Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. METHODS: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. RESULTS: The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged. CONCLUSIONS: Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.

Prognostic value of preoperative carcinoembryonic antigen/tumor size in rectal cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) is a commonly used biomarker in colorectal cancer. However, controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer. Here, we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level, which may better reflect the malignancy of rectal cancer. AIM: To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer. METHODS: We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012. These patients were randomly divided into two cohorts for cross-validation: training cohort and validation cohort. The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model. Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size. The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. RESULTS: In all, 556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort (2/3 of 556, n = 371) and the validation cohort (1/3 of 556, n = 185). The cutoff was 2.429 ng/mL per cm. Comparison of the baseline data showed that high CEA/tumor size was correlated with older age, high TNM stage, the presence of perineural invasion, high CEA, and high carbohydrate antigen 19-9 (CA 19-9). Kaplan-Meier curves showed a manifest reduction in 5-year OS (training cohort: 56.7% vs 81.1%, P < 0.001; validation cohort: 58.8% vs 85.6%, P < 0.001) and DFS (training cohort: 52.5% vs 71.9%, P = 0.02; validation cohort: 50.3% vs 79.3%, P = 0.002) in the high CEA/tumor size group compared with the low CEA/tumor size group. Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS (training cohort: hazard ratio (HR) = 2.18, 95% confidence interval (CI): 1.28-3.73, P = 0.004; validation cohort: HR = 4.83, 95%CI: 2.21-10.52, P < 0.001) as well as DFS (training cohort: HR = 1.47, 95%CI: 0.93-2.33, P = 0.096; validation cohort: HR = 2.61, 95%CI: 1.38-4.95, P = 0.003). CONCLUSION: Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer. Higher CEA/tumor size is associated with worse OS and DFS.

[Influence of online social software on HIV transmission among men who have sex with men].

The prevention and control of human immunodeficiency virus (HIV) infection is important for public health. Sexual contact transmission has replaced blood transmission as a major route of HIV transmission in China. The incidence of HIV infection increased significantly among young men who have sex with men (MSM). Online social software instead of traditional venues has become a main means of seeking sexual partners. The application of online social software may contribute to an increased incidence of HIV among young MSMs by promoting such risky behaviors as having occasional or multiple sexual partners and drug abuse. Compared with the MSMs enrolled from traditional venues, those recruited online showed significant differences in the educational level, sexual behaviors, and HIV knowledge. Online social software is a promising way to improve the prevention and control of HIV as well as HIV-related epidemic surveys.

The prevalence rates of major chronic diseases in retired and in-service Chinese military officers (2000-2016): a meta-analysis.

BACKGROUND: Chronic diseases cause a tremendous burden to the military medical system. However, the prevalence rates of major chronic diseases among military officers remain unclear in China. METHODS: China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), PubMed and Web of Science were searched for studies (from 2000 to 2016) concerning 6 major chronic diseases: hypertension, hyperlipidemia, diabetes mellitus, heart diseases, cerebrovascular diseases, and chronic obstructive pulmonary diseases (COPD) in Chinese military officers following strict inclusion and exclusion criteria. Three researchers independently extracted data from the included studies, and a fourth researcher reviewed and solved every disagreement. Statistical analysis was performed with STATA 14.0 and R 3.3.2. Heterogeneity was evaluated by the I 2 value. A random effect model was performed to combine the heterogeneous data. The Egger test was performed to test the publication bias. RESULTS: A total of 90,758 military officers derived from 75 articles were pooled together. Publication bias was only observed in 37 studies reporting heart disease (P Egger test = 0.01). The overall prevalence rates of hypertension, hyperlipidemia, diabetes mellitus, heart diseases, cerebrovascular diseases, and COPD were 46.6% (95% CI 41.8-51.5%), 30.9% (26.4-35.7%), 20.7% (16.5-25.7%), 48.2% (41.7-54.9%), 20.2% (14.8-26.9%) and 16.6% (12.9-21.0%), respectively. The prevalence rates of hypertension, diabetes, heart disease, cerebrovascular disease, and COPD, rather than hyperlipidemia, increased with age in Chinese military officers. Heart diseases (P Q-test  < 0.001) and hypertension (P Q-test  < 0.001) increased sharply in retired officers compared with officers in service. Cerebrovascular disease was more frequent in Northern Theater Command than in any other theater command (P Q-test  < 0.001). CONCLUSIONS: Major chronic diseases heavily affect Chinese military officers, especially retirees. Medical intervention should be enforced on the prevention of cerebrovascular diseases in those working in cold areas in the north, as well as hypertension and heart diseases in retirees.

Prohibitin, relocated to the front ends, can control the migration directionality of colorectal cancer cells.

Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis. VEGF bound to its receptor, neuropilin-1, can stimulate the activation of cell division cycle 42, which recruits intra-mitochondrial PHB to the front end of a CRC cell. This intracellular relocation of PHB results in the polymerization and reorganization of filament actin extending to the front end of the cell. As a result, the migration directionality of CRC cells is targeted towards VEGF. Together, these findings identify PHB as a key modulator of directional migration of CRC cells and a target for metastasis.

Downregulation of SAFB Sustains the NF-κB Pathway by Targeting TAK1 during the Progression of Colorectal Cancer.

Purpose: To investigate the role and the underlying mechanism of scaffold attachment factor B (SAFB) in the progression of colorectal cancer (CRC).Experimental Design: SAFB expression was analyzed in the Cancer Outlier Profile Analysis of Oncomine and in 175 paraffin-embedded archived CRC tissues. Gene Ontology analyses were performed to explore the mechanism of SAFB in CRC progression. Western blot, RT-PCR, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to detect the regulation of transforming growth factor-ß-activated kinase 1 (TAK1) and NF-κB signaling by SAFB The role of SAFB in invasion, metastasis, and angiogenesis was investigated using in vitro and in vivo assays. The relationship between SAFB and TAK1 was analyzed in CRC tissues.Results: SAFB was downregulated in CRC tissues, and low expression of SAFB was significantly associated with an aggressive phenotype and poorer survival of CRC patients. The downregulation of SAFB activated NF-κB signaling by targeting the TAK1 promoter. Ectopic expression of SAFB inhibited the development of aggressive features and metastasis of CRC cells both in vitro and in vivo The overexpression of TAK1 could rescue the aggressive features in SAFB-overexpressed cells. Furthermore, the expression of SAFB in CRC tissues was negatively correlated with the expression of TAK1- and NF-κB-related genes.Conclusions: Our results show that SAFB regulated the activity of NF-κB signaling in CRC by targeting TAK1 This novel mechanism provides a comprehensive understanding of both SAFB and the NF-κB signaling pathway in the progression of CRC and indicates that the SAFB-TAK1-NF-κB axis is a potential target for early therapeutic intervention in CRC progression. Clin Cancer Res; 23(22); 7108-18. ©2017 AACR.

Strategy and technology to prevent hospital-acquired infections: Lessons from SARS, Ebola, and MERS in Asia and West Africa.

Hospital-acquired infections (HAIs) are serious problems for healthcare systems, especially in developing countries where public health infrastructure and technology for infection preventions remain undeveloped. Here, we characterized how strategy and technology could be mobilized to improve the effectiveness of infection prevention and control in hospitals during the outbreaks of Ebola, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) in Asia and West Africa. Published literature on the hospital-borne outbreaks of SARS, Ebola, and MERS in Asia and West Africa was comprehensively reviewed. The results showed that healthcare systems and hospital management in affected healthcare facilities had poor strategies and inadequate technologies and human resources for the prevention and control of HAIs, which led to increased morbidity, mortality, and unnecessary costs. We recommend that governments worldwide enforce disaster risk management, even when no outbreaks are imminent. Quarantine and ventilation functions should be taken into consideration in architectural design of hospitals and healthcare facilities. We also recommend that health authorities invest in training healthcare workers for disease outbreak response, as their preparedness is essential to reducing disaster risk.

Prediction and prophylaxis of hepatocellular carcinoma occurrence and postoperative recurrence in chronic hepatitis B virus-infected subjects.

Hepatocellular carcinoma (HCC) is one of the most common and highly fatal malignancies worldwide. Chronic infection with hepatitis B virus (HBV) is a major cause of HCC. High HBV replication rate and related non-resolving inflammation are the major risk factors of HCC occurrence and postoperative recurrence. Early prophylactic options are effective in reducing HCC occurrence and improving survival. Therefore, it is important to identify HBV-infected patients who are at a higher risk of developing HCC and HBV-HCC patients who are more likely to relapse after surgery, thus providing them with more precise prophylactic strategies. Several prediction models of HCC occurrence have been constructed, with satisfactory predictive accuracy and discriminatory ability. However, there is a lack of consensus for their clinical implementation. Several staging systems have been proposed for HCC prognosis. However, the accuracy of these staging systems based on demographic characteristics and clinical measurements needs to be further improved, possibly by systematically incorporating viral and inflammatory factors. Since antiviral treatments are effective in promoting liver function reserve, reducing HCC occurrence and prolonging postoperative survival in some HBV-infected subjects, it is very important to identify subgroups of HBV-infected patients who would most benefit from antiviral treatment.

Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma.

UNLABELLED: Systemic analyses using large-scale genomic profiles have successfully identified cancer-driving somatic copy number variations (SCNVs) loci. However, functions of vast focal SCNVs in "protein-coding gene desert" regions are largely unknown. The integrative analysis of long noncoding RNA (lncRNA) expression profiles with SCNVs in hepatocellular carcinoma (HCC) led us to identify the recurrent deletion of lncRNA-PRAL (p53 regulation-associated lncRNA) on chromosome 17p13.1, whose genomic alterations were significantly associated with reduced survival of HCC patients. We found that lncRNA-PRAL could inhibit HCC growth and induce apoptosis in vivo and in vitro through p53. Subsequent investigations indicated that the three stem-loop motifs at the 5' end of lncRNA-PRAL facilitated the combination of HSP90 and p53 and thus competitively inhibited MDM2-dependent p53 ubiquitination, resulting in enhanced p53 stability. Additionally, in vivo lncRNA-PRAL delivery efficiently reduced intrinsic tumors, indicating its potential therapeutic application. CONCLUSIONS: lncRNA-PRAL, one of the key cancer-driving SCNVs, is a crucial stimulus for HCC growth and may serve as a potential target for antitumor therapy.

Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer.

AIM: To investigate the expression and oncogenic role of nemo-like kinase (NLK) in colorectal cancer. METHODS: Expression of NLK protein was assessed by immunohistochemistry in tissue specimens from 56 cases of normal colorectal mucosa, 51 cases of colorectal adenoma, and 712 cases of colorectal cancer. In addition, NLK expression was knocked down using a lentivirus carrying NLK small hairpin RNA in colorectal cancer cells. Cell viability methylthiazoletetrazolium assays, colony formation assays, flow cytometry cell cycle assays, Transwell migration assays, and gene expression assays were performed to explore its role on proliferation and migration of colorectal cancer. RESULTS: Expression of NLK protein progressively increased in tissues from the normal mucosa through adenoma to various stages of colorectal cancer. Overexpression of NLK protein was associated with advanced tumor-lymph node-metastasis stages, poor differentiation, lymph node and distant metastases, and a higher recurrence rate of colorectal cancer (P < 0.05). Multivariate analyses showed that NLK expression was an independent prognostic factor to predict overall survival (hazard ratio 2.57, 95% confidence interval: 1.66-3.98; P < 0.001) and disease-free survival (hazard ratio 1.96, 95% confidence interval: 1.40-2.74: P < 0.001) of colorectal cancer patients. Furthermore, knockdown of NLK expression in colorectal cancer cell lines reduced cell viability, colony formation, and migration, and arrested tumor cells at the G0/G1 phase of the cell cycle. At the gene level, knockdown of NLK expression inhibited matrix metalloproteinase-2 expression in colorectal cancer cells. CONCLUSION: NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis.

Ebola virus disease: from epidemiology to prophylaxis.

The outbreak of Ebola virus disease (EVD) continues to spread through West Africa. Since the first report of EVD in March 2014, the number of cases has increased rapidly, with the fatality rate of >50%. The most prevalent Ebola virus belongs to the species of Zaire ebolavirus, with a fatality rate as high as 90%. Although there were cases introduced into other continents, Africa is the endemic area where fruit bats and apes are suspected to be Ebola virus carriers. The virus might be transmitted from the host animals to humans if humans consume raw or not fully cooked and contaminated meats. However, human-to-human transmission via close contact is the major route of current outbreaks. EVD can occur during any season and affect people of any race and age group. Direct contact with body fluids of EVD patients or living in contaminated environments greatly increases the risk of being infected. Transmission via aerosol less likely, but transmission via virus-containing droplets is possible in humans. Thus, health care providers are facing danger of getting Ebola virus infection. To date, vaccines, drugs and/or therapies to prevent Ebola virus infection or treat EVD are limited. Medical workers should follow the current standard prophylactic procedures. The military can orchestrate efficient care to mass EVD patients. Although it is necessary to speed up the pace of developing effective vaccine and therapeutics for the prevention and treatment of EVD, public health prevention and management should be important issue at present to control the spread of this disease cost-effectively.

Phosphatase and tensin homologue genetic polymorphisms and their interactions with viral mutations on the risk of hepatocellular carcinoma.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). Some HBV mutants and dysregulation of phosphatase and tensin homolog (PTEN) may promote the development of HCC synergistically. We aimed to test the effects of PTEN genetic polymorphisms and their interactions with important HBV mutations on the development of HCC in HBV-infected subjects. METHODS: Quantitative polymerase chain reaction was applied to genotype PTEN polymorphisms (rs1234220, rs2299939, rs1234213) in 1012 healthy controls, 302 natural clearance subjects, and 2011 chronic HBV-infected subjects including 1021 HCC patients. HBV mutations were determined by sequencing. The associations of PTEN polymorphisms and their interactions with HBV mutations with HCC risk were assessed using multivariate logistic regression analysis. RESULTS: Rs1234220 C allele was significantly associated with HCC risk compared to healthy controls (adjusted odds ratio [AOR] = 1.35, 95% confidence interval [CI] = 1.07-1.69) and HCC-free HBV-infected subjects (AOR = 1.27, 95% CI = 1.01-1.57). rs1234220 C allele was significantly associated with increased frequencies of HCC-risk A1652G, C1673T, and C1730G mutations in genotype B HBV-infected subjects. Rs2299939 GT genotype was inversely associated with HCC risk in HBV-infected patients (AOR = 0.75, 95% CI = 0.62-0.92). The interaction of rs2299939 variant genotypes (GT+TT) with A3054T mutation significantly increased HCC risk (AOR = 2.41, 95% CI = 1.08-5.35); whereas its interaction with C3116T mutation significantly reduced HCC risk (AOR = 0.34, 95% CI = 0.18-0.66). These significant effects were only evident in males after stratification. CONCLUSIONS: PTEN polymorphisms and their interactions with HBV mutations may contribute to hepatocarcinogenesis in males. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.

Expression of ITGB1 predicts prognosis in colorectal cancer: a large prospective study based on tissue microarray.

BACKGROUND: ITGB1 is a heterodimeric cell-surface receptor involved in cell functions such as proliferation, migration, invasion and survival. The aim of this study was to assess ITGB1 expression in colorectal cancer and correlate it with clinicopathological features, as well as to evaluate its potential prognostic significance. MATERIALS AND METHODS: In this study, we examined the expression of ITGB1 using tissue microarrays containing analyzed specimens by immunohistochemistry. ITGB1 expression was further correlated with clinicopathological and prognostic data. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. A multivariate study with the Cox's proportional hazard model was used to evaluate the prognostic aspects. RESULTS: ITGB1 expression was present in 88.5% of the analyzed specimens. Significant differences in ITGB1 expression were found between normal mucosa and carcinomas (P<0.001). High ITGB1 expression was associated with poor prognosis, and it independently correlated with shortened overall survival and disease-free survival in colorectal cancer patients (P<0.001). More so, ITGB1 expression, bowel wall invasion, lymph node metastasis and distant metastasis were independent prognostic factors for overall survival. Additionally, significant differences in ITGB1 expression were observed in adenomas and tumors from patients with familial adenomatous polyposis compared to normal colon mucosa (P<0.05) CONCLUSION: The results of this study indicate that ITGB1 overexpression in colorectal tumors is associated with poor prognosis, as well as aggressive clinicopathological features. Therefore, ITGB1 expression could be used as potential prognostic predictor in colorectal cancer patients.

Environmental and psycho-social factors related to prostate cancer risk in the Chinese population: a case-control study.

OBJECTIVE: To study the risk environmental and psycho-social factors associated to prostate cancer (PCa) in Chinese population. METHODS: 250 PCa patients and 500 controls were enrolled in this case-control study. Information was collected and logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between lifestyle, eating habits and psycho-social factors with PCa risk. RESULTS: Green vegetables and green tea were associated with a decreased risk of PCa (OR=0.39, 95% CI: 0.28-0.53; OR=0.59, 95% CI: 0.40-0.87, respectively). Family history of PCa (OR=7.16, 95% CI: 2.01-25.49), history of prostate diseases (OR=2.28, 95% CI: 1.53-3.41), alcohol consumption (OR=1.97, 95% CI: 1.33-2.90), red meat consumption (OR=1.74, 95% CI: 1.20-2.52), barbecued (OR=2.29, 95% CI: 1.11-4.73) or fried (OR=2.35, 95% CI: 1.24-4.43) foods were related with increased PCa risk. Negative psycho-social factors including occupational setbacks (OR=1.61, 95% CI: 1.00-2.59), marital separation (OR=1.94, 95% CI: 1.29-2.91), self-contained suffering (OR=2.37, 95% CI: 1.58-3.55), and high sensitivity to the personal comments (OR=1.73, 95% CI: 1.18-2.54) were related to PCa. CONCLUSION: Regular consumption of green vegetables and green tea may suggest protective effects on PCa. Alcohol consumption, red meat consumption and barbecued or fried foods were associated with PCa. Negative psycho-social factors may also play a role in the incidence of PCa in Chinese population.

Virus-related liver cirrhosis: molecular basis and therapeutic options.

Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8(+) T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.

Inflammation-related factors predicting prognosis of gastric cancer.

Gastric cancer (GC), which is mainly induced by Helicobacter pylori (H. pylori) infection, is one of the leading causes of cancer-related death in the developing world. Active inflammation initiated by H. pylori infection and maintained by inherent immune disorders promotes carcinogenesis and postoperative recurrence. However, the presence with H. pylori in tumors has been linked to a better prognosis, possibly due to the induction of antitumor immunity. Tumor infiltrations of tumor-associated macrophages, myeloid-derived suppressor cells, neutrophils, Foxp3(+) regulatory T cells are correlated with poor prognosis. Tumor infiltrating CD8(+) cytotoxic T lymphocytes, dendritic cells, and CD45RO T cells are generally associated with good prognosis of GC, although some subsets of these immune cells have inverse prognosis prediction values. High ratios of Foxp3(+)/CD4(+) and Foxp3(+)/CD8(+) in tumors are associated with a poor prognosis; whereas high Th1/Th2 ratio in tumors predicts a good prognosis. High levels of interleukin (IL)-6, IL-10, IL-32, and chemokine C-C motif ligands (CCL)7 and CCL21 in circulation, high expression of CXC chemokine receptor 4, chemokine C-C motif receptor (CCR)3, CCR4, CCR5, CCR7, hypoxia-inducible factor-1α, signal transducer activator of transcription-3, cyclooxygenase-2, and orphan nuclear receptor 4A2 in tumors are associated with an unfavorable prognosis. Increased serum levels of matrix metalloproteinases (MMP)-3, MMP-7, and MMP-11 and increased levels of MMP-9, MMP-12, and MMP-21 in tumors are consistently associated with poor survival of GC. Further emphasis should be put on the integration of these biomarkers and validation in large cohorts for personalized prediction of GC postoperative prognosis.

Downregulation of ATP-binding cassette subfamily C member 4 increases sensitivity to neoadjuvant radiotherapy for locally advanced rectal carcinoma.

OBJECTIVE: This study was designed to verify the effect of ATP-binding cassette subfamily C member 4 on radiosensitivity of locally advanced rectal carcinoma. SETTING: The expression of ATP-binding cassette subfamily C member 4 protein in 121 pretreatment tissue samples from locally advanced rectal carcinoma patients was detected by immunohistochemistry. DESIGN: Pathological response to radiotherapy was evaluated according to tumor regression grading by postoperative histological examinations after they received long-course preoperative neoadjuvant radiotherapy, and the association between clinicopathological data and tumor regression grading was analyzed retrospectively. For further validation, short hairpin RNA was constructed and transfected into colorectal carcinoma cell line HT29. The knockdown efficiency was confirmed at both RNA and protein levels. The altered radiosensitivity was evaluated by methylthiazolyl tetrazolium assay, colony formation assay, flow cytometry, and Hoechst 33258 staining. RESULTS: Univariate analysis revealed that ATP-binding cassette subfamily C member 4 expression (p < 0.001), P53 type (p = 0.069), and CEA (p = 0.100) were possibly associated with tumor regression grading, and multivariate analysis demonstrated that ATP-binding cassette subfamily C member 4 expression (p < 0.001) and P53 type (p = 0.039) were positively correlated with response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients. Lentiviral vector was successfully introduced into HT29 cells and inhibited ATP-binding cassette subfamily C member 4 expression efficiently and persistently. Downregulation of ATP-binding cassette subfamily C member 4 expression significantly enhanced inhibition of cell proliferation, decreased colony formation capacity, and increased cell apoptosis induced by irradiation, as examined by a series of experiments in vitro. In addition, radiobiological parameters calculated according to the single-hit multitarget model were also decreased significantly. CONCLUSIONS: Our data indicate that ATP-binding cassette subfamily C member 4 may be a useful molecular marker in predicting radiosensitivity, and a potential target in improving the response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients.

[Effect of PTPRD rs2279776 gene and interaction with hepatitis B virus mutations on the risk of hepatocellular carcinoma].

OBJECTIVE: To investigate the effect of rs2279776 at the PTPRD and its interactions on hepatitis B virus (HBV)mutations as well as related risk on hepatocellular carcinoma (HCC). METHODS: A total of 3023 individuals, including 1012 healthy controls, 990 HCC-free HBV-infected subjects, and 1021 HBV-caused hepatocellular carcinoma patients (HCC)were involved in this study. PTPRD rs2279776 was genotyped, using quantitative PCR. HBV enhancer II/basal core promoter/precore (Enh II/BCP/preC) and preS regions were amplified by nested PCR and directly sequenced. Logistic regression analysis was performed to test the association among rs2279776 polymorphism, HBV mutations, and their interactions on the risk of HCC. RESULTS: The distributions of rs2279776 genotypes and allelic frequencies between HCC patients and healthy controls, HCC patients and HBsAg-positive subjects without HCC, HCC patients and HCC-free population (HBsAg-positive subjects without HCC and healthy controls) showed no statistically significant differences. However, the interactions of GC genotype on HBV mutations T1753V and preS deletion significantly increased on the risk of HCC in female HBV-infected subjects. Same result was also seen for rs2279776 C allele (GC+CC). The interaction of rs2279776 GC genotype with G1896A could reduce the risk of HCC in HBV genotype B infected subjects and the interaction of CC genotype with A1652G significantly reduced the risk of HCC in HBV genotype C infected subjects. CONCLUSION: PTPRD rs2279776 did not directly contribute to the genetic susceptibility on HCC risk. However, it might affect the risk of HCC via interacting with HBV mutations.

Cancer incidence and patient survival rates among the residents in the Pudong New Area of Shanghai between 2002 and 2006.

With the growing threat of malignancy to health, it is necessary to analyze cancer incidence and patient survival rates among the residents in Pudong New Area of Shanghai to formulate better cancer prevention strategies. A total of 43,613 cancer patients diagnosed between 2002 and 2006 were recruited from the Pudong New Area Cancer Registry. The incidence, observed survival rate, and relative survival rate of patients grouped by sex, age, geographic area, and TNM stage were calculated using the Kaplan-Meier, life table, and Ederer II methods, respectively. Between 2002 and 2006, cancer incidence in Pudong New Area was 349.99 per 100,000 person-years, and the 10 most frequently diseased sites were the lung, stomach, colon and rectum, liver, breast, esophagus, pancreas, brain and central nervous system, thyroid, and bladder. For patients with cancers of the colon and rectum, breast, thyroid, brain and central nervous system, and bladder, the 5-year relative survival rate was greater than 40%, whereas patients with cancers of the liver and pancreas had a 5-year relative survival rate of less than 10%. The 1-year to 5-year survival rates for patients grouped by sex, age, geographic area, and TNM stage differed significantly (all P < 0.001). Our results indicate that cancer incidence and patient survival in Pudong New Area vary by tumor type, sex, age, geographic area, and TNM stage.

[The incidence and mortality of lung cancer among residents in Yangpu district of Shanghai from 2002 to 2010].

OBJECTIVE: To analyze the incidence and mortality of lung cancer patients among residents in Yangpu District of Shanghai from 2002 to 2010. METHODS: The data of lung cancer cases in permanent residents of Yangpu district were collected from the database of the registration and management system in Shanghai city. Temporal trend in the incidence of lung cancer was analyzed by using annual percent change (APC) mode1. The survivals were calculated using SPSS 16.0 and Joinpoint Regression Program 3.5.1 software. RESULTS: A total of 5726 cases of lung cancer were diagnosed from January 2002 to December 2010. Of those, 3865 were males with an average age of onset 70.08 years, and 1861 were females with an average age of onset 70.88 years. The crude incidence rate was 77.36/10(5) in men, significantly higher than 39.31/10(5) in women (U = 24.84, P < 0.01). The standardized incidence rate was 25.23/10(5) in men, significantly higher than 13.47/10(5) in women (U = 13.24, P < 0.01). A total of 5248 cases died of the disease in this period. Of those, 3586 were men. The crude mortality was 71.77/10(5) in men, significantly higher than 35.11/10(5) in women (U = 24.67, P < 0.01). The standardized mortality was 21.72/10(5) in men, significantly higher than 11.08/10(5) in women (U = 13.01, P < 0.01). Both the incidence and mortality rates increased apparently in those older than 45 years. The 1- to 5-year survival rates in all cases were 37.42%, 22.71%, 15.73%, 12.32%, and 10.53%, respectively. The 1- to 5-year survival rates in male cases were significantly lower than those in female cases (P < 0.05 for each comparison). The 1- to 5-year survival rates of the patients whose tumor had been surgically removed were significantly higher than those in the patients without surgery (P < 0.05 for each comparison). CONCLUSIONS: The incidence of lung cancer is close to the mortality in the residents of Yangpu District of Shanghai city. Surgical resection treatment improves the prognosis of lung cancer.