OBJECTIVETo explore the relationship of polymorphisms in the xeroderma pigmentosum group D (XPD) gene and the glutathione-S transferees M1 (GSTM1) gene with susceptibility to primary hepatic carcinoma (PHC) in Tibetans from the Qinghai region.

METHODSThis case-control study compared equal groups (n=102 each) of patients with PHC and healthy individuals recruited from Qinghai, Tibet.PCR and denaturing high-performance liquid chromatography (DHPLC) was used to detect each participant's genotypes for the XPD and GSTM1 genes.Non-conditional logistic regression modeling was used in multivariate analysis to evaluate the predictive value for PHC, to compare the risk of different genotypes for PHC, and to assess the risk of gene polymorphisms and environmental factors for PHC.

RESULTSSix factors, including smoking, carnivorous diet, alcohol consumption, hepatitis B virus (HBV) infection, immediate family members with HBV infection and immediate family members with history of PHC, were included in the logistic regression model (alpha =0.05).The XPD751C mutation genotype distribution frequencies were significantly higher in the cases than in the controls (21.6% vs. 10.8%, P=0.036). The risk of PHC increased 2.275 times (95% CI, 1.04-4.98). The frequencies of the GSTM1 genotype were remarkably higher in the cases than in the controls (60.4% vs. 39.6%, P=0.017), suggesting this as an exposure factor. Individuals with the GSTM1 genotype had 1.963 times higher risk of PHC than individuals without the GSTM1 genotype (95% CI, 1.124-3.428). With both the XPD751C mutation and the GSTM1 genotype as exposure factors, the risk incidence increased to 3.030 times (95% CI, 1.165-7.881), indicating that the combined genotypes have a synergistic effect.Application of unconditioned logistic stepwise regression analysis of the genotypes and environmental risk factors showed an interaction between the XPD751C mutation and HBV infection, alcohol consumption and immediate family members with history of PHC. In addition, an interaction between the GSTM1 genotype and HBV infection was found.

CONCLUSIONAlcohol consumption, HBV infection and the presence of immediate family members with HBV infection are the main environmental risk factors of PHC in Qinghai Tibetans.Qinghai Tibetans who carry the XPD751C gene mutation and the GSTM 1 genotype are at increased risk of PHC, compared to individuals carrying only one or the other.The XPD751C mutation may increase risk of PHC when combined with the environmental factors.

Alcohol Drinking ; Carcinoma, Hepatocellular ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Glutathione ; Glutathione Transferase ; genetics ; Humans ; Incidence ; Liver Neoplasms ; genetics ; Logistic Models ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors ; Smoking ; Tibet ; Xeroderma Pigmentosum Group D Protein ; genetics

OBJECTIVE: To explore the protective effect and possible mechanisms of bloodletting acupuncture at Jing-well points (BAJP) pre-treatment on acute hypobaric hypoxia (AHH)-induced myocardium injury rat. METHODS: Seventy-five rats were randomly divided into 5 groups by a random number table: a control group (n=15), a model group (n=15), a BAJP group (n=15), a BAJP+3-methyladenine (3-MA) group (n=15), and a BANA (bloodletting at nonacupoint; tail bleeding, n=15) group. Except for the control group, the AHH rat model was established in the other groups, and the corresponding treatment methods were adopted. Enzyme-linked immunosorbent assay (ELISA) was used to detect creatine kinase isoenzyme MB (CK-MB) and cardiac troponins I (CTnI) levels in serum and superoxide dismutase (SOD) and malondialdehyde (MDA) levels in myocardial tissue. Hematoxylin-eosin (HE) staining was used to observe myocardial injury, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was used to observe cell apoptosis. Transmission electron microscopy detection was used to observe mitochondrial damage and autophagosomes in the myocardium. The mitochondrial membrane potential of the myocardium was analyzed with the fluorescent dye JC-1. Mitochondrial respiratory chain complex (complex I, III, and IV) activities and ATPase in the myocardium were detected by mitochondrial respiratory chain complex assay kits. Western blot analysis was used to detect the autophagy index and hypoxia inducible factor-1α (HIF-1α)/Bcl-2 and adenovirus E1B 19k Da-interacting protein 3 (BNIP3) signaling. RESULTS: BAJP reduced myocardial injury and inhibited myocardial cell apoptosis in AHH rats. BAJP pretreatment decreased MDA levels and increased SOD levels in AHH rats (all P<0.01). Moreover, BAJP pretreatment increased the mitochondrial membrane potential (P<0.01), mitochondrial respiratory chain complex (complexes I, III, and IV) activities (P<0.01), and mitochondrial ATPase activity in AHH rats (P<0.05). The results from electron microscopy demonstrated that BAJP pretreatment improved mitochondrial swelling and increased the autophagosome number in the myocardium of AHH rats. In addition, BAJP pretreatment activated the HIF-1α/BNIP3 pathway and autophagy. Finally, the results of using 3-MA to inhibit autophagy in BAJP-treated AHH rats showed that suppression of autophagy attenuated the treatment effects of BAJP in AHH rats, further proving that autophagy constitutes a potential target for BAJP treatment of AHH. CONCLUSION BAJP is an effective treatment for AHH-induced myocardial injury, and the mechanism might involve increasing HIF-1α/BNIP3 signaling-mediated autophagy and decreasing oxidative stress.
Animals ; Rats ; Acupuncture Therapy ; Altitude ; Apoptosis ; Autophagy ; Bloodletting ; Hypoxia/metabolism* ; Membrane Proteins/pharmacology* ; Mitochondrial Proteins/pharmacology* ; Oxidative Stress ; Rats, Sprague-Dawley

OBJECTIVE: To explore the protective effect of bloodletting acupuncture at twelve Jing-well points on hand (BAJP) on acute hypobaric hypoxia (AHH)-induced brain injury in rats and its possible mechanisms. METHODS: Seventy-five Sprague Dawley rats were divided into 5 groups by a random number table (n=15), including control, model, BAJP, BAJP+3-methyladenine (3-MA), and bloodletting acupuncture at non-acupoint (BANA, tail tip blooding) groups. After 7-day pre-treatment, AHH models were established using hypobaric oxygen chambers. The levels of S100B, glial fibrillary acidic protein (GFAP), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method were used to assess hippocampal histopathology and apoptosis. Transmission electron microscopy assay was used to observe mitochondrial damage and autophagosomes in hippocampal tissues. Flow cytometry was used to detect mitochondrial membrane potential (MMP). The mitochondrial respiratory chain complexes I, III and IV activities and ATPase in hippocampal tissue were evaluated, respectively. Western blot analysis was used to detect the protein expressions of Beclin1, autophagy protein 5 (ATG5), microtubule-associated protein 1 light chain 3 beta (LC3B), phosphatase and tensin homolog induced kinase 1 (PINK1), and Parkin in hippocampal tissues. The mRNA expressions of Beclin1, ATG5 and LC3-II were analyzed by quantitative real-time polymerase chain reaction. RESULTS: BAJP treatment reduced hippocampal tissue injury and inhibited hippocampal cell apoptosis in AHH rats. BAJP reduced oxidative stress by decreasing S100B, GFAP and MDA levels and increasing SOD level in the serum of AHH rats (P<0.05 or P<0.01). Then, BAJP increased MMP, the mitochondrial respiratory chain complexes I, III and IV activities, and the mitochondrial ATPase activity in AHH rats (all P<0.01). BAJP improved mitochondrial swelling and increased the autophagosome number in hippocampal tissue of AHH rats. Moreover, BAJP treatment increased the protein and mRNA expressions of Beclin1 and ATG5 and LC3-II/LC3-I ratio in AHH rats (all P<0.01) and activated the PINK1/Parkin pathway (P<0.01). Finally, 3-MA attenuated the therapeutic effect of BAJP on AHH rats (P<0.05 or P<0.01). CONCLUSION BAJP was an effective treatment for AHH-induced brain injury, and the mechanism might be through reducing hippocampal tissue injury via increasing the PINK1/Parkin pathway and enhancement of mitochondrial autophagy.

Objective To investigate the effect of HCV RNA on virological and immunological response to highly active antiretroviral therapy (HAART),liver function and blood lipid levels in HIV/HCV co-infected patients.Methods In a cohort study,275 HIV/HCV co-infected former blood donors receiving HAART were followed up every six month in Henan province in China.HCV RNA,HIV RNA,CD+4 T cell counts,indexes of liver function and lipid levels were periodically tested.The differences of HIV viral load suppression,immunological response,liver injury and blood lipid levels between HCV RNA positive group and negative group were compared by x2 test and two independent-samples tests.Result There was no significant difference of HIV viral load suppression between HCV RNA positive group and HCV RNA negative group six-month treatment (45.6% vs.38.5% ,X2=1.150,P>0.05) and CD+4 T cell counts before (286 cells/μ1 vs.209 cells/μ1,Z=0.734,P=0.463)and after 6-month (310 cells/μ1 vs.362 cells/μl,Z=0.562,P=0.574) ,12-month(378 cells/μ1 vs.289 cells/μ1,Z=1.091,P=0.275),18-month(363 cells/μ1 vs.288 cells/μl,Z=1.435,P=0.151) ,24-month(413 cells/μ1 vs.348 cells/μ1,Z=0.939,P=0.348) HAART.The mean levels of serum ALT (55.0 U/L vs.29.5 U/L,Z=6.789,P<0.01),AST(46.0 U/L vs.33.0 U/L,Z=4.890,P<0.01)、TBIL(9.3 mmol/L vs.7.2 mmol/L,Z=3.748,P<0.01)were significantly higher in HCV RNA positive group than that in HCV RNA negative group.HCV RNA was the independent variables associated with liver injury after HAART (aOR=3.8,P<0.01).The serum triglyceride level was higher in HCV RNA positive group than that in HCV RNA negative group(1.2 mmoL/L vs.1.4 mmol/L,Z=1.936,P=0.043) .The serum HDL level was higher in HCV RNA positive group than that in HCV RNA negative group (1.5 mmol/L vs.1.3 mmol/L,Z=2.251,P=0.024).Conclusions HCV RNA does not affect HIV virological responses to HAART and CD+4 T recovery.HCV RNA is an independent risk factor associated with liver injury in HIV/HCV co-infected patients receiving HAART,but appears to provide significant protection against HAART-ieduced hyperlipidemia.

Objective To investigate the association between APOBEC3G mRNA levels in peripheral blood mononuclear cells(PBMCs)of HIV/AIDS patients and disease progression in Henan province.Methods Real-time PCR was used to detect the mRNA levels of APOBEC3G in PBMCs of HIV/AIDS patients at difierent disease progression stage.Flow cytometry and automated viral load analyzer were used to count CD4+ T cells and plasma HIV viral loads.Results The mRNA levels of APOBEC3G in HIV/AIDS patients were lower than in HIV-negative controls(t=4.887,P＜0.01),and APOBEC3G levels were significantly higher in slow development group than those in HIV and AIDS groups(P＜0.05).The levels of APOBEC3G mRNA correlated positively with CD4+ T cell counts(R2=0.190,P=0.002)and negatively with HIV-1 viral loads(R2=0.094.P=0.038).Conclusions The APOBEC3G mRNA levels in PBMC of HIV infected individuals are associated with HIV disease pmgression. Higher mRNA expression levels of APOBEC3G may be one of the protective factors which can play important role in delaying disease progression.

Objective To investigate the impact of hepatitis C virus (HCV)-RNA levels on human immunodeficiency virus (HIV)-1 disease progression in Chinese HIV/HCV co-infected individuals. Methods Cross-sectional analysis was performed among 391 HIV-infected patients for assessment of HCV-IgG, HCV-RNA, HIV-RNA, CD4 cell counts and cell surface markers of immune activation, to compare the difference of viral and immune indexes between HCV-RNA high group and HCV-RNA low group, and to elucidate the association between HCV-RNA, HIV-RNA and CD4 cell counts in HIV/HCV co-infected patients. Results (1) The percentage of anti HCV-IgG positive of former plasma donor group (93%) and drug-injection group (97.5%) were significantly higher than that of sexual transmission group (20.1%). The percentage of HCV-RNA positive of drug-injection group (89.9%) was significantly higher than that of former plasma donor group (48.3%) and sexual transmission group (62.5%), P<0.01, respectively. (2) HCV-RNA levels were positively correlated to HIV-RNA levels (r=0.237,P

Objective: To evaluate the outcome of negative pressure closed drainage with chitosan membrane in the treatment of multiple drug-resistant bacterial infections. Methods: From January 2015 to December 2017, 108 patients with skin ulcer wound complicated by multiple drug-resistant bacterial infection were admitted in the department of burn and plastic surgery, Qingdao Jiaozhou Central Hospital. Among them, 36 patients had pressure ulcers, 40 cases had diabetic foot wounds, and 32 were traumatic skin ulcer wounds. Patients were divided into group A or group B for different treatments. In group A, besides the basic surgical dressing change, patients were treated by negative pressure closed drainage with chitosan membrane. The patients in Group B were only treated with basic surgical dressing change. The changes of wound were closely observed during the phases, and the wound bacterial culture and antimicrobial drug sensitivity test were performed regularly. The therapeutic effects of the 2 groups were compared. The changes of bacterial species of wound infection and the healing time were recorded. Results: In group A, the healing time of wound infection was: pressure ulcers (14.00±1.28) days, diabetic foot wounds (13.40±1.27) days, traumatic skin ulcer wounds (12.44±1.55) days. In group B, the wound healing time was: pressure ulcers (25.17±2.73) days, diabetic foot wounds (23.85±1.73) days, traumatic skin ulcer wounds (19.81±1.94) days. The wound healing time of group A was shorter than group B. In group A, the multiple drug-resistant bacteria was replaced by non-multiple drug-resistant bacteria, or there was no pathogenic bacterial growth. The differences between the two groups was statistically significant (all P<0.05). Conclusions Additional to the basic surgical dressing change, negative pressure closed drainage with chitosan membrane could promote wound healing, when it′s associated with multiple drug-resistant bacteria infection. This method has benefits in efficient drainage, preventing the formation of bacterial biofilm and changing local microenvironment for the dominant propagation. Therefore, it could effectively control the multiple drug-resistant bacterial infections, promote wound healing and save treatment time.

Objective: To investigate the clinical effects of the " rectangle plus triangle flaps" methods to repair the post-burn pseudo anal stenosis. Methods: From Oct. 2014 to Jan. 2017, five cases of pseudo anal stenosis were hospitalized and the durations of their scar contraction were 0.5 to 2 years. Flaps were located: at 3 o′clock and 9 o′clock directions of anus with prone position. Flaps were designed as one rectangle flap plus two triangle flaps. Rectangle flap was located from the exit of the diverticulum (pedicle) to the anus (distal end). Triangle flaps were located between the anus and the distal end of the rectangle flap, perpendicular to the rectangle flap. Flap transfer: ① the rectangle flap was advanced to the anus direction and sutured with the incision edge of the triangle flap closer to the anus; ② the two triangle flaps were rotated by 90 degrees and transferred to the two longitudinal incisions of the rectangle flap. Results: This design could enlarge the diverticulum exit and shorten its distance to the anus. All flaps survived and were well-healed. The follow-ups at 0.5 to 2 years presented favorable clinical results. No flap contracture, recurrent stenosis, unobstructed defecation or cleaning convenience occurred. Conclusions The " rectangle plus triangle flaps" methods was an effective way to repair the post-burn pseudo anal stenosis, which could enlarge the diverticulum exit and relocate the anus by making use of the perianal scar tissue.

Objective To assess the risk of hyperperfusion induced intracranial hemorrhage (HICH) after carotid artery stenting (CAS) in patients with symptomatic severe carotid stenosis.Methods From June 2009 to June 2015,the clinical data of 210 patients with symptomatic severe carotid stenosis (70％-99％) treated with CAS at Department of Neurosurgery,Changhai Hospital,the Second Military Medical University,were analyzed retrospectively.Seven of them (3.3 ％) developed HICH after operation.The relationship between the clinical baseline and imaging characteristics and HICH were assessed.All patients received the evaluation of cerebral CT perfusion examination.The time to peak (TTP) index of cerebral blood flow was defined as the TTP ratio of the affected and contralateral sides,t test was used to conduct the comparison of measurement data,and Poisson test was used to conduct the comparison of the enumeration data.Results There was significant difference in the TTP index between the HICH group and non-HICH group (1.15 ± 0.10 vs.1.30 ± 0.15,t =4.461,P ＜ 0.01).The receiver operating characteristic (ROC)curve analysis results suggested that the TTP index ＞ 1.22 could be used as a risk factor for predicting HICH (sensitivity 100％,specificity 75.9％).Conclusion Under the condition of prompting the preoperative TTP index ＞ 1.22,the risk of HICH may be higher after CAS in patients with severe carotid stenosis.

Quantity is the key factor to ensure the safety and effectiveness of medicines. It is very important to study and determine the traditional measuring units and their quantity values of Tibetan medicine. Based on the literature records of Tibetan medicine and combined with modern experimental verification and investigation research, this study determined the reference, name, and conversion rate of traditional measuring units of Tibetan medicine. Meanwhile, through large sample sampling and repeated quantification of refe-rence of basic units, its weight and volume were clarified. The modern SI volume and weight unit values corresponding to the traditional volume and weight units of Tibetan medicine were deduced, and the correctness, reliability, and practicability of these determination results were demonstrated. This study also put forward some specific suggestions and reference values for formulating the standards of measuring units of weight and volume of Tibetan medicine. It is of great significance in guiding the processing, production, and clinical treatment of Tibetan medicine, and promoting the standardization and standardized development of Tibetan medicine.
Medicine, Tibetan Traditional ; Reproducibility of Results