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Background: Insomnia and depression often co-occur. Cognitive behavioral therapy for insomnia (CBT-I) seems to be effective and safe for mitigating insomnia and depression. However, the efficacy of digitally-delivered CBT-I (dCBT-I) remains unclear. Therefore, this meta-analysis of randomized controlled trials (RCTs) was to systematically review and evaluate the efficacy of dCBT-I in adults with insomnia and depression. Methods: A systematic search in PubMed, Cochrane, Embase, and Web of Science databases (as of June 5, 2022) was conducted for RCTs on dCBT-I. Statistical analyses were performed using Revan Manager. The effects of dCBT-I on insomnia and depression were expressed as standardized mean difference (SMD) with 95% confidence intervals (CIs). Results: Seven studies involving 3,597 participants were included. This meta-analysis showed that dCBT-I reduced the severity of insomnia (SMD = -0.85, 95% CI [-1.00 to -0.69], p < 0.001) and depression (SMD = -0.47, 95% CI [-0.55 to -0.38], p < 0.001) in short terms, and also mitigated the severity of insomnia (SMD = -0.71, 95% CI [-1.00 to -0.44], p < 0.001) and depression (SMD = -0.42, 95% CI [-0.68 to -0.15], p = 0.002) in long terms. The effect of dCBT-I was comparable to that of traditional face-to-face CBT-I, and was generally maintained at follow-ups of 6 weeks to 6 months. Conclusion: dCBT-I seems to be effective in alleviating insomnia and depression and might be considered as a viable treatment option for depression.

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This study presents an architectural framework for the blockchain-based usage-based insurance (UBI) policy auction mechanism in the internet of vehicles (IoV) applications. The main objective of this study is to analyze and design the specific blockchain architecture and management considerations for the UBI environment. An auction mechanism is developed for the UBI blockchain platform to enhance consumer trust. The study identifies correlations between driving behaviors and associated risks to determine a driver's score. A decentralized bidding algorithm is proposed and implemented on a blockchain platform using elliptic curve cryptography and first-price sealed-bid auctions. Additionally, the model incorporates intelligent contract functionality to prevent unauthorized modifications and ensure that insurance prices align with the prevailing market value. An experimental study evaluates the system's efficacy by expanding the participant pool in the bidding process to identify the winning bidder and is investigated under scenarios where varying numbers of insurance companies submit bids. The experimental results demonstrate that as the number of insurance companies increases exponentially, the temporal overhead incurred by the system exhibits only marginal growth. Moreover, the allocation of bids is accomplished within a significantly abbreviated timeframe. These findings provide evidence that supports the efficiency of the proposed algorithm.

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PURPOSE: To determine the prognostic value of tumour contour irregularity degree (CID) in surgical strategy options for T1bN0M0 renal cell carcinoma (RCC). MATERIALS AND METHODS: We performed a retrospective multi-institutional review of 489 patients with T1bN0M0 RCC treated between January 2009 and June 2019. Cox regression and Kaplan-Meier analyses were performed to analyse the impact of CID on disease-free survival (DFS). RESULTS: The median follow-up time was 55 months (interquartile range, 40-81 months) for 55 (11.2 %) patients with metastasis or recurrence. Logistic analysis indicated that CID was associated with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grades III-IV (odds ratio, 1.015; 95 % confidence interval [CI], 1.008-1.023; p < 0.001). After being classified into high CID (≥50 %) and low CID (<50 %) groups, those with a high CID showed a significantly higher ratio of WHO/IUSP grades III-IV (74/277 [26.7 %] vs 25/212 [11.8 %]) and shorter DFS than the low CID group (p < 0.001). Multivariable Cox regression showed that partial nephrectomy (PN; hazard ratio [HR], 1.889; 95 % CI, 1.020-3.499; p = 0.043), high CID (HR, 6.685; 95 % CI, 2.776-16.100; p < 0.001), and WHO/ISUP grade III-IV (HR, 1.950; 95 % CI, 1.100-3.458; p = 0.022) were independent prognostic factors for DFS. The Kaplan-Meier plot showed that PN had a DFS rate comparable to that of radical nephrectomy (RN; p = 0.994). In the low CID group, patients who underwent PN showed comparable DFS to those who underwent RN (p = 0.903). Furthermore, patients with a high CID tended to have worse DFS in the PN versus RN group (p = 0.044). Multivariable Cox regression showed that PN (HR, 2.049; 95 % CI, 1.065-3.942; p = 0.032) and WHO/ISUP grade III-IV (HR, 2.148; 95 % CI, 1.189-3.881; p = 0.011) were independent prognostic factors of DFS in the high CID group. CONCLUSIONS: CID is a reliable preoperative parameter which is positively correlated with WHO/ISUP grade and can help with surgical decision-making in patients with T1bN0M0 RCC.

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BACKGROUND: To assess the impact of malignant cystic renal masses (CRM) rupture on oncologic outcomes. METHODS: The study included 406 cases with partial nephrectomy (PN) and 17 cases with cyst decortication confirmed as malignant CRM by pathology. Recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank test. Cox regression was used to identify risk factors associated with RFS, MFS, CSS, and OS. Logistic regression was performed to explore predictors of rupture. RESULTS: Tumor rupture occurred in 32 of 406 cases (7.9%). With median follow-up of 43 months, 4 (12.5%) and 5 (1.3%) cases experienced recurrence in rupture and non-rupture group, respectively (P = 0.003). Estimated RFS, MFS, and CSS were shorter in cyst ruptured (CR) group than non-ruptured (nonCR) cases (P < 0.001; P = 0.001; P < 0.001). Cox regression analysis indicated that CR was an independent prognostic factor for RFS (HR = 7.354; 95% CI = 1.839-29.413; P = 0.005), MFS (HR = 8.069; 95% CI = 1.804-36.095; P = 0.006), and CSS (HR = 9.643; 95% CI = 2.183-42.599; P = 0.003). Multivariable logistic regression showed that Bosniak IV was a protective factor for CR (OR = 0.065; 95% CI = 0.018-0.239; P < 0.001). However, compared to Bosniak III and I-IIF, Bosniak IV CRMs showed higher rate of clear cell renal cell carcinoma (ccRCC) (76.8% vs 36.5% vs 81.4%) (P < 0.001) and lower rate of Fuhrman I staging (11.2% vs 66.7% vs 7.4%) (P < 0.001). Therefore, in ruptured cases, the recurrence rate was higher in CRM with Bosniak IV (50%, 2/4) than Bosniak I-III (4.4%, 2/45) (P = 0.029). CONCLUSIONS: Intraoperative malignant CRM rupture had negative impacts on oncologic outcomes. Bosniak IV was more aggressive than Bosniak I-III and had a higher risk of recurrence after rupture. However, Bosniak IV had a lower risk of rupture, which could weaken even cover-up of the true effect of tumor rupture on oncologic outcomes.

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PURPOSE: To explore the predictive value of renal tumor contour irregular degree (CID) in pathological T3a upstaging of clinical T1 renal cell carcinoma (RCC). MATERIALS AND METHODS: We performed a retrospective multi-institutional review of 1,487 patients with clinical T1N0M0 RCC between January 2009 and June 2019. Kaplan-Meier survival curve and Cox regressions were used to analyze the prognostic factors of disease-free survival (DFS). Logistic regressions were performed to determine predictors of pathological T3a upstaging in clinical T1 RCC. RESULTS: Among 1,487 patients with cT1 RCC, 96 (6.5%) were pathological T3a upstaging. Multivariable logistic regression analysis showed that age (odds ratio [OR] = 1.022, 95% confidence interval [CI] = 1.001-1.042, P = 0.036), tumor maximum diameter(OR = 1.242, 95% CI = 1.042--1.480, P = 0.015) and CID (OR = 1.067, 95% CI = 1.051-1.083, P < 0.001) were independent predictors of pathological T3a upstaging. The area under the curve (AUC) of the prediction model that included the CID was 0.846, while the AUC of the prediction model that did not include CID was only 0.741, the difference was statistically significant (P < 0.001). Kaplan-Meier survival curve showed that patients with pathological T3a upstaging had significantly worse DFS than patients without pathological T3a upstaging (P < 0.001). Multivariable Cox analysis showed that pathological T3a upstaging (HR = 1.836, 95% CI = 1.013-3.329, P = 0.002) is an independent prognostic factor for DFS in patients with cT1N0M0 RCC. CONCLUSIONS: The predictive model of CID combined with tumor maximum diameter and age significantly improved the ability to predict pathological T3a upstaging in clinical T1 RCC, compared with the prediction model of tumor maximum diameter combined with age. The predictive model of CID combined with tumor maximum diameter and age may be applicable to patients considering partial vs. radical nephrectomy.

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BACKGROUND: Radical prostatectomy (RP) is the primary treatment of localized prostate cancer. Immediate urinary incontinence post-RP was still common and depressing without specific reason. METHODS: A multicenter cohort of 154 consecutive patients from 2018 to 2020, who was diagnosed with localized prostate cancer underwent either modified mini-incision retropubic radical prostatectomy (Mmi-RRP) or laparoscopic radical prostatectomy (LRP) or robotic-assisted radical prostatectomy (RARP). Seventy-two patients with Denonvilliers' fascia (DF) spared were included in DFS (Denonvilliers' fascia sparing) group. Whereas eighty-two patients with DF completely or partially dissected were set as Group Control. The primary outcome was immediate continence (ImC). Continuous data and categorical data were analyzed with t-test and Chi-square test, respectively. Odds ratios (ORs) were calculated with logistic regression. RESULTS: Urinary continence of Group DFS was significantly better than that of Group Control at each time point within one year after operation. Incidence rate of continence in Group DFS and Group Control were 83.3% vs 13.4% (P < 0.01) for ImC, 90.3% vs 30.5% (P < 0.01) at 3 months, 91.7% vs 64.6% (P < 0.01) at 6 months, and 93.1% vs 80.5% (P = 0.02) at 1 year after operation, respectively. Positive surgical margin (PSM) showed no significant difference (20.8% vs 20.7%, P = 1.0). In multivariate analysis, DFS showed importance for ImC post RP (OR = 26.4, P < 0.01). CONCLUSIONS: Denonvilliers' fascia acted as the fulcrum and hammock for continence post RP. Preservation of DF contributed to better continence after RP without increase of PSM. Trail registration Our research was conducted retrospectively and approved by the ethical committees of Minhang Hospital, but not registered.

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Curcumin has been shown to inhibit the growth of a variety of tumor cells. However, the biological functions of curcumin in prostate cancer (PCa) have not yet fully elucidated. The objective of the present study was to investigate the role of curcumin on the proliferation, migration, invasion and apoptosis of PCa cells and the underlying mechanism. Cell Counting Kit-8 and flow cytometry were used to detect the effects of curcumin at different concentrations on the proliferation and apoptosis of PCa cell lines, PC-3 and DU145. BrdU and Transwell assays, western blotting and reverse transcription-quantitative PCR were used to determine the effect of curcumin on cell proliferation, migration and invasion, apoptosis-related protein expression, and microRNA (miR)-30a-5p and PCNA clamp associated factor (PCLAF) expression, respectively. In addition, bioinformatics analysis and Pearson's correlation test were used to verify the relationship between miR-30a-5p and PCLAF. Curcumin was observed to impede the proliferation, migration and invasion of PCa cells, and promote their apoptosis in a time- and dose-dependent manner. Curcumin enhanced miR-30a-5p expression and inhibited PCLAF expression; furthermore, there was a negative correlation between miR-30a-5p and PCLAF expression in PCa tissues. In addition, transfection of miR-30a-5p inhibitors partially reversed the function of curcumin on cell proliferation, migration, invasion and apoptosis. Overall, curcumin suppressed the malignant biological behaviors of PCa cells by regulating the miR-30a-5p/PCLAF axis.

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BACKGROUND: To establish a robust, individualized DNA repair-related gene signature to estimate prognosis for patients with localized clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We retrospectively analyzed gene expression profiles of 541 localized ccRCC patients from two public ccRCC cohorts. The DNA repair-related gene pair index (DRPI) was constructed with the least absolute shrinkage and selection operator (LASSO) regression model. The associations between DRPI, overall survival (OS), and disease-specific survival (DSS) were evaluated by Kaplan-Meier analysis, univariate analysis, and multivariate Cox regression survival analysis. We compared the predictive accuracy of different risk models with Harrel's C-index. RESULTS: In the primary univariate analysis, patients in DRPI-high-risk group had significantly shorter OS [P < 0.001, HR (95% CI) 2.093 (1.431-3.061)] and DSS [P < 0.001, HR (95% CI) 3.567 (2.017-6.339)]. After adjusted for stage and grade, DRPI-high-risk group remained an independent adverse risk factor for both OS [P = 0.026, HR (95% CI) 1.629 (1.094-2.452)] and DSS [P = 0.010, HR (95% CI) 2.209 (1.217-4.010)]. DPRI showed comparable predictive accuracy with cell cycle proliferation (CCP) score and ccA/ccB signature. Copy number alterations and tumor mutation burden were enriched in DRPI-high tumors. There were elevated number of Treg cells and higher T cell exhaustion marker expression in DRPI-high-risk tumors. The combined DNA repair-clinical score outperformed other risk models in terms of C-index. CONCLUSION: We validated the proposed DRPI as a predictor of clinical outcome in localized ccRCC patients. It provides an individualized and more accurate risk assessment beyond clinicopathological characteristics.

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AIMS: The present study was designed to study changes and its potential mechanisms in human bladder smooth muscle subjected to stretch. METHODS: Bioinformatics analyses including differential expression analysis, overrepresentation enrichment analysis, principal component analysis, and weighted gene coexpression network analysis were used to analyze a microarray dataset (GSE47080) of partial bladder outlet obstruction (pBOO) in rat to find the potential changes of gene expressions. Bladder from pBOO model and human bladder smooth muscle cells (HBSMCs) subjected to sustained prolonged stretch were collected for Western blot analysis, real-time polymerase chain reaction, and fluorescence analysis to verify the changes of gene expressions and preliminarily study the potential role of signaling pathway regulation in treatment of pBOO. RESULTS: The bioinformatics analysis showed that chronic obstruction activated mitogen-activated protein kinase pathway and changed cytoskeleton structure in bladder smooth muscle. In in vivo experiments in mice, pBOO was verified by cystometry. Partial BOO activated the extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 protein kinase (p90RSK)/nuclear factor-κB (NF-κB) signaling pathway in DM. The messenger RNA (mRNA) expressions of contractile phenotypic proteins increased after pBOO. In in vitro experiments of HBSMCs, mechanical stretch activated ERK/p90RSK/NF-κB in HBSMCs in a time-dependent manner. The mRNA expressions of α-smooth muscle actin and SM22 also increased and filamentous actin (F-actin) polymerization was enhanced as well. Inhibition of ERK/p90RSK/NF-κB pathway reversed mechanical stretch-induced changes of contractile phenotypic expression and F-action polymerization. CONCLUSIONS: Continuous stretch increases expressions of contractile phenotypic proteins and promotes the polymerization of F-actin. This process partially goes through ERK/p90RSK/NF-κB pathway.

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OBJECTIVE: Curcumin as an effective anticancer bioactive extract has been proved to induce apoptosis in many cancer cells. Notch signaling regulates prostate cancer apoptosis, but it is still unknown whether curcumin induces apoptosis in DU-145 cells by regulating Notch pathway. The aim of this study was to investigate the effect of curcumin on regulating Notch signaling and provide basic data for using curcumin in prostate cancer therapy. METHODS: Notch pathway signal related proteins Notch 1, Jagged-1 and NICD were detected using Western blotting and RT-PCR. The proliferation and apoptosis were determined by MTT method and Elisa kits after curcumin treatment, respectively. Dual-Luciferase Reporter Assay was carried out to confirm that curcumin could target Notching signaling. In order to study whether Notch 1 expression could be downregulated by curcumin, Notch 1 siRNA and Notch 1 plasmid were used in Notch 1 down-regulation and over-expression. The effects of curcumin on cell cycle distribution and apoptosis related proteins expression were analyzed by flow cytometry and western blotting, separately. RESULTS: We found that Notch 1 signaling was down regulated in Notch 1 siRNA or Notch 1 plasmid transfected 145 cells after curcumin treatment. Curcumin induced G0/G1 arrest in DU-145 cells, and G0/G1 phase related regulatory factors Cyclin D1 and CDK2 expressions were inhibited. Meanwhile, p21 and p27 were up regulated. The apoptosis related protein p53 expression was increased, and apoptosis suppressor Bcl-2 was inhibited in DU-145 after curcumin treatment. Additionally, Caspase-3 and Caspase-9 were activated by curcumin. CONCLUSION: Curcumin induced apoptosis and G0/G1 arrest in DU-145 cells by down regulating Notch signaling.

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BACKGROUND: Porcine circovirus type 2 (PCV2) is associated with post-weaning multisystemic wasting syndrome (PMWS), an emerging swine disease that causes progressive weight loss, dyspnea, tachypnea, anemia, jaundice, and diarrhea in piglets. Although baculovirus is an enveloped virus that infects insects in nature, it has emerged as a vaccine vector, and we used it to develop a novel candidate vaccine for a preventive or therapeutic strategy to control PCV2 infections. METHODS: Immunoblotting analysis of recombinant baculovirus and immunofluorescent staining of baculovirus-infected cells were followed using anti-ORF2 monoclonal antibodies. The BALB/c mice were immunized intramuscularly with this baculovirus. The titers of antibodies were mensurated with a Cap-protein-specific enzyme-linked immunosorbent assay (ELISA) and a serum neutralization assay. The IFN-γ response in splenocytes harvested from immunized mice was measured by ELISA. Student's t-test was used to compare immune responses of different groups. RESULTS: In this study, we successfully constructed a dual-expression-system-based recombinant baculovirus BV-GD-ORF2, which can display the PCV2 capsid (Cap) protein and VSV-G protein on the viral envelope and also expressing Cap protein on transduced mammalian cells, thereby functioning as both a subunit and a DNA vaccine. After infection, the Cap protein was expressed and displayed on the viral surface, as demonstrated with an indirect fluorescence assay and immunoblotting. The vaccination of mice with recombinant baculovirus BV-GD-ORF2 successfully induced robust Cap-protein-specific humoral and cellular immune responses. CONCLUSIONS: Our findings collectively demonstrate that the recombinant baculovirus BV-GD-ORF2 is a potential vaccine against PCV2 infections.

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Dichlorodiphenyltrichloroethane (p,p'-DDT), an organochlorine pesticide known to have deleterious health effects in humans, has been linked to hepatocellular carcinoma (HCC) in rodents. A recent study has reported that p,p'-DDT and its most persistent metabolite, dichlorodiphenyldichloroethylene (p,p'-DDE), may also be associated with HCC in humans. To examine whether there is an association between p,p'-DDT and/or p,p'-DDE in a population at high-risk of developing HCC, a nested case-control study was conducted within the 83,794 person Haimen City Cohort in China. Sera and questionnaire data were collected from all participants between 1992 and 1993. This study included 473 persons who developed HCC and 492 who did not, frequency matched on sex, age and area of residence. p,p'-DDT and p,p'-DDE levels were determined by mass spectrometry. Hepatitis B viral infection status (based on hepatitis B virus surface antigen; HBsAg) was also determined. p,p'-DDT and/or p,p'-DDE serum levels were significantly associated with sex, area of residence, occupation, alcohol consumption and cigarette smoking. Adjusting for age, sex, area of residence, HBsAg, family history of HCC, history of acute hepatitis, smoking, alcohol, occupation (farmer vs. other) and levels of p,p'-DDT or p,p'-DDE, odds ratios (OR) and 95% confidence intervals (CI) were calculated via unconditional logistic regression. Overall, the highest quintile of p,p'-DDT was associated with an increased risk of HCC, OR = 2.96 95% CI; 1.19-7.40. There were no statistically significant associations with p,p'-DDE. Overall, these results suggest that recent exposure to p,p'-DDT may increase risk of HCC.

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BACKGROUND: Survivin, one of the strongest apoptosis inhibitors, plays a critical role in the development and progression of hepatocellular carcinoma (HCC). By comparison, relatively little is known about the effect of survivin gene polymorphisms on HCC susceptibility. Our study aimed to investigate the association of survivin gene polymorphisms with the risk of HCC in Chinese han population. METHODS: A case-control study was conducted in Chinese han population consisting of 178 HCC cases and 196 cancer-free controls. Information on demographic data and related risk factors was collected for all subjects. Polymorphisms of the survivin gene, including three loci of rs8073069, rs9904341 and rs1042489, were selected and genotyped by a polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique. Association analysis of genotypes/alleles and haplotypes from these loci with the risk of HCC was conducted under different genetic models. RESULTS: Using univariate analysis of rs8073069, rs9904341 and rs1042489 under different genetic models, no statistically significant difference was found in genotype or allele distribution of HCC cases relative to the controls (P > 0.05). Linkage disequilibrium (LD) analysis showed that these loci were in LD. Multivariate logistic regression indicated that with no G-C-T haplotype as reference, the haplotype of G-C-T from these loci was associated with a lower risk for HCC under the recessive model (OR = 0.46, 95% confidence interval (CI): 0.24~0.90, P = 0.023). Both HBsAg+ and the medical history of viral hepatitis type B were risk factors for HCC. However, no statistically significant haplotype-environment interaction existed. CONCLUSIONS: No association between rs8073069, rs9904341 or rs1042489 in survivin gene and the risk of HCC is found in Chinese han population, but rs8073069G-rs9904341C- rs1042489T is perhaps a protective haplotype for HCC.

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Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR=1.10, 95%CI=0.64-1.89) or in Linxian (OR=1.47, 95%CI=0.70-3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79-1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC.

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BACKGROUND: Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. RESULTS: The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. CONCLUSION: BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.

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OBJECTIVE: To predict the trend of hepatocellular carcinoma (HCC) mortality and investigate the features of its mortality including age, period, and birth cohort in males living in Haimen city of Jiangsu province, China. METHODS: Grey model (GM) was modeled using standardized mortality rate (SMR) of HCC from 1993 to 2006, and was applied to predicting SMR until 2012. Based on the mortality density (MD) for a four-year period, the goodness-of-fit of models and comparisons between models were evaluated so as to obtain the best one among these models including the effects of intercept, age-period-cohort (APC), age-period (AP), age-cohort (AC), period-cohort(PC), and APC. Both APC full model and the best model were used to estimate effects of age, period, and cohort on HCC mortality. In addition, MD form 2005 to 2012 was predicted by the best model. RESULTS: Predictions based on GM (1,1) showed that SMR was 48.578 pre 100 000 population (relative error=-1.267%) in 2007 year, which declined between 2008 and 2012. The lowest value was 45.578 pre 100 000 people (in the 2012 year). The results of fitted models and comparisons between models showed that AP model was the best one (ΔG(2) = 9.065, AIC = 202.544). The curvatures of the effects of the three factors from APC model suggested that significances existed in changes of curvatures of 36.5 - 40.5 years old-(-0.368) and 64.5 - 68.5 years old-(-0.489) as well as in the change of 1956 - 1959 birth cohort (C(2)(1949.5, 1967.5) = -0.492). The estimation of relative risks for AP model showed that the age effects were upward to 64.5 - 68.5 years old-, then downward; and that the period effects were found to be declined between 1993 and 2004. Predictions based on AP model suggested the decrease of HCC mortality. CONCLUSION: The slightly decreasing trend of HCC mortality for males might be explained by age, period and a minor birth cohort effects in Haimen of China.

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Sex and hepatitis B virus (HBV) infection are both important risk factors for primary liver cancer. However, their possible biologic interaction has not been well studied. The authors examined data from 89,789 subjects aged 25-69 years who participated in a 14-year cohort study (1992-2006) conducted in Haimen, China. An age-stratified Cox proportional hazards model was used for multivariate analysis. The authors assessed the combined effect of sex and HBV infection on liver cancer mortality by calculating 3 interaction measures: the relative risk due to interaction, the attributable proportion of interaction, and the synergy index. There was a greater risk difference between hepatitis B surface antigen carriers and noncarriers among men than among women. After adjustment for potential confounders, the relative risk due to interaction, the attributable proportion of interaction, and the synergy index were 33.27 (95% confidence interval (CI): 22.54, 43.99), 0.59 (95% CI: 0.55, 0.63), and 2.49 (95% CI: 2.13, 2.90), respectively, suggesting a significant synergistic effect of the interaction between sex and HBV infection on liver cancer mortality. HBV infection had a larger impact on liver cancer mortality in men than in women, which may explain at least part of the sex difference in liver cancer risk.

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BACKGROUND: Studies in experimental animals suggest that low folate levels may play a role in liver damage and hepatocarcinogenesis. To examine this association in humans, folate levels in blood and risk for subsequent liver damage and hepatocellular carcinoma (HCC) were assessed in a population at high risk of liver cancer in China. METHODS: Four hundred fifteen hepatitis B surface antigen-positive participants of the Haimen City Cohort were prospectively followed between 1998 and 2002. Serum and RBC folate levels were determined at baseline. Alanine aminotransferase (ALT) and hepatitis B virus DNA levels were measured semiannually. Logistic regression modeling was used to examine the presence of hepatitis B virus DNA and HCC, whereas linear regression with a log-link function was used to examine ALT levels. RESULTS: There was a statistically significant inverse association between serum folate level and ALT level. ALT levels decreased with each quartile increase in serum folate (adjusted odds ratio, 0.86; 95% confidence interval, 0.76-0.97 for the highest compared with the lowest quartile; Ptrend = 0.002). After exclusion of three persons with prevalent HCC, 20 (4.9%) of the 412 study participants developed HCC during follow-up, with a median time between enrollment and HCC diagnosis of 2.66 years (interquartile range, 1.8-4.1). When comparing persons in the lowest quartile RBC folate to persons in all other quartiles, the analysis found that higher RBC folate levels were associated with reduced risk of hepatocarcinogenesis (odds ratio, 0.33, 95% confidence interval, 0.13-0.86; P(trend) = 0.02). CONCLUSIONS: This study suggests that increased folate levels in humans may be inversely associated with the development of liver damage and HCC.

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The overexpression of cyclic AMP (cAMP)-dependent protein kinase (PKA) has been reported in patients with cancer, and PKA inhibitors have been tested in clinical trials as a novel cancer therapy. The present study was designed to characterize the population distribution of extracellular activity of cAMP-dependent protein kinase (ECPKA) and its potential value as a biomarker for cancer detection and monitoring of cancer therapy. The population distribution of ECPKA activity was determined in serum samples from a Chinese population consisting of a total of 603 subjects (374 normal healthy volunteers and 229 cancer patients). The serum ECPKA was determined by a validated sensitive radioassay, and its diagnostic values (including positive and negative predictive values) were analyzed. The majority of normal subjects (>70%) have undetectable or very low levels of serum ECPKA. In contrast, the majority of cancer patients (>85%) have high levels of ECPKA. The mean ECPKA activity in the sera of cancer patients was 10.98 units/mL, 5-fold higher than that of the healthy controls (2.15 units/mL; P < 0.001). In both normal subjects and cancer patients, gender and age had no significant influence on the serum ECPKA. Among factors considered, logistic analysis revealed that the disease (cancer) is the only factor contributing to the elevation of ECPKA activity in cancer patients. In conclusion, ECPKA may function as a cancer marker for various human cancers and can be used in cancer detection and for monitoring response to therapy with other screening or diagnostic techniques.

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