17β-estradiol inhibits interleukin-1β-induced rat nucleus pulposus cell apoptosis through the PI3K/Akt/mTOR signal pathway / 生理学报

The apoptosis of nucleus pulposus cells (NPCs) is the main cellular process of intervertebral disc degeneration (IVDD). Our previous studies showed that 17β-estradiol (E

Madecassoside impedes invasion of rheumatoid fibroblast-like synoviocyte from adjuvant arthritis rats via inhibition of NF-κB-mediated matrix metalloproteinase-13 expression / 中国天然药物

Fibroblast-like synoviocytes (FLS) play a pivotal role in Rheumatoid arthritis (RA) pathogenesis through aggressive migration and invasion. Madecassoside (Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis (AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase (MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec (10 and 30 μmol·L) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β (IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.

Madecassoside impedes invasion of rheumatoid fibroblast-like synoviocyte from adjuvant arthritis rats via inhibition of NF-κB-mediated matrix metalloproteinase-13 expression / 中国天然药物

Fibroblast-like synoviocytes (FLS) play a pivotal role in Rheumatoid arthritis (RA) pathogenesis through aggressive migration and invasion. Madecassoside (Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis (AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase (MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec (10 and 30 μmol·L) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β (IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.

Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.</p><p><b>METHODS</b>Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.</p><p><b>RESULTS</b>The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465).</p><p><b>CONCLUSIONS</b>These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.</p>

Genetic polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 associated with the susceptibility on esophageal cancer / 中华流行病学杂志

Objective To evaluate the impact of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms on the susceptibility of esophageal cancer. Methods A case-control study including 221 cases of esophageal cancer and 191 controls was carried out in Taixing city of Jiangsu province. ADH2 and ALDH2 genotypes were tested by PCR and denaturing high -- performance liquid chromatography (DHPLC). Results (1) Compared with ALDH2 G/G carriers, ALDH2 A/A (OR=5.69, 95%CI: 2.51-12.18) and ALDH2 G/A (OR=1.70, 95%CI: 1.08-2.68) carriers showed a significantly elevated risk of developing esophageal cancer, especially among alcohol drinkers with ALDH2 A/A (OR=8.63,95% CI: 2.07-35.95). (2) Statistical relation was not found between ADH2 genotypes and the risk of esophageal cancer, with regard to the status of alcohol consumption. (3) Whether subjects with whatever ADH2 genotype, ALDH2 G/A or A/A carriers was found to have significantly increased the risk of developing esophageal cancer, with ALDH2 A/A carriers appeared having higher esophageal cancer risk than those ALDH2 G/A carriers. (4)Compared those non-drinkers with both ALDH2 G/G and ADH2 A/A , drinkers with ALDH2 G/A or A/A and ADH2 C,/A or G/G genotypes showed a significantly elevated risk of developing esophageal cancer (OR=8.36, 95% CI: 2.98-23.46). Conclusion These results revealed that it was not ADH2 but ALDH2 polymorphisms and drinking alcohol had a significant interaction with the development of esophageal cancer, suggesting that in order to help lowering the risk of esophageal cancer, individuals who are carrying ALDH2 A/A or G/A genotypes should be encouraged to reduce their consumption of alcohols.

Establishment of a multiplex ligation-dependent SNP genotyping method and its application in the detection of genes related to chemotherapeutic drugs in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a method for SNP genotyping of multi-genes by allele-specific oligonucleotide probe ligation mediated by a thermostable ligase, and to explore the genetic polymorphisms of drug-metabolizing enzymes in breast cancer patients and their association with chemotherapeutic responses.</p><p><b>METHODS</b>10 SNP loci of enzyme genes related to chemotherapeutic drugs such as taxanes, anthracyclines and cyclophosphamide were selected, and were genotyped for blood samples from 126 breast cancer patients by the established method. Their correlations with therapeutic responses were retrospectively evaluated.</p><p><b>RESULTS</b>The lower detection limit of genomic DNA by this developed method was 6.25 ng. The fluorescent peak locations of ligation products on ABI PRISM 377 DNA sequencer were accurate and consistent with prospective sizes in bases (Bias range 0.08 - 0.69 bp, x(-) = 0.31 bp, s = 0.18 bp). Same genotyping results were obtained for repeat tests of 8 random samples, which were further confirmed by sequencing analysis. The 10 SNP loci were polymorphic of different frequency in the breast cancer patients. The combinations with GSTP1 genotypes and GSTM1 genotypes were related to anthracycline-based chemotherapy efficacy (P = 0.037), and the low GSTs activity group (GSTP1 variant allele + GSTM1 null) showed the best effects (85.7%). GSTM1 genotypes and their combinations with GSTP1 and/or CYP3A5*3 genotypes were related to taxane-based therapy efficacy (P < 0.05 for all), and both the low GSTs activity group and the drug slow-metabolising group (low GSTs activity group + CYP3A5*3 wild allele) showed better effects (100%).</p><p><b>CONCLUSION</b>The established method is reliable and applicable in multiplex SNPs genotyping of multi-genes. SNPs combination may have a better clinical application value for prediction of chemotherapeutic responses.</p>

MTHFR polymorphisms, dietary folate intake and risks to breast cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5, 10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk.</p><p><b>METHODS</b>A case-control study was conducted with 669 cases and 682 population-based controls in Jiangsu province of China. MTHFR C677T and A1298C genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Dietary folate intake was assessed by using an 83-item food frequency questionnaire. Odds ratios (OR) were estimated with an unconditional logistic model.</p><p><b>RESULTS</b>The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37% (202/624), 48.88% (305/624) and 18.75% (117/624) in cases and 37.66% (235/624), 48.24% (301/624) and 14. 10% (88/624) in controls, respectively. The difference in distribution was significant (chi2 = 6.616, P = 0.037), the T/T genotype being associated with an elevated OR for breast cancer (1.62, 95% CI: 1.14 -2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47% (446/624), 27.08% (169/624) and 1.44% (9/624) in cases and 68.11%(425/624), 30.13% (188/624) and 1.76% (11/624)in controls,with no significant differences found (chi2 = 1.716, P= 0.424). Folate intake of cases [(263.00 +/- 137.38) microg/d] was significantly lower than that of controls [(285.12 +/- 149.61) microg/d] (t = -2. 830, P =0.005). Compared with the lowest tertile (< or = 199.08 microg/d) of folate intake, the adjusted OR for breast cancer in the top tertile (> or = 315.11 microg/d) was 0.70 (95% CI: 0.53 -0.92). Among individuals with the MTHFR A1298C A/A genotype,adjusted OR for breast cancer were 0.89 (95% CI: 0.62 - 1.27) and 1.69 (95% CI: 1.20 - 2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (X2trend = 11.372, P = 0.001).</p><p><b>CONCLUSION</b>The findings of the present study suggest that MTHFR genetic polymorphisms,and dietary intake of folate may modify susceptibility to breast cancer.</p>

Study on the diagnosis, treatment and requirement of epilepsy patients in urban communities / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis,treatment and requirement of epilepsy patients in some urban communities in China, and to provide the evidence of searching for effective treatment and management on epilepsy under the China's context.</p><p><b>METHODS</b>A face-to-face survey were conducted in 3 urban communities in Shanghai, Beijing and Changsha, respectively. The questions in the questionniare were general information, hospital visit, treatment, the level and way of getting on the knowledge of epilepsy, as well as the current obstacles and needs.</p><p><b>RESULTS</b>Most of the patients selected the regular hospitals (90.8%) and the departments (92.3%) for their epielspy diagnosis and treatment. They used AEDs modo dictu (77.4%), and had controlled the seizures quite well (82.6%). A small part of patients still could not deeply understand the basic knowledge on epilepsy (13.5%). They ignored to follow up the drug concentration (45.8%) in blood and the blood biocheminstry indicators (43.9%). Some patients went to private clinics (12.9%) and used lay people remedies (7.7%). Longtime waiting (36.8%), inconvenient traffic (23.2%), and high expenses (22.6%) were the main problems influencing the timely treatment. The main obstacles of the patients were employment (47.2%), marriage (29.9%), psychological conditions (44.4%) and interpersonal relationship (29.9%). The main requirements were the effectiveness (87.0%) and cheap AEDs (40.9%) as well as the convenience of hospital visit (37.0%).</p><p><b>CONCLUSION</b>It is very important to emphasize knowledge and publicity/education on epilepsy as well as the psychological treatment according to the requirements of patients.</p>

A case-control study on the polymorphisms of methylenetetrahydrofolate reductase 1298A-->C and susceptibility of esophageal cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between polymorphisms of methylenetetra-hydrofolate reductase gene 1298A-->C (MTHFR 1298A-->C) and its susceptibility of esophageal cancer (EC).</p><p><b>METHODS</b>We conducted a case-control study with 141 cases of EC and 228 population-based controls in Huaian city of Jiangsu province, China. Epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were identified by polymerase chain reaction.</p><p><b>RESULTS</b>(1) The frequency of MTHFR 1298AA, AC and CC genotype were 63.8%, 34.0% and 2.1% in EC and 71.9%, 28.1% and 0.0% in controls, respectively (chi(2)(MH) = 6.69, P = 0.035). The frequency of the MTHFR 1298C allele was 0.19 for EC and 0.14 for controls. (2) Individuals having MTHFR 1298C allele and smoking habit were at a significantly higher risk of developing EC (adjusted OR = 3.48, 95% CI: 1.57 - 7.71) compared with those who having AA genotype but no smoking habit. Individuals having MTHFR 1298C allele and habit of frequent alcohol drinking were at an increased risk of developing EC (adjusted OR = 2.91, 95% CI: 1.20 - 7.08) compared with those with AA genotype and low consumption of alcohol. Individuals having MTHFR 1298C allele but no habit of tea drinking had a 3.52-fold (95% CI: 1.64 - 7.54) increased risk of developing EC compared with tea drinkers with AA genotype. As compared with subjects having AA genotype, low consumption of alcohol, no smoking habit but having habit of drinking tea, the individuals having 1298C allele, habits of frequent alcohol drinking, smoking but no habit of tea drinking had a 12.64-folds (95% CI: 1.39 - 114.65) increased risk of developing EC.</p><p><b>CONCLUSION</b>Results in the present study suggested that there was a coordinated effect between MTHFR 1298 genotypes and habits of smoking, alcohol drinking and tea consumption in the development of EC.</p>

Polymorphism of methylenetetrahydrofolate reductase and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the response to fluoropyrimidine (5-FU)-based chemotherapy in advanced stomach cancer (SC).</p><p><b>METHODS</b>75 cases with advanced SC were analyzed. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method.</p><p><b>RESULTS</b>(1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0%, 44.0% and 24.0%, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotype were 69.3%, 29.3% and 1.3%, respectively. The overal response rate to 5-FU-based chemotherapy was 29.3%. (2) The response rate to therapy among MTHFR C677T T/T genotype patients (83.3%) was significantly higher than the C677T C/T genotype (15.2%, chi(2) = 22.27, P = 0.000) or the C677T C/C genotype (8.3%, chi(2) = 23.44, P = 0.000). As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to 5-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95% CI: 3.14 - 18.62). The response rate to therapy among patients with MTHFR A1298C A/A genotype (36.5%) was significantly higher than patients with A1298C C allele (13.0%, chi(2) = 4.19, P = 0.041, adjusted OR = 3.75, 95% CI: 0.94 - 14.87). The response rate to therapy among patients with MTHFR C677T T/T and A1298C A/A genotypes (86.7%) was significantly higher than other groups of C677T and A1298C genotypes (15.0%, Fisher exact: P = 0.000, adjusted OR = 6.57, 95% CI: 2.8 - 15.6). (3) The incidence rates of nausea/vomiting in MTHFR C677T T/T, C/T or A1298C A/A genotypes were significantly higher than other genotypes, but the incidence rates of other treatment-related adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different.</p><p><b>CONCLUSION</b>These results in the present study suggested that the polymorphisms of MTHFR were associated with clinical response to 5-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.</p>

Interactions between lifestyle, methylanetetrahydrofolate reductase gene and polymorphisms in thymidylate synthase gene with risk of stomach cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate interactions between lifestyle, methylanetetrahydrofolate reductase gene (MTHFR) and polymorphisms in the 3'-untranslated region (3'-UTR) of the thymidylate synthase gene (TS) with reference to development of stomach cancer (SC).</p><p><b>METHODS</b>We conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. TS genotypes were identified by polymerase chain reaction.</p><p><b>RESULTS</b>(1) The frequencies of TS genotypes (+6 bp/+6 bp, +6 bp/-6 bp and -6 bp/-6 bp) among the cases were 5.6%, 47.7% and 46.7% and among the controls were 9.0%, 54.0% and 37.0%, respectively. Individuals identified as -6 bp/-6 bp genotype had a slightly higher risk for SC than those individuals with +6 bp alleles (the crude OR = 1.49, 95% CI: 0.90 - 2.47; adjusted OR = 1.36, 95% CI: 1.00 - 1.78, P = 0.047). (2) Individuals having TS -6 bp/-6 bp genotype and having smoking habit were at a significantly higher risk of developing SC (adjusted OR = 2.79, 95% CI: 1.51 - 5.18) compared with those who had +6 bp alleles with no smoking habit. Individuals having TS -6 bp/-6 bp genotype and habit of frequent alcohol drinking were at an increased risk of developing SC (adjusted OR = 1.76, 95% CI: 1.07 - 2.90) compared with those with +6 bp alleles and low consumption of alcohol. As compared with individuals with +6 bp alleles and who had habit of tea drinking, individuals who had TS -6 bp/-6 bp genotype and but without habit of tea drinking had an increased risk of developing SC (adjusted OR = 2.34, 95% CI: 1.43 - 3.82). (3) Individuals with TS -6 bp/-6 bp genotype and with MTHFR T alleles had an increased risk of developing SC (adjusted OR = 2.67, 95% CI: 1.07 - 6.70) compared with those with +6 bp alleles and with MTHRF C/C genotype.</p><p><b>CONCLUSION</b>Results in the present study suggested that there was a combined effect between lifestyle, MTHFR C/T or T/T genotype and TS -6 bp/-6 bp genotype in the development of SC.</p>

Decreased treatment gap in epilepsy after intervention in five rural areas of China / 中华神经科杂志

Objective To evaluate the change of treatment gap of epilepsy after intervention in rural areas of China.Method Six months after being stopped from the intervention project in 2004,using the same method as the first survey at the baseline,a door-to-door epidemiological survey was conducted again in 5 rural areas where the intervention measures had been carried out for about 3 years.Results Three hundred and twenty cases of epilepsy were diagnosed in the total sample population,yielding a prevalence rate of 0.62% and the prevalence of active epilepsy 0.44%.The prevalence and the active prevalence of epilepsy in the survey in 2000 were 0.70% and 0.46% respectively.Of the people with epilepsy,39.1% were treated regularly which increased about 14% than that in the baseline survey (24.8%).The treatment gap for active epilepsy was 49.8%,which decreased by 12.8% than that in the first survey (62.6%). Conclusion The treatment gap of epilepsy in the demonstration areas has decreased remarkably,proving that the intervention measures used in the study are effective and feasible in rural areas of China.