Polymorphisms in XRCC1 Gene, Alcohol drinking, and Risk of Colorectal Cancer: a Case-control Study in Jiangsu Province of China

Gao, Chang-Ming,Ding, Jian-Hua,Li, Su-Ping,Liu, Yan-Ting,Cao, Hai-Xia,Wu, Jian-Zhong,Tang, Jin-Hai,Tajima, Kazuo Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

To evaluate the relationship between alcohol drinking, XRCC1 codon 194 and 399 polymorphisms and risk of colorectal cancer, we conducted a case-control study with 315 colorectal cancer cases (105 colon, 210 rectal) and 439 population-based controls in Jiangsu Province of China. The XRCC1 codon 194 and 399 genotypes were identified using polymerase chain reaction and restrictrion fragment length polymorphism methods (PCR-RFLP). A structured questionnaire was used to elicit detailed information. Odds ratios (ORs) were estimated with an unconditional logistic model. In this study no significant differences were observed among the studied groups with regard to the genotype distribution of the XRCC1 codons 194 and 399 and the risk of colorectal cancer did not appear to be significantly influenced by genotype alone, whereas alcohol consumption showed a positive association (P for trend <0.01). When combined effects of XRCC1 polymorphisms and alcohol consumption were analyzed, we found that the 194Trp or 399Gln alleles further increased the colorectal cancer risk due to high alcohol intake. These findings support the conclusion that colorectal cancer susceptibility may be altered by gene-environment interactions.

Growth Hormone 1 T1663A Polymorphism, Recreational Physical Activity and BMI, and Breast Cancer Risk in Chinese Women

Gao, Chang-Ming,Ding, Jian-Hua,Wu, Jian-Shong,Cao, Hai-Xia,Li, Su-Ping,Liu, Yan-Ting,Tang, Jin-Hai,Tajima, Kazuo Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13

To evaluate the relationship between the growth hormone 1 (GH1) T1663A polymorphism, recreational physical activity and body mass index (BMI) with reference to breast cancer, we conducted a case-control study with 669 cases of breast cancer and 682 population-based controls in Jiangsu Province, China. A structured questionnaire was used to elicit detailed information. All subjects completed an in-person interview. GH1 genotypes were identified using PCR-RFLP methods. Odds ratios (ORs) were estimated with an unconditional logistic model. The distribution of GH1 genotypes was not significantly different between controls and cases ($x^2$=2.576, P=0.276). Results of stratified analysis by the participation status of the recreational physical activity showed that the persons with GH1 A allele were at a decreased risk of breast cancer (adjusted-OR=0.66; 95% CI, 0.50-0.87) only among inactive individuals. Stratified analysis by BMI showed that the genotype A/A was associated with a decreased risk of breast cancer only among individuals of the BMI <25 (adjusted-OR=0.80; 95% CI, 0.66-0.98). The findings of this study suggest that recreational physical activity and BMI may modify any association between the GH1 T1663A polymorphism and breast cancer risk.

Intravenous Flurbiprofen Axetil Enhances Analgesic Effect of Opioids in Patients with Refractory Cancer Pain by Increasing Plasma β-Endorphin

Wu, Ting-Ting,Wang, Zhi-Gang,Ou, Wu-Ling,Wang, Jun,Yao, Guo-Qing,Yang, Bo,Rao, Zhi-Guo,Gao, Jian-Fei,Zhang, Bi-Cheng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma ${\beta}$-endorphin levels in cancer patients. Materials and Methods: A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma ${\beta}$-endorphin levels were measured by radioimmunoassay. Results: With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma ${\beta}$-endorphin levels. After the treatment, plasma ${\beta}$-endorphin level in group B was $62.4{\pm}13.5pg/ml$, which was higher than that in group A ($45.8{\pm}11.2pg/ml$) (p<0.05). Conclusions: Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma ${\beta}$-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

Decitabine in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes, Which Combined with Complex Karyotype Respectively

Gao, Su,Li, Zheng,Fu, Jian-Hong,Hu, Xiao-Hui,Xu, Yang,Jin, Zheng-Ming,Tang, Xiao-Wen,Han, Yue,Chen, Su-Ning,Sun, Ai-Ning,Wu, De-Pei,Qiu, Hui-Ying Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. Materials and Methods: From April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a complex karyotype diagnosed in the First Affiliated Hospital of Soochow University were included for retrospective analysis. All patients were treated with decitabine alone ($20mg/m^2$ daily for 5 days) or combination AAG chemotherapy (Acla 20mg qod*4d, Ara-C $10mg/m^2$ q12h*7d, G-CSF $300{\mu}g$ qd, the dose of G-CSF adjusted to the amount in blood routinely). Results: In 35 patients, 15 exhibited a complete response (CR), and 6 a partial response (PR), the overall response rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and overall survival was 14 months. In the 15 MDS patients with a complex karyotype, the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the overall response rate was 65% (13 of 20). The response rate of decitabine alone (22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13 cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5 chromosomal abnormalities, 52.9% had a response. In the total of 35 patients, with one course (23 patients) and ${\geq}$two courses (12 patients), the overall response rate was 40.9% and 92.3% (P<0.05). Grade III to IV hematological toxicity was observed in 27 cases (75%). Grade III to IV infections were clinically documented in 7 (20%). Grades I to II non-hematological toxicity were infections (18 patients), haematuria (2 patients), and bleeding (3 patients). With follow-up until September 2013, 7 patients were surviving, 18 had died and 10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic stem cell transplantation (HSCT) all were still relapse-free survivors. Conclusions: Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype. Increasing the number of courses can improve efficiency. This approach with fewer treatment side effects in patients with a better tolerance should be employed in order to create an improved subsequent chance for HSCT.

Polymorphisms in the Thymidylate Synthase Gene and Risk of Colorectal Cancer

Gao, Chang-Ming,Ding, Jian-Hua,Li, Su-Ping,Liu, Yan-Ting,Cao, Hai-Xia,Wu, Jian-Zhong,Tajima, Kazuo Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

To evaluate the relationship between polymorphisms (28 bp repeated sequences in 5'-UTR and 6-bp ins/del in 3'-UTR) in then thymidylate synthetase gene (TS) and risk of colorectal, colon and rectal cancers, we conducted a case-control study with 315 cases of colorectal cancer and 439 population-based controls in Jiangsu province, China. TS genotypes were identified using PCR.RFLP (restriction fragment length polymorphism) methods. Odds ratios (ORs) were estimated with an unconditional logistic regression model. We found that the distributions of 5'-UTR genotypes in TS were significantly different between controls and male colon cases (${\chi}^2$=8.25, P = 0.016). Compared with 3R/3R genotype, individuals with the 2R allele were at an increased risk of colon cancer (age-, BMI-, smoking- and alcohol drinking-adjusted OR=1.98, 95%CI: 1.11-3.53) among men. In ccontrast, the 6-bp ins/del polymorphism at the TS 3'- UTR did not influence risk of the colorectal, colon and rectal cancers. When combined genotypes for both TS 5'-UTR and 3'-UTR polymorphisms were evaluated, individuals with the 5'-UTR 2R allele had a OR of 3.61 (95%CI: 1.38-9.49) for colon cancer among men with the 3'-UTR .6bp/-6bp genotype. These results show that the polymorphism of the 28 bp repeated sequences in TS 5'-UTR could influence susceptibility to colon cancer and that there was a coordinated effect between TS 3'-UTR and 5'-UTR polymorphisms in increasing risk of colon cancer among Chinese men.

Decreased vitamin D-binding protein level portends poor outcome in acute-on-chronic liver failure caused by hepatitis B virus

Daxian Wu,Qunfang Rao,Zhongyang Xie,Xiaoqing Zhu,Jian Wu,Hainv Gao,Jingyu Zhang,Zhouhua Hou,Xiaoyu Cheng,Zeyu Sun 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.4

Background/Aims: Acute-on-chronic liver failure (ACLF) is a catastrophic illness. Few studies investigated the prognostic value of vitamin D-binding protein (VDBP) for hepatitis B virus (HBV)-related ACLF (HBV-ACLF) resulted in conflicting results. Methods: Two prospective HBV-ACLF cohorts (n=287 and n=119) were enrolled to assess and validate the prognostic performance of VDBP. Results: VDBP levels in the non-survivors were significantly lower than in the survivors (P<0.001). Multivariate Cox regression demonstrated that VDBP was an independent prognostic factor for HBV-ACLF. The VDBP level at admission gradually decreased as the number of failed organs increased (P<0.001), and it was closely related to coagulation failure. The areas under the receiver operating characteristic curve (AUCs) of the Child-Pugh-VDBP and chronic liver failuresequential organ failure assessment (CLIF–SOFA)-VDBP scores were significantly higher than those of Child-Pugh (P<0.001) and CLIF-SOFA (P=0.0013). The AUCs of model for end-stage liver disease (MELD)-VDBP were significantly higher than those of MELD (P= 0.0384) only in the case of cirrhotic HBV-ACLF patients. Similar results were validated using an external multicenter HBV-ACLF cohort. By longitudinal observation, the VDBP levels gradually increased in survivors (P=0.026) and gradually decreased in non-survivors (P<0.001). Additionally, the VDBP levels were found to be significantly decreased in the deterioration group (P=0.012) and tended to be decreased in the fluctuation group (P=0.055). In contrast, they showed a significant increase in the improvement group (P=0.036). Conclusions: The VDBP was a promising prognostic biomarker for HBV-ACLF. Sequential measurement of circulating VDBP shows value for the monitoring of ACLF progression.

Diabetes Mellitus Is Associated with Inferior Prognosis in Patients with Chronic Lymphocytic Leukemia: A Propensity Score-Matched Analysis

Rui Gao,Tian-Shuo Man,Jin-Hua Liang,Li Wang,Hua-Yuan Zhu,Wei Wu,Lei Fan,Jian-Yong Li,Tao Yang,Wei Xu 대한암학회 2020 Cancer Research and Treatment Vol.52 No.1

Purpose Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival outcome in malignancies. The objective of this study was to evaluate the prognostic value of preexisting DM in chronic lymphocytic leukemia (CLL). Materials and Methods Six hundred and thirty-three subjects with newly-diagnosed CLL between 2007 and 2016 were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Univariate and multivariate Cox regression analyses screened the independent risk indicators for time-to-first-treatment (TTFT) and cancer-specific survival (CSS) of CLL. Receiver operator characteristic curves and the corresponding areas under the curve assessed the predictive accuracy of CLL–International Prognostic Index (IPI) together with DM. Results The results showed that 111 patients had pre-existing DM. In the propensity-matched cohort, DM was correlated with inferior TTFT and CSS in CLL patients, and it was an independent prognostic factor for both CSS and TTFT. Pre-diabetics also shared undesirable prognostic outcome compared with patients with no diabetic tendency, and a positive association between longer diabetic duration and poorer prognosis of CLL was identified. DM as one additional point to CLL-IPI had larger area under the curve compared with CLLIPI alone in CSS prediction and could improve the prognostic capacity of CLL-IPI. Conclusion Pre-existing DM was found to be a valuable prognostic predictor and could help predict life expectancy and build refined prognostication models for CLL.

Implications for new physics from ^B¯0→^π0^π0 and ^B¯0→^K¯0^K0

Cheng, Jian-Feng,Gao, Yuan-Ning,Huang, Chao-Shang,Wu, Xiao-Hong Elsevier 2006 Physics letters: B Vol.637 No.4

<P><B>Abstract</B></P><P>We have analyzed the <SUP>B¯0</SUP>→<SUP>π0</SUP><SUP>π0</SUP> puzzle in three kinds of models beyond the standard model (SM). It is shown that the minimal flavor violation (MFV) models, the minimal supersymmetric standard model (MSSM), and the two Higgs doublet models (2HDM) I and II cannot give an explanation of the <SUP>B¯0</SUP>→<SUP>π0</SUP><SUP>π0</SUP> puzzle within 1<I>σ</I> experimental bounds and the model III 2HDM can explain the puzzle without a conflict with other experimental measurements. If the constraint on <SUB>C8g</SUB> from b→sg is not imposed, for all kinds of insertions considered there are regions of parameter space, where the scalar quark mass is larger (much larger) than the gluino mass in the case of <I>LR</I> or <I>RL</I> (<I>LL</I> or <I>RR</I>), in which the puzzle can be resolved within 1<I>σ</I> experimental bounds.</P>

Cloning and analysis of b-amyrin synthase gene in Bupleurum chinense

Ke Gao,Su-rui Wu,Ling Wang,Yan-hong Xu,Jian-he Wei,Chun Sui 한국유전학회 2015 Genes & Genomics Vol.37 No.9

Bupleurum chinense DC. is one of the source plants of a well-known crude drug, Chai hu (Radix Bupleuri), producing triterpenoid saponins (saikosaponins) with a wide-spectrum of pharmacological applications. The biosynthesis of triterpenoid saponins involved with the cyclizing of the precursor 2,3-oxidosqualene to produce the first committed triterpene b-amyrin catalyzed by b-amyrin synthase (b-AS), whereafter diverse of triterpenoid saponins was biosynthesized. In addition, 2,3-oxidosqualene could be catalyzed by cycloartenol synthase directing to the synthesis of phytosterol. b-AS was thus defined as an important branch point between primary and secondary metabolisms, and may play a regulating role in the control of triterpenoid saponins biosynthesis. In this study, the promoter and protein-encoding regions of a b-AS gene (designated bcAS1) were isolated by genome walking and PCR from B. chinense. Several important cis-acting elements for gene regulation were identified within the promoter region including light-responsive, hormoneresponsive and various other stress-related elements. Approximate 0.8 kb fragment on upstream of ATG start codon of bcAS1 was sub-cloned into pAN580 vector to replace the 35S promoter driving the expression of green fluorescent protein (GFP) gene. The promoter activity was detected by transient expression in onion epidermis cells by the expression of GFP. Approximately 6 kb length of bcAS1 gene was cloned, containing 18 exons and 17 introns. Although a dozen of b-AS cDNA was isolated, seldom the promoter and gene of it was reported. This work was a valuable foundation for further studies on the regulatory role of b-AS in biosynthesis of saikosaponins.

Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn`s disease

( Kai Chun Wu ),( Zhi Hua Ran ),( Xiang Gao ),( Minhu Chen ),( Jie Zhong ),( Jian Qiu Sheng ),( Michael A Kamm ),( Simon Travis ),( Kori Wallace ),( Nael M Mostafa ),( Marisa Shapiro ),( Yao Li ),( Ro 대한장연구학회 2016 Intestinal Research Vol.14 No.2

Background/Aims: This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn`s disease (CD). Methods: Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220-450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8-26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored. Results: Mean adalimumab serum concentrations during the induction phase were 13.9-18.1 μg/mL (160/80 mg group) and 7.5-9.5 μg/mL (80/40 mg group). During the double-blind period, higher remission/ response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups. Conclusions: Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported. (Intest Res 2016;14:152-163)