Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis(LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded.METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health(Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM(49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012.RESULTS: The baseline serum direct bilirubin concentration was(median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin(2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin wasindependently associated with LNM(OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that:(1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification;(2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and(3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis.CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.

Diabetes mellitus and hepatocellular carcinoma:Comparison of Chinese patients with and without HBV-related cirrhosis

AIM:To determine the role of diabetes mellitus(DM) and other associated factors in Chinese hepatocellular carcinoma(HCC) patients with cirrhosis,compared with those HCC patients without cirrhosis,in the single setting of hepatitis B virus(HBV) infection,after other known concomitant diseases were excluded.METHODS:A total of 482 patients,treated at the China-Japan Friendship Hospital,Ministry of Health(Beijing,China),in the period January 2003 to June 2009,and with a hospital discharge diagnosis of HCC,were included.Demographic,clinical,laboratory,metabolic and instrumental features were analyzed.RESULTS:Of the total,310 patients were diagnosed with HBV infection and,following the inclusion and exclusion criteria,224 were analyzed,including 122 patients(54.5%) with cirrhosis(the case group) and 102 patients without cirrhosis(the control group).Twentyseven patients(12.1%) were diabetic,including 19 in the case group and 8 in the control group(19/122=15.6% vs 8/102=7.8%,P=0.077).Thirty-one possible relevant parameters were compared by univariate analysis,and 9 variables were selected for multivariable analysis,including DM(P=0.077),past history of HBV infection(P=0.005),total bilirubin(P<0.001),albumin level(P<0.001),international normalized ratio(INR)(P<0.001),alanine aminotransferase(P=0.050),platelet(P<0.001),total cholesterol(P= 0.047),and LDL cholesterol(P=0.002) levels.Diabetes showed a statistical difference by multivariable analysis [odds ratio(OR) 4.88,95% confidence interval(CI):1.08-21.99,P=0.039],although no significant difference was found in univariate analysis.In addition,three cirrhosis-related parameters remained statistically different,including INR(OR 117.14,95% CI:4.19-3272.28,P=0.005),albumin(OR 0.89,95% CI:0.80-0.99,P=0.027),and platelet count(OR 0.992,95% CI:0.987-0.999,P=0.002).CONCLUSION:Besides the three cirrhosis-related parameters,DM was found to be the sole independent factor associated with HCC in patients with HBV-related cirrhosis,compared with those without cirrhosis.

Increased international normalized ratio level in hepatocellular carcinoma patients with diabetes mellitus

AIM: To determine the association of diabetes mellitus (DM) and international normalized ratio (INR) level in hepatocellular carcinoma (HCC) patients. METHODS: Our present study included 375 HCC patients who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to April 2012, and with a hospital discharge diagnosis of HCC. The demographic, clinical, laboratory, metabolic and instrumental features were analyzed. χ2 test, Student's t test and Mann-Whitney U test were used to compare the differences between HCC patients with and without DM. Unconditional multivariable logistic regression analysis was used to determine the association of DM and INR level in HCC patients. A sub-group analysis was performed to assess the effect of liver cirrhosis or hepatitis B virus (HBV) infection on the results. The Pearson correlation test was used to determine the relationship between INR level and fasting glucose. In addition, association between diabetes duration, and diabetes treatment and INR level was determined considering the potentially different effects. RESULTS: Of the total, 63 (16.8%) patients were diabetic (diabetic group) and 312 (83.2%) patients were diagnosed without diabetes (non-diabetic group). Their mean age was 56.4 ± 11.0 years and 312 (83.2%) patients were male. Compared with patients without DM, the HCC patients with diabetes were older (59.5 ± 10.3 vs 55.8 ± 11.1, P=0.015), had a lower incidence of HBV infection (79.4% vs 89.1%, P=0.033), had increased levels of systolic blood pressure (SBP) (133 ± 17 vs 129 ± 16 mmHg, P=0.048) and INR (1.31 ± 0.44 vs 1.18 ± 0.21, P=0.001), had lower values of hemoglobin (124.4 ± 23.9 vs 134.2 ± 23.4, P=0.003) and had a platelet count (median/interquartile-range: 113/64-157 vs 139/89-192, P=0.020). There was no statistically significant difference in the percentages of males, overweight or obesity, drinking, smoking, cirrhosis and Child classification. After controlling for the confounding effects of age, systolic blood pressure, hemoglobin, platelet count and HBV infection by logistic analyses, INR was shown as an independent variable [odds ratio (OR)=3.650; 95%CI: 1.372-9.714, P=0.010]. Considering the effect of liver cirrhosis on results, a sub-group analysis was performed and the study population was restricted to those patients with cirrhosis. Univariate analysis showed that diabetic patients had a higher INR than non-diabetic patients (1.43 ± 0.51 vs 1.25 ± 0.23, P=0.041). After controlling for confounding effect of age, SBP, hemoglobin, platelet count and HBV infection by logistic analyses, INR level remained as the sole independent variable (OR=5.161; 95%CI: 1.618-16.455, P=0.006). No significant difference in the relationship between INR level and fasting glucose was shown by Pearson test (r=0.070, P=0.184). Among the 63 diabetic patients, 35 (55.6%) patients had been diagnosed with DM for more than 5 years, 23 (36.5%) received oral anti-diabetic regimens, 11 (17.5%) received insulin, and 30 (47.6%) reported relying on diet alone to control serum glucose levels. No significant differences were found for the association between DM duration/treatment and INR level, except for the age at diabetes diagnosis. CONCLUSION: The INR level was increased in HCC patients with DM and these patients should be monitored for the coagulation function in clinical practice.

Potential role of diabetes mellitus in the progression of cirrhosis to hepatocellular carcinoma:a cross-sectional case-control study from Chinese patients with HBV infection

BACKGROUND: Diabetes mellitus (DM) is regarded as a new risk factor for hepatocellular carcinoma (HCC), but few studies have focused on the potential role of DM in the progression of cirrhosis to HCC as well as in patients with simple HBV infection. METHODS: A cohort of 1028 patients, treated at our hospital and with a hospital discharge diagnosis of HCC and/or cirrhosis, was screened. Among them, 558 were diagnosed with chronic HBV infection and 370 were analyzed statistically according to the diagnostic, inclusion and exclusion criteria. The demographic, clinical, metabolic, virological, biochemical, radiological and pathological features were analyzed and the multivariate logistic regression model was used to determine the potential role of DM. RESULTS: In 248 cirrhotic patients, 76 were diabetic and their mean duration of DM was 4.6 years. In 122 HCC patients with cirrhosis, 25 were diabetic and their mean duration of DM was 4.4 years. Univariate analysis showed that compared with cirrhotic patients, the HCC patients had a higher percentage in males (P=0.001), a lower percentage in DM patients (P=0.039), a higher percentage in cigarette smokers (P=0.005), a higher percentage in patients with AFP】400 ng/mL (P【0.001), higher values of white blood cells (P【0.001), hemoglobin (P【0.001) and platelet (P【0.001), increased levels of ALT (P【0.001) and GGT (P【0.001), higher total bilirubin (P=0.018) and albumin levels (P【0.001), and a lower international normalized ratio (P【0.001). Multivariate logistic regression analysis showed that DM was anindependent associated factor for HCC [odds ratio (OR)=0.376; 95% CI, 0.175-0.807; P=0.012]. Even after the HCC patients were restricted to those with decompensated cirrhosis and compared with decompensated cirrhotic patients, the similar result was observed (OR=0.192; 95% CI, 0.054-0.679; P=0.010). CONCLUSIONS: DM is an independent factor in the progression of cirrhosis to HCC, but the role may be contrary to our current viewpoint. To clarify the causal relationship of DM and HCC, prospective and experimental studies are required.

Molecular pathological epidemiology in diabetes mellitus and risk of hepatocellular carcinoma

Molecular pathological epidemiology(MPE) is a multidisciplinary and transdisciplinary study field,which has emerged as an integrated approach of molecular patho-logy and epidemiology,and investigates the relationship between exogenous and endogenous exposure factors,tumor molecular signatures,and tumor initiation,progression,and response to treatment.Molecular epidemiology broadly encompasses MPE and conventional-type molecular epidemiology.Hepatocellular carcinoma(HCC) is the third most common cause of cancer-associated death worldwide and remains as a major public health challenge.Over the past few decades,a number of epidemiological studies have demonstrated that diabetes mellitus(DM) is an established independent risk factor for HCC.However,how DM affects the occurrence and development of HCC remains as yet unclearly understood.MPE may be a promising approach to investigate the molecular mechanisms of carcinogenesis of DM in HCC,and provide some useful insights for this pathological process,although a few challenges must be overcome.This review highlights the recent advances in this field,including:(1) introduction of MPE;(2) HCC,risk factors,and DM as an established independent risk factor for HCC;(3) molecular pathology,molecular epidemiology,and MPE in DM and HCC;and(4) MPE studies in DM and risk of HCC.More MPE studies are expected to be performed in future and I believe that this field can provide some very important insights on the molecular mechanisms,diagnosis,personalized prevention and treatment for DM and risk of HCC.

Novel coronavirus"Omicron subtype variant strain BA.2":The latest research progress

Since the outbreak of COVID-19,with the emergence of a series of novel coronavirus variants of different types,COVID-19 has continued to spread across the globe,posing a huge threat to the lives and health of people around the world and posing a severe challenge to global public health security.Recently,the World Health Organization(WHO)announced that novel coronavirus variant strain"Omicron"subtype variant strain BA.2 has been found in 57 countries and regions.It has higher vaccine and antibody tolerance and is more infectious than omicron(B.1.1.529).In this paper,we briefly review the recent studies on the omicron subtype variant strain BA.2.

The latest research progress of the Corona Virus Disease 2019 mutant strain"Omicron"

Coronavirus disease 2019(COVID-19)that broke out at the end of December 2019 has been raging for 3 years,bringing unpredictable harm to the physical and mental health of all mankind and global economic development.The new type of coronavirus pneumonia is a new type of respiratory infectious disease with a high incidence and fatality rate caused by SARS-CoV-2.Up to now,hundreds of millions of people have been infected with new coronary pneumonia worldwide,and millions of people have died.Due to the specificity of the new coronavirus itself and its high mutation rate,a series of different new coronavirus variants have appeared,which has caused the new crown pneumonia epidemic to repeat.Recently,the World Health Organization(WHO)announced a new variant"omicron"(omicron,B.1.1.529),and declared that the mutant strain may be highly infectious,antibody tolerant and highly resistant to vaccines.This article briefly reviews the latest research progress of the"omicron"variants.

Research progress on detection methods of the asymptomatic COVID- 19 infected persons

The global pandemic of COVID-19 has brought great harm and challenges to many countries and regions around the world.The majority of COVID-19 patients have typical clinical manifestations,but the number of asymptomatic infections is increasing as COVID-19 research continues and SARS-CoV-2 testing improves.Many asymptomatic COVID-19 patients with no obvious clinical symptoms are able to transmit the virus to others due to the presence of SARS-CoV-2 in their bodies,thus greatly accelerating the worldwide pandemic and posing great difficulty and threat to global epidemic prevention and control.Therefore,early detection and identification of asymptomatic infected persons through various testing methods are effective measures to control the COVID-19 pandemic.This article will provide a brief review of the available methods and techniques for detecting asymptomatic COVID-19 patients.

Statin use and risk of liver cancer: A meta-analysis of 7 studies involving more than 4.7 million patients

AIM: To pool data currently available to determine the association between statin use and the risk of liver cancer.METHODS: A computerized literature search was conducted to identify those relevant studies between January 1966 and March 2013. Stata 11.0(Stata Corp, College Station, Texas) was used for statistical analyses. Pooled relative risk(RR) estimates with 95%CI were calculated for overall analysis and subgroup analyses, using the random- and fixed-effects models. Heterogeneities between studies were evaluated by Cochran's Q test and I2 statistic. The Begg's funnel plot and Egger's regression asymmetry test were used to detect the publication bias.RESULTS: Seven studies were included in our metaanalysis according to the selection criteria, including four cohort studies and three case-control studies. These studies involved 4725593 people and 9785 liver cancer cases. The overall analysis showed that statin use was statistically associated with a significantly reduced risk of liver cancer(random-effects model, RR = 0.61, 95%CI: 0.49-0.76, P < 0.001; fixed-effects model, RR = 0.64, 95%CI: 0.57-0.71, P < 0.001); however, significant heterogeneity was found between studies(Cochran's Q statistic = 19.13, P = 0.004; I2 = 68.6%). All subgroup analyses provided supporting evidence for the results of overall analysis. Begg's(Z = 0.15, P = 0.881) and Egger's test(t =-0.44, P = 0.681) showed no significant risk of having a publication bias.CONCLUSION: Statin use was associated with the reduced risk of liver cancer. To clearly clarify this relationship, more high quality studies are required.

Imatinib blocks tyrosine phosphorylation of Smad4 and restores TGF-β growth-suppressive signaling in BCR-ABL1-positive leukemia

Loss of TGF-β-mediated growth suppression is a major contributor to the development of cancers,best exemplified by loss-offunction mutations in genes encoding components of the TGF-βsignaling pathway in colorectal and pancreatic cancers.Alternatively,gain-of-function oncogene mutations can also disrupt antiproliferative TGF-βsignaling.However,the molecular mechanisms underlying oncogene-induced modulation of TGF-βsignaling have not been extensively investigated.Here,we show that the oncogenic BCR-ABL1 of chronic myelogenous leukemia(CML)and the cellular ABL1 tyrosine kinases phosphorylate and inactivate Smad4 to block antiproliferative TGF-βsignaling.Mechanistically,phosphorylation of Smad4 at Tyr195,Tyr301,and Tyr322 in the linker region interferes with its binding to the transcription co-activator p300/CBP,thereby blocking the ability of Smad4 to activate the expression of cyclin-dependent kinase(CDK)inhibitors and induce cell cycle arrest.In contrast,the inhibition of BCR-ABL1 kinase with Imatinib prevented Smad4 tyrosine phosphorylation and re-sensitized CML cells to TGF-β-induced antiproliferative and pro-apoptotic responses.Furthermore,expression of phosphorylation-site-mutated Y195F/Y301F/Y322F mutant of Smad4 in Smad4-null CML cells enhanced antiproliferative responses to TGF-β,whereas the phosphorylation-mimicking Y195E/Y301E/Y322E mutant interfered with TGF-βsignaling and enhanced the in vivo growth of CML cells.These findings demonstrate the direct role of BCR-ABL1 tyrosine kinase in suppressing TGF-βsignaling in CML and explain how Imatinib-targeted therapy restored beneficial TGF-βanti-growth responses.

Preparation and H_2S Gas-Sensing Performances of Coral-Like SnO_2–CuO Nanocomposite

Nanocomposites composed of SnO2 and CuO were prepared by hydrothermal method. The microstructures of obtained SnO2-CuO powders were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and nitrogen adsorption-desorption test. The results show that the nanocomposites exhibited coral-like nanostructure, and the average crystalline size of SnO2 was 12 nm. The specific surface area of the four samples, SnO2- 0.2CuO, SnO2-0.5CuO, SnO2-1.0CuO and SnO2-2.0CuO are 72.97, 58.77, 49.72 and 54.95 m2/g, respectively. The gas sensing performance of the four samples to ethanol, formaldehyde and H2S was studied. The sensor of SnOa-0.5CuO exhibited high response to hydrogen sulfide （4173 to 10 ppm H2S, where ppm represent 10-6）, and low response to ethanol and formaldehyde. The good selectivity exhibited that the SnO2-0.5CuO nanocomposite can be a promising candidate for highly sensitive and selective gas-sensing material to H2S.

从交易成本理论看我国自然人涉税信息有效获取

制约我国自然人税收征管的关键在于获取自然人涉税信息的成本过高。本文立足交易成本理论,从正式规则、非正式规则、实施机制三个方面分析我国自然人涉税信息获取中存在的问题,在此基础上探讨进一步加强自然人涉税信息有效获取的路径和建议。