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Incidence and mortality of liver cancer in Henan province in 2015

Cao XIAO-QIN ; Cao RU-FEI ; Liu SHU-ZHENG ; Chen QIONG ; Quan PEI-LIANG ; Luo SU-XIA

Chronic Diseases and Translational Medicine.2019;5(3):197-202.

Objective: Liver cancer is one of the most common types of cancer. We aimed to use the cancer registration data in 2015 to estimate the incidence and mortality of liver cancer in Henan province. Methods: The data from 37 population-based cancer registries in Henan province were collected for this study. The pooled data were stratified by area, sex, and age group. New cases of liver cancer and deaths due to the disease were estimated using age-specific rates and provincial population in 2015. All incidence and death rates were age standardized to the 2000 Chinese standard pop-ulation and Segi's population, which were expressed per 100,000 populations. Results: After clearance and assessment, data from 30 population-based cancer registries (5 in urban and 25 in rural areas) were included in the analysis. All 30 cancer registries encompassed a total population of 23,421,609 (3,507,984 in urban and 19,913,625 in rural areas), accounting for 21.84% of the provincial population. The proportion of morphological verification (MV%), per-centage of cancer cases identified with death certification only (DCO%), and mortality-to-incidence ratio (M/I) were 38.55%, 2.34%, and 0.81, respectively. Approximately 31,639 new cases of liver cancer were diagnosed and 26,057 deaths from liver cancer occurred in Henan in 2015. The crude incidence rate of liver cancer was 27.05/100,000 (36.24/100,000 in men and 17.35/100,000 in women). Age-standardized incidence rates by Chinese standard population and world standard population were 21.10/100,000 and 20.95/100,000, respectively. Liver cancer was more common in men than in women. The incidence rates in urban (26.31/100,000) and rural (27.18/100,000) areas were similar. The crude mortality rate of liver cancer was 21.98/100,000 (29.33/100,000 in males and 14.22/100,000 in females). Age-standardized mortality rates by Chinese standard population and world standard population were 16.93/100,000 and 16.90/100,000, respectively. There was no distinct difference in mortality rates of liver cancer between urban (22.55/100,000) and rural (21.87/100,000) areas. Conclusions: Liver cancer has posed a heavy burden on people in Henan province. Comprehensive measures should be conducted to prevent the increase in the incidence of liver cancer.

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Programmed death ligand-1/programmed death-1 inhibition therapy and programmed death ligand-1 expression in urothelial bladder carcinoma

Yu WEI-BO ; Rao JIAN-YU

Chronic Diseases and Translational Medicine.2019;5(3):170-177.

After two decades of unchanged paradigms, the treatment strategies for advanced urothelial bladder cancer have been revolu-tionized by emerging programmed death ligand-1 (PD-L1)/programmed death-1 (PD1) inhibition therapy. Increased evidence is demonstrating the efficacy of PD-L1/PD1 inhibition therapy in both second-line and first-line settings. However, the percentage of patients who benefit from anti-PD-L1/anti-PD1 therapy is still low. Many questions have been raised in the development of biomarker-driven approaches for disease classification and patient selection. In this perspective, we discuss PD-L1/PD1 expression in urothelial bladder carcinoma, review approved anti-PD-L1/anti-PD1 agents for bladder cancer treatment and current ongoing studies investi-gating combination treatment strategies, and explore PD-L1 expression status for the evaluation of bladder cancer immunotherapy.

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Cyclin-dependent kinase 7 inhibitor THZ1 in cancer therapy

Li BIN-BIN ; Wang BO ; Zhu CHENG-MING ; Tang DI ; Pang JUN ; Zhao JING ; Sun CHUN-HUI ; Qiu MIAO-JUAN ; Qian ZHI-RONG

Chronic Diseases and Translational Medicine.2019;5(3):155-169.

Current cancer therapies have encountered adverse response due to poor therapeutic efficiency, severe side effects and acquired resistance to multiple drugs. Thus, there are urgent needs for finding new cancer-targeted pharmacological strategies. In this review, we summarized the current understanding with THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), which demonstrated promising anti-tumor activity against different cancer types. By introducing the anti-tumor behaviors and the po-tential targets for different cancers, this review aims to provide more effective approaches to CDK7 inhibitor-based therapeutic agents and deeper insight into the diverse tumor proliferation mechanisms.

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Cross-talk between Myc and p53 in B-cell lymphomas

Yu LI ; Yu TIAN-TIAN ; Ken H. YOUNG

Chronic Diseases and Translational Medicine.2019;5(3):139-154.

Myc and p53 proteins are closely associated with many physiological cellular functions, including immune response and lymphocyte survival, and are expressed in the lymphoid organs, which are sites for the development and activation of B-cell malignancies. Genetic alterations and other mechanisms resulting in constitutive activation, rearrangement, or mutation of MYC and TP53 contribute to the development of lymphomas, progression and therapy resistance by gene dysregulation, activation of downstream anti-apoptotic pathways, and unfavorable microenvironment interactions. The cross-talk between the Myc and p53 proteins contributes to the inferior prognosis in many types of B-cell lymphomas. In this review, we present the physiological roles of Myc and p53 proteins, and recent advances in understanding the pathological roles of Myc, p53, and their cross-talk in lymphoid neoplasms. In addition, we highlight clinical trials of novel agents that directly or indirectly inhibit Myc and/or p53 protein functions and their signaling pathways. Although, to date, these trials have failed to overcome drug resistance, the new results have highlighted the clinical efficiency of targeting diverse mechanisms of action with the goal of optimizing novel therapeutic op-portunities to eradicate lymphoma cells.

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Who benefits from R0 resection? A single-center analysis of patients with stage Ⅳ gallbladder cancer

Chen CHEN ; Wang LIN ; Zhang RUI ; Li QI ; Zhao YA-LING ; Zhang GUAN-JUN ; Li WEN-ZHI ; Geng ZHI-MIN

Chronic Diseases and Translational Medicine.2019;5(3):188-196.

Objectives: Most patients with gallbladder cancer (GBC) present with advanced-stage disease and have a poor prognosis. Radical resection remains the only therapeutic option to improve survival in patients with GBC. This study aimed to analyze the prognostic factors in patients with stage Ⅳ GBC and to identify a subgroup of patients who might benefit from R0 resection. Methods: A total of 285 patients with stage Ⅳ GBC were retrospectively analyzed at our institution from January 2008 to December 2012. Factors potentially influencing the prognosis of GBC after surgery were analyzed by univariate and multivariate analyses. Results: The 1-, 3-, and 5-year overall survival rates were 6.6% (15/229), 0.9% (2/229), and 0 (0/229), respectively. Ascites (relative risk [RR] ＝ 1.631, 95% confidence interval [CI]: 1.221-2.180, P ＝ 0.001), pathological grade (RR ＝ 1.337, 95% CI: 1.050-1.702, P ＝ 0.018), T stage (RR ＝ 1.421, 95% CI: 1.099-1.837, P ＝ 0.000), M stage (RR ＝ 1.896, 95% CI: 1.409-2.552, P＝0.000), and surgery (RR＝1.542, 95% CI: 1.022-2.327, P＝0.039) were identified as independent risk factors influencing prognosis. The median survival time (MST) was significantly higher in patients undergoing R0 resection than in those undergoing R1/R2 resection (6.0 vs. 2.7 months; P<0.001). In subgroup analyses, stageⅣA patients benefited from R0 resection (MST for R0 vs. R1/R2, 11.0 vs. 4.0 months; P ＝ 0.003), while R0 resection had a significant survival benefit than R1/R2 resection in patient with stage ⅣB GBC without distant metastasis (MST for R0 vs. R1/R2, 6.0 vs. 3.0 months; P ＝0.007). Conclusion: Ascites, pathological grade, T stage, M stage, and surgery were independent risk factors influencing prognosis in patients with stage Ⅳ GBC. N2 lymph node metastasis did not preclude curative resection, and radical resection should be considered in patients with stageⅣGBC without distant metastasis once R0 margin was achieved.

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The role of Fusobacterium nucleatum in colorectal cancer: from carcinogenesis to clinical management

Sun CHUN-HUI ; Li BIN-BIN ; Wang BO ; Zhao JING ; Zhang XIAO-YING ; Li TING-TING ; Li WEN-BING ; Tang DI ; Qiu MIAO-JUAN ; Wang XIN-CHENG ; Zhu CHENG-MING ; Qian ZHI-RONG

Chronic Diseases and Translational Medicine.2019;5(3):178-187.

Colorectal cancer (CRC) is a common malignant tumor that affects people worldwide. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum (F. nucleatum) in colorectal carcinoma tissue; many studies have indicated that F. nucleatum is closely related to the colorectal carcinogenesis. In this review, we provide the latest information to reveal the related molecular mechanisms. The known virulence factors of F. nucleatum promote adhesion to intestinal epithelial cells via FadA and Fap2. Besides, Fap2 also binds to immune cells causing immunosuppression. Furthermore, F. nucleatum recruits tumor-infiltrating immune cells, thus yielding a pro-inflammatory microenvironment, which promotes colorectal neoplasia progression. F. nucleatum was also found to potentiate CRC development through toll-like receptor 2 (TLR2)/toll-like receptor 4 (TLR4) signaling and microRNA (miRNA)-21 expression. In addition, F. nucleatum increases CRC recurrence along with chemoresistance by mediating a molecular network of miRNA-18a*, miRNA-4802, and autophagy components. Moreover, viable F. nucleatum was detected in mouse xenografts of human primary colorectal adenocarcinomas through successive passages. These findings indicated that an increased number of F. nucleatum in the tissues is a biomarker for the diagnosis and prognosis of CRC, and the underlying mo-lecular mechanism can probably provide a potential intervention treatment strategy for patients with F. nucleatum-associated CRC.

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Association of hemoglobin with arterial stiffness evaluated by carotid-femoral pulse wave velocity among Chinese adults

Zhang ZHEN-ZHEN ; Wang PING ; Kong XIANG-LEI ; Mao WEN-LI ; Cui MEI-YU

Chronic Diseases and Translational Medicine.2019;5(2):122-128.

Objective:Increased hemoglobin (Hb) levels are known to be associated with increased cardiovascular events and mortalities.Therefore,we assumed that high Hb levels were associated with arterial stiffness.Pulse wave velocity (PWV) is a simple and noninvasive method for measuring arterial stiffness to assess cardiovascular disease in general populations.Accordingly,we conducted a cross-sectional study to explore the association of Hb with PWV.Methods:A total of 6642 adults aged 54.5 ± 11.2 years undergoing physical examinations were enrolled,71.7％ of whom were males.Arterial stiffness was evaluated by carotid-femoral PWV (cfPWV).Multivariable regression analyses were performed to determine the relationship between Hb and increased cfPWV.Results:In this study,the mean Hb (per 10 g/L increase) was 144.7 ± 13.9 g/L,and the mean cfPWV was 15.1 ± 3.1 m/s.cfPWV was significantly higher in high hemoglobin groups ≥15.4 g/L (Quartile 4) than in the lowest hemoglobin group (Quartile 1 ≤ 13.6 g/L;P ＜ 0.001).Multiple linear regression analysis revealed that Hb positively correlated with cfPWV (β =0.16,P ＜ 0.01).Univariate Logistic regression analysis revealed that Hb was associated with increased cfPWV,with an odd ratio (OR) of 1.46 (95％ confidence interval [CI],1.39-1.54).After adjusting for potential confounders,Hb and the highest Hb quartile group were also independently associated with increased cfPWV,with a fully adjusted OR of 1.11 (95％ CI,1.02-1.20) and 1.45 (95％ CI,1.01-2.08),respectively.Conclusion:This study demonstrated that Hb levels significantly correlate with increased cfPWV.

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Association of handgrip strength with the prevalence of hypertension in a Chinese Han population

Manthar Ali MALLAH ; Liu MIN ; Liu YU ; Xu HAI-FENG ; Wu XIAO-JUN ; Chen XIAO-TIAN ; Wang HUI ; Liu CHUN-LAN ; Tian YUAN-RUI ; Li MENG-XIA ; Li QUN ; Fu JUN ; Shen CHONG

Chronic Diseases and Translational Medicine.2019;5(2):113-121.

Objective:Handgrip strength (HGS) exercise has been reported to reduce blood pressure in both hypertensive and normotensive patients.In this study,we evaluated the association of HGS with hypertension in a Chinese Han Population.Methods:A total of 11,151 subjects mainly consisting of a rural population were recruited with a multi-stage sampling method in Jurong city,Jiangsu Province,China.Besides hypertension and diabetes,major chronic diseases were excluded.HGS was categorized into tertiles by age and gender.Logistic regression was used to estimate the association of HGS and hypertension with the odds ratio (OR) and 95％ confidence interval (CI).Results:From low to high tertiles of HGS,diastolic blood pressure (DBP) was significantly increased (74.52 ± 7.39,74.70 ± 7.03,and 75.54 ± 7.01 mmHg,respectively;Ptrend =0.001),as well as in females (Ptrend=0.003).The differences in DBP among the tertiles of HGS were still significant in females even after adjusting for covariates (Ptrend=0.048).No significant differences in systolic blood pressure (SBP) were observed among the tertiles of HGS (P＞0.05).Compared to low HGS,high HGS was significantly associated with hypertension after adjustment for age and gender (adjusted OR,1.19;95％ CI,1.06-1.34;P =0.004).A stratified analysis showed that the significant association of high HGS and hypertension was also observed with the following factors even after adjusting for age and gender:female gender (adjusted OR,1.25;95％ CI,1.08-1.46;P=0.004),ages of 60-69 years (adjusted OR,1.29;95％ CI,1.06-1.57;P-0.011),and married (adjusted OR,1.20;95％ CI,1.06-1.37;P=0.005).However,no significant associations were found after adjusting for age,gender,smoking status,drinking status,body mass index,physical activity level,glucose,high-and low-density lipoprotein cholesterol,total cholesterol,and triglyceride (P＞0.05).Conclusion:The findings of the current study suggest that HGS was positively correlated with DBP in a rural population,and high HGS was associated with hypertension in females;however,the association may be modified by smoking status,drinking status,body mass index,physical activity,cholesterol level,and glucose level.Further utilization of HGS exercises to intervene in the development and prognosis of hypertension should be verified in the future.

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Occupational exposure to heavy metals, alcohol intake, and risk of type 2 diabetes and prediabetes among Chinese male workers

Yang AI-MIN ; Hu XIAO-BIN ; Liu SIMIN ; Cheng NING ; Zhang DE-SHENG ; Li JUAN-SHENG ; Li HAI-YAN ; Ren XIAO-WEI ; Li NA ; Sheng XI-PIN ; Ding JIAO ; Zheng SHAN ; Wang MIN-ZHENG ; Zheng TONG-ZHANG ; Bai YA-NA

Chronic Diseases and Translational Medicine.2019;5(2):97-104.

Objective:Both exposure to heavy metals and alcohol intake have been related to the risk of type 2 diabetes (T2D).In this study,we aimed to assess the potential interactions between metal exposure and alcohol intake on the risk of T2D and prediabetes in a cohort of Chinese male workers.Methods:We conducted a cross-sectional analysis of 26,008 Chinese male workers in an occupational cohort study from 2011 to 2013.We assessed metal exposure and alcohol consumption at baseline in these workers who were aged ≥20 years.Based on occupations which were categorized according to measured urine metal levels,multiple logistic regression analyses were used to evaluate the independent and joint effects of metal and alcohol exposure on the risk of T2D and prediabetes.Results:Risks of T2D (Ptrend =0.001) and prediabetes (Ptrend =0.001) were significantly elevated with increasing number of standard drinks per week,years of drinking,and lifetime alcohol consumption.An adjusted odds ratio (OR) of 6.1 (95％ confidence interval [CI]:4.8-7.8) was observed for the smelting/refining workers (highest metal exposure levels) who had the highest lifetime alcohol consumption (＞873 kg) (Pinteraction =0.018),whereas no statistically significant joint effect was found for prediabetes (Pinteraction =0.515).Conclusions:Both exposures to metal and heavy alcohol intake were associated with the risk of diabetes in this large cohort of male workers.There was a strong interaction between these two exposures in affecting diabetes risk that needs to be confirmed in future studies.

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Preferences and attitudes of young Chinese clinicians about using a shared decision making tools for communicating cardiovascular risk

Huang RONG-CHONG ; Song XIAN-TAO ; Zhang DONG-FENG ; Xu JIA-YING ; R.Boehmer KASEY ; A.Leppin AARON ; R.Gionfriddo MICHAEL ; H.Ting HENRY ; M.Montori VICTOR

Chronic Diseases and Translational Medicine.2019;5(2):105-112.

Objective:This study assesses the attitudes and preferences of Chinese clinicians toward their involvement in shared decision making (SDM).Methods:From May 2014 to May 2015,200 Chinese clinicians from two hospitals were enrolled to complete a survey on their attitude towards SDM.We conducted the survey via face-to-face interviews before and after an educational intervention on SDM among young Chinese clinicians.The clinicians were asked to give the extent of agreement to SDM.They also gave the extent of difficulty in using decision aids (DAs) during the SDM process.The variation in the range of responses to each question before and after the SDM intervention was recorded.The frequency of changed responses was analyzed by using JMP 6.0 software.Data were statistically analyzed using Chi-square and Mann-Whitney U tests,as appropriate to the data type.Multiple logistic regressions were used to test for those factors significantly and independently associated with preference for an approach for each scenario.Results:Of the 200 young Chinese clinicians sampled,59.0％ indicated a preference for SDM and a desire to participate in SDM before receiving education or seeing the DA,and this number increased to 69.0％ after seeing the DA with the sample video of the SDM process on Statin Choice.However,28.5％ of the respondents still reported that,in their current practice,they make clinical decisions on behalf of their patients.The clinicians who denied a desire to use the DA stated that the main barriers to implement SDM or DA use in China are lack of time and knowledge of SDM.Conclusions:Most young Chinese clinicians want to participate in SDM.However,they state the main barriers to perform SDM are lack of experience and time.The educational intervention about SDM that exposes clinicians to DAs was found to increase their receptivity.

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