Fourth Hospital of Hebei Medical University

The Modification of Diet in Renal Disease (MDRD) equations provide a rapid method of assessing GFR in patients with chronic kidney disease (CKD). However, previous research indicated that modification of these equations is necessary for application in Chinese patients with CKD. The objective of this study was to modify MDRD equations on the basis of the data from the Chinese CKD population and compare the diagnostic performance of the modified MDRD equations with that of the original MDRD equations across CKD stages in a multicenter, cross-sectional study of GFR estimation from plasma creatinine, demographic data, and clinical characteristics. A total of 684 adult patients with CKD, from nine geographic regions of China were selected. A random sample of 454 of these patients were included in the training sample set, and the remaining 230 patients were included in the testing sample set. With the use of the dual plasma sampling (99m)Tc-DTPA plasma clearance method as a reference for GFR measurement, the original MDRD equations were modified by two methods: First, by adding a racial factor for Chinese in the original MDRD equations, and, second, by applying multiple linear regression to the training sample and modifying the coefficient that is associated with each variable in the original MDRD equations and then validating in the testing sample and comparing it with the original MDRD equations. All modified MDRD equations showed significant performance improvement in bias, precision, and accuracy compared with the original MDRD equations, and the percentage of estimated GFR that did not deviate >30% from the reference GFR was >75%. The modified MDRD equations that were based on the Chinese patients with CKD offered significant advantages in different CKD stages and could be applied in clinical practice, at least in Chinese patients with CKD.

BACKGROUND: From 2003 to 2005, standardised 5-year cancer survival in China was much lower than in developed countries and varied substantially by geographical area. Monitoring population-level cancer survival is crucial to the understanding of the overall effectiveness of cancer care. We therefore aimed to investigate survival statistics for people with cancer in China between 2003 and 2015. METHODS: We used population-based data from 17 cancer registries in China. Data for the study population was submitted by the end of July 31, 2016, with follow-up data on vital status obtained on Dec 31, 2015. We used anonymised, individual cancer registration records of patients (aged 0-99 years) diagnosed with primary, invasive cancers from 2003 to 2013. Patients eligible for inclusion had data for demographic characteristics, date of diagnosis, anatomical site, morphology, behaviour code, vital status, and last date of contact. We analysed 5-year relative survival by sex, age, and geographical area, for all cancers combined and 26 different cancer types, between 2003 and 2015. We stratified survival estimates by calendar period (2003-05, 2006-08, 2009-11, and 2012-15). FINDINGS: There were 678 842 records of patients with invasive cancer who were diagnosed between 2003 and 2013. Of these records, 659 732 (97·2%) were eligible for inclusion in the final analyses. From 2003-05 to 2012-15, age-standardised 5-year relative survival increased substantially for all cancers combined, for both male and female patients, from 30·9% (95% CI 30·6-31·2) to 40·5% (40·3-40·7). Age-standardised 5-year relative survival also increased for most cancer types, including cancers of the uterus (average change per calendar period 5·5% [95% CI 2·5-8·5]), thyroid (5·4% [3·2-7·6]), cervix (4·5% [2·9-6·2]), and bone (3·2% [2·1-4·4]). In 2012-15, age-standardised 5-year survival for all patients with cancer was higher in urban areas (46·7%, 95% CI 46·5-47·0) than in rural areas (33·6%, 33·3-33·9), except for patients with oesophageal or cervical cancer; but improvements in survival were greater for patients residing in rural areas than in urban areas. Relative survival decreased with increasing age. The increasing trends in survival were consistent with the upward trends of medical expenditure of the country during the period studied. INTERPRETATION: There was a marked overall increase in cancer survival from 2003 to 2015 in the population covered by these cancer registries in China, possibly reflecting advances in the quality of cancer care in these areas. The survival gap between urban and rural areas narrowed over time, although geographical differences in cancer survival remained. Insight into these trends will help prioritise areas that need increased cancer care. FUNDING: National Key R&D Program of China, PUMC Youth Fund and the Fundamental Research Funds for the Central Universities, and Major State Basic Innovation Program of the Chinese Academy of Medical Sciences.

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Main Outcomes and Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.

Limited population-based cancer registry data available in China until now has hampered efforts to inform cancer control policy. Following extensive efforts to improve the systematic cancer surveillance in this country, we report on the largest pooled analysis of cancer survival data in China to date. Of 21 population-based cancer registries, data from 17 registries (n = 138,852 cancer records) were included in the final analysis. Cases were diagnosed in 2003-2005 and followed until the end of 2010. Age-standardized relative survival was calculated using region-specific life tables for all cancers combined and 26 individual cancers. Estimates were further stratified by sex and geographical area. The age-standardized 5-year relative survival for all cancers was 30.9% (95% confidence intervals: 30.6%-31.2%). Female breast cancer had high survival (73.0%) followed by cancers of the colorectum (47.2%), stomach (27.4%), esophagus (20.9%), with lung and liver cancer having poor survival (16.1% and 10.1%), respectively. Survival for women was generally higher than for men. Survival for rural patients was about half that of their urban counterparts for all cancers combined (21.8% vs. 39.5%); the pattern was similar for individual major cancers except esophageal cancer. The poor population survival rates in China emphasize the urgent need for government policy changes and investment to improve health services. While the causes for the striking urban-rural disparities observed are not fully understood, increasing access of health service in rural areas and providing basic health-care to the disadvantaged populations will be essential for reducing this disparity in the future.

In preparation for a collaborative multidisciplinary study of the pathogenesis of esophageal cancer, the authors reviewed the published literature to identify similarities and differences between Japan and China in esophageal cancer epidemiology. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type, while the incidence of esophageal adenocarcinoma remains extremely low in both countries. Numerous epidemiologic studies in both countries show that alcohol consumption and cigarette smoking are contributing risk factors for ESCC. There are differences, however, in many aspects of esophageal cancer between Japan and China, including cancer burden, patterns of incidence and mortality, sex ratio of mortality, risk factor profiles, and genetic variants. Overall incidence and mortality rates are higher in China than in Japan, and variation in mortality and incidence patterns is greater in China than in Japan. During the study period (1987-2000), the decline in age-adjusted mortality rates was more apparent in China than in Japan. Risk factor profiles differed between high- and low-incidence areas within China, but not in Japan. The association of smoking and drinking with ESCC risk appears to be weaker in China than in Japan. Genome-wide association studies in China showed that variants in several chromosome regions conferred increased risk, but only genetic variants in alcohol-metabolizing genes were significantly associated with ESCC risk in Japan. A well-designed multidisciplinary epidemiologic study is needed to examine the role of diet and eating habits in ESCC risk.

PURPOSE To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node–positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m 2 , once a day] on day 1 and capecitabine [1,000 mg/m 2 , twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P &lt; .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group ( P &lt; .001). CONCLUSION Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.

The aim of this study is to report assemblage of a large multi-institutional international database of esophageal cancer patients, patient and tumor characteristics, and survival of patients undergoing esophagectomy alone and its correlates. Forty-eight institutions were approached and agreed to participate in a worldwide esophageal cancer collaboration (WECC), and 13 (Asia, 2; Europe, 2; North America, 9) submitted data as of July 1, 2007. These were used to construct a de-identified database of 7884 esophageal cancer patients who underwent esophagectomy. Four thousand six hundred and twenty-seven esophagectomy patients had no induction or adjuvant therapy. Mean age was 62 +/- 11 years, 77% were men, and 33% were Asian. Mean tumor length was 3.3 +/- 2.5 cm, and esophageal location was upper in 4.1%, middle in 27%, and lower in 69%. Histopathologic cell type was adenocarcinoma in 60% and squamous cell in 40%. Histologic grade was G1 in 32%, G2 in 33%, G3 in 35%, and G4 in 0.18%. pT classification was pTis in 7.3%, pT1 in 23%, pT2 in 16%, pT3 in 51%, and pT4 in 3.3%. pN classification was pN0 in 56% and pN1 in 44%. The number of lymph nodes positive for cancer was 1 in 12%, 2 in 8%, 3 in 5%, and >3 in 18%. Resection was R0 in 87%, R1 in 11%, and R2 in 3%. Overall survival was 78, 42, and 31% at 1, 5, and 10 years, respectively. Unlike single-institution studies, in this worldwide collaboration, survival progressively decreases and is distinctively stratified by all variables except region of the world. A worldwide esophageal cancer database has been assembled that overcomes problems of rarity of this cancer. It reveals that survival progressively (monotonically) decreased and was distinctively stratified by all variables except region of the world. Thus, it forms the basis for data-driven esophageal cancer staging. More centers are needed and encouraged to join WECC.

PURPOSE Pyrotinib, an irreversible pan-ErbB inhibitor, showed promising antitumor activity and acceptable tolerability in a phase I trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both in combination with capecitabine, in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in an open-label, multicenter, randomized phase II study. PATIENTS AND METHODS Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab were assigned (1:1) to receive 400 mg pyrotinib or lapatinib 1,250 mg orally once per day for 21-day cycles in combination with capecitabine (1,000 mg/m 2 orally twice per day on days 1 to 14). The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. RESULTS Between May 29, 2015, and March 15, 2016, 128 eligible patients were randomly assigned to the pyrotinib (n = 65) or lapatinib (n = 63) treatment groups. The overall response rate was 78.5% (95% CI, 68.5% to 88.5%) with pyrotinib and 57.1% (95% CI, 44.9% to 69.4%) with lapatinib (treatment difference, 21.3%; 95% CI, 4.0% to 38.7%; P = .01). The median progression-free survival was 18.1 months (95% CI, 13.9 months to not reached) with pyrotinib and 7.0 months (95% CI, 5.6 to 9.8 months) with lapatinib (adjusted hazard ratio, 0.36; 95% CI, 0.23 to 0.58; P &lt; .001). The most frequent grade 3 to 4 adverse events were hand-foot syndrome in 16 of 65 patients (24.6%) in the pyrotinib group versus 13 of 63 (20.6%) in the lapatinib group; diarrhea in 10 patients (15.4%) versus three patients (4.8%), respectively; and decreased neutrophil count in six patients (9.2%) versus two patients (3.2%), respectively. CONCLUSION In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.

Abstract Two major treatment strategies employed in non-small cell lung cancer, NSCLC, are tyrosine kinase inhibitors, TKIs, and immune checkpoint inhibitors, ICIs. The choice of strategy is based on heterogeneous biomarkers that can dynamically change during therapy. Thus, there is a compelling need to identify comprehensive biomarkers that can be used longitudinally to help guide therapy choice. Herein, we report a 18 F-FDG-PET/CT-based deep learning model, which demonstrates high accuracy in EGFR mutation status prediction across patient cohorts from different institutions. A deep learning score (EGFR-DLS) was significantly and positively associated with longer progression free survival (PFS) in patients treated with EGFR-TKIs, while EGFR-DLS is significantly and negatively associated with higher durable clinical benefit, reduced hyperprogression, and longer PFS among patients treated with ICIs. Thus, the EGFR-DLS provides a non-invasive method for precise quantification of EGFR mutation status in NSCLC patients, which is promising to identify NSCLC patients sensitive to EGFR-TKI or ICI-treatments.

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.

Therapeutic antibodies targeting PD-1 have made major breakthroughs in cancer treatment. However, the majority of colorectal cancer (CRC) cases are microsatellite stable (MSS) and do not respond to anti-PD-1-based immunotherapy. Combination therapy will be an ideal strategy to overcome this limitation. Gegen Qinlian decoction (GQD), a classical traditional Chinese medicine (TCM) formula, has been clinically proven to be effective in the treatment of ulcerative colitis (UC) and type 2 diabetes mellitus. Here, a systemic pharmacological study revealed that GQD acts through multiple targets and pathways in the human body. Combination therapy with GQD and anti-mouse PD-1 potently inhibited the growth of CT26 tumours in a xenograft model. Gut microbiota analysis revealed that combination therapy with GQD and anti-mouse PD-1 significantly enriched for s__Bacteroides_acidifaciens and s__uncultured_organism_g__norank_f__Bacteroidales_S24-7_group. Based on metabolomic analyses, profoundly altered metabolites were identified in the combination therapy group. Two metabolic signalling pathways, namely, glycerophospholipid metabolism and sphingolipid metabolism, were explored. In particular, we found that combination therapy with GQD and anti-mouse PD-1 significantly increased the proportion of CD8+ T cells in peripheral blood and tumour tissues. Direct treatment with GQD and anti-mouse PD-1 increased the expression of IFN-γ, which is a critical factor in antitumour immunotherapy. In addition, combination therapy with GQD and anti-mouse PD-1 downregulated PD-1 and increased IL-2 levels, suggesting that the combination therapy could effectively restore T-cell functions by suppressing inhibitory checkpoints. The application of the Chinese medicinal formula GQD with PD-1 blockade-based immunotherapy can be a novel therapeutic strategy for CRC patients with MSS tumours.

Abstract Objective To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy. Design Randomised, double blind, placebo controlled, phase 3 study. Setting 146 medical centres across Asia, Europe, and North America, between 13 December 2018 and 28 February 2023. Participants 1657 patients aged ≥18 years with human epidermal growth factor receptor 2 negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease. Interventions Patients were randomly (1:1) assigned to receive either tislelizumab 200 mg or placebo intravenously every three weeks in combination with chemotherapy (investigator’s choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator’s choice of chemotherapy. Treatment continued until disease progression or unacceptable toxicity. Main outcome measures The primary endpoint was overall survival, both in patients with a PD-L1 tumour area positivity (TAP) score of ≥5% and in all randomised patients. Safety was assessed in all those who received at least one dose of study treatment. Results Of 1657 patients screened between 13 December 2018 and 9 February 2021, 660 were ineligible due to not meeting the eligibility criteria, withdrawal of consent, adverse events, or other reasons. Overall, 997 were randomly assigned to receive tislelizumab plus chemotherapy (n=501) or placebo plus chemotherapy (n=496). Tislelizumab plus chemotherapy showed statistically significant improvements in overall survival versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5% (median 17.2 months v 12.6 months; hazard ratio 0.74 (95% confidence interval 0.59 to 0.94); P=0.006 (interim analysis)) and in all randomised patients (median 15.0 months v 12.9 months; hazard ratio 0.80 (0.70 to 0.92); P=0.001 (final analysis)). Grade 3 or worse treatment related adverse events were observed in 54% (268/498) of patients in the tislelizumab plus chemotherapy arm versus 50% (246/494) in the placebo plus chemotherapy arm. Conclusions Tislelizumab added to chemotherapy as primary treatment for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5%, and in all randomised patients. Trial registration ClinicalTrials.gov NCT03777657

AIM: The Wnt signaling pathway plays a pivotal role in cellular developmental processes and human carcinogenesis. The aim of this study was to investigate the effects of quercetin on the growth of the colon carcinoma cell line and the regulation effect of quercetin on the Wnt/beta-catenin signaling pathway. METHODS: MTT assay was used to determine the reduction of cell viability of quercetin on SW480 cells and clone 26 cells. The apoptotic rate and cell-cycle analysis after treatment with quercetin was determined by flow cytometry. Effects of quercetin on mRNA expression of cyclin D(1) and survivin were detected by semiquantitative RT-PCR. After treatment with quercetin, the protein expression of cyclin D(1) and survivin in SW480 cells was analyzed by Western blot analysis. We built a Wnt/beta-catenin signaling pathway reporter gene model. The regulation effect of quercetin on the Wnt/beta-catenin signaling transcription was investigated by using this reporter gene model. RESULTS: Quercetin reduced cell viability in a dose- and time-dependent manner in SW480 and clone 26 cells. The percentages of SW480 cells and clone 26 cells at G(2)/M phase were increased significantly after treatment with 40 approximately 80 micromol/L quercetin for 48 hours. Quercetin induced the apoptosis of SW480 cells in a dose-dependent manner at the concentration of 20, 40, 60, anf 80 micromol/L. However, quercetin only induced the apoptosis of clone 26 cells at the concentration of 80 micromol/L. Quercetin downregulated transcriptional activity of beta-catenin/Tcf in SW480 cells transiently transfected with the TCF-4 reporter gene. Within 24 hours of treatment, a 160-mumol/L concentration of quercetin reduced beta-catenin/Tcf transcriptional activity by about 18-fold. Cyclin D(1) and the survivin gene were downregulated markedly by quercetin in a dose-dependent manner at both the transcription and protein expression levels. CONCLUSION: The results indicate that the molecular mechanism underlying the antitumor effect of quercetin in SW480 colon cancer cells is related to the inhibition of expression of cyclin D(1) and survivin as well as the Wnt/beta-catenin signaling pathway. Therefore, the Wnt/beta-catenin signaling pathway could be qualified as one of the promising targets for innovative treatment strategies of colorectal cancer.

INTRODUCTION: Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality. METHODS: We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included. RESULTS: A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027-1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691-4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142-5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141-4.420) were significantly associated with mortality. CONCLUSIONS: Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.

Importance: There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC). Objective: To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone. Design, Setting, and Participants: JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers. Interventions: Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Main Outcome: Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety. Results: Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group. Conclusions and Relevance: The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03581786.

OBJECTIVES: To estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China. DESIGN: This multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group. RESULTS: Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively. CONCLUSION: Among individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality.

Epidermal growth factor receptor (EGFR) mutations are the strongest response predictors to EGFR tyrosine kinase inhibitors (TKI) therapy, but knowledge of the EGFR mutation frequency on lung adenocarcinoma is still limited to retrospective studies. The PIONEER study (NCT01185314) is a prospective molecular epidemiology study in Asian patients with newly diagnosed advanced lung adenocarcinoma, aiming to prospectively analyze EGFR mutation status in IIIB/IV treatment-naïve lung adenocarcinomas in Asia. We report the mainland China subset results. Eligible patients (≥20 yrs old, IIIB/IV adenocarcinoma and treatment-naïve) were registered in 17 hospitals in mainland China. EGFR was tested for mutations by amplification refractory mutation system using biopsy samples. Demographic and clinical characteristics were collected for subgroup analyses. A total of 747 patients were registered. Successful EGFR mutation analysis was performed in 741, with an overall mutation rate of 50.2%. The EGFR active mutation rate is 48.0% (with 1.3% of combined active and resistance mutations). Tobacco use (>30 pack-year vs. 0-10 pack-year, OR 0.27, 95%CI: 0.17-0.42) and regional lymph nodes involvement (N3 vs. N0, OR 0.47, 95%CI: 0.29-0.76) were independent predictors of EGFR mutation in multivariate analysis. However, even in regular smokers, the EGFR mutation frequency was 35.3%. The EGFR mutation frequency was similar between diverse biopsy sites and techniques. The overall EGFR mutation frequency of the mainland China subset was 50.2%, independently associated with the intensity of tobacco use and regional lymph nodes involvement. The relatively high frequency of EGFR mutations in the mainland China subset suggest that any effort to obtain tissue sample for EGFR mutation testing should be encouraged.

BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) are of great importance in development of different types of tumors, while the function of lncRNA ZFAS1 is rarely discussed in esophageal squamous cell carcinoma (ESCC). Therefore, we performed this study to explore the expression of exosomal lncRNA ZFAS1 and its molecular mechanism on ESCC progression. METHODS: Expression of ZFAS1 and miR-124 in ESCC tissues was detected. LncRNA ZFAS1 was silenced to detect its function in the biological functions of ESCC cells. A stable donor and recipient culture model was established. Eca109 cells transfected with overexpressed and low expressed ZFAS1 plasmid and miR-124 inhibitor labeled by Cy3 were the donor cells, and then co-cultured with recipient cells to observe the transmission of Cy3-ZFAS1 between donor cells and recipient cells. The changes of cell proliferation, apoptosis, invasion, and migration in recipient cells were detected. The in vivo experiment was conducted for verifying the in vitro results. RESULTS: LncRNA ZFAS1 was upregulated and miR-124 was down-regulated in ESCC tissues. Silencing of ZFAS1 contributed to suppressed proliferation, migration, invasion and tumor growth in vitro and induced apoptosis of ESCC cells. LncRNA ZFAS1 was considered to be a competing endogenous RNA to regulate miR-124, thereby elevating STAT3 expression. Exosomes shuttled ZFAS1 stimulated proliferation, migration and invasion of ESCC cells and restricted their apoptosis with increased STAT3 and declined miR-124. Furthermore, in vivo experiment suggested that elevated ZFAS1-exo promoted tumor growth in nude mice. CONCLUSION: This study highlights that exosomal ZFAS1 promotes the proliferation, migration and invasion of ESCC cells and inhibits their apoptosis by upregulating STAT3 and downregulating miR-124, thereby resulting in the development of tumorigenesis of ESCC.

BACKGROUND: Previous studies have indicated that the performance of glomerular filtration rate (GFR) estimation equations vary according to the races of the target population. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has not been validated in the Chinese population including patients with chronic kidney disease (CKD) and healthy controls. METHODS: A total of 977 adult persons (682 patients with CKD and 295 healthy volunteers) from nine renal institutes of university hospitals located in nine geographic regions of China were enrolled in the study. A diagnostic test study comparing the CKD-EPI two-level and four-level race equation, the Modification of Diet in Renal Disease (MDRD) Study equation and the modified MDRD equation for Chinese (the Chinese equation). The (99m)Tc- diethylenetriamine pentaacetic acid dual plasma clearance was used as a reference method for measuring GFR. RESULTS: The mean age of participants was 48.3 ± 16.0 years and 479 (49.0%) were male. The CKD-EPI two-level race equation and the Chinese equation performed better than the MDRD Study equation and CKD-EPI four-level race equation, with less bias (median difference between estimated GFR and reference GFR, 0.2 and 0.3 versus -2.4 and 3.0 mL/min/1.73 m(2)), improved precision (interquartile range of the difference, 20.5 and 20.8 versus 23.4 and 20.5 mL/min/1.73 m(2)) and greater accuracy (percentage of estimated GFR within 30% of reference GFR, 73.4 and 73.0% versus 69.8 and 70.1%). CONCLUSIONS: The CKD-EPI two-level race equation and the Chinese equation performed similarly in the Chinese population, and both performed better than the MDRD Study equation and the CKD-EPI four-level race equation.