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Purpose Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). Patients and methods From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). Results Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9%vs.36.5%, P=0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4%vs.21.7%, P=0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P Conclusion Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.

Hypoxia in the tumor microenvironment (TME) greatly limits the tumor-killing therapeutic efficacy of sonodynamic therapy (SDT); this phenomenon is further exacerbated by increased glutathione (GSH) levels in cancer cells. Simultaneously, cancer starvation therapy is increasingly recognized nowadays as a promising clinical translation but the efficacy of glucose oxidase (GOx)-based starvation therapy is also limited by the lack of oxygen in the tumor. Glucuronide 3-phosphate dehydrogenase (GADPH) is a key glycolytic enzyme and can therefore be a target for starvation therapy in the absence of oxygen engagement. Here, we innovatively proposed thiol–ene click reactions based on a two-dimensional metal–organic framework (MOF) modification for tumor treatments to enable the combination of SDT and starvation therapy. Experimental studies demonstrated that the prepared material could consume GSH and GADPH free from oxygen in TME, which benefited from the thiol–ene click reactions between the MOF and thiol substances in cancer cells. Further experiments in vitro and in vivo indicated the prepared MOF materials could kill cancer cells efficiently. This study is expected to create a promising avenue for thiol–ene click reactions in SDT therapy and cancer starvation therapy for cancer.

Background: Loss of dystrophin protein causes Duchenne muscular dystrophy (DMD), characterized by progressive degeneration of cardiac and skeletal muscles, and mortality in adolescence or young adulthood. Although cardiac failure has risen as the leading cause of mortality in patients with DMD, effective therapeutic interventions remain underdeveloped, in part, because of the lack of a suitable preclinical model. Methods: We analyzed a novel murine model of DMD created by introducing a 4-bp deletion into exon 4, one of the exons encoding the actin-binding domain 1 of dystrophin (referred to as Dmd E4* mice). Echocardiography, microcomputed tomography, muscle force measurement, and histological analysis were performed to determine cardiac and skeletal muscle defects in these mice. Using this model, we examined the feasibility of using a cytidine base editor to install exon skipping and rescue dystrophic cardiomyopathy in vivo. AAV9-based CRISPR/Cas9-AID (eTAM) together with AAV9-sgRNA was injected into neonatal Dmd E4* mice, which were analyzed 2 or 12 months after treatment to evaluate the extent of exon skipping, dystrophin restoration, and phenotypic improvements of cardiac and skeletal muscles. Results: Dmd E4* mice recapitulated many aspects of human DMD, including shortened life span (by ≈50%), progressive cardiomyopathy, kyphosis, profound loss of muscle strength, and myocyte degeneration. A single-dose administration of AAV9-eTAM instituted >50% targeted exon skipping in the Dmd transcripts and restored up to 90% dystrophin in the heart. As a result, early ventricular remodeling was prevented and cardiac and skeletal muscle functions were improved, leading to an increased life span of the Dmd E4* mice. Despite gradual decline of AAV vector and base editor expression, dystrophin restoration and pathophysiological rescue of muscular dystrophy were long lasted for at least 1 year. Conclusions: Our study demonstrates the feasibility and efficacy to institute exon skipping through an enhanced TAM (eTAM) for therapeutic application(s).

Aberrant lipid metabolism is an essential feature of hepatocellular carcinoma (HCC). Fatty acid transport protein-5 (FATP5) is highly expressed in the liver and is involved in the fatty acid transport pathway. However, the potential role of FATP5 in the pathogenesis of HCC remains largely unknown. Herein, we showed that FATP5 was downregulated in HCC tissues and even much lower in vascular tumor thrombi. Low expression of FATP5 was correlated with multiple aggressive and invasive clinicopathological characteristics and contributed to tumor metastasis and a poor prognosis in HCC patients. FATP5 inhibited the epithelial–mesenchymal transition (EMT) process and suppressed HCC cell migration and invasion, while silencing FATP5 had the opposite effects. Mechanistically, knockdown of FATP5 promoted cellular glycolytic flux and ATP production, thus suppressing AMP-activated protein kinase (AMPK) and activating its downstream signaling mammalian target of rapamycin (mTOR) to support HCC progression and metastasis. Activation of AMPK using metformin reversed the EMT program and impaired the metastatic capacity of FATP5-depleted HCC cells. Collectively, FATP5 served as a novel suppressor of HCC progression and metastasis partly by regulating the AMPK/mTOR pathway in HCC, and targeting the FATP5-AMPK axis may be a promising therapeutic strategy for personalized HCC treatment.

Background Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection. Methods From a Chinese multicenter database, patients were categorized as AYA (aged 13–39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR. Results Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age ( Conclusions Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.

Hypertonic dextrose prolotherapy (HDP) is an injection of a concentrated dextrose solution for the purpose of local treatment of musculoskeletal pain and possible enhancement of repair mechanisms. This systematic review and meta-analysis examines the clinical utility of HDP injection for treatment of knee osteoarthritis (OA). Randomized controlled trials (RCTs) utilizing HDP to treat knee OA were retrieved from MEDLINE, EMBASE, and Cochrane Library (CENTRAL). Identification and inclusion of RCTs utilizing intra-articular and extra-articular administration of HDP vs administration of other injectate or physical therapy as control for knee OA were included. Primary clinical outcomes were changes in knee WOMAC, pain and function score. Secondary outcomes were adverse events related to HDP. For continuous outcomes with same or different measurements, we calculated, respectively the weighted mean difference (WMD) or the standardized mean difference (SMD), respectively. Results were pooled using DerSimonian and Laird random effect models across the included studies and heterogeneity between studies was estimated using the I2 index. Five studies comprising a total of 319 treated patients met inclusion criteria and were included in the final analysis. At a mean of 22.8 weeks follow-up, HDP treatment significantly improved total WOMAC score (WMD = 13.77, 95% CI: 6.75–20.78; p

Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma (HCC). Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis, predicting responses to specific therapies, evaluating prognosis before or after therapy, as well as serving as novel therapeutic targets. Detection and analysis of proteins, metabolites, circulating nucleic acids, circulating tumor cells, and extracellular vesicles in body fluids (e.g., blood and urine) and gut microbiota (e.g., in feces) have excellent capabilities to improve different aspects of management of HCC. Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis, treatment, and monitoring responses of HCC to conventional therapies, most of which may improve diagnosis and management of HCC in the future. This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.

Acute myocardial infarction (MI) resulting from coronary ischemia is a major cause of disability and death worldwide. Transplantation of human embryonic stem cell (hESC)‐derived cardiovascular progenitor cells (hCVPCs) promotes the healing of infarcted hearts by secreted factors. However, the hCVPC‐secreted proteins contributing to cardiac repair remain largely unidentified. In this study, we investigated protective effects of neurotrophin (NT)‐3 secreted from hCVPCs in hearts against myocardial ischemia/reperfusion (I/R) injury and explored the underlying mechanisms to determine the potential of using hCVPC products as a new therapeutic strategy. The implantation of hCVPCs into infarcted myocardium at the beginning of reperfusion following 1 hour of ischemia improved cardiac function and scar formation of mouse hearts. These beneficial effects were concomitant with reduced cardiomyocyte death and increased angiogenesis. Moreover, hCVPCs secreted a rich abundance of NT‐3. The cardioreparative effect of hCVPCs in the I/R hearts was mimicked by human recombinant NT‐3 (hNT‐3) but canceled by NT‐3 neutralizing antibody (NT‐3‐Ab). Furthermore, endogenous NT‐3 was detected in mouse adult cardiomyocytes and its level was enhanced in I/R hearts. Adenovirus‐mediated NT‐3 knockdown exacerbated myocardial I/R injury. Mechanistically, hNT‐3 and endogenous NT‐3 inhibited I/R‐induced cardiomyocyte apoptosis through activating the extracellular signal‐regulated kinase (ERK) and reducing the Bim level, resulting in the cardioreparative effects of infarcted hearts together with their effects in the improvement of angiogenesis. These results demonstrate for the first time that NT‐3 is a cardioprotective factor secreted by hCVPCs and exists in adult cardiomyocytes that reduces I/R‐induced cardiomyocyte apoptosis via the ERK‐Bim signaling pathway and promotes angiogenesis. As a cell product, NT‐3 may represent as a noncell approach for the treatment of myocardial I/R injury., Neurotrophin (NT)‐3 contributes to the cardioreparative effects of human embryonic stem cell (hESC)‐derived cardiovascular progenitor cells (hCVPCs) characterized by reduction of ischemia/reperfusion (I/R)‐induced cardiomyocyte apoptosis in adult mice via the extracellular signal‐regulated kinase (ERK)‐Bim signaling pathway and promotion of angiogenesis, resulting in the cardiac function improvement and fibrosis limitation in the infarcted hearts.

Background Repeat hepatectomy is a feasible treatment modality for intrahepatic recurrence after hepatectomy of hepatocellular carcinoma, yet the survival benefit remains ill-defined. The objective of the current study was to define long-term, oncologic outcomes after repeat hepatectomy among patients with early and late recurrence. Methods Patients undergoing curative-intent repeat hepatectomy for recurrent hepatocellular carcinoma were identified using a multi-intuitional database. Early and late recurrence was defined by setting 1 year after initial hepatectomy as the cutoff value. Patient clinical characteristics, overall survival, and disease-free survival were compared among patients with early and late recurrence before and after propensity score matching. Results Among all the patients, 81 had early recurrence and 129 had late recurrence from which 74 matched pairs were included in the propensity score matching analytic cohort. Before propensity score matching, 5-year overall survival and disease-free survival after resection of an early recurrence were 41.7% and 17.9%, respectively, which were worse compared with patients who had resection of a late recurrence (57.0% and 39.4%, both P Conclusion Repeat hepatectomy for early recurrence was associated with worse overall survival and disease-free survival compared with late recurrence. These data may help inform patients and selection of patients being considered for repeat hepatectomy of recurrent hepatocellular carcinoma.

Introduction:Ambulatory appointments are typically scheduled in fixed increments, resulting in suboptimal time utilization. Advanced analytics are rarely applied to address operational chal...

Background Ultra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population. Methods A population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers. Results After an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36–1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50–1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76–1.17). A nonlinear dose–response pattern was observed for overall cardiovascular and heart disease mortality (all Pnonlinearity Pinteraction Conclusions High consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.

Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. Results The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. Conclusions This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

This study was designed to investigate the prognostic value of the number and sites of extracranial metastasis (ECM) in NSCLC patients with BM. NSCLC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were enrolled in analysis. Patients from 2010 to 2013 were included in the training set and those from 2014 to 2015 in the validation set. ECM sites among different subtypes of NSCLC were compared by Chi‐square tests. Kaplan–Meier methods and Cox regression models were performed to analyze survival data. Competing‐risks analysis was used to predict cumulative incidence rates for CSS and non‐CSS cause. We included 5974 patients in the training cohort and 3561 patients in the validation cohort. Most (nearly 80%) NSCLC patients with BM showed 0–1 involved extracranial organ, with the most and least common ECM organ being bone and distant lymph nodes (DLNs) among all subtypes of NSCLC, respectively. The number of involved extracranial organs was an independent prognostic factor for patients with BM from NSCLC (p, Prognostic value of extracranial organ involvement the Surveillance, Epidemiology and End Results (SEER) database Tailored treatments would be reasonable for BM patients from NSCLC with different metastasis patterns.

Purpose To evaluate the accuracy of inflammatory biomarkers in differentiating patients with asthma-COPD overlap (ACO) from those with COPD alone. Methods Clinical data of 134 patients with COPD and 48 patients with ACO admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 were retrospectively analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the best cut-off values of fractional exhaled nitric oxide (FeNO), blood eosinophil counts (EOS), and neutrophil to lymphocyte ratio (NLR) for differentiating between ACO and COPD alone. Spearman correlation analysis was conducted to evaluate the relationships between these inflammatory biomarkers and the forced expiratory volume in one second/prediction (FEV1%pred). Results FeNO and EOS in the ACO patients were significantly higher than those in the COPD patients (FeNO: median 37.50 vs 24.50 ppb, P < 0.001; EOS: median 0.20 vs 0.10 ×109/L, P = 0.004). FeNO was positively correlated with FEV1%pred (r = 0.314, P = 0.030), while NLR was negatively correlated with FEV1%pred (r = -0.372, P = 0.009) in patients with ACO. In addition, a positive correlation between FeNO and EOS was also found in ACO, especially in patients without history of inhaled corticosteroids (ICS) use (r = 0.682, P < 0.001). The optimal cut-off value of FeNO was 31.5 ppb (AUC = 0.758, 95% CI = 0.631-0.886) in patients with smoking history, with 70.0% sensitivity and 89.9% specificity for differentiating ACO from COPD. In patients without history of ICS use, the best cut-off value of FeNO was 39.5 ppb (AUC = 0.740, 95% CI = 0.610-0.870), with 58.3% sensitivity and 84.9% specificity. Among patients without history of ICS use and smoking, 27.5 ppb was optimal cut-off level for FeNO (AUC = 0.744, 95% CI = 0.579-0.908) to diagnose ACO, with 81.8% sensitivity and 60.7% specificity, and the sensitivity was improved to 91.7% when FeNO was combined with EOS. Conclusion The inflammatory biomarkers FeNO and EOS can be used as indicators for differentiating between ACO and COPD alone.

Heart diseases (HDs) are the leading cause of morbidity and mortality worldwide. Despite remarkable clinical progress made, current therapies cannot restore the lost myocardium, and the correlation of genotype to phenotype of many HDs is poorly modeled. In the past two decades, with the rapid developments of human pluripotent stem cell (hPSC) biology and technology that allow the efficient preparation of cardiomyocytes from individual patients, tremendous efforts have been made for using hPSC-derived cardiomyocytes in preclinical and clinical cardiac therapy as well as in dissection of HD mechanisms to develop new methods for disease prediction and treatment. However, their applications have been hampered by several obstacles. Here, we discuss recent advances, remaining challenges, and the potential solutions to advance this field.

Aging of the population and prolonged life expectancy have significantly increased the number of elderly patients undergoing hepatectomy for hepatocellular carcinoma (HCC). However, potential benefits, especially long-term oncologic outcomes of hepatectomy for elderly patients with HCC remain unclear.Patients treated with curative-intent hepatectomy for HCC in 8 Chinese hospitals were enrolled. Patients were divided into the elderly (≥70 years old) and younger (70 years old) groups. Overall survival (OS), cancer-specific survival (CSS), and time-to-recurrence (TTR) were compared. Risk factors of CSS and TTR were evaluated by univariable and multivariable competing-risk regression analyses.Of 2134 patients, 259 (12.1%) and 1875 (87.9%) were elderly and younger aged, respectively. Postoperative 30-day and 90-day mortality was comparable among elderly and younger patients. Compared with younger patients, the elderly had a worse 5-year OS (49.4% vs. 55.3%, P = 0.032), yet a better 5-year CCS (74.5% vs. 61.0%, P = 0.005) and a lower 5-year TTR (33.7% vs. 44.9%, P 0.001), respectively. Multivariable analyses identified that elder age was independently associated with more favorable CSS (HR 0.74, 95%CI 0.58-0.90, P = 0.011) and TTR (0.69, 0.53-0.88, P 0.001) but was not associated with OS (P = 0.136).Age by itself is not a contraindication to surgery, and selected elderly patients with HCC can benefit from hepatectomy. Compared with younger patients, elderly patients have noninferior oncologic outcomes following hepatectomy for HCC.

Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. This rapidly spreading, infectious disease affects ducks in particular, with a high morbidity and low mortality rate, causing huge economic losses. This study analyzed the evolution of NGPV isolated from Jing-Xi partridge duck with SBDS in South China. Complete genome sequences of the NGPV strains GDQY1802 and GDSG1901 were homologous with other GPV/NGPV and Muscovy duck parvovirus (MDPV) strains. Phylogenetic analysis showed that the NGPV isolated from mainland China was related to the Taiwan 82-0321v strain of GPV. In contrast to 82-0321v and the SDLC01 strain, which was first isolated from China, the two isolates showed no deletions in the inverted terminal repeat (ITR) region. Further, in these isolates, 24 amino acid sites of the replication protein were different compared to that of GPV live vaccine strain 82-0321v, and 12 sites were unique across all NGPV isolates. These isolates also showed differences in 17 amino acid sites of the capsid protein from that of 82-0321v, two of which were the same as those in MDPV. Recombination analysis identified the major parents of GDSG1901 and GDQY1802 as the NGPV-GD and NGPV-Hun18 strains, and the minor parents as the classical GPV 06-0329 and GPV LH strains, respectively. GDQY1802 and GDSG1901 are recombinant GPV-related parvovirus isolated from domesticated partridge duck. Recombination is evident in the evolution of NGPV, and as such, the use of live attenuated vaccines for NGPV requires further study.

This study examines the distribution of sleep disorder prevalence across socioeconomic status (SES) and investigates the relationship between sleep disorders and hypertension among southwest China's rural older adult population.A cross-sectional survey was conducted in rural Yunnan Province, China from 2017 to 2018, consisting of 4833 consenting participants aged ≥60 years. Each participant completed a structured interview and had their blood pressure measured. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Multivariate logistic regression was used to model variations in prevalence of sleep disorders and hypertension.In the study population, the prevalence rates of sleep disorders and hypertension were 46.5% and 50.3%, respectively. Women had higher prevalence of both chronic illnesses (53.4% vs. 38.7%, 53.1% vs. 47.6%, P 0.01). After adjusting for age, sex, and residential status, older adults of minority ethnicity had a higher prevalence of sleep disorders than the Han ethnic majority (P 0.01). Attainment of higher levels of education and lower annual household income were also associated with a greater risk of sleep disorders (P 0.01). Further, logistic regression analysis indicated that older adults with sleep disorders had a greater risk of being hypertensive (P 0.01).Sleep disorders are highly prevalent in rural southwest China. Future interventions to improve sleep quality would benefit from tailoring to address individual SES. Improving sleep quality profoundly reduces prevalence of hypertension.

Background With an increase in life expectancy and improvement of surgical safety, more elderly patients with hepatocellular carcinoma (HCC), even with large tumors, are now considered for hepatectomy. This study aimed to clarify the impact of age on short- and long-term outcomes after major hepatectomy (≥3 segments) for large HCC (≥5 cm). Patients and methods Using a multicenter database, patients who underwent curative-intent major hepatectomy for large HCC between 2006 and 2016 were identified. Postoperative morbidity and mortality, overall survival (OS) and recurrence-free survival (RFS) were compared between the elderly (≥65 years) and younger ( Results Of 830 patients, 92 (11.1%) and 738 (88.9%) were elderly and younger patients, respectively. There were no significant differences in postoperative 30-day mortality and morbidity between the two groups (5.4% vs 2.6% and 43.5% vs 38.3%, both P>0.05). The 5-year OS and RFS rates in elderly patients were also comparable to younger patients (35.0% vs 33.2% and 20.0% vs 20.8%, both P>0.05). In the entire cohort, multivariable Cox-regression analyses identified that old age was not independently associated with OS and RFS. However, in the elderly cohort, preoperative alpha-fetoprotein level >400 μg/L, multiple tumors, macrovascular invasion and microvascular invasion were independently associated with decreased OS and RFS. Conclusion Carefully selected elderly patients benefited from major hepatectomy for large HCC as much as younger patients, and their long-term prognosis was determined by preoperative alpha-fetoprotein level, tumor number and presence of macro- or micro-vascular invasion.

Background: Low serum L1 cell adhesion molecule (L1CAM) has been found in several malignant tumors. Here, we aimed to evaluate the diagnostic potential for serum L1CAM in patients with gastric cancers (GC) and esophagogastric junction adenocarcinoma (EJA). Methods: Enzyme-linked immunosorbent assay (ELISA) was carried out to detect L1CAM level in sera of 148 GC patients, 59 EJA patients and 148 healthy controls. Receiver operating characteristics (ROC) was employed to evaluate diagnostic accuracy. Results: The concentrations of serum L1CAM were significantly lower in GC and EJA than those in healthy controls (P

Background Lung adenocarcinoma (ADC) is a major form of lung cancer, which is a main cause of global cancer-related death in male and female patients. LncRNAs are implicated in tumor development. However, the functions and mechanisms of the LncRNA HOTAIRM1 in ADC are not known. Materials and methods Here, the downregulated HOTAIRM1 in ADC was selected by TCGA analysis. Subsequently, qRT-PCR, CCK-8, EdU, cell apoptosis, cell cycle and cell invasion assays were utilized for evaluating the roles of HOTAIRM1 in ADC. Finally, we explored the mechanism of HOTAIRM1 in ADC. Results HOTAIRM1 expression was considerably decreased in ADC tissues. The knockdown of HOTAIRM1 promoted the cell cycle, growth, and invasion of ADC. Moreover, HOTAIRM1 competitively bound miR-498 to regulate the expression of WWOX. Conclusion HOTAIRM1 suppressed the proliferation and invasion of ADC cells via the modulation of miR-498/WWOX axis. This finding suggested that it might be clinically valuable as a biomarker for ADC. Furthermore, the findings suggest LncRNA HOTAIRM1 as a candidate therapeutic target in ADC.

Summary Background Effective adjuvant treatment after hepatectomy for hepatocellular carcinoma (HCC) is an important area of research. Radioactive iodine (131I)-labelled metuximab is a radiolabelled monoclonal antibody against the CD147 (also known as basigin or HAb18G) antigen that is expressed in HCC. We aimed to examine the role of 131I-metuximab as an adjuvant therapy after HCC resection. Methods This randomised, controlled, multicentre, open-label, phase 2 trial was done at five medical centres in China. Patients aged 18–75 years who underwent curative-intent resection of histologically confirmed HCC expressing CD147 were randomly assigned (1:1) by a computer-generated random sequence, stratified by centre, to receive either adjuvant transarterial injection of one dose of 27·75 MBq/kg 131I-metuximab 4–6 weeks after the hepatectomy (treatment group) or no adjuvant treatment (control group). Patients and physicians were not masked to the study groups. The primary outcome was 5-year recurrence-free survival (RFS) in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , NCT00819650 . Findings Between April 1, 2009, and Nov 30, 2012, 485 patients were screened for eligibility. 329 (68%) of these patients were excluded and 156 (32%) were randomly assigned to receive either 131I-metuximab (n=78) or no adjuvant treatment (n=78). The median follow-up was 55·9 months (IQR 18·6–79·4). In the intention-to-treat population, the 5-year RFS was 43·4% (95% CI 33·6–55·9) in the 131I-metuximab group and 21·7% (14·2–33·1) in the control group (hazard ratio 0·49 [95% CI 0·34–0·72]; Z=2·96, p=0·0031). 131I-metuximab-associated adverse events occurred within the first 4 weeks in 34 (45%) of 76 patients, seven (21%) of whom had grade 3 or 4 adverse events. These adverse events were all resolved with appropriate treatment within 2 weeks of being identified. Interpretation Adjuvant 131I-metuximab treatment significantly improved the 5-year RFS of patients after hepatectomy for HCC tumours expressing CD147. This treatment was well tolerated by patients. Funding State Key Project on Infectious Diseases of China.

Background A clear definition of “early recurrence” after hepatocellular carcinoma (HCC) resection is still lacking. This study aimed to determine the optimal cutoff between early and late HCC recurrence, and develop nomograms for pre- and postoperative prediction of early recurrence. Methods Patients undergoing HCC resection were identified from a multi-institutional Chinese database. Minimum P-value approach was adopted to calculate optimal cut-off to define early recurrence. Pre- and postoperative risk factors for early recurrence were identified and further used for nomogram construction. The results were externally validated by a Western cohort. Results Among 1501 patients identified, 539 (35.9%) were recurrence-free. The optimal length to distinguish between early (n = 340, 35.3%) and late recurrence (n = 622, 64.7%) was 8 months. Multivariable logistic regression analyses identified 5 preoperative and 8 postoperative factors for early recurrence, which were further incorporated into preoperative and postoperative nomograms (C-index: 0.785 and 0.834). The calibration plots for the probability of early recurrence fitted well. The nomogram performance was maintained using the validation dataset (C-index: 0.777 for preoperative prediction and 0.842 for postoperative prediction). Conclusions An interval of 8 months was the optimal threshold for defining early HCC recurrence. The two web-based nomograms have been published to allow accurate pre- and postoperative prediction of early recurrence. These may offer useful guidance for individual treatment or follow up for patients with resectable HCC.

This study aimed to explore whether the polymorphisms of CYP4F2 and CYP3A5 are correlated with the risk of lung cancer development. A case–control study was conducted among 510 patients with pathologically confirmed lung cancer as the case group and 504 healthy individuals as the control group. Four single-nucleotide polymorphisms of the CYP4F2 and CYP3A5 genes were genotyped, and their correlations with the risk of lung cancer were examined using Chi-square test and logistic regression analysis. Stratified analysis found that the rs3093105 and rs3093106 loci of CYP4F2 gene were significantly associated with lower risk of lung cancer (P = 0.012, OR 0.64, 95% CI 0.45–0.91). The correlation was related to patients’ age and sex and pathological type of lung cancer. Similarly, the rs10242455 loci of CYP3A5 gene showed a statistical significance between the case group and the control group (P = 0.018, OR 0.71, 95% CI 0.53–0.94), which also was associated with reduced risk of squamous cell lung cancer in the dominant and additive models (dominant: OR 0.66, 95% CI 0.46–0.94, P = 0.021; additive: OR 0.71, 95% CI 0.53–0.95, P = 0.023). CYP4F2 and CYP3A5 gene polymorphisms are associated with the reduced risk of non-small cell lung cancer, and its correlation is related to patients’ age and sex and pathological type of lung cancer.

This study aimed to examine the correlation between right posteroinferior bile duct (RPBD) angulation and the occurrence of bile duct stones in patients with hepatolithiasis. Patients presenting with hepatolithiasis in our hospital from January 2011 to July 2016 were divided into two groups according to whether their RPBD was affected by stones. A statistical analysis for the relevant factors associated with bile duct stone formation in the RPBD was performed. The binary logistic regression results showed that stenosis of the right hepatic duct [odds ratio (OR): 7.313; 95% confidence interval (CI) 4.131–12.945)] and the angle of the RPBD (OR 0.896; 95%CI 0.877–0.916) were risk factors associated with the formation of RPBD stones. Further, the receiver operating characteristic curve indicated that, when the angle of the RPBD was less than 44.58°, stones were able to form more easily in the RPBD. The occurrence of bile duct stones is well correlated with sharp bile duct angulation.

Background Morbidity remains a common problem following hepatic resection. The aim of this study was to investigate the association between preoperative body mass index (BMI) and morbidity in patients undergoing liver resection for hepatocellular carcinoma (HCC). Methods Patients were divided into three groups according to preoperative BMI: low-BMI (≤18.4 kg/m2), normal-BMI (18.5–24.9 kg/m2) and high-BMI (≥25.0 kg/m2). Baseline characteristics, operative variables, postoperative 30-day mortality and morbidity were compared. Univariable and multivariable analyses were performed to identify independent risk factors associated with postoperative morbidity. Results Among 1324 patients, 108 (8.2%), 733 (55.4%), and 483 (36.5%) were low-BMI, normal-BMI, and high-BMI, respectively. There were no differences in postoperative 30-day mortality among patients based on BMI (P = 0.199). Postoperative 30-day morbidity was, however, higher in low-BMI and high-BMI patients versus patients with a normal-BMI (33.3% and 32.1% vs. 22.9%, P = 0.018 and P Conclusion Compared with normal-BMI patients, low-BMI and high-BMI patients had higher postoperative morbidity, including a higher incidence of SSI after liver resection for HCC.

BACKGROUND Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-L-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908–0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875–0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% CI, 0.929–0.952)] and was validated in the validation cohort [AUC, 0.931 (95% CI, 0.909–0.953)]. CONCLUSIONS Our results demonstrated that a web-based calculator including age, sex, AFP, and PIVKA-II accurately predicted the presence of HCC in patients with CHB. ClinicalTrials.gov Identifier NCT03047603

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and unfavorable prognosis. Ferroptosis is a form of regulated cell death with an iron-dependent way that is involved in the development of various diseases. Whereas the prognostic value of ferroptosis-related genes (FRGs) in IPF remains uncertain and needs to be further elucidated.Methods: The FerrDb database and the previous studies were screened to explore the FRGs. The data of patients with IPF were obtained from the GSE70866 dataset. Wilcoxon's test and univariate Cox regression analysis were applied to identify the FRGs that are differentially expressed between normal and patients with IPF and associated with prognosis. Next, a multigene signature was constructed by the least absolute shrinkage and selection operator (LASSO)-penalized Cox model in the training cohort and evaluated by using calibration and receiver operating characteristic (ROC) curves. Then, 30% of the dataset samples were randomly selected for internal validation. Finally, the potential function and pathways that might be affected by the risk score-related differently expressed genes (DEGs) were further explored.Results: A total of 183 FRGs were identified by the FerrDb database and the previous studies, and 19 of them were differentially expressed in bronchoalveolar lavage fluid (BALF) between IPF and healthy controls and associated with prognosis (p < 0.05). There were five FRGs (aconitase 1 [ACO1], neuroblastoma RAS viral (v-ras) oncogene homolog [NRAS], Ectonucleotide pyrophosphatase/phosphodiesterase 2 [ENPP2], Mucin 1 [MUC1], and ZFP36 ring finger protein [ZFP36]) identified as risk signatures and stratified patients with IPF into the two risk groups. The overall survival rate in patients with high risk was significantly lower than that in patients with low risk (p < 0.001). The calibration and ROC curve analysis confirmed the predictive capacity of this signature, and the results were further verified in the validation group. Risk score-related DEGs were found enriched in ECM-receptor interaction and focal adhesion pathways.Conclusion: The five FRGs in BALF can be used for prognostic prediction in IPF, which may contribute to improving the management strategies of IPF.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide, which lacks effective inhibition of progression and metastasis in the advanced clinical stage. Mesoporous silica nanoparticle (MSN)–based cytotoxic or immunoregulatory drug–loading strategies have attracted widespread attention in the recent years. As a representative of mesoporous biomaterials, MSNs have good biological characteristics and immune activation potential and can cooperate with adjuvants against HCC. This review summarizes the possible future development of the field from the perspective of tumor immunity and aims to stimulate the exploration of the immune mechanism of MSN-based therapy. Through this point of view, we hope to develop new clinical immune drugs that can be applied to HCC clinical management in the future.

Background and aims Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. Methods From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. Results A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child–Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. Conclusions Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.

Food allergy is a serious health problem affecting more than 10% of the human population worldwide. Medical treatments for food allergy remain limited because immune therapy is risky and costly, and anti-allergic drugs have many harmful side effects and can cause drug dependence. In this paper, we review natural bioactive substances capable of alleviating food allergy. The sources of the anti-allergic substances reviewed include plants, animals, and microbes, and the types of substances include polysaccharides, oligosaccharides, polyphenols, phycocyanin, polyunsaturated fatty acids, flavonoids, terpenoids, quinones, alkaloids, phenylpropanoids, and probiotics. We describe five mechanisms involved in anti-allergic activities, including binding with epitopes located in allergens, affecting the gut microbiota, influencing intestinal epithelial cells, altering antigen presentation and T cell differentiation, and inhibiting the degranulation of effector cells. In the discussion, we present the limitations of existing researches as well as promising advances in the development of anti-allergic foods and/or immunomodulating food ingredients that can effectively prevent or alleviate food allergy. This review provides a reference for further research on anti-allergic materials and their hyposensitizing mechanisms.

Clinical staining and targeting CREB3L1 facilitates precise stratification and a potential treatment strategy for thyroid cancer., Understanding of dedifferentiation, an indicator of poo prognosis for patients with thyroid cancer, has been hampered by imprecise and incomplete characterization of its heterogeneity and its attributes. Using single-cell RNA sequencing, we explored the landscape of thyroid cancer at single-cell resolution with 46,205 cells and delineated its dedifferentiation process and suppressive immune microenvironment. The developmental trajectory indicated that anaplastic thyroid cancer (ATC) cells were derived from a small subset of papillary thyroid cancer (PTC) cells. Moreover, a potential functional role of CREB3L1 on ATC development was revealed by integrated analyses of copy number alteration and transcriptional regulatory network. Multiple genes in differentiation-related pathways (e.g., EMT) were involved as the downstream targets of CREB3L1, increased expression of which can thus predict higher relapse risk of PTC. Collectively, our study provided insights into the heterogeneity and molecular evolution of thyroid cancer and highlighted the potential driver role of CREB3L1 in its dedifferentiation process.

BackgroundHepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC).MethodsPatients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM.ResultsAmong 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081).ConclusionComparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.

The treatment of lung cancer is one of the major challenges in the field of oncology. According to statistics from the National Cancer Center of China in 2015, lung cancer has the highest incidence and mortality, with 733,300 new cases and 610,200 deaths across the country (1). About 85% of lung cancers are non-small cell lung cancer (NSCLC), of which 30% to 40% are considered resectable tumors, including most stage I-II and a small portion of stage IIIA tumors (2). Very early-stage NSCLC (IA) can be cured by surgery. However, more than 50% of NSCLC patients who undergo surgical treatment will relapse or metastasize within 5 years. Even if there is no lymph node metastasis and the primary

Metal mobility and toxicity of the municipal solid waste incineration (MSWI) fly ash from different seasons in Beijing were studied using leaching toxicity procedures, sequential extraction procedures, and bioavailability procedures. The X-ray diffraction results showed that MSWI fly ash contained CaSO4, CaCO3, and KCl. The Pb, Zn, and Cd contents of MSWI fly ash were high, especially during autumn, being 42, 77, and 1260 times higher than that of their soil backgrounds, respectively. Leaching toxicity experiments showed that MSWI fly ash is hazardous, since Pb exceeded the maximum threshold (5 mg/L). The main alkali metal ions and anions, heavy metals total content, leaching concentration, chemical speciation, and bioavailability varied seasonally. The Pb and Zn leaching concentrations in summer and autumn were higher than that of the other two seasons. Sequential extraction procedures indicated that Pb, Zn, and Cd showed extremely high metal mobility, i.e., the residual states of Pb and Cd in spring were 5.83% and 1.21%, respectively, and that of Zn in autumn was 10.68%. These results will help industries, governments, and the public better understand the risk of MSWI fly ash and will urge them to pay more attention to preventing harm to the ecosystem and human beings.

Objective The present study applied iTRAQ and LC-MS/MS techniques for proteome analysis and compared data between specimens of papillary thyroid microcarcinoma (PTMC) vs appropriate controls, in order to investigate the mechanisms underlying the invasion and metastasis process in PTMC development. Materials and methods Fresh-tissue specimens were collected from 40 patients with thyroid disease who underwent surgical treatment. Specimens were divided into four groups: normal histology (NH; n = 8), benign thyroid tumor (BTT; n = 10), classic PTMC with lymph node metastasis (PTC-LNM(+); n = 11), and classic PTMC without lymph node metastasis (PTC-LNM(−); n = 11). Proteomic studies were conducted on PTMC tissue samples without capsule invasion and with tumor diameter ranging from 0.5 cm to 1 cm, so as to focus the study on PTMC development excluding metastasis. Results A total of 8036 proteins were identified in the four groups. Based on protein function analysis, proteins that might be associated with PTMC invasion and metastasis were screened: alpha-actinin-1, alpha-1-antitrypsin, hepatoma-derived growth factor (HDGF), high-mobility group protein HMGI-C, and carbonic anhydrase 4. In addition, proteins involved in the focal adhesion pathway were examined. Immunohistochemistry confirmed the reliability of the iTRAQ results and the universality of differentially expressed proteins. The data showed that HDGF and high-mobility group protein HMGI-C are up-regulated in PTMC and that the focal adhesion pathway that promotes PTMC LNM is activated. Conclusions These findings provide insight into the mechanisms underlying PTMC invasion and metastasis.

Fibrosis is a final pathological feature of many chronic diseases, but few interventions are available that specifically target the pathogenesis of fibrosis. The highlights of common cellular and molecular mechanisms of fibrosis facilitate the discovery of effective antifibrotic drugs. The renin-angiotensin system (RAS) plays a central physiological role in the control of blood pressure and fluid homeostasis. Emerging evidence has revealed that activation of RAS was consistently found in fibrotic tissue. At the same time, as more components of the RAS are described, other pot Potential therapeutic targets emerge, so it seems sensible to revisit the contribution of RAS in anti-fibrotic therapy. So far, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) are the main commercial available drugs for intervening RAS. However, RAS inhibitors had lots of limitations in long-term application owing to occurring AngII and aldosterone escape. Over the past decades, natural products have aroused growing attention as potential RAS inhibitors due to their high efficacy and low risk of side effects. In this review, we revisit the contribution of RAS and its new members to anti-fibrotic therapy. Ultimately, we summarize and evaluate the use of natural products including isolated compounds, crude extracts and traditional Chinese herbal formulas to regulate RAS. These natural products can retard tissue fibrosis by targeting different RAS components, which provide us new therapeutic strategies to discover anti-fibrotic drugs.

Surgical resection for hepatocellular carcinoma (HCC) is potentially curative, but long-term survival remains unsatisfactory. There is currently no effective neoadjuvant or adjuvant therapy for HCC. We sought to evaluate the impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term prognosis after surgical resection of huge HCCs (≥ 10 cm). Using a multicenter database, consecutive patients who underwent curative-intent resection for huge HCC without macrovascular invasion between 2004 and 2014 were identified. The association between preoperative TACE with perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) was assessed before and after propensity score matching (PSM). Among the 377 enrolled patients, 88 patients (23.3%) received preoperative TACE. The incidence of perioperative mortality and morbidity was comparable among patients who did and did not undergo preoperative TACE (3.4% vs. 2.4%, p= 0.704, and 33.0% vs. 31.1%, p= 0.749, respectively). PSM analysis created 84 matched pairs of patients. In examining the entire cohort as well as the PSM cohort, median OS (overall cohort: 32.8 vs. 22.3 months, p= 0.035, and PSM only: 32.8 vs. 18.1 months, p= 0.023, respectively) and RFS (12.9 vs. 6.4 months, p= 0.016, and 12.9 vs. 4.1 months, p= 0.009, respectively) were better among patients who underwent preoperative TACE vs. patients who did not. After adjustment for other confounding factors on multivariable analyses, preoperative TACE remained independently associated with a favorable OS and RFS after the resection of huge HCC. Preoperative TACE did not increase perioperative morbidity or mortality, yet was associated with an improved OS and RFS after liver resection of huge HCC (≥ 10 cm).

Rationale Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with “early” stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). Objectives To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. Methods Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. Results Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005–1.379], p = 0.043). Conclusions Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. Trial registration NCT01581229. Registered 19 April 2012 Electronic supplementary material The online version of this article (10.1186/s13054-019-2575-6) contains supplementary material, which is available to authorized users.

More than two-thirds of patients with hepatocellular carcinoma (HCC) cannot receive curative therapy and have poor survival due to late diagnosis and few prognostic directions. In our study, nontargeted and targeted metabolomics analyses were conducted by liquid chromatography-mass spectrometry to characterize metabolic features of HCC and identify diagnostic and prognostic biomarker candidate incorporating liver tissue and serum metabolites. A total of 552 subjects, including 432 with liver tissue and 120 with serum specimens, were recruited in China. In the discovery cohort, a series of 138 metabolites were identified to discriminate HCC tissues from matched nontumor tissues. Retinol presented with the highest area under the curve (AUC) of 0.991 and associated with Edmondson grade. In the validation cohort, all metabolites in retinol metabolism pathway were examined and the levels of retinol and retinal in tumor tissue and serum decreased in the order of normal to cirrhosis to HCC of Edmondson Grades I to IV. Retinol and retinal levels could also differentiate between HCC and cirrhosis, with AUCs of 0.996 and 0.994, respectively, in tissue and 0.812 and 0.744, respectively, in serum. The AUC of the combined retinol and retinal panel in serum was 0.852. Univariate and multivariate Cox regression identified this panel as an independent predictor for HCC and showed that low expression of retinol and retinal correlated with decreased survival time. In conclusion, the retinol metabolic signature had considerable diagnostic and prognostic value for identifying HCC patients who would benefit from prompt therapy and optimal prognostic direction.

Clinical guidelines recommend surveillance in high-risk population to early detect hepatocellular carcinoma (HCC), when curative treatment such as liver resection can be applied. However, it is largely unknown whether surveillance would provide long-term survival benefits to these high-risk patients who have received curative liver resection for HCC. A prospectively maintained database on patients with chronic hepatitis B infection who underwent curative liver resection for HCC from 2003 to 2014 was reviewed. Patients’ overall survival and recurrence were compared between the groups of patients whose HCCs were diagnosed by surveillance or non-surveillance, as well as between the groups of patients operated in the first (2003–2008) and second (2009–2014) 6-year periods. Of 1075 chronic hepatitis B patients with HCC, 452 (42.0%) patients were diagnosed by preoperative surveillance. Compared with the non-surveillance group, the OS and RFS rates were significantly better in the surveillance group (both P

The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for hepatocellular carcinoma (HCC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes.Using multi-institutional data, the different impact of the RM status (narrow,1 cm, or wide, ≥1 cm) and MVI (positive or negative) on overall survival (OS) and recurrence-free survival (RFS) after curative liver resection of solitary HCC without macrovascular invasion was analyzed.In 801 patients, 306 (38%) had a narrow RM and 352 (44%) had positive MVI. The median OS and RFS were 109.8 and 74.8 months in patients with wide RMnegative MVI, 93.5 and 53.1 months with wide RMpositive MVI, 79.2 and 41.6 months with narrow RMnegative MVI, and 69.2 and 37.5 months with narrow RMpositive MVI (both P 0.01). On multivariable analyses, narrow RMpositive MVI had the highest hazard ratio with reduced OS and RFS (HR 2.96, 95% CI 2.11-4.17, and HR 3.15, 95% CI, 2.09-4.67, respectively).Concomitant having narrow RM and positive MVI increases the risks of postoperative death and recurrence by about 2-fold in patients with solitary HCC.

Tumor microenvironment plays a vital role in tumor progression, metastasis and aggressiveness. The interaction between tumor and surrounding stromal cells, especially fibroblasts, is closely related to antitumor drug sensitivity. We developed a novel 3-dimensional (3D) multicellular tumor model with the coculture of breast cancer MCF-7 and mouse fibroblast NIH-3T3 cells simulating the in vivo tumor microenvironment for cancer drug screening. MCF-7 and NIH-3T3 cells were engineered to express enhanced green fluorescent protein and red fluorescence protein, respectively. These cells were cocultured in polyethylene terephthalate (PET) fibrous matrices as 3D scaffolds in microbioreactors modified from a 384-well plate, and their growth was monitored in real time by the dual fluorescence signals measured with a plate reader. The 3D coculture was used to evaluate cytotoxicity or IC50 of three antitumor drugs: tamoxifen, oxaliplatin and cisplatin. In general, the drug resistance or IC50 of MCF-7 increased significantly when cocultured with NIH-3T3. These drugs also showed lower cytotoxicity to NIH-3T3 cells, versus MCF-7 cells, confirming that they are cancer-specific agents and relatively harmless to non-cancerous cells. The dual fluorescence 3D coculture assay can provide a reliable high throughput platform for screening cancer drugs whose efficacy may be impacted by fibroblasts in tumor stroma.

Background Cytochrome P450 (CYPs) are heme proteins involved in the metabolism of a variety of endogenous and exogenous substances and play an important role in the carcinogenesis mechanisms of environmental and hereditary factors. The objective of this study was to investigate how polymorphisms of CYPs correlate with lung cancer (LC) susceptibility. Methods Six single nucleotide polymorphisms (SNPs) were genotyped in this study. The chi‐square test and unconditional logistic regression model were used to evaluate the correlation between SNPs and LC susceptibility. The expressions and survival data of genes in patients with LC were mined using Oncomine and Kaplan‐Meier Plotter database. Results Four SNPs were found to be significantly associated with the risk of LC development (P

Purpose: The aim of this meta-analysis was to investigate polymorphism of Bsm1, Apal, Taq1 and Cdx-2 in vitamin D receptor (VDR) associations in relation to lung cancer (LC) susceptibility. Methods: 9 literatures were recruited into this meta-analysis from PubMed, PMC, Embase, Web of Science, Cochrane library and CNKI. STATA version 15.1 was used for statistical tests. The heterogeneity was tested using I2 statistics. According to the value of I2 , the random-effect model (REM) or fixed-effect model (FEM) was selected to combine data from studies, respectively. Potential publication bias was evaluated by Egger's test. Sensitivity analysis was also performed to evaluate the stability and reliability in results. Results: Decreased susceptibility of LC was found in all genetic models contrast in Bsm1 gene of VDR (a vs. A: OR = 0.62, 95 % CI = 0.44-0.87; aa vs. AA: OR = 0.76, 95 % CI = 0.60-0.96; Aa vs. AA: OR = 0.59, 95 % CI = 0.39-0.88; aa vs. AA+Aa: OR = 0.80, 95 % CI = 0.64-0.99; Aa+aa vs. AA: OR = 0.57, 95 % CI = 0.37-0.86). The similar results were also found in partial genetic models of Taq1 (a vs. A: OR = 0.88, 95 % CI = 0.79-0.98; aa vs. AA+Aa: OR = 0.84, 95 % CI = 0.73-0.98) and Cdx-2 (Aa vs. AA: OR = 0.80, 95 % CI = 0.66-0.98; Aa+aa vs. AA: OR = 0.79, 95 % CI = 0.65-0.96). Likewise, significant correlation between Bsm1, Taq1 polymorphism and LC risk was detected among Asians. Cdx-2 polymorphism was considered as a protective factor in Caucasians, whereas no association of Apal polymorphism with LC risk was observed in Asians and Caucasians for all genetic models. Conclusion: The results of this meta-analysis suggested that Bsm1, Taq1 and Cdx-2 polymorphism may contribute to lung cancer susceptibility, more studies need be conducted to confirm in the future.

Aim: To evaluate the diagnostic performance of serum AFU for early stage hepatocellular carcinoma (HCC). Methods: Concentration of AFU and AFP were measured in 512 patients. The performance was compared for AFU and AFP alone or in combination. Results: The area under the curve (AUC) for AFU was 0.68, with a sensitivity of 56.1% and specificity of 69.2% at the cut-off value of 24 U/l; whereas the AUC for AFP was 0.83, with a sensitivity of 58.2% and specificity of 85.2% at cut-off value of 20 ng/ml. The AUC of AFU alone or the combination with AFP were lower than that of AFP alone. Conclusion: AFU is a suboptimal biomarker for early detection of HCC.

Colorectal cancer (CRC) is the third most common malignancy and a leading cause of cancer-related death worldwide. GEF-H1 is considered a RhoA-specific guanine nucleotide exchange factor. GEF-H1 upregulation may contribute to cancer cell migration and invasion and tumor progression. However, the expression and role of GEF-H1 in CRC have not yet been elucidated. This study attempted to elucidate how GEF-H1 drives tumor formation, motility, invasion and metastasis in colon cancer (CC). The expression of GEF-H1 in CC tissue microarrays (TMAs) was analyzed by immunohistochemistry (IHC). GEF-H1 was upregulated in CC tissues compared with adjacent non-tumoral tissues. In addition, we found that high GEF-H1 expression correlated with shorter overall survival and distant metastasis. Migration and invasion assays showed that GEF-H1 upregulation increased CC cell motility, invasion and metastasis. In contrast, functional knockdown of GEF-H1 by RNAi rescued the effects caused by GEF-H1 overexpression in CC cells. Overexpression of GEF-H1 re-organized the actin cytoskeleton, with increased punctate paxillin staining and F-actin stress fibers. Furthermore, western blotting showed that RhoA activation triggered by GEF-H1 overexpression caused phosphorylation of its downstream target, MLC2, in CC cells. In summary, the present study revealed that GEF-H1 is upregulated in CC tissues and plays a key role in CC metastasis through the GEF-H1-RhoA-MLC2 signaling pathway.

Background Thyroid stimulating hormone (TSH) suppression therapy after differentiated thyroid carcinoma surgery causes cognitive impairment. However, data on naming difficulties (anomia)—related specific cognitive impairment are lacking. Methods A prospective cohort study was conducted, in which, patients with differentiated thyroid carcinoma and benign thyroid nodules were given oral L-T4 therapy after surgery, after meeting the criteria of TSH suppression therapy and thyroxine replacement therapy, respectively, the patients were continually given l-T4 therapy for 6 and 12 months, and then, the neuropsychological test was performed. Results Of the 255 subjects, 212 cases (83.13%) completed all the tests, including 33 cases in the normal control group (NC group), 110 cases in the TSH suppression therapy group (TS group), and 69 cases in the thyroxine replacement therapy group (TR group). There was no significant difference in background data among the three groups (P > 0.05). The scores of mini-mental state examination, clock drawing test, digit symbol substitution test, personal history, temporal and spatial orientation, digit order relation, visual object recognition, associative learning, and color naming in the TS and TR groups were not significantly different from those in the NC group after 6 and 12 months of L-T4 therapy (P > 0.05); the scores of picture recall, visual recall, comprehension memory, and digit span forward in the TS and TR groups were notably lower than those in the NC group (P