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Autophagy-related genes (ATGs) play critical roles in tumorigenesis and progression in gastric cancer (GC). The present study aimed to identify immune-based prognostic ATGs and verify their functions in tumor immune microenvironment (TIME) in GC. Macrophage infiltration was found to negatively correlate with prognosis in GC patients. After stratifying by infiltration levels of macrophages, we screened The Cancer Genome Atlas and Human Autophagy Database to identify the differentially expressed ATGs (DE-ATGs). Of 1,433 differentially expressed genes between the two groups, seven genes qualified as DE-ATGs. Of these

The impact of diabetes mellitus (DM) on the survival of patients with hepatocellular carcinoma (HCC) is still unclear. The present study aims to draw a firm conclusion in terms of evaluating the impact of DM on the prognosis of HCC after hepatectomy.The pattern of recurrence for HCC was often stratified into early-stage (2 years) and late-stage (≥2 years) recurrence. Because the early-stage recurrence was mainly attributed to aggressive tumor pathological characteristics, patients who recurrence or die within 2 years were excluded. Cumulative overall survival (OS) and recurrence-free survival (RFS) were determined by the method of Kaplan-Meier, and the independent risk factors of OS/RFS were determined by Cox regression analysis.A total of 426 patients were eventually included. The 3- and 5-year OS in patients with and without DM was 83.7%, 55.1%; and 90.9%, 77.4%, respectively. Multivariate analysis showed that DM was an independent risk factor for OS (HR 1.166, 95% CI 1.056-2.036,DM is an independent risk factor for long-term prognosis in patients with HCC. Patients with DM after hepatectomy for HCC, thus, need to actively control DM and closer follow-up.

Background Microsatellite instability, programmed death-ligand 1 and tumor-infiltrating leukocytes are prognostic biomarkers in colorectal cancer but unknown toward familial adenomatous polyposis. Aim To investigate the prognostic and clinicopathological roles of microsatellite instability, programmed death-ligand 1 and tumor-infiltrating leukocytes in familial adenomatous polyposis. Methods Clinical data and paraffin embedded tissues from 45 familial adenomatous polyposis patients were collected. Microsatellite instability was detected by immunohistochemistry and polymerase chain reaction. Programmed death-ligand 1 was detected by immunohistochemistry. Tumor-infiltrating leukocytes comprising CD8+ T cells, M1 and M2 tumor associated macrophages, CD56bright and CD56dim natural killer cells were analyzed using multiple fluorescence immunohistochemistry. Results Microsatellite instability high was noted in 6 samples but not associated with overall survival or progression-free survival. Programmed death-ligand 1 is negative on tumor cells but positive on tumor-infiltrating leukocytes, and positive programmed death-ligand 1 expression on tumor-infiltrating leucocytes is associated with overall survival. Low CD56bright natural killer cell infiltration was associated with longer progression-free survival and was an independent prognostic factor in FAP. Conclusion For familial adenomatous polyposis, microsatellite instability high can be found but has no correlation with prognosis; programmed death-ligand 1 on tumor-infiltrating leukocytes is related with overall survival; CD56bright natural killer cell is an independent prognostic factor associating with longer progression-free survival.

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.

To explore the genetic etiology of a fetus with Cornelia de Lange syndrome type 1.Clinical data of the fetus was collected. Genomic DNA was extracted from amniotic fluid and peripheral blood samples of the parents and subjected to low-depth copy number variant sequencing, whole exome sequencing (WES) and Sanger sequencing. Pathogenicity of the candidate variant was predicted based on the guidelines of American College of Medical Genetics and Genomics (ACMG). Minigene assay was used to assess the effect of the variant on mRNA splicing.WES revealed that the fetus has harbored a heterozygous c.5808+5gGA variant in the intron of the NIPBL gene, which was predicted to affect the mRNA splicing. The same variant was not detected in either parent. The variant was not recorded in ExAC, 1000G and dbSNP databases. Comprehensive analysis showed that the variant was deleterious and may result in skipping of exon 31 during mRNA splicing.The fetus was diagnosed with Cornelia de Lange syndrome type 1. Splicing variant identified by WES may be verified by minigene assay in vitro, which can provide more evidence for the prediction of its pathogenicity.

Background Perfluoroalkyl substances can disrupt hepatic metabolism and may be associated with liver function biomarkers. We examined individual and mixture associations of PFAS on liver function biomarkers in a representative sample of Canadian adults. We explored the potential for effect modification by sex and body mass index, as well as by physical activity level which may attenuate the deleterious effect of PFAS on metabolic disorders. Methods We analyzed data from participants aged 20–74 from the Canadian Health Measures Survey. We used linear regression to examine associations between plasma concentrations of PFOA, PFOS, PFHxS, PFNA, PFDA, and PFUDA on serum concentrations of aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin. We used quantile g-computation to estimate associations with a PFAS mixture for each simultaneous, one-quartile change in PFAS concentrations. Results Each doubling of PFOA, PFOS, PFHxS, or PFNA concentrations was associated with higher AST, GGT, and ALP concentrations. Each doubling of PFOA concentrations was associated with 16.5% (95%CI: 10.4, 23.0) higher GGT concentrations among adults not meeting Canada’s physical activity guidelines vs. 6.6% (95%CI: -1.6, 15.5) among those meeting these guidelines. Sex and BMI also modified some associations, though to a lesser extent. We did not observe associations between ALT and PFOA (1.2% change; 95%CI: -2.5, 4.9), PFOS (2.2% change; 95%CI: -0.8, 5.3), or PFHxS (1.5% change; 95%CI: -0.4, 3.4). We also did not observe consistent associations for PFDA and PFUDA or with total bilirubin. In quantile g-computation models, each simultaneous one-quartile increase in the PFAS mixture was positively associated with AST (7.5% higher; 95%CI: 4.0, 10.4), GGT (9.7% higher; 95%CI: 1.7, 17.0), and ALP (2.8% higher; 95%CI: 0.5, 5.4). Conclusion Higher plasma concentrations of PFOA, PFOS, PFHxS, and PFNA – both individually and as a mixture – were associated with higher serum concentrations of liver function biomarkers. These results contribute to emerging evidence suggesting that higher levels of physical activity appear to be protective against the hepatotoxic effects of PFOA. This work contributes to a growing body of evidence supporting the hepatotoxic effects of PFAS.

The presence of apoptosis inhibition proteins renders the cancer cells resistant to apoptosis, severely compromising the antitumor efficacy of sonodynamic therapy (SDT). Here, an intelligent anticancer nanoplatform based on an Aza-boron-dipyrromethene dye (denoted as Aza-BDY) is elaborately established for ferroptosis augmented SDT through cysteine (Cys) starvation. After endocytosis by tumor cells, Aza-BDY serves as both a ferroptosis inducing agent and a sonosensitizer for tumor treatment. The specific Cys response facilitates the disruption of redox homeostasis and initiation of cellular ferroptosis. Meanwhile, the released sonosensitizer causes efficient SDT and augments ferroptosis under ultrasound irradiation. Detailed in vitro and in vivo investigations demonstrate that the synergistic effect of Cys depletion and singlet oxygen (1 O2 ) generation significantly induces cancer-cell death and suppresses tumor proliferation with a high inhibition rate of 97.5 %. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) We greatly acknowledge the financial support from the National Natural Science Foundation of China (32171391 and 51902336), the Shanghai Science and Technology Program (21010500100), the Basic Research Program of Shanghai Municipal Government (21JC1406002), the Shanghai Rising-Star Program (22QA1403600), the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03), and the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081).

MET exon 14 skipping (METex14) is a validated oncogenic driver in lung cancer and MET tyrosine kinase inhibitors are now available as effective clinical treatments. The majority of known METex14 alterations are typical donor/acceptor splicing or ubiquitination site mutations. Herein, two new METex14 variants were detected in two patients with lung adenocarcinoma by targeted next generation sequencing (NGS). Reverse transcription (RT)-based analysis confirmed that these mutations led to MET exon 14 skipping. Our analysis provided evidence for possible targeted therapy options for patients carrying these MET mutations or similar METex14 analogs.

HOXC-AS3 has been reported to be an oncogenic lncRNA in several types of cancer, while its role in ovarian cancer (OC) is unknown. This study aimed to explore the involvement of HOXC-AS3 in OC. The expression levels of HOXC-AS3, mature miR-96, and miR-96 precursor (premature miR-96) in OC and paired non-tumor tissues from 62 OC patients were determined by RT-qPCR. Correlations were analyzed by linear regression. The expression levels of mature miR-96 and miR-96 precursor in OC cells with the overexpression of HOXC-AS3 were determined by RT-qPCR. The roles of HOXC-AS3 and mature miR-96 in regulating the proliferation of OC cells were explored by CCK-8 assay. HOXC-AS3 was upregulated in OC, while mature miR-96 and miR-96 precursor were downregulated in OC. In OC tissues, HOXC-AS3 was inversely correlated with mature miR-96, but not miR-96 precursor. In OC cells, overexpression of HOXC-AS3 reduced the expression levels of mature miR-96, but not miR-96 precursor. Cell proliferation analysis showed that overexpression of HOXC-AS3 resulted in increased cell proliferation, while overexpression of miR-96 suppressed cell proliferation. In addition, overexpression of HOXC-AS3 attenuated the effects of overexpression of miR-96. HOXC-AS3 suppresses the formation of mature miR-96 in OC cells to promote cell proliferation.

During cancer therapy, phagocytic clearance of dead cells plays a vital role in immune homeostasis. The nonapoptotic form of cell death, ferroptosis, exhibits extraordinary potential in tumor treatment. However, the phagocytosis mechanism that regulates the engulfment of ferroptotic cells remains unclear. Here, we establish a novel pathway for phagocytic clearance of ferroptotic cells that is different from canonical mechanisms by using diverse ferroptosis models evoked by GPX4 dysfunction/deficiency. We identified the oxidized phospholipid, 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH), as a key eat-me signal on the ferroptotic cell surface. Enriching the plasma membrane with SAPE-OOH increased the efficiency of phagocytosis of ferroptotic cells by macrophage, a process that was suppressed by lipoprotein-associated phospholipase A2. Ligand fishing, lipid blotting, and cellular thermal shift assay screened and identified TLR2 as a membrane receptor that directly recognized SAPE-OOH, which was further confirmed by TLR2 inhibitors and gene silencing studies. A mouse mammary tumor model of ferroptosis verified SAPE-OOH and TLR2 as critical players in the clearance of ferroptotic cells in vivo. Taken together, this work demonstrates that SAPE-OOH on ferroptotic cell surface acts as an eat-me signal and navigates phagocytosis by targeting TLR2 on macrophages.

Colorectal cancer (CRC) is one of the most prevalent cancers and one of the leading causes of cancer death. Recent studies have provided evidence that N6-methyladenosine (m6A), the most abundant RNA modifications in eukaryote, performs many functions in RNA metabolism including translation, splicing, storage, trafficking and degradation. Aberrant regulation of m6A modification in mRNAs and noncoding RNAs found in CRC tissues is crucial for cancer formation, progression, invasion and metastasis. Further, m6A regulators and m6A-related RNAs may become promising biomarkers, prognosis predictors as well as therapeutic targets. Here, we review the biological and clinical roles of m6A modification in CRC, and discuss the potential of m6A in clinical translation.

Purpose Gastric cancer (GC) is one of the most common and fatal malignancies globally. While microsatellite instability (MSI) index has earlier been correlated with survival outcome in gastric cancer patients, the present study aims to construct a risk-stratification model based on immune-related genes in GC patients with varying MSI status. Results The univariate and multivariate Cox regression analyses identified SEMA7A, NUDT6, SCGB3A1, NPR3, PTH1R, and SHC4 as signature genes, which were used to build the prognostic model for GC patients with microsatellite instability-low (MSI-L) and microsatellite stable (MSS). Whereas, for GC patients with microsatellite instability-high (MSI-H), prognostic model was established with three genes (SEMA6A, LTBP1, and BACH2), based on the univariate and multivariate Cox regression, and Kaplan-Meier survival analyses. Conclusion The prognostic immune-related gene signature identified in this study may offer new targets for personalized treatment and immunotherapy for GC patients with MSI-H or MSI-L/MSS status. Methods The Cancer Genome Atlas (TCGA) and ImmPort databases were used to extract expression data and to explore prognostic genes from the immune-related genes (IRGs), respectively. Univariate and multivariate Cox regression analysis were applied to identify IRGs correlated with patient prognosis. The regulatory network between prognostic IRGs and TFs were performed using R software.

Increased life expectancy and improved perioperative management have resulted in increased utilization of hepatectomy for hepatocellular carcinoma (HCC) among elderly patients. However, individualized model for predicting the surgical safety and efficacy is lacking. The present study aimed to develop a safety and efficacy-associated risk calculator for HCC in the elderly after resection (SEARCHER).From an international multicenter database, elderly patients who underwent curative-intent hepatectomy for HCC were stratified by patient age: 65-69 years, 70-74 years, 75-79 years, and ≥80 years. Short- and long-term outcomes among the 4 groups were compared. Univariate and multivariate analyses of risk factors of postoperative major morbidity, cancer-specific survival (CSS) and overall survival (OS) were performed in the training cohort. A nomogram-based online calculator was then constructed and validated in the validation cohort.With increasing age, the risk of postoperative major morbidity and worse OS increased (P = 0.001 and 0.020), but not postoperative mortality and CSS (P = 0.577 and 0.890) among patients across the 4 groups. Based on three nomograms to predict major morbidity, CSS and OS, the SEARCHER model was constructed and made available at https://elderlyhcc.shinyapps.io/SEARCHER. The model demonstrated excellent calibration and optimal performance in both the training and validation cohorts, and performed better than the several commonly-used conventional scoring and staging systems of HCC.With higher potential postoperative major morbidity and worse OS as patients age, the decision of whether to perform a hepatectomy for HCC needs to be comprehensively considered in the elderly. The proposed SEARCHER model demonstrated good performance to individually predict safety and efficacy of hepatectomy in elderly patients with HCC.

Objective Whether preoperative serum carbohydrate antigen 19–9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified. Methods Consecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale. Results A total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5–62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724). Conclusions Preoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

To improve the therapeutic effect of a hydrogel on damaged tissue, a series of hydroxybutyl chitosan (HBC) and poly(sulfobetaine methacrylate) (PSBMA) composite hydrogels (HBC-PSB) with thermosensitivity, self-healing, antibiofouling, and synergistic antibacterial activity are prepared by mechanical blending. The electrostatic interaction among PSBMA and hydrophobic association among HBC are the main drive force to form a full physically crosslinked hydrogel. HBC can avoid the aggregation and precipitation of PSBMA caused by intermolecular strong association. Meanwhile, the existence of the PSBMA network can promote the sol-gel transition of HBC. Due to the reversible physical crosslinking, the HBC-PSB hydrogel shows excellent self-healing behaviors, and can be stored as dry powder. Intriguingly, the composite hydrogel has good synergistic antibacterial performance

The objective of this study was to predict the preoperative pathological grading and survival period of Pseudomyxoma peritonei (PMP) by establishing models, including a radiomics model with greater omental caking as the imaging observation index, a clinical model including clinical indexes, and a combined model of these two. A total of 88 PMP patients were selected. Clinical data of patients, including age, sex, preoperative serum tumor markers [CEA, CA125, and CA199], survival time, and preoperative computed tomography (CT) images were analyzed. Three models (clinical model, radiomics model and combined model) were used to predict PMP pathological grading. The models’ diagnostic efficiency was compared and analyzed by building the receiver operating characteristic (ROC) curve. Simultaneously, the impact of PMP’s different pathological grades was evaluated. The results showed that the radiomics model based on the CT’s greater omental caking, an area under the ROC curve ([AUC] = 0.878), and the combined model (AUC = 0.899) had diagnostic power for determining PMP pathological grading. The imaging radiomics model based on CT greater omental caking can be used to predict PMP pathological grading, which is important in the treatment selection method and prognosis assessment.

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.

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.

Clinical studies and trials have shown that oxytocin can effectively reduce postpartum bleeding, whether by intramuscular (IM) injection or intravenous (IV) injection. These two methods are widely used in the prevention and treatment for the third stage of childbirth. However, it is unclear whether the subtle differences between the mode of these routes have any effect on maternal outcomes. To systematically evaluate the efficacy and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labor after vaginal birth. Computerized retrieval of PubMed, the Cochrane Library, Web of Science, Embase, and ClinicalTrials.gov was conducted to collect randomized controlled trials (RCT) on the effects of IM and IV oxytocin on the third stage of labor. After independent literature screening, data extraction and evaluation of the bias risk of included studies by two evaluators, RevMan 5.3 software was used for a meta-analysis. Six studies with 7734 women were included in this study. Meta-analysis results showed that: the severe postpartum hemorrhage (PPH) rate [risk ratio (RR) 1.54, 95% confidence interval (95% CI) 1.08–2.20, P = 0.02], PPH rate (RR 1.31, 95% CI 1.11–1.55, P = 0.001), incidence of blood transfusion (RR 2.30, 95% CI 1.35–3.93, P = 0.002) and the need of manual removal of placenta (RR 1.44, 95% CI 1.05–1.96, P = 0.02) for IM group were higher than IV group, but there were no significant differences in the use of additional uterotonics (P = 0.31) and the incidence of serious maternal morbidity and adverse effects between two groups. None of the included studies reported maternal death. For clinical practice, intravenous injection oxytocin 10 IU may be a good, safe option in the management of the third stage of labor. Medical conditions, available resources, adverse effects, and women’ s preferences should also be considered. If an IV line is already in place at delivery, IV administration may be preferable to IM injection.

BACKGROUND: Although sex disparities in hepatocellular carcinoma (HCC) incidence have been well described, there are limited data examining sex disparities in HCC prognosis. AIM: To characterize sex differences in HCC presentation and prognosis METHODS: We performed a retrospective study of consecutive patients (n=1110, 23.5% women) diagnosed with HCC between 2008–2017 at two U.S. health systems. We used Cox proportional hazard and multivariable logistic regression models to identify factors associated with overall survival, early tumor detection, and response to HCC treatment (per the modified Response Evaluation Criteria in Solid Tumors [mRECIST] criteria). RESULTS: Women were older at HCC diagnosis (mean 62.5 vs 59.2 years, p

Background Resistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet. Methods Chemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α. Results In this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin. Conclusion In conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies with few effective treatment options all around the world. The efficacy of the arisen immune checkpoint therapy is still uncertain due to local immunosuppression. In order to further overcome T cell suppression in the tumor immune microenvironment while promoting the immune response of antigen-presenting cells, a biointerfacing antagonizing T-cell inhibitory nanoparticles (BAT NPs) has been developed by cloaking platelet membrane on the PLGA microsphere surface to load T-cell immunoglobulin domain and mucin domain-3 antibodies (anti-TIM-3) as well as PD-L1. Notably, in addition to activating the proliferation and migration of T cells, the contained anti-TIM-3 can cooperate with PD-L1 checkpoint blockade to exert therapeutic effects. Furthermore, the components of BAT NPs like anti-TIM-3 and platelet can act together for collagen deposition in tumor starvation treatment. Thus, a novel targeting therapeutic strategy that can effectively reverse the immune-inhibiting microenvironment is effectively applied to PD-L1 checkpoint combination therapy. Such therapeutic effect can subsequently activate the effector T lymphocytes and antigen presentation of dendritic cells as well as the polarization of M1-type macrophages. Last, the study presented the synergistic effect of immune therapeutic adjuvants and BAT NPs components in achieving tumor inhibition and prolonging tumor-burden survival.

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.

There appears to be a paucity of knowledge about the biomechanics of locking plates for the fixation of metacarpal shaft fractures. A thorough understanding of the biomechanics of locking plates is needed to apply them correctly, optimize outcomes, and avoid complications. The purpose of this study is to investigate the biomechanics of the fixation of metacarpal fractures using locking plate-screw constructs with different numbers of screws.The difference in the number of screws in the locking plate influenced the biomechanical outcome of the metacarpal fracture.Finite element models of third metacarpal fractures with locking plate-screw constructs were established, and the magnitude and distribution of their stresses and displacements were investigated when a vertical load of 100N was applied.For the metacarpal fracture with a locking plate and screws, the stress in the metacarpal was largely shared by the plate-screw construct. For the plate-screw construct, the stress is concentrated in the area close to the fracture line, and the 6-screw Group has the lowest failure risk since it has the lowest plate stress and the second-lowest screw stress. The implant-bone construct with 8 screws has better biomechanical stability because of minimal displacement, but increased stress on both the metacarpal bone and the screws, leading to increased failure rates.The stresses in the metacarpal were mostly shared by the plate-screw constructs and the screws closest to the fracture line were the most likely to break or loosen. For the implant-bone constructs, the locking plate with 2 screws was the most vulnerable to break or loosen, whereas the locking plate with 6 screws was the least likely to break or loosen. The implant-bone construct with 8 screws had better biomechanical stability, but the stresses in both the metacarpal and the screws were increased, which increased the risk of failure.IV, basic science study.

Maternal stress has been associated with poor birth outcomes, including preterm birth, infant mortality, and low birth weight. Bone development disorders in the embryo as a result of maternal stress are believed to be mediated through oxidative stress damage. Various species of free radicals, such as alkoxyl radicals, can be formed through endogenous redox response or exogenous stimuli in the womb and transmitted to embryos. Yet, whether these free radicals lead to abnormal fetal bone development is unclear. Here, we demonstrate prenatal bone growth retardation and ferroptosis-related signals of chondrocytes were induced by classic alkoxyl radical generators. We also show that alkoxyl radicals lead to significant accumulation of oxidized phospholipids in chondrocytes, through the iron-mediated Fenton reaction in embryos. We further demonstrate a role for the lipid peroxidation end product, 4-HNE, which forms adducts with the pivotal chondrogenesis transcription factor SOX9, leading to its degradation, therefore dampening chondrogenesis. Our data define a critical role for phospholipid peroxidation in alkoxyl radicals-evoked abnormal chondrogenesis, and pinpoint it being a precise target for treating oxidative stress-related bone development disorders.

PurposeThis study aimed to explore the value of preoperative ultrasonography (US) in evaluating the peritoneal cancer index (PCI) of pseudomyxoma peritonei (PMP).MethodsAn ultrasound examination was performed on 59 patients with PMP before surgery, and the ultrasound PCI was evaluated. The accuracy of ultrasound PCI score was evaluated with the surgical PCI score as the gold standard.ResultsThe preoperative ultrasound PCI was compared with the surgical PCI. The Spearman correlation coefficient of the total PCI score was 0.608 (P 20%) was concentrated mainly in areas 2 and 4–8 for 2 points, and underestimation (ConclusionThe ultrasound examination can be used to score the preoperative PCI, judge the severity, and predict the prognosis in patients with PMP.

Background The imbalance of expression of microRNA-802 may have a significant place in tumor progression. However, the bio-function of epithelial ovarian cancer cells remains unclear. Therefore, we setup this study to explore the pathogenesis of epithelial ovarian cancer based on microRNA-802. Methods RT-qPCR analysis was used to measure the expression level of microRNA802 and YWHAZ in epithelial ovarian cancer. CCK-8, colony formation, flow cytometry and transwell assay were used to detect the effects of microRNA-802 on cell proliferation, apoptosis, invasion and migration. Target gene prediction and screening, luciferase reporting experiments were applied to validate the downstream target genes of microRNA-802. The effects of microRNA-802 on the expression of YWHAZ and its biological effects were measured by Western blotting and RT-qPCR. Results Compared with normal cell lines and tissues, the expression level of microRNA-802 was obviously down-regulated in cancer related cell lines and tissues. Overexpression of microRNA-802 could obviously inhibit the invasion and proliferation and induce apoptosis. In addition, YWHAZ was the binding target protein of miR-802 for epithelial ovarian cancer cells. YWHAZ was obviously up-regulated in human epithelial ovarian cancer cells, and YWHAZ was negatively correlated with the expression of miR-802. YWHAZ can partly eliminate the inhibitory effect caused by overexpression of miR-802 on growth and metastasis of epithelial ovarian cancer cells. Conclusion miR-802 can regulate the occurrence and development of epithelial ovarian cancer by targeting YWHAZ.

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.

Male patients with multiple morphological abnormalities of the sperm flagella (MMAF) are infertile and exhibit absent, short, coiled, bent and/or irregular sperm flagella. Mutations in the SPEF2 gene reduce sperm motility and cause sperm tail defects in animal models and humans. In the present study, we performed a genetic analysis on an MMAF patient and identified novel biallelic mutations in the SPEF2 gene. The biallelic mutations were confirmed by Sanger sequencing and in silico analysis revealed that, these variations were deleterious. The expression of truncated SPEF2 protein was reduced significantly in the patient's spermatozoa. The spermatozoa harbored biallelic mutations and showed severe ultrastructural defects in the axoneme and mitochondrial sheath. Our data suggest that biallelic mutations in SPEF2 can cause severe sperm flagellum defects, thus providing a novel candidate genetic pathogen for the human MMAF phenotype.

In this report, we designed and synthesized a series of cobalt(II)-Schiff base complexes (CoSBC) with competent MEK1 (mitogen-activated protein kinase kinase−1) inhibitory activity. Based on our previous report, the CoSBC exhibited high binding affinity with MEK1 protein. To further explore metal complexes as MEK1 inhibitors, a series of transition metals and ligands were employed to build a library of various metal Schiff base complexes. The MEK inhibition assays revealed that only CoSBC exhibited obvious inhibitory activity, complex 2b showed the best inhibition both in BRaf (B-rapidly accelerated fibrosarcoma)/MEK1 and MEK1/ERK2 (extracellular signal-regulated kinases-2) cascading (IC50 is 1.988 ± 0.14 μM and 1.589 ± 0.054 μM respectively). In addition, homogeneous time-resolved fluorescence test method was used to prove that CoSBC as ATP-noncompetitive MEK1 inhibitor. MEK kinase selectivity assay indicated that CoSBC can selectively inhibit MEK1/2 kinases rather than other MAPKs (mitogen-activated protein kinases) family kinases. Moreover, the interaction mode of 2b with MEK1 protein has been demonstrated by computer aided drug design.

A series of novel aminopyrimidine and diaminopyrimidine derivatives were designed and optimized to improve their potency and permeability relative to lead compound 1 (IC50 = 37.4 μM), which was discovered in a previous virtual screening. The potency of the optimized compound, 13g (IC50 = 1.4 μM), was 26-fold greater than that of 1 based on a fluorescence resonance energy transfer assay, and a parallel artificial membrane permeability assay suggested that it could pass through the blood-brain barrier. Additionally, several compounds containing selenium showed good potencies and deserve further investigation as anti-Alzheimer's agents.

Background and aims Metabolomics serves as an important tool in distinguishing changes in metabolic pathways and the diagnosis of human disease. Hepatocellular carcinoma (HCC) is a malignance present of heterogeneous metabolic disorder and lack of effective biomarker for surveillance and diagnosis. In this study, we searched for potential metabolite biomarkers of HCC using tissue and serum metabolomics approach. Methods A total of 30 pairs of matched liver tissue samples from HCC patients and 90 serum samples (30 HCC patients, 30 liver cirrhosis patients, and 30 healthy individuals) were assessed. Metabolomics was performed through ultra performance liquid chromatography-mass spectrometry in conjunction with multivariate and univariate statistical analyses. Results A total of six differential metabolites including chenodeoxycholic acid (CDCA), glycocholic acid (GCA), LPC20:5, LPE18:0, succinyladenosine and uridine were present in HCC tissue and serum samples. CDCA, LPC20:5, succinyladenosine and uridine were used to construct a diagnostic model based on logistic regression. The four-metabolite panel discriminated HCC from liver cirrhosis with an AUC score of 0.938, sensitivity of 93.3% and specificity of 86.7%. For all HCC and cirrhosis patients, the diagnostic accuracy increased to 96.7% and 90.0%, respectively. Conclusion The combination of CDCA, LPC20:5, succinyladenosine and uridine can be used as a biomarker panel to improve HCC sensitivity and specificity. This panel significantly benefits HCC diagnostics and reveals new insight into HCC pathogenesis.

Rationale: Colorectal cancer (CRC) is a malignant tumor with the third highest morbidity rate among all cancers. Driven by the host's genetic makeup and environmental exposures, the gut microbiome and its metabolites have been implicated as the causes and regulators of CRC pathogenesis. We assessed human fecal samples as noninvasive and unbiased surrogates to catalog the gut microbiota and metabolome in patients with CRC. Methods: Fecal samples collected from CRC patients (CRC group, n = 50) and healthy volunteers (H group, n = 50) were subjected to microbiome (16S rRNA gene sequencing) and metabolome (gas chromatography-mass spectrometry, GC-MS) analyses. The datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches. Results: Fecal metabolomic analysis led to the identification of 164 metabolites spread across 40 metabolic pathways in both groups. In addition, there were 42 and 17 metabolites specific to the H and CRC groups, respectively. Sequencing of microbial diversity revealed 1084 operational taxonomic units (OTUs) across the two groups, and there was less species diversity in the CRC group than in the H group. Seventy-six discriminatory OTUs were identified for the microbiota of H volunteers and CRC patients. Integrated analysis correlated CRC-associated microbes with metabolites, such as polyamines (cadaverine and putrescine). Conclusions: Our results provide substantial evidence of a novel interplay between the gut microbiome and metabolome (i.e., polyamines), which is drastically perturbed in CRC. Microbe-associated metabolites can be used as diagnostic biomarkers in therapeutic explorations.

Cancer metastasis is the main cause for the high mortality in breast cancer patients. In this work we developed a polymer POEG-st-Pmor for targeted co-delivery of IL-36γ expression plasmid and doxorubicin (Dox) to lung metastasis of breast cancer. The polymer readily formed micelles that were effective in loading Dox and simultaneously forming complexes with IL-36γ plasmid. Interestingly, particles co-loaded with Dox and plasmid was significantly smaller and more stable than the particles loaded with Dox only. Gene transfection in both lungs and s.c. tumors was significantly higher with our polymer compared to PEI. In addition, the Dox + IL-36γ/POEG-st-Pmor not only could bring improved anti-metastatic effect but synergistically enhance the type I immune response by increasing the IFN-γ positive CD4+ and CD8+ T cells and simultaneously decreasing the immunosuppressive myeloid-derived suppressor cells in the lung. POEG-st-Pmor may represent a simple and effective delivery system for an optimal chemo-gene combination therapy.

Background/Aims: Cullin 4A (CUL4A) is vital in cell survival, development, growth and cell cycle, it plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of CUL4A expression in colorectal cancer is unknown; in particular, the prognostic value of CUL4A combined with TP53 expression has not been explored. Methods: We analyzed the expression of CUL4A in both public database (Oncomine) and 180 cases of colorectal cancer and paired normal tissues by real-time polymerase chain reaction and western blotting. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of CUL4A in CRC proliferation and metastasis in vitro and in vivo. Markers of epithelial to mesenchymal transition (EMT) were evaluated by western blotting. Immunohistochemistry (IHC) was used to analyse the relationship between CUL4A expression and E-cadherin expression. Results: CUL4A and TP53 protein expression was significantly higher in cancerous tissues compared to normal tissues. Significant correlation between CUL4A and TP53 expression was observed. CUL4A expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Interestingly, patients with tumors that had both CUL4A overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P < 0.001). Multivariate analysis showed that patients with both CUL4A+ and TP53+ positive tumors had extremely poor OS and DFS. Knockdown of CUL4A by a short interfering RNA (siRNA) significantly suppressed the progression of EMT, proliferation, migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. ZEB1 silencing blocked CUL4A-driven these processes. Conclusion: CUL4A expression correlated positively with the prognosis of colorectal cancer. Mechanistically, ZEB1 was confirmed to mediate the function of CUL4A in regulating the EMT. The assessment of both CUL4A and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

We read with great interests the study by Dr. John et al. In this retrospective study using national data on USA Veterans, multivariate competing risk analysis identified that male gender was independently associated with a higher risk of death/transplantation, and liver-related death/transplantation for patients with primary biliary cholangitis (PBC) and cirrhosis.

The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for intrahepatic cholangiocarcinoma (ICC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes.A total of 711 consecutive patients who underwent curative liver resection for hepatitis B virus-related ICC were retrospectively analyzed. 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) were analyzed.The 1-, 3-, and 5-year OS rates were 67.6%, 42.5%, and 33.2% in wide RMMVI (-), 58.0%, 36.1%, and 26.5% in narrow RMMVI (-), 51.0%, 27.0%, and 24.3% in wide RMMVI (+), and 39.0%, 20.4% and 14.3% in narrow RMMVI (+) (Combined analysis of RM and MVI can better stratify the risks of postoperative death and recurrence in patients with HBV-related ICC, which may help subsequent adjuvant therapy and closer follow-up.

Postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC.The data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity.Among 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P 0.001) and TTR (median: 19.8 vs. 46.1 months; P 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126-1.451; P 0.001) and recurrence (1.187; 1.058-1.331; P = 0.004).This large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.

Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6 months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6 months following resection. Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6 months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves. Independent factors associated with death within 6 months of surgery included age, Child–Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542–0.748). An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6 months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.

People are often concurrently exposed to numerous chemicals. Here we sought to leverage existing large biomonitoring datasets to improve our understanding of multi-chemical exposures in a population. Using nationally-representative data from the 2012–2015 Canadian Health Measures Survey (CHMS), we developed Exposure Load, a metric that counts the number of chemicals measured in people above a defined concentration threshold. We calculated Exposure Loads based on five concentration thresholds: the analytical limit of detection (LOD) and the 50th, 75th, 90th and 95th percentiles. Our analysis considered 44 analyte biomarkers representing 26 chemicals from the 2012–2015 CHMS; complete biomarker data were available for 1858 participants aged 12–79 years following multiple imputation of results that were missing due to sample loss. Chemicals may have one or more biomarkers, and for the purposes of Exposure Load calculation, participants were considered to be exposed to a chemical if at least one biomarker was above the threshold. Distributions of Exposure Loads are reported for the total population, as well as by age group, sex and smoking status. Canadians had an Exposure Load between 9 and 21 (out of 26) when considering LOD as the threshold, with the majority between 13 and 18. At higher thresholds, such as the 95th percentile, the majority of Canadians had an Exposure Load between 0 and 3, although some people had an Exposure Load of up to 15, indicating high exposures to multiple chemicals. Adolescents aged 12–19 years had significantly lower Exposure Loads than adults aged 40–79 years at all thresholds and adults aged 20–39 years at the 50th and 75th percentiles. Smokers had significantly higher Exposure Loads than nonsmokers at all thresholds except the LOD, which was expected given that tobacco smoke is a known source of certain chemicals included in our analysis. No differences in Exposure Loads were observed between males and females at any threshold. These findings broadly suggest that Canadians are concurrently exposed to many chemicals at lower concentrations and to fewer chemicals at high concentrations. They should assist in identifying vulnerable subpopulations disproportionately exposed to numerous chemicals at high concentrations. Future work will use Exposure Loads to identify prevalent chemical combinations and their link with adverse health outcomes in the Canadian population. The Exposure Load concept can be applied to other large datasets, through collaborative efforts in human biomonitoring networks, in order to further improve our understanding of multiple chemical exposures in different populations.

The safety and feasibility of laparoscopic versus open liver resection (LLR vs. OLR) associated lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) are still controversial. The aim of the present study was to compare short and long-term outcomes. We reviewed data on 43 consecutive patients who underwent curative liver resection with associated lymphadenectomy for ICC. The short-term outcomes including postoperative morbidity and mortality, and the long-term outcomes including overall survival (OS) and recurrence-free survival (RFS) were compared. The median survival, 1- and 3-year OS in LLR and OLR groups were 22.5 months, 76.9% and 47.1%, and 12.1 months, 43.1% and 20.0%, respectively. The median survival, 1- and 3-year RFS in LLR and OLR groups were 10.3 months, 27.8% and 0%, and 8.1 months, 24.0% and 4.0%, respectively. The results showed that LLR obviously reduced intraoperative blood loss (median, 375 vs. 500ml, p = 0.016) and postoperative hospital stay (median, 6 vs. 9 days, p = 0.016). Moreover, there was no significant difference in short-term outcomes including postoperative morbidity (including wound infection, bile leakage, liver failure and pneumonia) and mortality within 30 days, and long-term outcomes including OS and RFS between LLR and OLR. (all p > 0.05). Multivariate analysis showed that CA19-9 level, TNM stage, and tumor differentiation were independent risk factors for OS and RFS. LLR for ICC is safety and feasibility compared with OLR. The advantage of LLR was to reduce intraoperative blood loss and postoperative hospital stay.

To explore the clinical and genetic characteristics of a patient with 17-hydroxylase/17,20-lyase deficiency.The patient was infertile without contraception. Laboratory examination showed her chromosomal karyotype to be 46, XX. DNA sequencing was performed to detect variants of CYP17A1 gene in the patient and her family members.Sanger sequencing revealed that the patient has carried homozygous variant c.1486CT in the exon 8 of the CYP17A1 gene, which resulted in substitution of arginine by cysteine (p.Arg496Cys). Her family members were all heterozygotes for the same variant.Homozygous variant of the CYP17A1 gene c.1486CT probably underlay the 17-hydroxylase deficiency in this patient. Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.

Aim: Advanced esophageal cancer has limited therapeutic options and a poor outcome. The efficacy of immunotherapy, as the first-line treatment of advanced esophageal cancer, is uncertain. Results: A stage IV advanced esophageal cancer patient received the first-line treatment with a combination of pembrolizumab and chemotherapy. Partial response (PR) was achieved after three cycles, and the efficacy was evaluated as stable after six cycles of immunochemotherapy and two cycles of maintenance monotherapy. Immune-related adverse events (irAEs) were not obvious. The patient was followed up till November 2019 when he died of gastrointestinal hemorrhage. Conclusion: The combination of an immune checkpoint inhibitor and chemotherapy is effective and safe for the initial treatment of advanced esophageal cancer. To confirm the evidence from this case, larger clinical trials are required in the future.