic strategy against cervical cancer.

Association of socioeconomic and lifestyle factors with chronic non-communicable diseases and multimorbidity among the elderly in rural southwest China.

BACKGROUND: This study estimates the prevalence of five chronic non-communicable disease (NCDs) (hypertension, diabetes, CHD, COPD and stroke) and its multimorbidity, and examines the relationship between SES and lifestyle factors and multimorbidity among older adults in rural southwest China. METHODS: A cross-sectional survey of 4833 consenting adults aged ≥60 years was conducted in 2017. Data on the demographics, smoking, drinking, height, weight, blood pressure and fasting blood glucose were collected. RESULTS: Among the participants, the overall prevalence of hypertension, diabetes, stroke, COPD and CHD was 50.6, 10.2, 6.4, 5.4 and 5.5%, respectively, and of multimorbidity was 16.1%. Females had a higher prevalence of hypertension, diabetes and multimorbidity of chronic NCDs, but a lower prevalence of COPD than males (P < 0.05). Older adults with good household assets and access to medical services were less likely to experience multimorbidity, whereas obese and centrally obese participants, current smokers, current drinkers and those with a family history of chronic NCDs had a greater probability of multimorbidity. CONCLUSIONS: The findings suggest that effective strategies for prevention and control of chronic NCDs and its multimorbidity are urgently needed, especially for low-income, elderly, ethnic minority adults with poor access to medical services.

High reduced/oxidized glutathione ratio in infectious spleen and kidney necrosis virus-infected cells contributes to degradation of VP08R multimers.

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. The ISKNV-infected cells in fish tissues are attached by lymphatic endothelial cells (LECs), which is a unique pathological phenomenon of ISKNV infection. The viral proteins VP23R and VP08R and the host protein nidogen-1 constitute the virus-mock basement membrane (VMBM) on the membrane of infected cells to provide attaching sites for LECs. VP08R can form cross-linked multimers via intermolecular disulfide bonds to make VMBM a compact and strong structure. A question is that when the virions mature, how do they penetrate VMBMs to be released from the cells? In this study, the redox state in ISKNV-infected cells was investigated. We demonstrated that the ratio of reduced/oxidized glutathione (GSH/GSSG) was significantly elevated in ISKNV-infected cells, suggesting the increasing of reducing power. Remarkable changes were also observed in activities of many GSH metabolic enzymes and in the ratio of NADPH/NADP. We further exhibited that the high ratio of GSH/GSSG could lead to degradation of the VP08R multimer in vitro. These may suggest that the high GSH/GSSG ratio in infected cells could act on the VP08R multimer to facilitate the disassembly of VMBMs after virus maturation.

Identification, characterization, and function analysis of the NF-κB repressing factor (NKRF) gene from Litopenaeus vannamei.

The NF-κB family transcription factors regulate a wide spectrum of biological processes, in particular immune responses. The studies in human suggest that the NF-κB repressing factor (NKRF) negatively regulates the activity of NF-κB through a direct protein-protein interaction. However, the function of NKRF has not been studied outside mammals up to now. The current study identified a NKRF gene (LvNKRF) from the Pacific white shrimp, Litopenaeus vannamei, which showed homology with NKRFs from insects, fishes and mammals. LvNKRF was high expressed in intestine, stomach and muscle tissues and was localized in the nucleus. LvNKRF could interact with both Dorsal and Relish, the two members of the shrimp NF-κB family. Interestingly, although sharing a similar protein structure with that of human NKRF, LvNKRF showed no inhibitory but instead enhancing effects on activities of Dorsal and Relish, which was contrary to those of mammalian NKRFs. The expression of LvNKRF could not be induced by Gram-positive and -negative bacteria and immunostimulants lipopolysaccharide (LPS) and poly (I:C) but was significantly up-regulated after white spot syndrome virus (WSSV) infection. Silencing of LvNKRF significantly decreased the mortalities of shrimp caused by WSSV infection and down-regulated the WSSV copies and the expression of WSSV structural gene in tissues. These suggested that LvNKRF could facilitate the infection of shrimp by WSSV, which may be an additional strategy for WSSV to hijack the host NF-κB pathway to favor its own replication. The current study could provide a valuable context for further investigating the evolutionary derivation of NKRFs and facilitate the study of regulatory mechanisms of invertebrate NF-κB pathways.

Long-term influence of cyanobacterial bloom on the immune system of Litopenaeus vannamei.

Cyanobacteria are ubiquitously distributed in water on the Earth. It has long been known that the cyanobacterial bloom in aquaculture ponds can cause acute and massive deaths of shrimp. However, the long-term and chronic effects of the cyanobacterial bloom on shrimp are still poorly understood. In this study, the immune state of white pacific shrimp, Litopenaeus vannamei, surviving a naturally occurring cyanobacterial bloom was investigated and tracked for 70 d. Compared with the control, the growth of shrimp suffering high concentrations of cyanobacteria was obviously postponed. In these shrimp, the activities of the NF-κB, JAK/STAT and P38 MAPK immune signaling pathways and the expression of many antimicrobial peptide genes were down-regulated, whereas the expression of C-type lectins was significantly up-regulated. Although the mRNA level of lysozyme was reduced, the expression of the invertebrate-type lysozyme gene was increased. Furthermore, the concentration of hemocytes in hemolymph was greatly decreased, but the phagocytic activity of hemocytes was increased. These suggested that the cyanobacterial bloom has significant and complex influences on the immune system of shrimp, and in turn, alteration of the immune state could be a factor by which few shrimp can survive the cyanobacterial bloom. Thus, the current study could help further understand the interactions between the aquaculture water environment and the immune system of shrimp.

Zebrafish models for assessing developmental and reproductive toxicity.

The zebrafish is increasingly used as a vertebrate animal model for in vivo drug discovery and for assessing chemical toxicity and safety. Numerous studies have confirmed that zebrafish and mammals are similar in their physiology, development, metabolism and pathways, and that zebrafish responses to toxic substances are highly predictive of mammalian responses. Developmental and reproductive toxicity assessments are an important part of new drug safety profiling. A significant number of drug candidates have failed in preclinical tests due to their adverse effect on development and reproductivity. Compared to conventional mammal testing, zebrafish testing for assessing developmental and reproductive toxicity offers several compelling experimental advantages, including transparency of embryo and larva, higher throughput, shorter test period, lower cost, smaller amount of compound required, easier manipulation and direct compound delivery. Toxicity and safety assessments using zebrafish have also been accepted by the FDA and EMEA for investigative new drug (IND) approval.

6'-O-Caffeoylarbutin inhibits melanogenesis in zebrafish.

6'-O-Caffeoylarbutin, an arbutin derivative, is a naturally occurring glucoside of hydroquinone from Vaccinium dunalianum. On anti-melanogenic effect assay, 6'-O-caffeoylarbutin expressed a stronger anti-melanin activity in a dose-dependent manner with about a two-fold more than that of arbutin, but with less toxicity about a two-fold lower than that of arbutin. In addition, melanin synthesis could be fully recovered after the removal of 6'-O-caffeoylarbutin. The result suggested that 6'-O-caffeoylarbutin could be a candidate natural product to serve as a skin-whitening ingredient with the merits of potent melanin inhibition, less toxicity and reversible melanin synthesis after stopping use.

Human cardiotoxic drugs delivered by soaking and microinjection induce cardiovascular toxicity in zebrafish.

Cardiovascular toxicity is a major challenge for the pharmaceutical industry and predictive screening models to identify and eliminate pharmaceuticals with the potential to cause cardiovascular toxicity in humans are urgently needed. In this study, taking advantage of the transparency of larval zebrafish, Danio rerio, we assessed cardiovascular toxicity of seven known human cardiotoxic drugs (aspirin, clomipramine hydrochloride, cyclophosphamide, nimodipine, quinidine, terfenadine and verapamil hydrochloride) and two non-cardiovascular toxicity drugs (gentamicin sulphate and tetracycline hydrochloride) in zebrafish using six specific phenotypic endpoints: heart rate, heart rhythm, pericardial edema, circulation, hemorrhage and thrombosis. All the tested drugs were delivered into zebrafish by direct soaking and yolk sac microinjection, respectively, and cardiovascular toxicity was quantitatively or qualitatively assessed at 4 and 24 h post drug treatment. The results showed that aspirin accelerated the zebrafish heart rate (tachycardia), whereas clomipramine hydrochloride, cyclophosphamide, nimodipine, quinidine, terfenadine and verapamil hydrochloride induced bradycardia. Quinidine and terfenadine also caused atrioventricular (AV) block. Nimodipine treatment resulted in atrial arrest with much slower but regular ventricular heart beating. All the tested human cardiotoxic drugs also induced pericardial edema and circulatory disturbance in zebrafish. There was no sign of cardiovascular toxicity in zebrafish treated with non-cardiotoxic drugs gentamicin sulphate and tetracycline hydrochloride. The overall prediction success rate for cardiotoxic drugs and non-cardiotoxic drugs in zebrafish were 100% (9/9) as compared with human results, suggesting that zebrafish is an excellent animal model for rapid in vivo cardiovascular toxicity screening. The procedures we developed in this report for assessing cardiovascular toxicity in zebrafish were suitable for drugs delivered by either soaking or microinjection.

[Analysis of association of economic burden of hypertension with tobacco exposure in Luoping county of Yunnan province].

OBJECTIVE: To analyze the association between hypertension and tobacco exposure Luoping county of Yunnan province and estimate the direct cost attributable to hypertension . METHODS: Using Probability proportional to size (PPS) sampling method, 5000 rural residents aged over 18 years were selected from 12 townships in Luoping county, Yunnan province in April 2011, from which 4611 subjects completed the survey. Self-designed questionnaires were used to collect general information, smoking status, costs for outpatient consultation, inpatient, treatment, medication, travel, accommodation and extra-nutrition caused by hypertension as well as the information of health-related behavior. Their height, weight, waist circumference, hip circumference and blood pressure were measured. The direct economic burden of hypertension was calculated. Chi-square (χ(2)) test was used to compare gender differences of hypertension prevalence, smoking and passive smoking. And t test was used to compare the differences of direct economic burden of hypertension among different gender, smoking and passive smoking status. Multivariable logistic regression model was used to analyze the influence factors of hypertension. RESULTS: Among the 4611 subjects, the age was (46.90 ± 16.74) years old. Male accounted for 49.8% (2294/4611) and female 50.2% (2317/4611) . The smoking rate was higher in males (75.7% (1736/2294)) than in females(1.6% (38/2317)) (χ(2) = 2669.21, P < 0.01). The passive smoking rate was lower in males (10.0% (230/2294)) than in females (46.2% (1070/2317)) (χ(2) = 744.27, P < 0.05). Non-tobacco exposure rate in males (14.3% (328/1537)) was lower than in females (52.2% (1209/1537)) (χ(2) = 744.37, P < 0.05) . The risk of hypertension in smokers and passive smokers were higher than those without tobacco exposure, OR (95%CI) was 1.41 (1.15-1.71) (P < 0.05) and 1.31 (1.07-1.63) (P < 0.05) respectively. The per capita direct cost of hypertension was (3444.09 ± 3067.83) Yuan. Of this, tobacco exposure (4552.46 ± 3189.05) Yuan was higher than non-tobacco exposure (1907.71 ± 1383.94) Yuan (t = -3.81, P < 0.05) . Moreover, smokers were (6951.71 ± 3422.87) Yuan higher than passive smokers (3128.09 ± 2083.17) Yuan (t = 3.19, P < 0.05) and males (5827.39 ± 3240.50) Yuan were higher than females (2633.03 ± 2569.01) Yuan (t = 3.22, P < 0.05) . The total direct costs of hypertension attributable to smoking and SHS was 41 million and 38 million, respectively. CONCLUSION: Both smoking and SHS had significant impact on prevalence and economic burden of hypertension in Luoping county. Implementing effective strategies to control tobacco exposure is useful to reduce the economic burden of hypertension in the study region.

A zebrafish phenotypic assay for assessing drug-induced hepatotoxicity.

INTRODUCTION: Numerous studies have confirmed that zebrafish and mammalian toxicity profiles are strikingly similar and the transparency of larval zebrafish permits direct in vivo assessment of drug toxicity including hepatotoxicity in zebrafish. METHODS: Hepatotoxicity of 6 known mammalian hepatotoxic drugs (acetaminophen [APAP], aspirin, tetracycline HCl, sodium valproate, cyclophosphamide and erythromycin) and 2 non-hepatotoxic compounds (sucrose and biotin) were quantitatively assessed in larval zebrafish using three specific phenotypic endpoints of hepatotoxicity: liver degeneration, changes in liver size and yolk sac retention. Zebrafish liver degeneration was originally screened visually, quantified using an image-based morphometric analysis and confirmed by histopathology. RESULTS: All the tested mammalian hepatotoxic drugs induced liver degeneration, reduced liver size and delayed yolk sac absorption in larval zebrafish, whereas the non-hepatotoxic compounds did not have observable adverse effect on zebrafish liver. The overall prediction success rate for hepatotoxic drugs and non-hepatotoxic compounds in zebrafish was 100% (8/8) as compared with mammalian results, suggesting that hepatotoxic drugs in mammals also caused similar hepatotoxicity in zebrafish. DISCUSSION: Larval zebrafish phenotypic assay is a highly predictive animal model for rapidly in vivo assessment of compound hepatotoxicity. This convenient, reproducible animal model saves time and money for drug discovery and can serve as an intermediate step between cell-based evaluation and conventional animal testing of hepatotoxicity.

[The quality of life among people living with HIV/AIDS (PLWHA) in Kunming].

OBJECTIVE: To explore the quality of life among people living with HIV/AIDS (PLWHA) and analyze the influencing factors in Kunming. METHODS: A cross-sectional survey was conducted from March to April in year 2011, and 247 PLWHA were selected by convenience sampling from Yunnan CDC, Yunnan and Kunming infectious disease hospitals. General questionnaires, the simplified Chinese edition of medical outcomes study-HIV health survey (MOS-HIV, including 11 dimensions) and Social Support Scale were used. t test and multivariable linear regression model were used to analyze the results. RESULTS: For the subjects investigated, the age was (39.8 +/- 11.9) years old, the median (quartile) value of symptoms related to HIV infection was 1(2). As to the scores of quality of life measured by MOS-HIV, physical summary score was 47.4 +/- 11.2, mental summary score was 43.6 +/- 9.7; for the scores of 11 dimensions of the MOS-HIV,that were general health (42.9 +/- 19.9), physical function (79.4 +/- 24.9), role function (59.8 +/- 48.2), social function (67.0 +/- 33.6), cognitive function (71.0 +/- 25.4), pain (81.3 +/- 26.2), mental health (62.0 +/- 22.3), vitality (49.3 +/- 23.8), health distress (74.4 +/- 21.0), quality of life (51.8 +/- 21.1), health transition (49.0 +/- 29.8). The total score of social support was 28.6 +/- 7.6, of which the score of subjective social support was 17.2 +/- 6.3, the score of the objective social support was 5.9 +/- 2.2; the score of the utilization of social support was 5.5 +/- 1.9. Multivariable linear regression analysis showed that the more the symptoms related to HIV infection, the lower the physical summary scores (standardized coefficients b' = -0.22), the general health (b' = - 0.31), the physical function (b' = -0.16), the role function (b' = -0.23), the pain (b' = -0.21), the mental health (b' = -0.22), the vitality (b' = -0.22) and the health distress scores (b' = - 0.24) (all P values < 0.05); the older the age, the lower the physical summary scores (b' = - 0.16), the mental summary scores (b' = - 0.16), the physical function (b' = -0.26), the vitality (b' = -0.26) and the quality of life scores (b' = -0.17) (all P values < 0.05); the higher the score of the subjective social support,the higher the physical summary scores (b' = 0.26), the mental summary scores (b' = 0.22), the general health (b' = 0.27), the social function (b' = 0.26), the mental health (b' = 0.15) and the quality of life scores (b' = 0.22) (all P values < 0.05); the higher the score of the utilization of social support, the higher the physical function (b' = 0.16) and the health transition scores (b' = 0.31) (all P values < 0.05). CONCLUSION: PLWHA in Kunming have relatively lower scores of quality of life. A large number of symptoms during infection, older age and lower score of subjective social support were the hazard factors of quality of life in PLWHA.

Application of GP5 protein to develop monoclonal antibody against porcine reproductive and respiratory syndrome virus.

In this study, a panel of monoclonal antibodies (mAbs) against Porcine reproductive and respiratory syndrome virus(PRRSV), named as 8C9 and4B4, were produced by fusing SP2/0 myeloma cells and spleen cells of BALB/c mice immunized with the PRRSV (TCID(50)=5.5), screened by the indirect ELISA and subjected to several limiting dilutions. mAbs were then identified by biological characterization. Among the two fusion cell strains, 8C9 belonged to the IgG1 subclass and 4B4 belonged to the IgG2a subclass. The titers in cell culture supernatant and abdomen liquor reached to 1:10(4)and 1:10(5), respectively. The specificity test indicated that the two cells had specific reactions for the PRRSV and GP5 protein respectively, and no reaction with Classical swine fever virus (CSFV) or Swine vesicular disease virus (SVDV). The molecular weights of the heavy chain and light chain were about 45.0 kDa and 25.0 kDa, respectively. In neutralization activity tests, the results showed that the prepared mAb 4B4 can protect 50% of cells with no CPE in dilution up to 1:512, but mAB 8C9 has no neutralization activities to PRRSV.

Indirect ELISA with recombinant GP5 for detecting antibodies to porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome is caused by the PRRS virus (PRRSV), which has six structural proteins (GP2, GP3, GP4, GP5, M and N). GP5 and N protein are important targets for serological detection by enzyme-linked immunosorbent assay (ELISA) and other methods. Toward this goal, we developed an indirect ELISA with recombinant GP5 antigens and this method was validated by comparison to the LSI PRRSV-Ab ELISA kit. The results indicated that the optimal concentration of coated recombinant antigen was 0.2 µg/well for a serum dilution of 1:40. The rate of agreement with the LSI PRRSV-Ab kit was 88.7% (266/300). These results support the potential use of recombinant GP5 as an antigen for indirect ELISA to detect PRRSV antibodies in pigs.

[Relationship between paraoxonase/glutathione S-transferase gene polymorphism and health conditions of floriculture farmers].

OBJECTIVE: In this study we conducted a cross-sectional study and reported on the distribution of two common genetic polymorphisms of the PON1 gene and two common genetic polymorphisms of the GST gene as well as the association between those polymorphisms and other predictors in a population of floriculture workers from Kunming city. METHODS: 136 pesticide-exposed farmers were recruited. PON1 and GST T1, M1 genotype were determined by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: (1) Compared with exposure group, the GLB in control group was higher (ß = -0.16, t = -2.30, P = 0.02), but the A/G in control group was lower (ß = 0.14, t = 2.09, P = 0.04); (2) Compared with the persons who carried QQ genotype, the accumulative symptom scores were lower in the persons who carried RR genotype (t = -2.78, P = 0.006); (3) Compared with GST T1 carriers, non-carriers' GLB (ß = -0.20, t = -3.01, P = 0.00) and IgG (ß = -0.20, t = -3.01, P = 0.00) were higher, but the A/G was lower; (4) The abnormities of cardiograms among people who had been exposed to pesticides were higher compared to people who did not expose to any pesticides (ß = 1.147, P = 0.042). CONCLUSION: PON1-192 and GST T1 gene were associated with the farmers health condition after pesticides exposure.