Enhanced immunity against SARS-CoV-2 in returning Chinese individuals.

Global COVID-19 vaccination programs effectively contained the fast spread of SARS-CoV-2. Characterizing the immunity status of returned populations will favor understanding the achievement of herd immunity and long-term management of COVID-19 in China. Individuals were recruited from 7 quarantine stations in Guangzhou, China. Blood and throat swab specimens were collected from participants, and their immunity status was determined through competitive ELISA, microneutralization assay and enzyme-linked FluoroSpot assay. A total of 272 subjects were involved in the questionnaire survey, of whom 235 (86.4%) were returning Chinese individuals and 37 (13.6%) were foreigners. Blood and throat swab specimens were collected from 108 returning Chinese individuals. Neutralizing antibodies against SARS-CoV-2 were detected in ~90% of returning Chinese individuals, either in the primary or the homologous and heterologous booster vaccination group. The serum NAb titers were significantly decreased against SARS-CoV-2 Omicron BA.5, BF.7, BQ.1 and XBB.1 compared with the prototype virus. However, memory T-cell responses, including specific IFN-γ and IL-2 responses, were not different in either group. Smoking, alcohol consumption, SARS-CoV-2 infection, COVID-19 vaccination, and the time interval between last vaccination and sampling were independent influencing factors for NAb titers against prototype SARS-CoV-2 and variants of concern. The vaccine dose was the unique common influencing factor for Omicron subvariants. Enhanced immunity against SARS-CoV-2 was established in returning Chinese individuals who were exposed to reinfection and vaccination. Domestic residents will benefit from booster homologous or heterologous COVID-19 vaccination after reopening of China, which is also useful against breakthrough infection.

Exploring the boost of steaming with wine on Ligustri Lucidi Fructus in treating postmenopausal osteoporosis based on superior "multi-component structure" and iron/bone metabolism coregulation.

BACKGROUND: Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years. PURPOSE: To reveal the "superior multi-component structure (SMCS)" and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL. DESIGNS AND METHODS: HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; the dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD. Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism. RESULTS: HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; the bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h (p < 0.05) in which the SMCS of P/I/T was converted to 1: 4: 1.8. NP discovered that BMP-Smad pathway is one of the potential mechanisms of FLL in anti PMOP and then regulated bone formation and iron overload simultaneously. MD revealed that 17 active ingredients and 10 core targets genes could spontaneously bind with appropriate affinity. Rats model verified that FLL and WFLL significantly reversed PMOP, based on the improvement in bone formation indexes (ALP, OPG, OGN), iron metabolism indicators (hepcidin, ferritin), bone microstructure (BMD, BV/TV, Tb. Th, Tb. N); Moreover, WFLL significant enhanced reversal effect in anti-PMOP compared to FLL (p < 0.05). FLL and WFLL increased genes and proteins expression (Hep, BMP-6, p-Smad1/5, Smad4) related to BMP-Smad pathway compared with model group, and WFLL was more superior than FLL (p< 0.05). CONCLUSION: The SMCS of FLL was optimized by wine-steam, WFLL represented a dual effect in downregulating iron overload and promoting bone formation, and the BMP-Smad pathway is one of the potential molecular mechanisms.

Interactions between long-term ambient particle exposures and lifestyle on the prevalence of hypertension and diabetes: insight from a large community-based survey.

INTRODUCTION: Evidence on the interaction of lifestyle and long-term ambient particle (PM) exposure on the prevalence of hypertension, diabetes, particularly their combined condition is limited. We investigate the associations between PM and these outcomes and whether the associations were modified by various lifestyles. METHODS: This was a large population-based survey during 2019-2021 in Southern China. The concentrations of PM were interpolated and assigned to participants by the residential address. Hypertension and diabetes status were from questionnaires and confirmed with the community health centres. Logistic regression was applied to examine the associations, followed by a comprehensive set of stratified analyses by the lifestyles including diet, smoking, drinking, sleeping and exercise. RESULTS: A total of 82 345 residents were included in the final analyses. For each 1 µg/m3 increase in PM2.5, the adjusted OR for the prevalence of hypertension, diabetes and their combined condition were 1.05 (95% CI 1.05 to 1.06), 1.07 (95% CI 1.06 to 1.08) and 1.05 (95% CI 1.04 to 1.06), respectively. We observed that the association between PM2.5 and the combined condition was greatest in the group with 4-8 unhealthy lifestyles (OR=1.09, 95% CI 1.06 to 1.13) followed by the group with 2-3 and those with 0-1 unhealthy lifestyle (P interaction=0.026). Similar results and trends were observed in PM10 and/or in those with hypertension or diabetes. Individuals who consumed alcohol, had inadequate sleep duration or had poor quality sleep were more vulnerable. CONCLUSION: Long-term PM exposure was associated with increased prevalence of hypertension, diabetes and their combined condition, and those with unhealthy lifestyles suffered greater risks of these conditions.

Histone demethylase KDM2A suppresses EGF-TSPAN8 pathway to inhibit breast cancer cell migration and invasion in vitro.

Metastasis is a major cause of breast cancer mortality and the current study found histone demethylase, KDM2A, expression to be negatively correlated with breast cancer metastasis. KDM2A knockdown greatly promoted migration and invasion of breast cancer cells. The histone demethylase activity of KDM2A downregulated EGF transcription and suppressed the EGF-TSPAN8 pathway. Inhibition of breast cancer cell migration was also dependent on the histone demethylase activity of KDM2A. A novel mechanism of KDM2A-suppression of the EGF-TSPAN8 pathway which inhibited breast cancer cell migration and invasion is reported.

Elaborate the Mechanism of Ancient Classic Prescriptions (Erzhi Formula) in Reversing GIOP by Network Pharmacology Coupled with Zebrafish Verification.

Osteoporosis is a degenerative disease that endangers human health. At present, chemical drugs used for osteoporosis have serious side effects. Therefore, it is valuable to search herbs with high safety and good curative effect in antiosteoporosis. Erzhi formula (EZF), an ancient classic compound, has been reported to have a beneficial effect in antiosteoporosis, but its mechanism is unclear. In this paper, the active compounds of EZF were found in Systems Pharmacology Database, and gene targets related to osteoporosis were obtained in GeneCards. The GO functional and KEGG pathway enrichment analysis were performed by Metascape. The network of "components-targets-signal pathway" was constructed by Cytoscape. Next, molecular docking between the active components and hub genes related to the PI3K-Akt signaling pathway was conducted by Autodock. In the verification experiment, the zebrafish induced by prednisolone (PNSL) was used to reproduce glucocorticoid-induced osteoporosis (GIOP) model, and then the reversal effects of EZF were systematically evaluated according to the behavior, skull staining area, bone mineralization area (BMA), average optical density (AOD), and cumulative optical density (COD). Finally, it was shown that 24 components in EZF could regulate 39 common gene targets to exert antiosteoporosis effect. Besides, the main regulatory mechanisms of EZF were 4 signaling pathways: PI3K-Akt, JAK-STAT, AGE-RAGE, and cancer pathway. In PI3K-Akt signaling pathway, wedelolactone, dimethyl wedelolactone, specnuezhenide, ursolic acid, acacetin, beta-sitosterol, apigenin, and kaempferol can bind tightly with EGF, IL-2, and IL-4 genes. Compared with the model group, the moving distance, swimming speed, and cumulative swimming time of zebrafish in EZF group were significantly increased (P < 0.05). Meanwhile, the BMA and COD of zebrafish were significantly improved after the intervention of EZF (P < 0.05). In summary, the 24 components of EZF exert their antiosteoporosis effects by regulating 39 related gene targets, among which the PI3K signaling pathway is crucial. EZF can promote bone formation and reversed GIOP through "multicomponent/multitarget/multipathway" and the medium dose of EZF may be the most suitable concentration for the treatment of GIOP in zebrafish model.

The Seroprevalence of Dengue Virus Infection and Its Association With Iron (Fe) Level in Pregnant Women in Guangzhou, China.

Dengue fever is regarded as the most prevalent mosquito-borne viral disease in humans. However, information of dengue virus (DENV) infection in pregnant women and the influence factors remain unclear. In this study, we extracted information of 2,076 pregnant women from the Prenatal Environment and Offspring Health (PEOH) birth cohort conducted since 2016 in Guangzhou, China. Peripheral blood and clean midstream urine samples of participants were collected during their hospitalization for childbirth. Indirect enzyme-linked immunosorbent assay (ELISA) was used to detect immunoglobulin G (IgG) antibodies of DENV in serum samples, and inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the Fe concentrations in the urine samples, which were then adjusted for by urine creatinine and transformed by natural logarithm (ln-Fe). The seroprevalence of DENV IgG antibody in all included participants was 2.22% (46/2,076). We observed higher seroprevalence of IgG antibody in women aged ≥35 years (2.9%), education ≤ 12 years (2.5%), yearly income per capita <100,000 yuan (2.4%), no use of air-conditioner (2.4%), no use of mosquito coils (2.3%), and no exercise during pregnancy (4.1%). A U-shaped relationship was found between ln-Fe concentration and the risk of positive IgG antibody. Compared with women with ln-Fe concentration of 2.0-2.9 µg/g creatinine, slightly higher risks of positive IgG antibody were found among women with ≤2.0 (RR = 4.16, 95% CI: 0.78, 19.91), 3.0-3.9 (RR = 1.93, 95% CI: 0.65, 7.08), 4.0-4.9 (RR = 2.19, 95% CI: 0.65, 8.51), and ≥5.0 µg/g creatinine of ln-Fe (RR = 2.42, 95% CI: 0.46, 11.33). Our findings suggested that the seroprevalence of dengue IgG antibody in pregnant women was comparable to the general population in Guangzhou, China. The risk of DENV infection may be associated with maternal demographic characteristics and behaviors. Both maternal low and high Fe concentrations may be positively associated with the risk of DENV infection.

Associations of county-level cumulative environmental quality with mortality of chronic obstructive pulmonary disease and mortality of tracheal, bronchus and lung cancers.

Chronic obstructive pulmonary disease (COPD) and tracheal, bronchus, and lung (TBL) cancers are among the leading causes of mortality worldwide. Many environmental factors have been linked to COPD and TBL cancers. This study examined the associations of cumulative environmental quality indices with COPD mortality and TBL cancers mortality, respectively. Environmental Quality Index (EQI) was constructed to represent cumulative environmental quality for the overall environment and 5 major environmental domains (e.g., air, water, built). Associations of each EQI indices with COPD mortality and TBL cancers mortality, across 3109 counties in the 48 contiguous states of the US, were examined using simultaneous autoregressive (SAR) models. Stratified analyses were conducted in females versus males and according to rural-urban continuum codes (RUCC) to assess the heterogeneity across the overall population. Overall poor environmental quality was associated with a percent difference (PD) of 0.75 [95% confidence intervals (95% CI), 0.46, 1.05] in COPD mortality and an PD of 1.22 (95% CI, 0.97, 1.46) in TBL cancers mortality. PDs were higher in females than in males for both COPD and TBL cancers. The built domain had the largest effect on COPD mortality (PD, 0.85; 95% CI, 0.58, 1.12) while the air domain had the largest effect on TBL cancers mortality (PD, 1.54; 95% CI, 1.31, 1.76). The EQI-mortality associations varied among different RUCCs, but no consistent trend was found. This result suggests that poor environmental quality, particularly poor air quality and built environment quality may increase the mortality risk for COPD and that for TBL cancers. Females appear to be more susceptible to the effect of cumulative environmental quality. Our findings highlight the importance of improving overall and domain-specific cumulative environmental quality in reducing COPD and TBL cancer mortalities in the United States.

Do multiple environmental factors impact four cancers in women in the contiguous United States?

BACKGROUND: Though there has been an increasing concern about the effects that environmental exposures have on cancer, limited knowledge exists regarding multiple environmental factors on cancers in women. METHODS: We performed a spatial autoregressive model to examine the association between the Environmental Quality Index (EQI) and mortalities of four cancers in women (breast, cervical, ovarian and uterine cancer) based on county-level data, and explored these associations by urbanicity. The EQI, which included five domains (air, water, land, built environment and sociodemographic domain) estimated from 2000 to 2005 data, was obtained from the United States Environmental Protection Agency. The mortality rates for 3107 counties in the US in 2014 were obtained from the Institute for Health Metrics and Evaluation. RESULTS: We found that each unit increase in the overall EQI was positively associated with the increased mortality of breast, ovarian and uterine cancer (2.5%, 3.6% and 3.1% respectively), but was negatively associated with cervical cancer mortality. Among the environmental domains, the air and sociodemographic EQIs were positively associated with increased risks of breast, ovarian and uterine cancers. Additionally, built environment EQI was associated with breast and ovarian cancers; land EQI was associated with uterine and ovarian cancers. The sociodemographic EQI was negatively associated with cervical cancer mortality. Furthermore, we have developed a novel Environmental Quality Health Index (EQHI) in identifying environment-health risk of cancers in women at county level. CONCLUSIONS: Our findings suggest that breast, ovarian, and uterine cancer mortalities are positively associated with multiple environmental factors, while cervical cancer mortality is mainly negatively associated with sociodemographic factors. The novel EQHI might help identify spatially-based environment-cancer risk.

Blocking the PD-1/PD-L1 axis in dendritic cell-stimulated Cytokine-Induced Killer Cells with pembrolizumab enhances their therapeutic effects against hepatocellular carcinoma.

Immune checkpoint therapies for cancer, like the anti-programmed cell death 1 (PD-1) agent pembrolizumab, have gained considerable attention. However, the use of immune checkpoint inhibitors in the context of adoptive immunotherapy is poorly characterized. We investigated the therapeutic efficacy of dendritic cell-stimulated CIK (DC-CIK) cells pretreated with pembrolizumab against hepatocellular carcinoma (HCC) in cytotoxicity assay in vitro and in a nude mouse xenograft model. We used time-lapse imaging to investigate tumor killing. We also performed a survival analysis based on lymphocyte subpopulation-specific mRNA signatures using The Cancer Genome Atlas (TCGA) HCC cohort (n=371 patients). The results indicated that PD-1 inhibition increased the anti-tumor effects of DC-CIK cells over those of DC-CIK cells alone, resulting in a survival benefit importantly. Time-lapse imaging revealed that DC-CIK cells appeared to be more effective and aggressive after anti-PD-1 treatment than after culture in control conditions. The PD-1 inhibitor also induced more effective immune cell infiltration of the tumor. Our analysis of the TCGA HCC cohort confirmed that a genetic signature consistent with a high degree of intratumoral CD8+ T cell infiltration is associated with good prognosis. These results suggest that blockade of the PD-1/PD-L1 axis in DC-CIK cells with a PD-1 inhibitor prior to infusion is a promising therapeutic strategy against HCC.

Air Pollution and Mortality in China.

Ambient air pollution has been an important environmental issue in most areas of China. This chapter summarized the mortality effects of short-term and long-term exposures to various air pollutants among Chinese population. The literature review identified sufficient information to support significant short-term mortality effects of various air pollutants from time series analyses and case-crossover studies, such as PM10, PM2.5, SO2, NO2, and O3. On the other hand, though the literature review suggested a positive effect of long-term exposure to air pollution on mortality and lung cancer risk, the evidence has been limited among Chinese population, indicating that more studies, especially cohort studies, are warranted.

Ambient PM2.5 and Stroke: Effect Modifiers and Population Attributable Risk in Six Low- and Middle-Income Countries.

BACKGROUND AND PURPOSE: Short-term exposure to ambient fine particulate pollution (PM2.5) has been linked to increased stroke. Few studies, however, have examined the effects of long-term exposure. METHODS: A total of 45 625 participants were interviewed and included in this study, the participants came from the Study on Global Ageing and Adult Health, a prospective cohort in 6 low- and middle-income countries. Ambient PM2.5 levels were estimated for participants' communities using satellite data. A multilevel logistic regression model was used to examine the association between long-term PM2.5 exposure and stroke. Potential effect modification by physical activity and consumption of fruit and vegetables was assessed. RESULTS: The odds of stroke were 1.13 (95% confidence interval, 1.04-1.22) for each 10 µg/m3 increase in PM2.5. This effect remained after adjustment for confounding factors including age, sex, smoking, and indoor air pollution (adjusted odds ratio=1.12; 95% confidence interval, 1.04-1.21). Further stratified analyses suggested that participants with higher levels of physical activity had greater odds of stroke, whereas those with higher consumption of fruit and vegetables had lower odds of stroke. These effects remained robust in sensitivity analyses. We further estimated that 6.55% (95% confidence interval, 1.97%-12.01%) of the stroke cases could be attributable to ambient PM2.5 in the study population. CONCLUSIONS: This study suggests that ambient PM2.5 may increase the risk of stroke and may be responsible for the astounding stroke burden in low- and middle-income countries. In addition, greater physical activity may enhance, whereas greater consumption of fruit and vegetables may mitigate the effect.

Molecular Detection and Phylogenetic Characterization of Bat and Human Adenoviruses in Southern China.

Several novel adenoviruses (AdVs) have recently been identified in humans and other animal species. In this study, we report the molecular detection of and phylogenetically characterize bat and human AdVs detected in fecal or rectal swab samples collected in southern China. To detect AdVs, a 252-261 bp fragment of the DNA polymerase (DPOL) gene was amplified using nested PCR. A total of 520 rectal swab samples were collected from eight bat species in four geographic regions of southern China (Guangzhou, Yunfu, Huizhou, and Haikou city). Thirty-six (6.9%) samples from the following species tested positive for AdVs: Myotis ricketti, Miniopterus schreibersii, Scotophilus kuhlii, Taphozous melanopogon, Rhinolophus blythi, and Cynopterus sphinx. Eight novel AdVs were detected in 13.3% of the samples from C. sphinx. Of 328 fecal samples from patients with diarrhea, 16 (4.9%) were positive for classical human AdVs. Phylogenetic analysis showed that human AdVs shared low similarity (57.1-69.3%) with bat AdVs in deduced amino acid sequences of the AdV DPOL region. Thus, our study indicated that bat AdVs and human AdVs are species specific. As such, there is no evidence of cross-species transmission of AdV between bats and humans based on current data.

High prevalence and diversity of viruses of the subfamily Gammaherpesvirinae, family Herpesviridae, in fecal specimens from bats of different species in southern China.

Several studies have reported the detection of herpesviruses (HVs) in bats. However, the prevalence and phylogenetic characteristics of HVs in bats are still poorly understood. To elucidate the epidemiological characteristics of bat HVs in southern China, 520 fecal samples from eight bat species were collected in four geographic regions of southern China. Of these samples, 73 (14.0 %) tested positive for HVs using nested polymerase chain reaction assay. Phylogenetic analysis revealed a high degree of molecular diversity of HVs in bats of different species from different geographic regions. Our study provides evidence for co-evolution of bats and HVs.

Disease Burden from Hepatitis B Virus Infection in Guangdong Province, China.

OBJECTIVE: To estimate the disease burden and financial burden attributed to hepatitis B virus (HBV) infection in Guangdong Province. METHODS: Based on the data of incidence, mortality and healthcare cost of HBV-related diseases and other socio-economic data in Guangdong Province, we estimated deaths, disability-adjusted life-years (DALYs) and economic cost for the three HBV-related diseases-hepatitis B, liver cirrhosis and liver cancer-in Guangdong following the procedures developed for the global burden of disease study. Then disease burden and economic cost attributed to HBV infection was estimated. RESULTS: HBV infection was estimated to have caused 33,600 (95% confidence interval (CI): 29,300-37,800) premature deaths and the loss of 583,200 (95% CI: 495,200-671,100) DALYs in Guangdong in 2005. The greatest loss of deaths and DALYs were from liver cancer. The 45-59 years age group had the greatest burden attributable to HBV infection. The estimated total annual cost of HBV-related diseases in Guangdong was RMB 10.8 (95% CI: 8.7-13.0) billion, the direct and indirect cost were RMB 2.6 (95% CI: 2.1-3.2) and 8.2 (95% CI: 6.6-9.8) billion. CONCLUSIONS: HBV infection is a great medical challenge as well as a significant economic burden to Guangdong Province. The results suggest that substantial health benefits could be gained by extending effective public health and clinical interventions to reduce HBV infection in Guangdong Province.

Overexpression of hypoxia-inducible factor-1α is a predictor of poor prognosis in cervical cancer: a clinicopathologic study and a meta-analysis.

BACKGROUND: Published data on the prognostic value of hypoxia-inducible factor-1α (HIF-1α) expression in cervical cancer are conflicting and heterogeneous. We aimed to derive a more precise estimation of them. METHODS: We conducted a clinicopathologic study in 74 patients with early-stage cervical cancer treated through surgery and performed a meta-analysis among patients with cervical cancer of all stages to estimate the prognostic importance of HIF-1α expression for disease-free survival (DFS) and overall survival (OS). Expression of HIF-1α was evaluated through immunohistochemistry. RESULTS: A positive nuclear expression of HIF-1α was found in 94.6% of all specimens. There were significant associations between HIF-1α expression and International Federation of Gynecology and Obstetrics stage (P = 0.024), tumor size (P = 0.003), and anemia (P = 0.010), respectively. Log-rank tests revealed significant correlations between HIF-1α expression, International Federation of Gynecology and Obstetrics stages, tumor grade, tumor size and DFS/OS, respectively. The multivariate Cox regression analyses revealed HIF-1α overexpression and high tumor grade to be independent predictors for impaired DFS (HIF-1α overexpression: hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.10-6.47; high tumor grade: HR, 5.56; 95% CI, 1.47-21.13) and OS (HIF-1α overexpression: HR, 2.57; 95% CI, 1.06-6.23; high tumor grade: HR, 6.23; 95% CI, 1.49-25.97). The results of 10 studies indicated that HIF-1α overexpression predicted poor DFS (HR, 1.98; 95% CI, 1.22-3.21) and OS (HR, 2.58; 95% CI, 1.86-3.56) for cervical cancer. CONCLUSIONS: The present clinicopathologic study and meta-analysis showed that HIF-1α overexpression is associated with poor survival of cervical cancer and emphasized the importance of HIF-1α as a predictor for cervical cancer.

Prognostic significance of cyclooxygenase-2 in cervical cancer: a meta-analysis.

Published data on the prognostic value of cyclooxygenase-2 (COX-2) overexpression in cervical cancer are conflicting and heterogeneous. We performed a meta-analysis to more precisely estimate its prognostic significance. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the effects. Twenty-three studies with 1,477 cervical cancer patients were selected to evaluate the association between COX-2 and overall survival (OS), disease-free survival (DFS), response to chemoradiation (RC) and clinicopathological parameters. High COX-2 expression predicted poor OS (HR: 2.53, 95% CI: 1.54-4.18), DFS (HR: 2.41, 95% CI: 1.58-3.69) and RC (OR: 3.03, 95% CI: 1.97-4.64). Subgroup analyses showed that COX-2 overexpression was related significantly with poor OS in patients treated by chemoradiation or surgery, and in patients with squamous cell carcinoma, respectively. Besides, COX-2 overexpression was related significantly with poor DFS in chemoradiation subgroup. Furthermore, COX-2 overexpression was associated with poor RC in patients who received "FP" regimen or "P" regimen. Additionally, there were significant associations between COX-2 expression and all clinicopathological parameters except tumor grade. The pooled ORs (95% CI) were as follows: 1.49 (1.09-2.04) for age, 1.77 (1.22-2.56) for lymph node metastasis, 1.04 (0.74-1.47) for tumor grade, 1.71 (1.12-2.64) for tumor size, 2.38 (1.28-4.45) for FIGO stage, 3.96 (2.32-6.77) for histological type, 2.45(1.10-5.42) for parametrical involvement. This meta-analysis indicated that COX-2 overexpression might be an unfavorable prognostic and a chemoradiation resistance predictive factor for cervical cancer; it could potentially help to stratify patients further in clinical treatment.

CYP1A1 Ile462Val is a risk factor for ovarian cancer development.

Published data on the association between CYP1A1 gene polymorphism and ovarian cancer risk are conflicting and heterogeneous. To derive a more precise estimation of the relationship, a meta-analysis was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed for heterozygous, homozygous, dominant model, recessive model and allele, respectively. A total of 15 case-control studies were identified, among which, 13 studies (1815 cases and 3501 controls) were eligible for CYP1A1 Ile(462)Val and nine studies (2495 cases and 3553 controls) were eligible for CYP1A1 Msp1. Overall, Ile(462)Val was significantly associated with ovarian cancer, with homozygous carriers (Val/Val vs. Ile/Ile: OR=2.64; 95% CI: 1.63-4.28) and recessive model (Val/Val vs. Ile/Ile and Ile/Val: OR=2.30; 95% CI: 1.45-3.65) being risk factors for ovarian cancer development. In the subgroup analysis by ethnicity, significantly increased risks were found for Caucasians (homozygous carriers: OR=4.91; 95% CI: 2.07-11.66; recessive model: OR=3.26; 95% CI: 1.41-7.50) and Asians (homozygous carriers: OR=3.06; 95% CI: 1.48-6.33; recessive model: OR=2.75; 95% CI: 1.40-5.41; Val allele: OR=1.67; 95% CI: 1.19-2.35). However, no significant associations were found between Msp1 and ovarian cancer in the overall analyses or the subgroup analyses by ethnicity. This meta-analysis denotes the importance for in-depth research regarding of gene-gene, gene-environment interactions, race-specific and histological subtypes specific to obtain a more conclusive response about the function of CYP1A1 in ovarian cancer.

Four polymorphisms of the CAPN 10 gene and their relationship to polycystic ovary syndrome susceptibility: a meta-analysis.

OBJECTIVE: To investigate the association between CAPN 10 gene polymorphism and polycystic ovary syndrome (PCOS) susceptibility. DESIGN: Meta-analysis of published case-control studies of four single nucleotide polymorphisms (SNPs) in CAPN 10 and PCOS susceptibility. PATIENTS: Women with PCOS. MEASUREMENTS: Odds ratios (ORs) and 95% confidence intervals (CIs) for heterozygous, homozygous, dominant model, recessive model and allele. RESULTS: A total of 11 studies were involved in the meta-analysis. UCSNP-63 was significantly associated with PCOS, with homozygous carriers (TT vs CC: OR = 0·64; 95% CI: 0·45-0·90) and recessive model (TT vs CC and CT: OR = 0·64; 95% CI: 0·45-0·90) being protective factors. In addition, UCSNP-19 was significantly associated with PCOS, with recessive model (ins/ins vs del/del and del/ins: OR = 0·72, 95% CI: 0·59-0·88) and insert allele (ins vs del: OR = 0·85, 95% CI: 0·76-0·96) being protective factors, while heterozygous carriers (del/ins vs del/del: OR = 1·56, 95% CI: 1·24-1·94) and deletion allele (del vs ins: OR = 1·18, 95% CI: 1·04-1·32) being risk factors. However, no significant associations were found between UCSNP-44, -43 and PCOS. Moreover, the results of the Rotterdam criteria subgroup analysis were similar with that of overall analysis. CONCLUSIONS: This is the first report on the association between CAPN 10 UCSNP-63 and PCOS in genotype, with homozygous carriers and recessive model being protective factors. Additionally, insert allele and recessive model of UCSNP-19 are protective factors, while deletion allele and heterozygous genotype are risk factors for PCOS development.