Development of a model based on the age-adjusted Charlson comorbidity index to predict survival for resected perihilar cholangiocarcinoma

BACKGROUND Perihilar cholangiocarcinoma(pCCA)has a poor prognosis and urgently needs a better predictive method.The predictive value of the age-adjusted Charlson comorbidity index(ACCI)for the long-term prognosis of patients with multiple malignancies was recently reported.However,pCCA is one of the most surgically difficult gastrointestinal tumors with the poorest prognosis,and the value of the ACCI for the prognosis of pCCA patients after curative resection is unclear.AIM To evaluate the prognostic value of the ACCI and to design an online clinical model for pCCA patients.METHODS Consecutive pCCA patients after curative resection between 2010 and 2019 were enrolled from a multicenter database.The patients were randomly assigned 3:1 to training and validation cohorts.In the training and validation cohorts,all patients were divided into low-,moderate-,and high-ACCI groups.Kaplan-Meier curves were used to determine the impact of the ACCI on overall survival(OS)for pCCA patients,and multivariate Cox regression analysis was used to determine the independent risk factors affecting OS.An online clinical model based on the ACCI was developed and validated.The concordance index(C-index),calibration curve,and receiver operating characteristic(ROC)curve were used to evaluate the predictive performance and fit of this model.RESULTS A total of 325 patients were included.There were 244 patients in the training cohort and 81 patients in the validation cohort.In the training cohort,116,91 and 37 patients were classified into the low-,moderate-and high-ACCI groups.The Kaplan-Meier curves showed that patients in the moderate-and high-ACCI groups had worse survival rates than those in the low-ACCI group.Multivariable analysis revealed that moderate and high ACCI scores were independently associated with OS in pCCA patients after curative resection.In addition,an online clinical model was developed that had ideal C-indexes of 0.725 and 0.675 for predicting OS in the training and validation cohorts.The calibration curve and ROC curve indicated that the model had a good fit and prediction performance.CONCLUSION A high ACCI score may predict poor long-term survival in pCCA patients after curative resection.High-risk patients screened by the ACCI-based model should be given more clinical attention in terms of the management of comorbidities and postoperative follow-up.

Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus

BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable postoperative treatment plan to improve their prognosis.AIM To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT.METHODS We retrospectively collected the clinicopathological data of 530 patients who un-derwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus.Fur-thermore,we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by asse-ssing the clinical and pathological features of the patients who met the inclusion criteria.We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses.The subgroups of pa-tients with stages Ⅰ,Ⅱ,and Ⅲ disease who received single-,dual-,or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0.RESULTS In all,530 eligible individuals with RGAVCT were enrolled in this study.The median overall survival(OS)of patients with RGAVCT was 24 months,and the survival rates were 80.2%,62.5%,and 42.3%at 12,24,and 59 months,respectively.Preoperative complications,tumor size,T stage,and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model.A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage Ⅰ or Ⅱ RGAVCT;however,chemotherapy did have an effect on OS of stage Ⅲ patients.Stage Ⅲ patients who were treated with chemotherapy consisting of dual-or triple-agent regimens had better survival than those treated with single-agent regimens,and no significant difference was observed in the survival of patients treated with chemo-therapy consisting of dual-or triple-agent regimens.CONCLUSION For patients with stage Ⅲ RGAVCT,a dual-agent regimen of postoperative chemotherapy should be recom-mended rather than a triple-agent treatment,as the latter is associated with increased frequency of adverse events.

Regulation of demethylation and re-expression of RASSF1A gene in gastric cancer cell lines by combined treatment of 5-Aza-CdR and NaB

AIM： To investigate the changes of methylation state and expression of RASSF1A gene in human gastric cancer cell lines SGC7901 and BGC823 which were treated in vitro with demethlylating agent 5-Aza-CdR in combination with histone deacetylase inhibitor NaB. METHODS： After SGC7901 and BGC823 cells were treated with 5-Aza-CdR and/or NaB, the methylation state of RASSFIA gene was detected by methylationspecific PCR, and the changes in expression of mRNA and protein level of RASSFIA gene were observed by RT-PCR and Western-blotting before and after drug treatment. RESULTS： Hypermethylation was detected in the promoter region of RASSF1A gene in both SGC7901 and BGC823 cells, and there was no expression of this gene at both mRNA and protein level. After treatment with 5-Aza-CdR, demethylation occurred in the promoter region of RASSFIA gene, which subsequently induced re-expression of this gene. The treatment with NaB alone showed no effect on the methylation state and expression of RASSFIA gene. The combined treatment of 5-Aza-CdR and NaB induced complete demethylation of RASSFIA gene, leading to a significantly higher reexpression of the mRNA and protein of RASSFIA than those treated with 5-Aza-CdR alone （P 〈 0.05）. CONCLUSION： Hypermethylation in the promoter region is related to inactivation of RASSFIA gene in human gastric cancer cell lines SGC7901 and BGC823, while demethlylating agent 5-Aza-CdR can reverse the methylation state of RASSF1A gene and induce itsre-expression. Histone deacetylase inhibitor NaB had a synergistic effect with 5-Aza-CdR in both demethylation and gene transcriptional regulation.

Preoperative predictors of short-term survival after hepatectomy for multinodular hepatocellular carcinoma

AIM： To investigate preoperative factors associated with poor shore-term outcome after resection for multi- nodular hepatocellular carcinoma （HCC） and to assess the contraindication of patients for surgery, METHODS： We retrospectively analyzed 162 multi- nodular HCC patients with Child-Pugh A liver function who underwent surgical resection. The prognostic significance of preoperative factors was investigated by univariate analysis using the log-rank test and by multivariate analysis using the Cox proportional hazards model. Each independent risk factor was then assigned points to construct a scoring model to evaluate the in- dication for surgical intervention. A receiver operating characteristics （ROC） curve was constructed to assess the predictive ability of this system.RESULTS： The median overall survival was 38.3 mo （range： 3-80 too）, while the median disease-free sur- vival was 18.6 mo （range： 1-79 too）. The 1-year mor- tality was 14%. Independent prognostic risk factors of 1-year death included prealburnin 〈 170 rng/L [hazard ratio （HR）： 5.531, P 〈 0.001], alkaline phosphatase 〉 129 U/L （HR： 3.252, P = 0.005）, α fetoprotein 〉 20 μg/L （HR： 7.477, P = 0.011）, total tumor size 〉 8 cm （HR： 10.543; P 〈 0.001）, platelet count 〈 100×109/L （HR： 9.937, P 〈 0.001）, and y-glutamyl transpeptidase 〉 64 U/L （HR： 3.791, P 〈 0.001）. The scoring model had a strong ability to predict 1-year survival （area under ROC： 0.925, P 〈 0.001）. Patients with a score ≥5 had significantly poorer short-term outcome than those with a score 〈 5 （1-year mortality： 62% vs 5%, P 〈 0.001; 1-year recurrence rate： 86% vs 33%, P 〈 0.001）. Patients with score ≥5 had greater possibility of microvascular invasion （P 〈 0.001）, poor tumor dif- ferentiation （P = 0.003）, liver cirrhosis with small nod- ules （P 〈 0.001）, and intraoperative blood transfusion （P = 0.010）. CONCLUSION： A composite preoperative scoring model can be used as an indication of prognosis of HCC patients after surgical resection. Resection should be considered with caution in patients with a score ≥5, which indicates a contraindication for surgery.

Prognostic signif icance of HIF-2α/EPAS1 expression in hepatocellular carcinoma

AIM: To evaluate the prognostic signif icance of HIF- 2α/EPAS1 expression in hepatocellular carcinoma (HCC). METHODS: Surgical specimens from 315 patients with HCC as well as 196 adjacent noncancerous lesions and 22 cases of normal liver tissue were investigated by immunohistochemistry (IHC) for HIF-2α/EPAS1 using a standard detection system. Correlations with clinicopathological factors, VEGF, microvessel density (MVD), and prognosis were analyzed. RESULTS: Immunoreactivity of HIF-2α/EPAS1 was positive in 69.5% of HCC, 55.6% of adjacent noncancerous tissue, and 0% of normal liver tissue. And it was significantly correlated with tumor grade, venous invasion, intrahepatic metastasis, necrosis, and capsule infiltration. Correlation analysis of HIF-2α/EPAS1 with angiogenic factor VEGF (P < 0.001), and MVD (P = 0.016) was also noted. HIF-2α/EPAS1 protein was less frequently expressed in low MVD cases, whereas a high rate of expression was noted in cases with both medium and high MVD (P = 0.042). By Kaplan-Meier analysis, strong HIF-2α/EPAS1 staining (> 50% of tumor cells) in HCC correlated with a shortened survival in patients (Cox's regression, P < 0.001, r = 3.699). CONCLUSION: We conclude that HIF-2α/EPAS1 expression may play an important role in tumor progression and prognosis of HCC. Assessment of HIF-2α/EPAS1 expression in HCC may be used as a diagnostic tool and possibly a target in the treatment of HCC.

Prevalence of Thyroid Nodules and Its Relationship with Iodine Status in Shanghai:a Population-based Study

Objective This study was designed to evaluate the prevalence of thyroid nodules（TNs） and its relationship with urine iodine concentrations（UICs） after the regional rapid economic growth and lifestyle changes. Methods A cross-sectional survey was conducted in the general population aged 15-69 years. A questionnaire regarding general and personal characteristics and relevant information was administered. Ultrasonography of the thyroid was performed, and serum triiodothyronine（T3）, tetraiodothyronine（T4）, serum thyroid stimulating hormone（TSH）, free triiodothyronine（FT3）, free tetraiodothyronine（FT4）, thyroglobulin antibody（Tg Ab）, thyroid peroxidase antibody（TPOAb）, and TSH receptor antibody（TRAb） levels were measured for each individual subject. Results The prevalence rates of TNs in the whole population, females and males were 27.76%, 34.04%, and 21.60%, respectively. The prevalence of multiple nodules increased with age, whereas the prevalence peaks differed between males and females. The median UICs in the whole population and females with non-TNs were higher than those of subjects with TNs（P=0.0035, P=0.0068）. The median UICs in subjects with a single TN were higher than those in subjects with multiple TNs（P=0.0164, P=0.0127）. The result showed a U-shaped curve relationship between UIC and prevalence of TNs. The prevalence of TNs was the lowest when the UIC was 140-400 μg/L. Conclusion The prevalence of TNs was nearly 30% and increased with age. The relationship between UIC and prevalence of TNs is U-shaped, with an increase in risk when the UIC was 〈140 μg/L and 〉400 μg/L. Very low or high UIC levels need attention and correction.

A case-control study of the relationship between hepatitis B virus DNA level and risk of hepatocellular carcinoma in Qidong,China

AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS:One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS:In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels ≥ 104 to < 105; ≥ 105 to < 106; ≥ 106 to < 107; ≥ 107 copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.CONCLUSION:The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 104-107 range.

A Time Series Analysis of Outdoor Air Pollution and Preterm Birth in Shanghai, China

Objective To investigate the relation between air pollution exposure and preterm birth in Shanghai, China. Methods We examined the effect of ambient air pollution on preterm birth using time-series approach in Shanghai in 2004. This method can eliminate potential confounding by individual risk factors that do not change over a short period of time. Daily numbers of preterm births were obtained from the live birth database maintained by Shanghai Municipal Center of Disease Control and Prevention. We used the generalized additive model （GAM） with penalized splines to analyze the relation between preterm birth, air pollution, and covariates. Results We observed a significant effect of outdoor air pollution only with 8-week exposure before preterm births. An increase of 10 μg/m^3 of 8-week average PM10, SO2, NO2, and O3 corresponded to 4.42% （95%CI 1.60%, 7.25%）, 11.89% （95%CI 6.69%, 17.09%）, 5.43% （95%CI 1.78%, 9.08%）, and 4.63% （95%CI 0.35%, 8.91%） increase of preterm birth. We did not find any significant acute effect of outdoor air pollution on preterm birth in the week before birth. Conclusion Ambient air pollution may contribute to the risk of preterm birth in Shanghai. Our analyses also strengthen the rationale for further limiting air pollution level in the city.

Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease,an Endemic Osteoarthritis,in China

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease （KBD） using six clinical markers： flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling.

A nursing protocol targeting risk factors for reducing postoperative delirium in patients following coronary artery bypass grafting:Results of a prospective before-after study

Objective: The results of postoperative delirium (POD) warrant testing for prevention. The purpose of this study was to determine whether a nursing intervention targeting risk factors could decrease the inci-dence of POD among patients who had coronary artery bypass grafting (CABG) in China.Methods: A prospective before-after study was conducted between April 2014 and April 2015. A nursing delirium intervention protocol targeting risk factors for delirium was performed for 141 patients un-dergoing CABG in a cardiothoracic ICU from November 2014 to April 2015. Intervention consisted of screening for delirium risk factors, followed by targeted risk factor modification, including pain control, early catheter removal, patient orientation using the 5W1H procedure, increased family visits, mini-mizing care-related interruptions, comfortable nursing and monitoring for sleeping difficulties. Out-comes of the Intervention Group were compared with those of the Control Group for 137 CABG patients from April 2014 to October 2014. Delirium was assessed using the confusion assessment method for the intensive care unit (CAM-ICU). The sample size was justified by PASS2000, based on previous data of delirium incidence in our institution (30%). Main results: Delirium incidence during the first seven postoperative days was significantly lower in the Intervention Group at 13.48%(19/141) vs. 29.93%(41/137) for the Control Group (x2=11.112, P=0.001). In addition, POD in the Intervention Group occurred between the 3rd and 6th postoperative days, while POD in the Control Group mainly occurred on the first three days postoperatively. Delirium in the Intervention Group occurred later than delirium in the Control Group (x2=12.743, P<0.001). Length of ICU stay was reduced significantly (Z= -6.026, P<0.001). Conclusion: The application of a nursing protocol targeting risk factors in this study seems to be asso-ciated with a lower incidence of POD in patients after CABG. This finding suggests that managing the predictors properly is one of the effective strategies to prevent delirium.

Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation

AIM to determine whether diabetes mellitus(DM) affects prognosis/recurrence after liver transplantation(Lt) for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC). METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent Lt with antiviral prophylaxis. Patient data were obtained from the China Liver transplant Registry(https://www.cltr.org/). to compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. RESULTS Univariate analysis of 1631 patients who underwent Lt found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after Lt between the two groups were significant(P = 0.041), but recurrence-free survival rates were not(P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years(P = 0.002), the presence of vascular invasion(P = 0.096), tumors ≤ 3 cm(P = 0.047), two to three tumor nodules(P = 0.007), Child-Pugh grade B(P = 0.018), and preLt alanine aminotransferase levels between 40 and 80 IU/L(P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/m L(P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM(P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after Lt. CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor Lt outcomes. Prevention strategies for HCC patients with DM are recommended.

Validation of the six-and-twelve criteria among patients with hepatocellular carcinoma and performance score 1 receiving transarterial chemoembolization

BACKGROUND Transarterial chemoembolization(TACE)is recommended for patients with intermediate hepatocellular carcinoma(HCC)according to treatment guidelines.However,a large number of patients with advanced HCC also receive TACE in clinical practice,especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score(ECOG)1.In view of previous studies,such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread;therefore,patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment,but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking.AIM To investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model.METHODS Patients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016.Overall survival(OS)was estimated using Kaplan–Meier curves and compared by the log-rank test.Multivariate Cox regression was used to develop the potential prognostic models.The discriminatory ability of the models was compared and validated in various patient subgroups.The individual survival prediction for six-and-twelve(6&12)criteria,defined as the algebraic sum of tumor size(cm)and tumor number,was illustrated by contour plot of 3-year survival probability and nomogram.RESULTS A total of 792 eligible patients were included.During follow-up,median OS reached 18.9 mo[95%confidence interval(CI):16.9-21.0].Three independent multivariate analyses demonstrated that tumor size,tumor number,α-fetoprotein level,albumin–bilirubin grade and total bilirubin were prognostic factors of OS(P<0.05).The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability.In addition,the 6&12 criteria was correlated with OS in various subgroups of patients.The patients were stratified into three strata with score≤6,>6 but≤12,and>12 with different median OS of 39.8 mo(95%CI:23.9-55.7),21.1 mo(95%CI:18.4-23.8)and 9.8 mo(95%CI:8.3-11.3),respectively(P<0.001).CONCLUSION TACE is effective for advanced HCC patients with ECOG 1 alone,and the 6&12 criteria may help with clinical decision-making.

Smoking and the risk of dry eye: a Meta-analysis

AIM： To collect the evidence to estimate the correlation between smoking and the incidence of dry eye. METHODS： The Pub Med,EMBASE,the Cochrane Central Register of Controlled Trials（CENTRAL,last issue）,CBM（Chinese Bio Medical Literature Database）,and CNKI（China National Knowledge Infrastructure/Chinese Academic Journals full-text Database） were searched for eligible studies published from January1964 to December 2015 to investigate the association of smoking with the risk of dry eye.The odds ratio（OR）and 95% confidence interval（CI） were summarized and calculated.The extracted studies were pooled by the fixed-effects model or a random-effects model. RESULTS： Two cohort studies and eight cross-sectional surveys were included in our Meta-analysis.There was no statistically significant relationship between current（OR=1.32; 95% CI： 0.99-1.76; P=0.055）or ever smoking（OR=1.12; 95% CI： 0.98-1.28; P=0.107）and the risk of dry eye among the studies,even when age and gender were adjusted（OR=1.16; 95% CI： 0.83-1.64; P=0.383）.In the sensitivity analysis in which only general population were included,the association was significant between smoking and dry eye（OR=1.50; 95%CI： 1.08-2.09; P=0.016）.CONCLUSION： This Meta-analysis suggests that smoking may associate with the risk of dry eye in general population.

High expression of protein phosphatase 2 regulatory subunit B''alpha predicts poor outcome in hepatocellular carcinoma patients after liver transplantation

BACKGROUND Protein phosphatase 2 regulatory subunit B''alpha(PPP2R3A)gene has been reported in other tumors,but the influence of PPP2R3A gene expression on the occurrence,development,and prognosis of hepatocellular carcinoma(HCC)remains unclear.AIM To investigate whether the PPP2R3A gene could be used to predict tumor recurrence and survival of HCC patients after liver transplantation(LT).METHODS Diseased liver tissues of HCC patients after LT were collected as well as their clinical data and follow-up information.The immunohistochemical method was used to detect the expression of PPP2R3A protein in the tissues of 108 patients with primary liver cancer.Theχ2 test was used to analyze the relationship between PPP2R3A protein expression levels and the clinicopathological features of tumors.The Kaplan-Meier method was used to analyze overall postoperative survival.The COX proportional hazard model was used to analyze adverse prognostic factors.RESULTS Immunohistochemistry showed that the PPP2R3A protein was mainly expressed in the cytoplasm of HCC cells.Compared to corresponding peritumoral tissues,expression was higher in HCC tissues(P≤0.001).Correlation analysis showed that high PPP2R3A expression was correlated with preoperative serum alphafetoprotein(AFP)levels(P=0.003),tumor-node-metastasis-t stage(P≤0.001),and envelope invasion(P=0.001).Univariate analysis showed that overall survival(P≤0.001)and recurrence-free survival(P=0.025)of patients with high PPP2R3A expression(≥4 points)were poor compared to those with low expression(<4 points).The overall survival rates or recurrence-free survival rates at 1,2,and 3 years with high PPP2R3A expression were 73%,38%,and 23%or 31%,23%,and 23%,respectively.Multivariate analysis showed that high PPP2R3A expression(hazard ratio=2.900,95%confidence interval:1.411–5.960,P=0.004)was an independent survival risk factor of HCC patients after LT,and it was also an independent predictor of postoperative tumor recurrence.This study also showed in patients with AFP≥400 ng/mL,the overall survival(P≤0.001)and recurrencefree survival(P=0.023)of those with high PPP2R3A expression were significantly worse compared to those with low PPP2R3A expression.When PPP2R3A expression was low,the overall survival rate(P=0.461)or recurrence-free survival rate(P=0.072)after LT in patients with AFP<400 ng/mL and≥400 ng/mL was not significantly difference.The 1,2,and 3 year survival rate of patients with low PPP2R3A expression and AFP<400 ng/mL were 98%,80%,and 69%,respectively,while patients who met Hangzhou criteria had a posttransplant 1,2,and 3 years overall survival rate of 89%,66%,and 55%,respectively.CONCLUSION High expression of PPP2R3A might be a potential marker for predicting poor prognosis of HCC after LT.Combined with serum AFP levels,PPP2R3A might enhance the accuracy of predicting HCC outcome in patients after LT and supplement the efficacy of the Hangzhou criteria.

Comparing irinotecan/cisplatin with etoposide/cisplatin in patients with ED-SCLC: A meta-analysis of efficacy and toxicity

Objective： Irinotecan in combination with cisplatin for extensive-stage disease small-ceU lung cancer （ED-SCLC） patients has gained wide interest. Varying results for this treatment underpin the need for a synthesis of evidence. Methods： We conducted a literature-based meta-analysis to quantify the magnitude of the benefit comparing irinotecan in combination with cisplatin （IP） with etoposide in combination with cisplatin （EP） in ED-SCLC patients. The primary outcome was overall survival （OS） and progression-free survival （PFS）; secondary outcomes included overall response rate, 1- and 2-year survival rates, disease control rate and toxicity. Results： Four trials including 1,541 patients were identified in the analysis. No positive results （P〈0.05） were seen： OS （HR=0.85, CI95%=0.71-1.01; P=-0.08） with high heterogeneity （Chi2=7.76, dr=-3 [P=-0.05]; I2=61%）, PFS （HR=0.91, CI95%=0.74-1.28; P=-0.36） with high heterogeneity （Chi2=11.96, df=3 [P=-0.008]; I2=75%）, overall response rate（OR=1.16; CI95%=0.79-1.70; P=0.45）, disease control rate （OR=1.01; CI95%=0.74-1.38; P=0.95）, 1-year survival rate （OR = 1.30; CI95%=0.98-1.72; P=0.07） and 2-year survival rate （OR=1.97; CI95%=0.95-4.09; P=-0.07）. Fewer patients who received IP suffered severe hematologic toxicities （grade≥3）, such as neutropenia, thrombocytopenia and leucopenia. However, severe non-hematologic toxicities （grade≥3）, such as diarrhea, nausea, vomiting, fatigue, anorexia, and dehydration, were more common among patients who received IP. Conclusion： IP does not lengthen the overall survival or progression-free survival compared with EP in patients with ED-SCLC Fewer patients receiving IP had grade ≥ 3 hematological toxicities of nentropenia, leucopenia and thrombocytopenia, but more had grade≥3 diarrhea, nausea, vomiting, fatigue, anorexia and dehydration.

Biomechanical Comparison of Anterior Lumbar Screw-plate Fixation versus Posterior Lumbar Pedicle Screw Fixation

Anterior lumbar interbody fusion （ALiF） followed by posterior pedicle screw fixation （PSF） in a second procedure is mostly used to implement lumbar spine fusion. ALIF followed by an- terior lumbar screw-plate has a lot of advantages, but its biomechanical stability requires confirma- tion. This study evaluated the biomechanical stability of a novel anterior lumbar locked screw-plate （ALLSP） by comparison with posterior lumbar PSF. Twelve fresh human cadaveric lumbar speci- mens （L4-L5） were assigned to four groups： ALIF^PSF group, ALIF＋ALLSP （both fixed） group, ALIF group and an untreated control （both non-fixed） group. The first three groups received implan- tation of a rectangular titanium cage. Tests under axial compression, flexion, extension, lateral bend- ing, or rotation showed that the fixed groups had significantly stronger stability than the non-fixed groups （P=-0.000 for all）. The ALIF＋ALLSP group had significantly greater axial stiffness under ap- plied axial compression and significantly less angular displacement under rotational forces than the ALIF＋PSF group. The angular displacement of the ALIF＋ALLSP group was less under flexion than that of the ALIF＋PSF, and the angular displacement under lateral bending and extension was greater, but these differences were not statistically significant. In summary, the ALLSP conforms to the ante- rior lumbar spine and has good biomechanical stability. It is a reliable choice for enhancing the sta- bility of ALIF.

Current situation on the reporting quality of randomized controlled trials in 5 leading Chinese medical journals

Objective:The Consolidated Standards for Reporting of Trials(CONSORT) statement has already proved to be an efficient standard for reporting quality of randomized controlled trials(RCTs).However,most of the Chinese medical journals have not endorsed the CONSORT statement.The current situation about the reporting quality of RCTs in Chinese medical journals is still unclear.The purpose of the study was to evaluate the reporting quality of RCTs on papers published in 5 leading Chinese medical journals.Methods:We evaluated 232 original RCT papers using a reporting quality scale based on CONSORT statement from 2001 to 2006 in 5 Chinese medical journals(Journal type 1) without adoption of CONSORT and Chinese Journal of Evidence-based Medicine(Journal type 2) which adopted CONSORT in 2004.We measured the inclusion of 26 items for the reporting quality scale and 6 core items of each RCT report,gave score to each item and calculated the total score obtained in each report and the proportion of reports including individual items.The reporting quality of RCT trials from 2001 to 2003(pre-adoption period) was compared with that from 2004 to 2006(post-adoption period).Results:The average reporting quality of RCTs was moderate(mean score,15.18),and the mean score of the 6 core items was low(mean score,1.09) in 5 leading journals.The difference in the total score and the score of the 6 core items between pre-adoption period(2001-2003) and post-adoption period(2004-2006) was statistically significant(P=0.003;P=0.000).Interaction between journal type and period was not significant(F=0.76;P=0.383).We concluded that the change tendency of reporting quality between Journal type 1 and 2 was not different.But as to the core items of sequence concealment and intention-to-treat analysis,the increases were greater for Journal type 2 when evaluated against Journal type 1(P=0.038;P=0.016).Conclusion:The reporting quality of RCT trials in 5 leading Chinese medical journals is improving.However,the lack of important items in RCT trials remains a serious problem.We recommend the endorsement of the Consolidated Standards for Reporting of Trials statement in Chinese medical journals and the continuing education on evidence-based medicine in China.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

BACKGROUND The treatment outcome of transarterial chemoembolization(TACE)in unresectable hepatocellular carcinoma(HCC)varies greatly due to the clinical heterogeneity of the patients.Therefore,several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE(re-TACE).AIM To investigate the correlations between prognostic systems and radiological response,compare the predictive abilities,and integrate them in sequence for outcome prediction.METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016.The Hepatoma Arterial-embolization Prognostic(HAP)score system and its modified versions(mHAP,mHAP2 and mHAP3),as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival(OS)prediction for first TACE.The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART(assessment for re-treatment with TACE)and ABCR(alpha-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh and Response)systems for post re-TACE survival(PRTS).RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE,and the six-and-twelve criteria exhibited the highest correlation(Spearman R=0.39,P=0.026)and consistency(Kappa=0.14,P=0.019),with optimal performance by area under the receiver operating characteristic curve of 0.71[95%confidence interval(CI):0.68-0.74].With regard to the prediction of OS,the mHAP3 system identified patients with a favorable outcome with the highest concordance(C)-index of 0.60(95%CI:0.57-0.62)and the best area under the receiver operating characteristic curve at any time point during follow-up;whereas,PRTS was well-predicted by the ABCR system with a C-index of 0.61(95%CI:0.59-0.63),rather than ART.Finally,combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo,compared with non-candidates with a median PRTS of 20.0 mo(logrank test P<0.001).CONCLUSION Radiological response to TACE is closely associated with tumor burden,but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Signature Based on Six Autophagy-related Genes to Predict Prognosis of Head and Neck Squamous Cell Carcinoma

Objective The present study aimed to develop an autophagy-related gene prognostic prediction model to provide survival risk prediction for head and neck squamous cell carcinoma(HNSCC)patients.Methods The K-mean cluster analysis was performed on HNSCC samples based on the expression values of 210 autophagy-related genes for candidate signature gene selection.LASSO Cox regression analysis was generated using the potential genes and the risk score was calculated from the prognosis model.The risk score was processed as an independent prognostic indicator to construct the nomogram model.The immune status including immune cell infiltration ratio and checkpoints of patients with HNSCC in high-and low-risk groups was also explored.Results LASSO Cox regression analysis was performed on the selected autophagy-related genes.According to the lambda value corresponding to the number of different genes in the LASSO Cox analysis,six genes(GABARAPL2,SAR1A,ST13,GAPDH,FADD and LAMP1)were finally chosen.The risk score based on the genes was generated,which was an independent prognostic marker for HNSCC.The prognostic prediction model(nomogram)was further optimized by the independent prognostic factors(risk score),which can better predict the prognosis and survival of patients.With the risk score and prognosis model,eight types of immune cells and six key immune checkpoints(CTLA4,PD1,IDO1,TDO2,LAG3,TIGIT)displayed expression specificity.Conclusion This study identified several potential prognostic biomarkers and established an autophagy-related prognostic prediction model for HNSCC,which provides a valuable reference for future clinical research.

Normalization strategy of microarray gene expression data

Objective： To discuss strategies and methods of normalization on how to deal with and analyze data for different chips with the combination of statistics, mathematics and bioinformatics in order to find significant difference genes. Methods： With Excel and SPSS software, high or low density chips were analyzed through total intensity normalization （TIN） and locally weighted linear regression normalization （LWLRN）. Results： These methods effectively reduced systemic errors and made data more comparable and reliable. Conclusion： These methods can search the genes of significant difference, although normalization methods are being developed and need to be improved further. Great breakthrough will be obtained in microarray data normalization analysis and transformation with the development of non-linear technology, software and hardware of computer.