Efficacy of intermittent versus daily vitamin D supplementation on improving circulating 25(OH)D concentration: a Bayesian network meta-analysis of randomized controlled trials.

Background: Vitamin D deficiency is a widespread issue globally, resulting in increased use of vitamin D supplements. However, it is unclear whether intermittent (weekly or monthly) vitamin D supplementation is as effective as daily supplementation in improving circulating 25-hydroxyvitamin D [25(OH)D] levels. Methods: Three databases including Medline, EMBASE, and the Cochrane Library were systematically searched up to 10 November 2020. The risk of bias was evaluated according to Cochrane Collaboration's tool for rating methodological quality assessment. Direct and indirect comparisons between interventions and controls were performed by a Bayesian network meta-analysis (NMA), where the mean difference (MD) and its 95% confidence interval (CI) were used to indicate the efficacy. Results: This NMA analysis included 116 RCTs with a total of 11,376 participants. Generally, we observed that 25(OH)D concentrations were significantly elevated regardless of vitamin D supplementation frequency. Although the findings of SUCRA indicated that daily vitamin D supplementation had a higher rank value than intermittent supplementation when the supplement dosage was similar, no statistically significant pooled mean differences of 25(OH)D concentration were noted between the daily supplementation group and intermittent supplementation group. Additionally, weekly supplementation with a total of 600,000 IU vitamin D supplementation during 3 months had the best efficacy in elevating 25(OH)D concentration (pooled MD = 63 nmol/L, 95%CI: 49-77). To achieve optimal 25(OH)D concentration (>75 nmol/L), we recommend 60,000 IU vitamin D supplementation monthly (~2,000 IU/day). Conclusion: The efficacy of intermittent vitamin D supplementation was similar to daily supplementation. Coupled with its convenience, the frequency and dosage of intermittent vitamin D supplements were recommended to reach the optimal 25(OH)D level.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=257257, PROSPERO CRD42021257257.

Association of Vitamin D in Different Trimester with Hemoglobin during Pregnancy.

The association between vitamin D and hemoglobin has been suggested. Vitamin D can affect erythropoiesis by the induction of erythroid progenitor cell proliferation and enhance iron absorption by regulating the iron-hepcidin-ferroportin axis in monocytes. However, this relationship in pregnant women is scarce. The purpose of this study was to investigate the association between plasma vitamin D levels with hemoglobin concentration in pregnant women considering each trimester and iron supplementation. The data were obtained from Zhoushan Pregnant Women Cohort, collected from 2011 to 2018. Plasma 25(OH)D was measured in each trimester using liquid chromatography−tandem mass spectrometry. Generalized estimating equations and multiple linear regressions were performed. Finally, 2962 pregnant women and 4419 observations in the first trimester were included in this study. Plasma 25(OH)D in first trimester (T1) (ß = 0.06, p = 0.0177), second trimester (T2) (ß = 0.15, p < 0.0001), and third trimester (T3) (ß = 0.12, p = 0.0006) were positively associated with Hb. Association between plasma 25(OH)D levels in T1 and Hb concentration was positively associated with gestational age (ß = 0.005, p = 0.0421). Pregnant women with VD deficiency in T1 (OR = 1.42, 95% CI: 1.07−1.88) or T2 (OR = 1.94, 95% CI: 1.30−2.89) presented an increased risk of anemia, compared with women without VD deficiency. Moreover, the significant relationship between VD and Hb was only observed among women with iron supplementation during pregnancy. Plasma 25(OH)D levels in each trimester were positively associated with Hb concentration. Iron supplementation might be an important factor affecting the relationship between VD and Hb.

Association of vitamin D pathway gene polymorphisms with vitamin D level during pregnancy was modified by season and vitamin D supplement.

BACKGROUND & AIMS: This study aims to explore the associations of vitamin D (VD) metabolic pathway gene with 25(OH)D level in pregnant women and the interactions of SNP with season and VD supplement. METHODS: A total of 2658 pregnant women were selected from Zhoushan Pregnant Women Cohort study. Gestational 25(OH)D level and single nucleotide polymorphism (SNP) of VD metabolic pathway gene were detected. Multilinear regression models were used to estimate associations of SNPs with gestational 25(OH)D levels. Stratified analyses were performed to test the interactions of SNP with season and VD supplements. RESULTS: The mutations of rs2298849 and rs7041 on the GC gene were respectively associated with higher 25(OH)D in the first and third trimester; the mutations of seven SNPs (rs1155563, rs16846876, rs17467825, rs2282679, rs2298850, rs3755967, and rs4588) on the GC gene were respectively associated with lower 25(OH)D both in the first and third trimester, and lower changes in 25(OH)D during late pregnancy. The mutations of above seven SNPs, except for rs1155563, were also respectively associated with lower 25(OH)D in the second trimester, but to a lesser extent; Besides, pregnant women with mutation on CYP24A1-rs2209314 had a higher increment in 25(OH)D than their counterparts in the second trimester. The increasing dose effect of Gc isoform on 25(OH)D was observed. The associations of GC and LRP2 genes with 25(OH)D modified by season and VD supplements. CONCLUSIONS: The polymorphisms of VD metabolic pathway gene were associated with gestational 25(OH)D, and the associations differ by seasons and VD supplements. Gc isoform exerted a profound influence on gestational 25(OH)D.

Hemoglobin concentration and iron supplement during pregnancy were associated with an increased risk of gestational diabetes mellitus.

BACKGROUND: Hemoglobin (Hb) measurement is a conventional test during perinatal visits. Hb concentration is related to iron supplement. However, studies focusing on Hb levels, iron supplement, and pregnancy outcomes are scarce. This study aimed to determine whether Hb levels and iron supplement were associated with the risk of gestational diabetes mellitus (GDM). METHODS: A running hospital-based cohort was conducted from August, 2011. The demographic data and medical information were collected individually through questionnaires and patient medical records. Multiple linear regression was applied for the association between Hb levels, iron supplement, and blood glucose. Multiple logistic regression was used for evaluating odds ratios between Hb levels, iron supplement, and GDM. RESULTS: Hb levels during first (T1) and second trimester (T2) of pregnancy were significantly and positively associated with blood glucose and GDM risk. After adjusting for age, prepregnancy body mass index, and other risk factors, pregnant women with Hb ≥ 11 g/dL and iron supplement had higher postprandial blood glucose at 1 hour (Hb ≥ 11 g/dL in T2 and iron supplement in T1: ß = 0.860，P = <0.001; Hb ≥ 11 g/dL in T2 and iron supplement in T2: ß = 0.960，P < 0.001; Hb ≥ 11 g/dL in T1 and iron supplement in T2: ß = 1.133, P = 0.033) and GDM risks (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.05-2.24; OR = 1.92, 95% CI: 1.13-3.35; OR = 2.15, 95% CI: 1.07-4.34, respectively), compared with those with Hb < 11 g/dL and without iron supplement. CONCLUSION: High Hb concentration and iron supplements without anemia increased postprandial blood glucose and risks for GDM. It indicates that pregnant women with good Hb levels should not be advised to take iron supplements during pregnancy.

Iron overload is related to elevated blood glucose levels in obese children and aggravates high glucose-induced endothelial cell dysfunction in vitro.

INTRODUCTION: This study was performed to investigate the role of iron overload in the early stage of hyperglycemia-induced vascular functional impairment. RESEARCH DESIGN AND METHODS: A total of 196 obese children were enrolled, and data regarding ferritin levels, blood glucose levels, intima-media thickness of carotid arteries, liver function and fibrosis index, hemoglobin, blood pressure, blood lipids, and inflammation indicators were collected. Ferritin levels were compared with a control group, which consisted of 148 healthy non-obese children who were age-matched and gender-matched. Endothelial cells were cultured in high glucose medium and supplemented with ferric citrate with or without iron remover (deferoxamine), a reducing agent (N-acetyl-cysteine), or a nuclear factor-κB (NF-κB) inhibitor (BAY 11-7082). Apoptosis, oxidative stress, nitric oxide levels, and endothelin content were evaluated. DNA microarray analysis was performed to analyze the expression of genes in the NF-κB signaling pathway. RESULTS: Obese children have significantly higher ferritin levels compared with the control group. Ferritin level was positively correlated with hemoglobin and was related to metabolic disorders, including impaired glucose tolerance, higher blood pressure, dyslipidemia, and impaired hepatic function. Endothelial cells treated with ferric citrate showed a significantly higher rate of apoptosis, higher levels of oxidative stress, and impaired vasomotor function under high glucose conditions. The above effects were rescued by treatment with an iron remover, reducing agent, or NF-κB inhibitor. Further, detection of phosphorylated-p65 distribution in cells confirmed activation of the NF-κB pathway. DNA microarrays and subsequent gene oncology enrichment analyses revealed the main processes activated in cells. CONCLUSION: Increased ferritin levels are related to impaired glucose tolerance and other metabolic disorders in obese children. At the cellular level, iron overload aggravated the endothelial cell dysfunction caused by high glucose.

HYR-PB21-LA, a potential extended-release bupivacaine formulation, produces long-lasting local anesthesia in rats and guinea pigs.

BACKGROUND: Effective postoperative pain management plays a key role in enhancing recovery of patients after surgery. Bupivacaine hydrochloride is one of the most commonly local anesthetics used for the postoperative pain control. However, the relatively short anesthesia duration of bupivacaine preparations limited their clinical application. METHODS: Both guinea pig pin-prick study and rat tail-flick test were performed to evaluate the local anesthesia efficacy of HYR-PB21-LA, a new microparticle suspension injection of bupivacaine pamoate. RESULTS: In the pin-prick test, the complete cutaneous trunci muscle reflex inhibitions were observed at 30 min in all treatment groups containing bupivacaine. In comparison with 6.7 mg/mL HYR-PB21-LA, both 10 and 20 mg/mL HYR-PB21-LA groups had significantly higher area under effect time curve (AUEC) values (p<0.001 and p<0.0001) and slower offset time (p<0.0001). Significantly higher AUEC (p<0.0001) and slower offset time (p<0.0001) were also found in 10 mg/mL HYR-PB21-LA treatment group compared with bupivacaine liposome injectable suspension (liposomal bupivacaine). In the rat tail-flick test, significantly increased local anesthesia effect was lasted for 5 hours after 2.5 mg/mL HYR-PB21-LA administration, which was fivefold longer than bupivacaine hydrochloride. The longer lasted efficacy of significantly increased local anesthesia was also observed in 5 mg/mLHYR-PB21-LA than those in liposomal bupivacaine (8 hour vs 1 hour). CONCLUSIONS: The results demonstrated that the HYR-PB21-LA produced longer local anesthesia effect than current clinical preparations of bupivacaine in two animal models. These findings raise the potential clinical value of HYR-PB21-LA as a long-lasting local anesthesia for controlling postsurgical pain in humans.

Vitamin D nutrient status during pregnancy and its influencing factors.

BACKGROUND: Little is known about variation of vitamin D (VD) status during pregnancy among Chinese women. This study is to assess the change of VD status during pregnancy and its influencing factors among Chinese women. METHODS: A running cohort study has being conducted in southeast China. The pregnant women were interviewed and the peripheral blood samples were collected at the first (T1), second (T2) and third trimester (T3), respectively. 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography tandem-mass spectrometry. Multiple linear and logistic regression models were applied to explore the associations of VD supplement with 25(OH)D concentration and VD deficiency, respectively. RESULTS: There were 4368 pregnant women enrolled in the current study. The 25(OH)D concentration increased notably with gestational week. The average plasma 25(OH)D concentration in T1, T2 and T3 was 18.94 ± 8.74, 23.05 ± 11.15, and 24.65 ± 11.59 ng/mL, respectively. Correspondingly, VD deficiency (25(OH)D < 20 ng/mL) rate was 65.26%, 33.56% and 32.12%. In T1 phase, higher pre-pregnancy BMI, more parity, sampling in summer/autumn were related to higher 25(OH)D level, and similar patterns were observed in T2 and T3 phase. There was positive dose-response effect between VD supplement frequency and 25(OH)D concentration during pregnancy, adjusting for potential confounders (T1: ß(SE) = 3.907 (0.319), P < 0.001; T2: ß(SE) = 2.780 (0.805), P < 0.001; T3: ß(SE) = 3.640 (1.057), P = 0.006). Not surprisingly, supplementing VD > 3 times/week reduced the risk of VD deficiency during pregnancy significantly, compared to without VD supplement (T1: OR = 0.30, 95% CI: 0.24-0.37; T2: 0.56, 0.38-0.82; T3: 0.67, 0.44-0.96). CONCLUSION: VD level increased with gestational week among Chinese pregnant women. High frequency of VD supplement during pregnancy is an effective way to reduce risk of VD deficiency, especially among the pregnant women with younger age, low prepregnancy BMI and primipara, and during winter and spring season.

A systematic review and meta-analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe.

BACKGROUND/OBJECTIVES: Optimal doses of vitamin D (VitD) supplement in different populations are unclear. We aim to evaluate the relationship between VitD supplementation and post-intervention serum 25-hydroxyvitamin D [25(OH)D] concentration, to provide a recommended dosage of VitD for achieving an optimal 25(OH)D concentration for different populations. SUBJECTS/METHODS: Literature search was conducted in Embase, etc. Randomized controlled trials about VitD supplemental intakes and their effect on 25(OH)D concentration were enrolled. The effect on 25(OH)D concentration between different supplementation doses in each population group was compared by meta-analysis. Multivariate meta-regression model is utilized to establish reference intake dosage of VitD. RESULTS: A total of 136 articles were included about children (3-17 years), adults (18-64 years), postmenopausal women, the elderly ( >64 years), pregnant, or lactating women. Overall, intervention groups obtained higher 25(OH)D concentration than controls and there was obvious dose-response effect between intake dose and 25(OH)D concentration. Baseline 25(OH)D concentration and age were significant indicators for 25(OH)D concentration. To reach sufficient 25(OH)D concentration (75 nmol/L), the recommended VitD supplemental intakes was 1340 and 2250 IU/day for children and pregnant women, 2519 and 797 IU/day for European adults aged 18-64 and 65-85 years, 729, 2026, and 1229 IU/day for adults in North America, Asia and Middle East and Africa, respectively. CONCLUSIONS: Regional- and age-specific recommended dosages of VitD supplements for population to achieve optimal 25(OH)D concentrations have been suggested.

Vitamin D pathway gene polymorphisms influenced vitamin D level among pregnant women.

AIMS: To explore the relationship between vitamin D pathway genes, gene-environment interactions and vitamin D level among southeast Chinese pregnant women. METHODS: 759 participants from Zhoushan Pregnant Women Cohort (ZPWC) study, were enrolled from August 2011 to April 2014 in China. Plasma 25(OH)D levels and genetic variants in vitamin D pathway (NADSYN1/DHCR7, GC, CYP3A4, CYP2R1, CYP27A1, CYP27B1, VDR, CYP24A1, and LRP2) were measured using the blood sample collected at the first trimester. Information on demographics, lifestyle, and health behavior were collected using a questionnaire. Multilinear regression and logistic regression models were performed to estimate the associations between SNPs and 25(OH)D level. RESULTS: Mean plasma 25(OH)D concentrations were 15.6 ng/mL among the pregnant women. Variants of GC rs16846876, rs17467825, rs2282679, rs3755967, rs2298850, rs4588, rs7041 and rs1155563, CYP3A4 rs2242480 and CYP24A1 rs2209314 were significantly associated with both 25(OH)D concentrations and vitamin D deficiency (25(OH)D < 15 ng/mL). Variants of NADSYN1/DHCR7 were significantly associated with 25(OH)D concentrations among pregnant women without vitamin D supplements. Pregnant women with vitamin D binding protein (Gc) Gc-1f (P = 0.02) and Gc-1s (P = 0.005) had higher plasma 25(OH)D levels compared to women with Gc-2. Genotype risk score (GRS) calculated from rs7041, rs2242480 and rs2209314 shown a significantly negative association with 25(OH)D levels. Participants with GRS > 3 had a higher risk for vitamin D deficiency than individuals with GRS ≤ 3 (OR = 1.71, 95% CI = 1.25-2.35). Interactions between seasons and CYP27A1 rs933994, CYP3A4 rs2246709 on plasma 25(OH)D concentrations were also observed. Haplotypes of GC and LRP2 genes shown significant associations with 25(OH)D levels among pregnant women, respectively. CONCLUSIONS: Genetic mutants in vitamin D pathway (GC, CYP3A4, CYP24A1, and NADSYN1/DHCR7) had significant associations with 25(OH)D levels among pregnant women in southeast China. Furthermore, their associations were modified by vitamin D supplementation and season.

Effect of Low-Dose Vitamin D Supplementation on Serum 25(OH)D in School Children and White-Collar Workers.

OBJECTIVE: Our study aimed to investigate the nutritional vitamin D status of school children aged 9-15 years and white-collar workers in Zhejiang province, and evaluate the efficacy of low-dose-oral vitamin D supplementation in both populations. METHODS: We conducted a prospective controlled trial during March 2014 to November 2015, comparing the efficacy of vitamin D supplements (400 IU/day) with non-intervention for 18 months in school children aged 9-15 years. Meanwhile, a before-after study was conducted among white-collar workers for 1 year. Serum 25(OH)D concentration was measured at baseline and after vitamin D supplementation, respectively. RESULTS: At the baseline, 95% of school children and 84% of adult participants had vitamin D deficiency (<20 ng/mL). In school children, no difference was observed between the intervention and control groups with regard to anthropometric data. Serum 25(OH)D concentrations of the school children intervention group, school children control group and white-collar workers were 12.77 ± 3.01 ng/mL, 14.17 ± 3.59 ng/mL and 16.58 ± 3.66 ng/mL at baseline and increased to 17.34 ± 3.78 ng/mL, 18.04 ± 4.01 ng/mL and 17.75 ± 5.36 ng/mL after vitamin D supplementation, respectively. Although, after adjusting for potential confounders, the 400 IU oral vitamin D supplementation increased serum 25(OH)D concentration in school children (ß = 0.81, p = 0.0426) as well as in white-collar workers (p = 0.0839), the prevalence of vitamin D deficiency was still very high among school children (79.23% in intervention group and 72.38% in control group) and white-collar workers (76.00%). CONCLUSIONS: High prevalence of vitamin D deficiency was common in these two study populations. Daily doses of 400 IU oral vitamin D supplementation was not able to adequately increase serum 25(OH)D concentrations. A suitable recommendation regarding the level of vitamin D supplementation is required for this Chinese population.

Association of short-term use of nonsteroidal anti-inflammatory drugs with stroke in patients with hypertension.

BACKGROUND AND PURPOSE: Limited studies have investigated the risk of cerebrovascular events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects at high risk. We examined the short-term (defined as 30-day period) effect of selective and nonselective NSAIDs use on the risk of ischemic and hemorrhagic stroke in patients with hypertension. METHODS: We conducted a case-crossover study using the National Health Insurance Research Database in Taiwan. We identified 1653 hypertensive subjects with stroke (defined as International Classification of Diseases-Ninth Revision-CM-codes: 433.x, 434.x, and 436.x for ischemic stroke; 430 and 431 for hemorrhagic stroke) in 2010. We investigated the transient effect of NSAIDs use on stroke using conditional logistic regressions with the adjustment of potential confounders. RESULTS: The results suggested that NSAIDs use during the 30 days before stroke was associated with a 1.57-fold increased risk of ischemic stroke, but not of hemorrhagic stroke (adjusted odds ratio, 1.57; 95% confidence interval, 1.26-1.97 for ischemic stroke; and adjusted odds ratio, 1.38; 95% confidence interval, 0.79-2.40 for hemorrhagic stroke). When classifying NSAIDs into selective and nonselective groups, nonselective NSAIDs use significantly increased the risk of ischemic stroke (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.94), but not of hemorrhagic stroke (adjusted odds ratio, 1.56; 95% confidence interval, 0.90-2.73). CONCLUSIONS: The results demonstrate an increased risk of stroke, specifically ischemic stroke among hypertensive subjects with NSAIDs use. It would be important to closely monitor the transient effect of initial NSAIDs treatment, particularly in patients with hypertension.

Evaluation of a systematic cardiovascular disease risk reduction strategy in primary healthcare: an exploratory study from Zhejiang, China.

BACKGROUND: In China, cardiovascular disease (CVD) risk reduction strategies are not systematically implemented in primary healthcare (PHC). We conducted an exploratory study to evaluate the preliminary effectiveness of our systematic CVD risk reduction package in one township hospital of Zhejiang. METHODS: Using the Asian Equation, we selected subjects aged 40-74 years with a calculated 10-year CVD risk of 20% or higher from the existing resident health records and research checkup. The subjects were provided, as appropriate, with the low-dose combination of CVD-preventive drugs (antihypertensive drugs, aspirin, statin), lifestyle modification and adherence strategies monthly. The intervention was piloted for three months in 2012, preceding the conduct of a cluster-based randomized controlled trial (RCT). RESULTS: A total of 153 (40%) subjects were recruited, with an average total 10-year risk of CVD of 28.5 ± 7.9%. After intervention, the appointment rate was up to 90%. An upward trend was observed for the use of CVD-preventive drugs. The smoking rates significantly reduced from 38 to 35%, with almost no change for salt reduction. The systolic blood pressure (BP) and diastolic BP decreased slightly. CONCLUSION: A holistic CVD risk reduction approach shows preliminary effects in a rural PHC setting of Zhejiang, China. However, further understanding is needed regarding its long-term effectiveness and feasibility in PHC practices. Our cluster-based RCT will provide the highest level of evidence for the policy development of preventing CVD in a rural PHC of China.

Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population.

The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)(AA+AG): 0.654, 95% confidence interval (CI): 0.406-1.055; P=0.082), rs4233532 (OR(CC): 1.667, 95% CI: 0.967-2.876; OR(CT): 1.435, 95% CI: 0.998-2.063; P=0.077), and rs2881930 (OR(CC): 0.263, 95% CI: 0.095-0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (OR(AA+AG): 1.233, 95% CI: 0.903-1.683), rs4233532 (OR(CC): 0.892, 95% CI: 0.640-1.243; OR(CT): 1.134, 95% CI: 0.897-1.433), and rs2881930 (OR(CC): 1.096, 95% CI: 0.620-1.938; OR(CT): 1.009, 95% CI: 0.801-1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319-2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.

Characteristics of high risk people with cardiovascular disease in Chinese rural areas: clinical indictors, disease patterns and drug treatment.

BACKGROUND AND AIMS: Current cardiovascular disease (CVD) prevention is based on diagnosis and treatment of specific disease. Little is known for high risk people with CVD at the community level. In rural China, health records of all residents were established after the recent health reforms. This study aims to describe the characters of the rural population with high CVD risk regarding their clinical indicators, disease patterns, drug treatment and adherence. METHODS AND RESULTS: 17042 (87%) of all the 19500 rural residents in the two townships had valid health records in 2009. We employed a validated tool, the Asian Equation, to screen 8182 (48%) resident health records of those aged between 40-75 years in 2010. Those who were identified with a CVD risk of 20% or higher were selected for a face-to-face questionnaire survey regarding their diagnosed disease and drug treatment. 453 individuals were identified as high risk of CVD, with an average age of 53 years, 62% males, 50% smoking rate and average systolic blood pressure of 161 mmHg. 386 (85%) participated in the survey, while 294 (76%) were diagnosed with and 88 (23%) were suspects of CVD, hypertension, diabetes or hyperlipidaemia. 75 (19%) took drug regularly and 125 (32%) either stopped treatment or missed drugs. The most often used drugs were calcium channel blockers (20%). Only 2% used aspirins and 0.8% used statins. The median costs of drugs were 17 RMB (USD2.66) per month. CONCLUSION: The majority of the high risk population in our setting of rural China had already been diagnosed with a CVD related disease, but very few took any drugs, and less still took highly effective drugs to prevent CVD. A holistic strategy focused on population with high risk CVD and based on the current China public health reform is suggested in the context of primary care.

PLA2G4A mutants modified protective effect of tea consumption against colorectal cancer.

PURPOSE: The primary aim was to respectively evaluate PLA2G4A mutants modifying protective effect of tea consumption against colorectal cancer (CRC), colon and rectal cancer. METHODS: All participants were recruited from January 2006 to April 2008. The information about tea consumption was collected by a structured questionnaire. CRC patients were diagnosed based on histology. Four single-nuclear polymorphisms (SNPs) in PLA2G4A gene were selected. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC, colon and rectal cancer. RESULTS: Three hundred patients with CRC and 296 controls well-matched were used in the final analyses. The significant individual associations between four SNPs (rs6666834, rs10911933, rs4650708 and rs7526089) and CRC were not observed. However, their CTAC haplotype was significantly associated with the increased risk of CRC (OR = 3.06; 95%CI = 1.52-6.19), compared with TCAC haplotype. Drinking tea was correlated with a decreased risk of CRC after adjustment for covariates (OR = 0.61; 95%CI = 0.39-0.97). Meanwhile, compared with no-tea drinkers with TT/CT genotype of rs6666834, tea drinkers with TT/CT or CC had significant lower risk of CRC (OR = 0.6, 95%CI = 0.36-1.00 for TT/CT; 0.38, 0.19-0.74 for CC). The joint effects between the remaining three SNPs and drinking tea on CRC were observed as well. Similar findings were observed on colon and rectal cancers. CONCLUSIONS: Tea consumption and haplotype of mutants in PLA2G4A gene were respectively associated with the risk of CRC. PLA2G4A mutants modified the protective effect of tea consumption against CRC, colon and rectal cancers in Chinese population.

The association of XPC polymorphisms and tea drinking with colorectal cancer risk in a Chinese population.

The xeroderma pigmentosum complementation group C (XPC) is responsible for removal of bulky helix-distorting DNA lesions. Several polymorphisms of XPC gene may modulate the colorectal cancer (CRC) susceptibility. We assessed the association of XPC Lys939Gln (A/C), Ala499Val (C/T), and PAT (-/+) polymorphisms with CRC risk in a population-based case-control study which included 421 CRC patients and 845 controls. For Lys939Gln, the CC genotype was associated with a significantly increased risk of CRC (odds ratio (OR)=1.5; 95% confidence interval (CI)=1.0-2.2) compared with the AA genotype. The subjects with PAT +/+ genotype had a significantly increased risk of CRC (OR=1.5; 95% CI=1.0-2.3), compared with those with PAT-/- genotype. Though no significant association between Ala499Val and CRC risk was observed, we found that individuals carrying the CT+TT genotypes showed a significantly decreased risk of rectal cancer (OR=0.7; 95% CI=0.5-1.0). Additionally, the haplotype C+C was associated with a significantly increased CRC risk (OR=1.3; 95% CI=1.0-1.6), compared with the most common haplotype A-T. Further, individuals with four or more risk alleles exhibited a significantly increased risk of CRC (OR=1.4; 95% CI=1.0-2.0), with a significant gene-dosage effect (P for trend=0.038). Besides, never tea drinking was associated with a significantly increased risk of CRC (OR=2.3; 95% CI=1.7-3.3). Our results suggest that the XPC polymorphisms may modulate CRC susceptibility independently or jointly, and tea drinking has a protective effect on CRC.