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Xiao-long Wu,1,* Zhi-yu Li,1,* Xin-yu Bi,1 Hong Zhao,1 Jian-jun Zhao,1 Jian-guo Zhou,1 Yue Han,2 Zhen Huang,1 Ye-fan Zhang,1 Jian-qiang Cai1 1Department of Hepatobiliary Surgery, 2Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China *These authors contributed equally to this work Background: Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI. Patients and methods: This study included 330 patients with HCC. The clinical parameters were reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and rs7768538, were genotyped using the MassARRAY system. Results: The rs3997872, rs7453920, and rs7768538 genotypes were found to be significantly associated with OS (P

Aim: We conducted network meta-analysis to assess cardiovascular toxicity of anaplastic lymphoma kinase-tyrosine kinase inhibitors ( ALK -TKIs). Materials & methods: Eleven articles involving 2855 patients and six interventions including crizotinib, alectinib, ceritinib, lorlatinib, brigatinib and chemotherapy were analyzed. Results: No significant difference was observed in overall cardiovascular risk among ALK -TKIs. Subgroup analysis showed that for cardiac toxicity, crizotinib and alectinib were more likely to cause myocardial rhythm abnormalities. Crizotinib and ceritinib had a higher risk of Q-T prolongation than chemotherapy. For vascular toxicity, crizotinib and ceritinib had a higher risk of thrombotic events than brigatinib. Crizotinib and lorlatinib were more likely to cause blood pressure abnormalities. Conclusion: Clinicians should carefully monitoring cardiovascular events when ALK -TKIs used in NSCLCs patients with baseline cardiovascular diseases.

Purpose: Microglia-like cells derived from stem cells (iMG) provide a plentiful cell source for studying the functions of microglia in both normal and pathological conditions. Our goal is to establish a simplified and effective method for generating iMG in a precisely defined system. Additionally, we aim to achieve functional maturation of iMG through coculture with retinal organoids., Methods: In this study, iMG were produced under precisely defined conditions. They were subjected to LPS and poly IC stimulation. Additionally, we examined distinct phenotypic and functional variances between iMG and HMC3, a commonly used human microglia cell line. To investigate how the retinal cell interaction enhances microglial properties, iMG were cocultured with retinal organoids, producing CC-iMG. We performed RNA sequencing, electrophysiological analysis, and transmission electron microscope (TEM) to examine the maturation of CC-iMG compared to iMG., Results: Our results demonstrated that iMG performed immune-responsive profiles closely resembling those of primary human microglia. Compared to HMC3, iMG expressed a higher level of typical microglial markers and exhibited enhanced phagocytic activity. The transcriptomic analysis uncovered notable alterations in the ion channel profile of CC-iMG compared to iMG. Electrophysiological examination demonstrated a heightened intensity of inward- and outward-rectifying K+ currents in CC-iMG. Furthermore, CC-iMG displayed elevated numbers of lysosomes and mitochondria, coupled with increased phagocytic activity., Conclusions: These findings contribute to advancing our understanding of human microglial biology, specifically in characterizing and elucidating the functions of CC-iMG, thereby offering an in vitro microglial model for future scientific research and potential clinical applications in cell therapy.

Objectives: To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model. Methods: This was a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method,patients were randomly divided into a model group( n =166) and a validation group( n =41) according to an 4︰1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M (IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (rang: 25.0~81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the risk of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,followed by internal and external validation of the model. Results: Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT,D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set,and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P =0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806,suggesting that the model had a good generalization prediction ability. Conclusions: The levels of ALT,D-dimer,and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Wang, Cai, Li, Yu, Wu, Meng, Wang, Yin, Wu, Huang, Li and Guan.)

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group, n =65) and an operation after receiving second-line chemotherapy group (second-line group, n =42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ 2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time( M (IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P >0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant ( P =0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant( P =0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant( P =0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant( P =0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS ( HR =1.809,95% CI : 1.067 to 3.067, P =0.028) and OS( HR =2.751,95% CI : 1.317 to 5.747, P =0.007). Second-line chemotherapy was not an independent prognostic factor for PFS ( HR =0.945, 95% CI :0.570 to 1.567, P =0.828) and OS ( HR =0.866,95% CI : 0.468 to 1.602, P =0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95% CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC ( P <0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% ( P =0.015), 89.3% and 86.5% ( P =0.732), 30.5% and 65.6% ( P =0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Purpose: To explore the feasibility and safety of centrally located hepatocellular carcinoma (CL-HCC) treated by narrow-margin resection combined with intraoperative electron radiotherapy (IOERT)., Methods and Materials: From November 2009 to November 2016, 37 consecutive patients were treated with IOERT as adjuvant treatment during narrow-margin resection for CL-HCC. Long-term outcomes, adverse events for surgery, and acute and chronic toxicities were analyzed., Results: The median follow-up was 57.82 months (range, 3.75-111.41 months). A total dose of 15 Gy (range 12 to 17Gy) (prescribed at the 90% isodose) was delivered with a 0.9cm (range 0.8-1.2 cm) median treatment depth targeting the narrow-margin. The 1-year, 3-year and 5-year OS rates were 91.39%, 88.34% and 88.34%, respectively. The 1-year, 3-year and 5-year DFS rates were 80.81%, 68.59% and 54.17%, respectively. In the univariate analysis, none of the treatment characteristics were predictive of overall survival. Fifteen (40.5%) patients suffered from a recurrence event. No patient had marginal recurrence. The 1-year, 3-year and 5-year intrahepatic recurrence rates were 19.75%, 25.92% and 39.58%, respectively. The 1-year, 3-year and 5-year extrahepatic recurrence rates were 2.7%, 5.95% and 9.87%, respectively. There was no 30-day surgical-related death. Three patients had grade 4, and 28 patients had grade 3 alanine aminotransferase (ALT) levels, and seven patients had grade 4, and 30 patients had grade 3 aspartate transaminase (AST) levels. All of them returned to normal within four months. There was no acute radiation-induced liver injury during follow-up. There were no acute or chronic toxicities associated with IOERT., Conclusion: IOERT for narrow-margin CL-HCC may achieve good long-term survival outcomes, without significantly increasing acute and chronic toxicities. An IOERT dose of 15Gy may be the safest and most feasible. IOERT might be considered as an adjuvant therapy for CL-HCC patients with a narrow-margin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Zhai, Li, Cai, Ma, Wang, Wu, Wang, Wu, Zeng, Chen, Li, Wu and Feng.)

Currently, the reports on esophageal endoscopic submucosal dissection (ESD) assisted by traction with a snare are rare. Because a snare is a commonly used endoscopic accessory and is easily available, its application in mucosal traction is worth exploring. The present study aims to evaluate the safety and effectiveness of snare-endoclip traction-assisted ESD for esophageal intraepithelial neoplasia. Cases of esophageal intraepithelial neoplasia resected using ESD in the Digestive Endoscopy Center of Guangzhou Nanfang Hospital, China from June 2013 to March 2019 were retrospectively analyzed. The procedure of snare-endoclip traction-assisted ESD was compared with nontraction-assisted ESD by using a propensity score matching analysis. Operation time, en bloc and R0 resection, intra- and postoperative complications, and surgery-related costs were mainly evaluated. Overall, 99 cases of esophageal intraepithelial neoplasia under tissue biopsy were included in the present study. Further, 22 exact matched pairs were obtained. There were no differences in en bloc and R0 resection rates, intra- and postoperative complications, and costs of disposable surgical accessories between the traction group and the nontraction group. However, median operation time showed a significant difference: traction group, 50.0 min (range, 20-100 min); nontraction group, 70.0 min (range, 35-133 min), P=0.012. In conclusion, snare-endoclip traction-assisted ESD for esophageal intraepithelial neoplasia was safe and shortened operation time in the study, thereby improving the efficiency of ESD. Despite the additional use of a snare and endoclips for traction, the total costs of endoscopic accessories seemed not to be increased., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The low resection and high recurrence rates in hepatocellular carcinoma (HCC) are the major challenges to improving prognosis. Neoadjuvant and conversion therapies are underlying strategies to overcome these challenges. To date, no guideline or consensus has been published on the neoadjuvant and conversion therapies in HCC. Recent studies showed that neoadjuvant therapy for resectable HCC and conversion therapy for unresectable HCC are safe, feasible, and effective. Neoadjuvant and conversion therapies have the following advantages in treating HCC: R0 resection with sufficient volume of future liver remnant, relatively simple operation, and wide applicability. Therefore, it was necessary to conduct a widely accepted consensus among the experts in China who have extensive expertise and experience in treating HCC using neoadjuvant and conversion therapies, which is important to standardize the application of neoadjuvant and conversion therapies for the management of HCC. The strategies of neoadjuvant therapy include the selection of the eligible patients, therapy regimen, cycles, effect evaluations, and multidisciplinary treatment. The management of patients with insufficient volume of future liver remnant and patients who cannot achieve R0 resection is the key to the strategies of conversion therapy. Here, we present the resultant evidence- and experience-based consensus to guide the application of neoadjuvant and conversion therapies in clinical practice., Competing Interests: Conflict-of-interest statement: The author has nothing to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of "bacteria, poison and inflammation" and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1β, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Yin, Li, Cai, Yang, Huang, Zheng, Xiong, Yu, Lu, Wang, Guan and Chen.)

Hepatocellular carcinoma is a serious disease that threatens the health of Chinese people. At present,various treatments for hepatocellular carcinoma have their own advantages and disadvantages,which are suitable for its specific individual patient. This article makes a brief review about the importance of standardized treatment for hepatocellular carcinoma. Meanwhile,it should be noticed that standardized staging system is the prerequisite for making a reasonable treatment plan,standardized pathological diagnosis is the basis of comprehensive treatment,standardized treatment is the key to the efficacy,and the multidisciplinary team is the organizational basis for standardized treatment.

Objective: The aim of this study was to determine whether adjuvant chemotherapy (AC) provides a survival benefit in patients with nonmetastatic poorly differentiated colorectal neuroendocrine carcinomas (CRNECs) following resection., Background: There is little evidence to support the association between use of AC and improved overall survival (OS) in patients with CRNECs., Methods: Patients with resected non-metastatic CRNECs were identified in the National Cancer Database (2004-2014). Inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS of patients in different treatment groups., Results: A total of 806 patients diagnosed between 2004 and 2014 met the study entry criteria. Of these, 394 patients (48.9%) received AC. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation [57.4 (interquartile range, IQR, 14.8-153.8) vs 38.2 (IQR, 10.4-125.4) months; P = 0.007]. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit [hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.64-0.84; P < 0.001]. The results were consistent across subgroups stratified by pathologic T stage, pathologic N stage, and surgical margin status. Subgroup analysis according to tumor location demonstrated improved OS in the adjuvant therapy cohort among patients with left-sided neuroendocrine carcinomas (HR, 0.55; 95% CI, 0.44-0.68), but not in those with right-sided disease (HR, 0.89; 95% CI, 0.74-1.07)., Conclusions: Patients with nonmetastatic CRNECs may derive survival benefit from AC. These findings support current guidelines recommending AC in patients with poorly differentiated neuroendocrine carcinomas in the colon and rectum. Efforts in education and adherence to national guidelines for NECs are needed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The complete resection of primary duodenal adenocarcinoma (PDA) offers a chance for a cure, but the clinical and pathological characteristics of survivors have not been well studied., Methods: Patients with stage I-III PDA who underwent surgical resection between 2013 and 2018 were identified retrospectively and followed until December 2019. All patients are from the Cancer Hospital Chinese Academy of Medical Sciences. The clinical and pathological information of the patients, such as age, gender, tumor location, operative procedure, pathologic features, TNM stage, common presenting symptoms, lymph node dissection status, serum tumor markers, etc., was collected in detail. The KaplanMeier method and a Cox proportional hazards model were used for the survival analysis., Results: In total, 85 patients with PDA were eligible for this study. Among these patients, 48 were male (56.5%), 37 were female (43.5%), the median age was 59 (range, 22-79) years, 44 (51.8%) patients were aged <60 years, and 41 (48.2%) patients were aged ≥60 years. The 1-, 3-, and 5-year survival rates were 93.7%, 79.4%, and 64.9%, respectively. The median overall survival (OS) was 27 months (range, 2-82 months), and the median follow-up was 27 months (range, 3-82 months). The patients with stage III disease had the worst prognosis (P=0.001). The univariate analysis showed that lymph node positivity (P=0.000), the N stage (P=0.000), the TNM stage (P=0.001) and carbohydrate antigen 19-9 (CA19-9) positivity (P=0.038) were related to OS. However, the total number of lymph nodes (LN) retrieved (P=0.723), tumor differentiation (P=0.136), carcinoembryonic antigen (CEA) (P=0.812), gender (P=0.477), operation type (P=0.860), tumor size (P=0.869), tumor site (P=0.120), age (P=0.733), intraoperative blood loss (P=0.660), and intraoperative blood transfusion (P=0.748) were not correlated with OS. The multivariate analysis suggested that the lymph node status was an independent prognostic risk factor for OS., Conclusions: In our study the median OS was 27 months (range, 2-82 months), and the 5-year survival rates was 64.9%. The lymph node status was the only prognostic factor for OS in PDA.

The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wang, Zhao, Cao, Liu, Sun, Shi, Cai, Shen and Tan.)

Background: Endoscopic resection, including endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (EFR), was used to resect small gastric submucosal tumors (SMTs). Our team explored a method of tumor traction using a snare combined with endoclips to assist in the resection of SMTs. This study aims to explore the safety and effectiveness of the method., Methods: This research performed a propensity-score-matching (PSM) analysis to compare ESD/EFR assisted by a snare combined with endoclips (ESD/EFR with snare traction) with conventional ESD/EFR for the resection of gastric SMTs. Comparisons were made between the two groups, including operative time, en bloc resection rate, perioperative complications, and operation-related costs., Results: A total of 253 patients with gastric SMTs resected between January 2012 and March 2019 were included in this study. PSM yielded 51 matched pairs. No significant differences were identified between the two groups in perioperative complications or the costs of disposable endoscopic surgical accessories. However, the ESD/EFR-with-snare-traction group had a shorter median operative time (39 vs 60 min, P  = 0.005) and lower rate of en bloc resection (88.2% vs 100%, P  = 0.027)., Conclusions: ESD/EFR with snare traction demonstrated a higher efficiency and en bloc resection rate for gastric SMTs, with no increases in perioperative complications and the costs of endoscopic surgical accessories. Therefore, the method seems an appropriate choice for the resection of gastric SMTs., (© The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database.We identified pNETs patients from SEER database (2004-2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed.A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (χ) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (P < .05 for all).The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.

Objective: To compare the safety and outcome between total laparoscopic and laparoscopy-assisted synchronous resection for colorectal cancer patients with liver metastases. Methods: The data of patients who underwent total laparoscopic or laparoscopy-assisted simultaneous resection of primary colorectal cancer and liver metastases in our hospital between December 2008 and December 2016 were collected and analyzed. The total laparoscopic surgery patients were matched 1∶2 to the laparoscopy-assisted surgery patients based on the propensity score. 22 patients were classified in the total laparoscopic group and 44 patients were classified in the laparoscopy-assisted group. The intraoperative conditions and postoperative outcomes of the two groups were compared. Results: There was no difference in the preoperative baseline data between the two groups ( P >0.05). The median operative time were 317.50 and 267.50 minutes in the total laparoscopic group and the laparoscopy-assisted group, respectively, and the median intraoperative blood loss were 100 and 200 ml, both with no statistically significant differences ( P >0.05). There were 1 case of intraoperative blood transfusion in the total laparoscopic group and 5 cases in the laparoscopy-assisted group, with no statistically significant difference ( P =0.650). The median postoperative hospital stay in the two groups were 11.0 and 10.0 days, the median postoperative defecation time were 4.0 and 4.0 days and postoperative complication rates were 13.6% and 20.5%, and none of these differences were statistically significant ( P >0.05). However, no Clavien-DindoⅡ level and above complications occurred in total laparoscopic group. The median disease-free survival (DFS) were 15.0 and 15.7 months in the total laparoscopic group and the laparoscopy-assisted group, the overall survival (OS) were 25.9 and 37.6 months, respectively, with no statistically significant differences ( P >0.05). Conclusion: Laparoscopy-assisted approaches are similar, so the appropriate approach should be chosen according to the clinical condition and surgeon's experience.

Aim: To compare feasibility and safety after gastrointestinal checkup by standing-type magnetically controlled capsule endoscopy (SMCE) and conventional gastroscopy., Methods: This was a prospective multicenter, blinded study that compared SMCE with gastroscopy in patients from April 2018 to July 2018. All patients first underwent SMCE and then subsequently had gastroscopy with i.v. anesthesia. We calculated the compliance rates of gastric lesion detection by SMCE using gastroscopy as the standard. Capsule retention rate, incidence of adverse events, and patient satisfaction were documented throughout the study., Results: One hundred and sixty-one patients who completed SMCE and gastroscopy were included in the analysis. Positive compliance rate among SMCE and gastroscopy was 92.0% (95% CI: 80.77%-97.78%). Negative compliance rate was 95.5% (89.80%, 98.52%). Moreover, overall compliance rate was 94.41% (89.65%, 97.41%). Sixty-four pathological outcomes were identified. Of these 64 outcomes, 50 were detected by both procedures. The gastroscopy method neglected seven findings (such as five erosions, one polyp, and one ulcer). Furthermore, SMCE also overlooked seven lesions (i.e. one erosion, two polyps, one atrophy, and three submucosal tumors). Capsule retention or related adverse events were not reported., Conclusion: Standing-type magnetically controlled capsule endoscopy provides equivalent agreement with gastroscopy and may be useful for screening of gastric illnesses without any anesthesia., (© 2019 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Blepharoptosis is a common and challenging clinical problem for oculoplastic surgeons, and various surgical techniques have been used to correct ptosis. The aims of this study were to present the clinical results of a modified technique using levator aponeurosis-Müller muscle-reinforced plication for blepharoptosis correction and to demonstrate its advantages over conventional advancement or plication methods., Methods: This study was conducted in the Plastic Surgery Department of Sir Run Run Shaw Hospital between April 2017 and September 2018. By using this modified technique, the levator-Müller complex was reinforced with a plication suture that pierced under and through the levator-Müller complex, and the posterior and lower part of the levator-Müller complex was advanced to the tarsus, which provided permanent, reliable adhesion. The primary outcome was marginal reflex distance 1 preoperatively and postoperatively. Secondary outcomes were the cosmetic outcome, complications, and operative time., Results: Eighty-six patients (169 eyelids) underwent this modified surgery. Patients' average age was 26 ± 7.6 years, and the median follow-up was 14 months. The preoperative and postoperative mean marginal reflex distance 1 values were 1.72 ± 0.32 and 3.69 ± 0.28 mm, respectively. The amount of plication ranged from 4 to 15 mm. The overall surgical success rate was 88.17%. Some complications were observed including undercorrection (5.92%), asymmetry (4.73%), lagophthalmos (0.59%), and conjunctival prolapse (0.59%)., Conclusions: The modified technique provided good functional and cosmetic outcomes for blepharoptosis correction by avoiding unpredicted adhesion, and it has its advantages including simplicity, easy adjustment of the eyelid height intraoperatively, minimal edema formation, and high success rate.

Self-assembly provides researchers powerful tools for creating ordered functional structures and complex architectures. Investigation of in vivo self-assembly reveals the assembly/aggregation-induced retention (AIR) effect and enhanced targeting effect, which can be applied to promising biomedical applications by enhancing molecular accumulation in the target region. These unique bioeffects inspire the interest of researchers in construction of self-assembled nanomaterials in biological systems. Although many efforts have been achieved, the in-depth analysis of the relationship between assemblies and functions is rarely reported. Here, we focus on the relationship of chlorophyll-derivative assemblies and their photoacoustic signals and attempt to establish a method for monitoring the aggregation efficiency in vivo based on photoacoustic signals. Three arginine-rich peptide-purpurin molecules were designed and synthesized. The assembled capabilities and assembly processes of these molecules were characterized and monitored by UV, fluorescence, and CD spectra images of gradually changing polarities in mixed solvents, and the morphologies of the assemblies were observed by TEM. Furthermore, the relationship between the aggregation ratios of the molecules and the ratiometric photoacoustic signals was systemically studied. We prospect that the fundamental research in revealing objective laws will be useful for future guidance in optimizing photoacoustic detection windows and assembled molecule design.

Objective: To investigate the clinical characteristics and therapeutic effect of benign paroxysm positional vertigo（BPPV） secondary to middle ear surgery. Method: A total of 1 126 patients who underwent tympanoplasty or radical mastoidectomy due to chronic suppurative otitis media and middle ear cholesteatoma in our hospital from January 2014 to December 2018 were collected. Clinical data of BPPV within 1 month after surgery were collected, The incidence, incidence side, involved semicircular canal, onset time, age of onset, and duration of operation of secondary BPPV after middle ear surgery were analyzed. All patients with secondary BPPV were treated by manual reduction, and the efficacy was evaluated 1 day, 1 week, and 1 month after reduction. Result: 2.13% （24 cases） of patients had secondary BPPV after operation, among which 2 cases were parietal incidence. 18 cases were involved in posterior semicircular canals and 6 cases were horizontal semicircular canals. The onset time was 1-12 days after the operation, with an average of （3.29±2.44） days. The mean age of onset was （51.62±10.15） years old, and there was no statistically significant difference between the age of patients without BPPV after middle ear surgery （ P >0.05）. The average operating time was （97.29±14.78） minutes, showing no statistically significant difference compared with patients in the group without BPPV （ P >0.05）. Fourteen cases （58.3%） were cured and 10 cases were improved after 1 day evaluation. Evaluated 1 week after treatment, 19 cases （79.17%） were cured and 5 cases were improved. Evaluated 1 month after treatment, all patients were cured without recurrence. Conclusion: BPPV secondary to middle ear surgery often appears 3 days after surgery, and the posterior semicircular canal of the operative ear is most commonly involved. Age and operation duration have no significant influence on the incidence of BPPV, and satisfactory therapeutic effect can be obtained through manipulative reduction., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: In predicting the risk for posthepatectomy complications, hepatectomy is traditionally classified into minor or major resection based on the number of resected segments. Recently, a new hepatectomy complexity classification was proposed. This study aimed to compare the value of the traditional and that of the new classification in perioperative outcomes prediction., Methods: Demographics, perioperative laboratory tests, intraoperative and postoperative outcomes, and follow-up data of patients with hepatocellular carcinoma who underwent liver resection were retrospectively analyzed., Results: A total of 302 patients were included in our study. Multivariable analysis of intraoperative variables showed that the complexity classification could independently predict the occurrence of blood loss > 800 mL, operation time > 4 h, intraoperative transfusion, and the use of Pringle's maneuver (all p < 0.05). For postoperative outcomes, the high-complexity group was independently associated with severe complications, and hepatic-related complications (all p < 0.05); the traditional classification was independently associated only with posthepatectomy liver failure (PHLF) (p = 0.004)., Conclusions: Complexity classification could be used to assess the difficulty of surgery and was independently associated with postoperative complications. The traditional classification did not reflect operation complexity and was associated only with PHLF.

To reveal the seedlings dynamics of dominant trees and their response to canopy changes (as indicated by changes in leaf area index), we analyzed the seedlings dynamics of dominant trees and canopy structure during forest regeneration based on three-year (2014 to 2016) censuses and hemispherical photography in a 4 hm 2 forest dynamics monitoring plot. The results showed that canopy LAI first decreased and then increased during the survey period, with significant interannual difference. The seedlings of 12 dominant tree species showed notable response to the change of canopy structure, with the response varying among different tree species. The relative abundance or frequency of seedlings for neutral tree species generally increased with the decreases of canopy LAI. The relative abundance or frequency of seedlings of light-demanding tree species generally decreased with the increases of canopy LAI. In multi-response permutation procedures by analyzing the numeric composition and distribution of dominant tree seedlings, there was significant difference among the three censuses. Such interannual difference gradually decreased from 2014 to 2016. Significant change occurred in the indicator species of dominant tree seedlings, reflecting their responses to the changes of canopy structure.

Background and study aims  Mucosal traction as a supportive technique is very useful for endoscopists during endoscopy. For gastric submucosal tumor (SMT), our team explored a method of pulling the SMT with a snare combined with endoclips (PSMT-SE). This study preliminarily explored its feasibility to assist resection of gastric SMT. Patients and methods  Operation-related data from patients who underwent gastric SMT removal assisted by PSMT-SE at the Gastrointestinal Endoscopy Center of Guangzhou Nanfang Hospital, China between January 2017 and October 2018 were retrospectively collected: tumor size and location, origin of tumor, total operation time, en bloc resection rate, intraoperative and postoperative complications. Results  Forty-two gastric SMTs in 41 patients were included in this study. Fifteen tumors were located in the gastric fundus, 11 in the gastric body, two in the gastric angle, 10 in the gastric antrum, and four in the greater curvature of the gastric fundus and the body junction. Further, 11 tumors originated from the submucosa and 31 originated from the muscularis propria. Endoscopic submucosal dissection and endoscopic full-thickness resection assisted by PSMT-SE were performed to resect 30 and 12 tumors, respectively. PSMT-SE could effectively expose the surgical field. Median diameter of resected tumors was 2.0 (0.7) cm, the total operation time was 45.5 (27.0) min, and the en bloc resection rate was 100 %. No intraoperative or postoperative complications were observed. Conclusion  PSMT-SE is a potentially useful method for assisting resection of gastric SMT with tumor traction. Further prospective studies with large sample sizes are warranted.

Background: Although the National Comprehensive Cancer Network (NCCN) guidelines recommend use of lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) > 2 cm, there is limited evidence to support the association between use of LND and overall survival (OS)., Methods: Patients with resected pNETs were identified in the National Cancer Database (2004-2014). The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS of patients in different treatment groups., Results: A total of 2664 patients diagnosed met the study entry criteria. Of these, 2132 patients (80.6%) received LND, with a median of nine nodes removed. Positive nodes were identified in 28.0% of patients who underwent LND. IPTW-adjusted Kaplan-Meier analysis showed that median OS was similar between the LND and LND-omitted groups (152.8 vs. 147.3 months; p = 0.61). In IPTW-adjusted Cox proportional hazards regression analysis, LND was not associated with an OS benefit (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.94-1.42; p = 0.18). The results were consistent across subgroups stratified by clinical T and N stages. Among patients with lymph node metastasis, the number of removed nodes (NRN) above the median was not associated with an improved OS (HR 0.82, 95% CI 0.60-1.13; p = 0.22)., Conclusions: LND had no additional therapeutic benefit among patients undergoing resection for pNETs. The present findings should be considered when managing patients with resectable pNETs.

Background: Percutaneous radiofrequency ablation (RFA) is used as a first-line treatment for colorectal liver metastases that recur after first liver resection in our institution. We aim to evaluate its therapeutic efficacy compared to repeated surgical resection., Methods: A retrospective review was performed in 104 patients treated with curative intent for resectable recurrent colorectal liver metastases., Results: Sixty-one patients underwent RFA and 43 patients underwent surgery. The overall recurrence rates were 82% in the RFA group and 65.1% in the resection group (P = 0.05). The local recurrence rate on a lesion-basis was markedly higher after RFA than that after resection (16.7% versus 7.3%, P = 0.04). The difference remained significant in patients with a maximum lesion diameter >3 cm (24.5% versus 7.6%, P = 0.01). RFA treatment was independently associated with recurrence on multivariate analyses (P = 0.01). 69.7% of RFA patients and 42.6% of surgery patients with intrahepatic recurrence were amenable to repeated local treatment (P = 0.05), leading to the equivalent actuarial 3-year progression free survival rates (RFA: 29.1% versus Resection: 33.1%, P = 0.48) and 5-year overall survival rates in the two treatment groups (RFA: 33% versus Resection: 28.4%, P = 0.36)., Conclusions: Surgery remains the treatment of choice for resectable recurrence. RFA may offer similar benefit in selected patients., (© 2019 Royal Australasian College of Surgeons.)

Background and Aim: Mucosal traction as a "second hand" in endoscopic submucosal dissection (ESD) is very helpful for ESD operators. The efficacy of using a snare combined with endoclips to assist in ESD (SC-ESD) was evaluated whether it could achieve peroral external traction (PET) and peroral internal traction (PIT) and real-time adjustment of mucosal traction position. This study aimed to preliminarily evaluate its feasibility., Methods: A snare was fixed using endoclips to the incised mucosal flap that was intended for dissection. Subsequently, the snare was adjusted to achieve mucosal traction. This study included 54 gastroesophageal neoplasias in 54 consecutive patients who underwent SC-ESD. The operative and clinical data were retrospectively collected., Results: Peroral external tractions were performed for 22 esophageal neoplasias, and PETs and PITs were performed for 32 gastric neoplasias. The median (interquartile range) sizes of lesions were 4.3 (2.5) and 4.2 (2.1) cm, operation times were 73.4 (43.8) and 60.0 (45.2) min, and submucosal dissection times were 27.0 (32.0) and 31.0 (34.5) min in the esophagus and stomach, respectively. Mucosal traction position could be effectively adjusted by fixing the snare to the incised mucosal flap intended for dissection during SC-ESD. All lesions in the esophagus and stomach were completely resected, with R0 resection rates of 100%. Besides postoperative bleeding in a patient with gastric neoplasia, no intraoperative and postoperative perforations occurred., Conclusions: SC-ESD seems to be feasible for resecting gastroesophageal neoplasia, and two types of mucosal tractions (PET and PIT) could be effectively achieved during SC-ESD. Further prospective comparative study with a large sample is warranted., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The neutrophil to lymphocyte ratio (NLR) is a marker of inflammation and is associated with poor outcomes. We aimed to evaluate the role of the pretreatment NLR in predicting the outcomes after preoperative chemotherapy in patients with colorectal liver metastases (CRLM)., Methods: A retrospective review was performed for 183 patients with CRLM. The NLR was measured before chemotherapy, and a receiver operating characteristic (ROC) curve was used to estimate the cutoff value. Logistic regressions were applied to analyze potential predictors of the pathological response. The Cox proportional hazard method was used to analyze survival., Results: The pre-chemotherapy NLR was 2.4 ± 1.1, whereas the post-chemotherapy NLR was 2.1 ± 1.6 (p < 0.001). The pretreatment NLR of 2.3 was a significant predictive marker for the pathological response. The pathological response rates were 67.1% in the patients with an NLR ≤ 2.3 and 48.1% in patients with an NLR > 2.3 (p = 0.01). Multivariate analysis revealed that the factors independently associated with pathological responses were a low pretreatment NLR (p = 0.043), radiological response to chemotherapy (p < 0.001), first-line chemotherapy (p = 0.001), and targeted therapy (p = 0.002). The median overall survival (OS) and recurrence-free survival (RFS) were worse in the increased NLR cohort than in the low NLR cohort (OS: 31.1 vs. 43.1 months, p = 0.012; RFS: 6.5 vs. 9.4 months, p = 0.06). According to multivariate analyses, a high pretreatment NLR was a significant predictor for both worse OS (HR = 2.43, 95%CI = 1.49-3.94, p < 0.001) and RFS (HR = 1.53, 95%CI = 1.08-2.18, p = 0.017)., Conclusions: An increased pretreatment NLR was a significant predictor of a poor pathological response and worse prognosis after preoperative chemotherapy. The NLR is a simple biomarker for assessing chemotherapy efficacy.

Objective: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need., Design and Results: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively., Conclusions: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group., Trial Registration: NCT01770431; Post-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

To explore the influence of prostate size on the outcome of Plasmakinetic enucleation of the prostate (PkEP) for the treatment of benign prostate hyperplasia (BPH), The data of 892 patients with symptomatic BPH who underwent PkEP were retrospectively reviewed. Among them, 199 (22.31%) had the prostate size smaller than 40 g (Group 1), 409 (45.85%) between 40 and 79 g (Group 2), 197 (22.09%) between 80 and 120 g (Group 3), and 87 (9.75%) larger than 120 g (Group 4). Perioperative variables, perioperative and postoperative complications were recorded. Patients were followed up for 36 months postoperatively. The efficiency of the surgery increased as the prostate size increased. Greater decreases in hemoglobin were noted in groups with larger prostates, while the duration of catheterization after the operation was similar across all groups. During the 3-year follow-up, the postoperative improvement in International Prostate Symptom Score (IPSS), Quality of Life (QOL), maximal flow rate (Qmax) and post-void residual urine volume (PVR), as well as longterm complications including urethral stricture and bladder-neck contracture were comparable across the 4 groups. These findings revealed that PkEP is more efficient for large prostate and can treat all prostates regardless of the size with equivalent symptom relief and micturition improvement., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people., Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations., Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Sepsis, an overwhelming systemic inflammatory disease, is the leading cause of acute lung injury (ALI). Despite plenty of researches have been done, effective drugs treating septic ALI are still eagerly needed in the clinic. Dexmedetomidine (Dex), a potent alpha-2 adrenoreceptor agonist, has been reported to possess antioxidant, anti-apoptosis and anti-inflammatory abilities. Taurine, a kind of intracellular free amino acid, has been used to treat various diseases. This study aimed to explore the combination effect of Dex and Taurine on septic ALI and the underlying mechanism in vivo. The establishment of septic ALI was set up in SD rats by cecal ligation and puncture (CLP) operation. Results indicated that Dex or Taurine could reduce septic ALI-induced cell apoptosis via decreasing caspase-3 activity. However, the combination of Dex or Taurine produced greater effect. Besides that, Dex combined with Taurine could better promote cell proliferation with remarkably elevated Ki67 expression. The combination of Dex and Taurine significantly suppressed the activation of NF-κB pathway via inhibiting P65 phosphorylation and P65 nuclear translocation, leading to the down-regulation of interleukin (IL)-6 and IL-1β. Moreover, co-administration of Dex and Taurine alleviated the imbalance of Th1/Th2 induced by septic ALI to a great extent. All in all, our study suggested the synergistic therapeutic effect of Dex and Taurine on septic ALI., (Copyright © 2018. Published by Elsevier Masson SAS.)

Objective: To investigate trends of mean age of diagnosis for liver cancer during 2000 to 2014, which may provide basic information for making feasible cancer prevention strategies. Methods: Based on the continuous cancer incidence data from 22 cancer registries of China between 1 January 2000 and 31 December 2014, the incidence by birth-cohort (year of birth between 1925 and 1994) and age specific incidence rates were calculated. The incidence of different age groups were also calculated. World Segi's population was used for age standardization. The liner regression model was applied to analyze the changing trend of mean age of diagnosis. Results: In 2014, the incidence rate for population with 80 years older and above was 108.21 per 100 000, whereas the rate for population at 30-39 years old was 5.09 per 100 000. But the mean age of diagnosis for liver cancer showed an increasing trend from 2000 to 2014. For male, it had increased from 58.80 to 62.35 ( t= 18.70, P< 0.001) . For female, it had increased from 64.02 to 68.99 ( t= 20.50, P< 0.001) . After age standardization, the mean age of diagnosis still showed increasing trend. Meanwhile, the proportion of liver cancer in people above 70 years old was 25.05% in 2014, which was higher than that in 2000 (22.49%). Conclusion: The mean age of liver cancer incidence was increasing during 2000-2014.

Objective: To investigate the correlation between postoperative peripheral blood neutrophil to lymphocyte ratio (NLR) and recurrence and prognosis of patients with hepatocellular carcinoma (HCC). Methods: The clinicopathological and follow-up data of 344 patients with HCC who underwent radical liver resection from May 2010 to April 2014 were analyzed retrospectively. Results: Of the 344 patients, 104 had early recurrence and 84 had late recurrence. Receiver operating characteristic (ROC) curve analysis showed that the NLR predicted area under the curve (AUC) of early recurrence was 0.622 ( P <0.001), the optimal cut-off value was 2.41. The AUC of late recurrence was 0.634 ( P =0.001), the optimal cut-off value was 2.15. Cox multivariate analysis showed the serum concentration of hepatitis B surface antigen ( HR =2.508, 95% CI : 1.311-4.798), microvascular invasion ( HR =2.422, 95% CI : 1.239-4.734), Milan criteria ( HR =2.373, 95% CI: 1.427-3.948) and postoperative NLR ( HR =2.285, 95% CI: 1.379-3.788) were independent risk factors of early recurrence after HCC resection. Postoperative NLR ( HR =2.927, 95% CI: 1.630-5.255), liver cirrhosis ( HR =2.531, 95% CI : 1.291-4.962) and serum concentration of albumin ( HR =2.257, 95% CI: 1.251-4.073) were independent risk factors of late recurrence after HCC resection. The median recurrence-free survival (RFS) of the 344 patients was 45.0 months, and the median overall survival (OS) was 63.2 months. ROC curve analysis showed that the postoperative NLR predicted 5-year survival AUC was 0.689 ( P <0.05), with an optimal cutoff of 2.29. Cox multivariate analysis showed microvascular invasion ( HR =2.247, 95% CI: 1.534-3.291), postoperative NLR ( HR =2.217, 95% CI: 1.653-2.974), and liver cirrhosis ( HR =1.685, 95% CI: 1.168-2.431), Milan criteria ( HR =1.679, 95% CI: 1.238-2.277), serum concentration of hepatitis B surface antigen ( HR =1.623, 95% CI: 1.102-2.392), serum concentration of albumin ( HR =1.43, 95% CI: 1.066-1.918) were independent factors of RFS after HCC resection, while microvascular invasion ( HR =3.862, 95% CI: 2.407-6.197), Barcelona staging ( HR =2.864, 95% CI: 1.600-5.125), postoperative NLR ( HR =2.688, 95% CI: 1.782-4.055), liver cirrhosis ( HR =2.039, 95% CI: 1.184-3.514), serum concentration of albumin ( HR =1.81, 95% CI: 1.204-2.720) were independent factors of OS. Conclusions: For HCC patients who receive radical liver resection, postoperative NLR ≥2.29 implicates poor prognosis. Moreover, postoperative NLR ≥2.41 suggests early recurrence, while NLR ≥2.15 suggests late recurrence.

Purpose: We sought to determine the impact of surgical margin status on overall survival (OS) and recurrence pattern stratified by tumor burden., Materials and Methods: Data were collected from patients undergoing resection for colorectal liver metastases (CRLM). Tumor burden was calculated according to a newly proposed Tumor Burden Score (TBS) system, defined as the distance from the origin on a Cartesian plane that incorporated maximum tumor size and number of liver lesions. Patients were divided into low tumor burden group and high tumor burden group accordingly, and the impact of resection margin on overall survival was examined., Results: A total of 286 patients were available, among which R1 resection was observed in 88 patients. The median TBS for the entire cohort was 3.84. Metastases in the R1 group were characterized by more advanced disease and more complex resections. Compared with a R0 resection, a R1 resection offered an lower 5-year overall survival rate (46.8% vs. 22.1%, p = 0.001). Multivariate analysis identified R1 resection (p = 0.03), high TBS (p = 0.002), lymph nodes metastases (p = 0.003) and lymphovascular invasion (p = 0.03) of the primary colorectal tumor as the factors independently associated with worse survival. The survival benefit associated with negative margins was greater in patients with low TBS (55.7% vs. 21.7%, p = 0.021) than in patients with high TBS (31.8% vs. 24.5%, p = 0.116). R1 resection was associated with an increased true margin recurrence rate in patients with low TBS (32.3% vs. 13.4%; p = 0.014) and an increased risk of new intrahepatic metastases in patients with high TBS (43.9% vs. 26.7%; p = 0.034)., Conclusions: Negative margin is an important determinant of survival. The impact of positive margins is more pronounced in patients with low tumor burden., (Copyright © 2017. Published by Elsevier Ltd.)

Gliomas are characterized by a malignant phenotype with proliferation, cell cycle arrest and invasion. To explore the biological consequences of epigenetically regulated miRNAs, we performed a microarray-based screening (whose expression was affected by 5-AZA treatment) followed by bisulfite sequencing validation. We found that miR-134 as an epigenetically regulated suppressor gene with prognostic value in gliomas. MicroRNA-134 was downregulated in high-grade gliomas, especially in GBM samples. Functional studies in vitro and in vivo in mouse models showed that overexpression of miR-134 was sufficient to reduce cell cycle arrest, cell proliferation and invasion. Target analysis and functional assays correlated the malignant phenotype with miR-134 target gene KRAS, an established upstream regulator of ERK and AKT pathways. Overall, our results highlighted a role for miR-134 in explaining the malignant phenotype of gliomas and suggested its relevance as a target to develop for early diagnostics and therapy.

We established a 4 hm 2 (200 m×200 m) temperate secondary forest plot in the montane region of eastern Liaoning Province, China, and analyzed the spatial patterns and interspecific spatial associations of tree seedlings at scales of 0-50 m. The results showed that under complete spatial randomness null model, 95% of the species at the scale of 0-20 m showed a significant aggregation pattern, and 19 species at the scale of 0-16 m showed an aggregation pattern. The proportion of species exhibiting aggregated patterns decreased with the spatial scale. At the scale of 50 m, the random distribution pattern became the main form of tree species distribution. Underheterogeneous Poisson process null model, 5% of the species at the scale of 0-24 m showed a significant aggregation pattern, and 42% and 58% of the species at the scale of 26-50 m showed a random distribution and regularity patterns, respectively. Under complete spatial randomness null model, the proportion of species pairs of positive correlation was the highest, and at the scale of 50 m, the proportion of species pairs showed positive correlation, uncorrelated and negative correlation tended to be equal. Under heterogeneous Poisson process null model, species pairs mainly showed negative correlation, and the proportion of species pairs exhibiting negative correlation increased with spatial scale. The results implied that seed dispersal limitation and habitat heterogeneity could explain the aggregation pattern of tree seedlings. The strong aggregation of tree seedlings also contributed to close interspecific spatial associations and poor stability of the regeneration community.

Objective: To establish a new scoring system based on the clinicopathological features of hepatocellular carcinoma (HCC) to predict prognosis of patients who received hepatectomy. Methods: A total of 845 HCC patients who underwent hepatectomy from 1999 to 2010 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. 21 common clinical factors were selected in this analysis. Among these factors, the cut-off values of alpha-fetoprotein (AFP), alkaline phosphatase (ALP) and intraoperative blood loss were evaluated by using a receiver operating characteristic (ROC) curve analysis.The Kaplan-Meier method and Cox regression model were used to evaluate the independent risk factors associated with the prognosis of HCC patients after hepatectomy. HCC postoperatively prognostic scoring system was established according to the minimum weighted method of these independent risk factors, and divided the patients into 3 risk groups, including low-risk, intermediate-risk and high-risk group. The relapse-free survival (RFS) and overall survival (OS) were compared among these groups. Results: The univariate analysis showed that clinical symptoms, preoperative α-fetoprotein (AFP) level, serum alkaline phosphatase (ALP) level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with median RFS of these HCC patients ( P <0.05). Alternatively, clinical symptoms, preoperative AFP level, serum ALP level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological lymphocyte invasion, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with the median OS of these HCC patients ( P <0.05). The multivariate analysis showed that AFP ≥20 ng/ml, clinical symptoms, tumor diameter ≥5 cm, multiple tumors, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, moderate and severe liver cirrhosis, non- anatomic resection were the independent risk factors of RFS and OS ( P <0.05). The independent risk factor of RFS was intraoperative bleeding loss ≥325 ml ( P <0.05); The independent risk factors of OS were abdominal lymph node metastasis and pathological tumors thrombus ( P <0.05). The respective weight of 11 independent factors was used to establish the scoring system (scores range from 0 to 26). In the score system, 0 to 5 points were defined as the low-risk group (286 cases), 6 to 12 points were determined as the intermediate-risk group (503 cases), more than 13 points were classified as the high-risk group (56 cases). The median RFS of the low-risk, intermediate-risk and high-risk group were 80, 27 and 6 months, respectively. The differences were statistically significant ( P <0.001). The median OS of the three groups were 134, 51 and 15 months, respectively, and the differences were statistically significant ( P <0.001). Conclusion: This new score system provides effective prediction of postoperative prognosis for HCC patients.

The aims of this study were to assess early recurrence predictive factors and elucidate the best early recurrence management. 255 patients with colorectal liver metastases (CRLM) who underwent hepatectomy were retrospectively analyzed. A total of 87 patients (34.1%) developed early recurrence, defined as recurrence that occurred within 6 months after resection. Multivariate analysis showed that preoperative carcino-embryonic antigen (CEA) level ≥ 30 ng/ml, primary tumor lymphovascular invasion (LVI), number of metastases ≥ 4, R1 resection and initially unresectable disease were independent predictors of early recurrence. A predictive scoring system for early recurrence was created by incorporating these factors, and this system showed good discrimination (concordance index of 0.78). In early recurrent patients who underwent salvage treatment, those with 0-2 risk factors demonstrated a significantly longer median survival after recurrence than patients with 3-5 risk factors (33.4 months vs. 20.2 months, p = 0.001). For patients who underwent chemotherapy alone, the median survival after recurrence between two groups was comparable (18.3 months vs. 22.6 months, p = 0.926). Multivariate analysis revealed that primary tumor lymph node metastases (HR = 1.96, p = 0.032), early recurrence (HR = 1.67, p = 0.045), salvage treatment for recurrence (HR = 0.47, p = 0.002) and predictive scores for early recurrence (HR = 1.39, p = 0.004) were independent factors for survival in patients with recurrence. In patients with early recurrence, bilobar distribution of metastases (HR = 2.05, p = 0.025) and salvage treatment for recurrence (HR = 0.46, p = 0.019) were independent factors for survival. In conclusion, we developed a predictive model that is a very useful tool for determining both the likelihood of early recurrence and the necessity for salvage treatment., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

The long-term outcome of 228 patients with colorectal liver metastases (CRLM) who underwent preoperative chemotherapy followed by hepatectomy ± RFA were retrospectively analyzed. Stratified by chemotherapy response, patients were divided into responding (n=129) and non-responding groups (n=99). Patients who underwent hepatectomy-RFA had a greater number of metastases (median of 4 vs. 2, p=0.000), a higher incidence of bilobar involvement (66.7% vs. 49.1%, p=0.014) and longer chemotherapy cycles (median of 6 vs. 4, p=0.000). In the responding group, the median overall survival (OS) and recurrence free survival (RFS) of hepatectomy-RFA and the hepatectomy alone subgroups were comparable (38.6 months vs. 43.2 months, p=0.824; 8.2 months vs. 11.4 months, p=0.623). In the non-responding group, the median OS and RFS of patients treated with hepatectomy-RFA were significantly shorter (18.5 months vs. 34.2 months, p=0.000; 5.1 months vs. 5.9 months, p=0.002). RFA was identified as the unfavorable independent factor for both OS (HR=3.60, 95%CI=1.81-7.16, p=0.039) and RFS (HR=1.70, 95%CI=1.00-2.86, p=0.048) in non-responsive patients. Local recurrence rate after hepatectomy-RFA was higher in the non-responding group (48.1% vs. 23.6%, p=0.018). Non-response to preoperative chemotherapy may be a contraindication to hepatectomy-RFA in patients with CRLM., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Background and Aims: Endoscopic submucosal tunneling dissection (ESTD) has been proved to be safe and effective for removal of esophageal submucosal tumors (SMTs) and can maintain the mucosal integrity compared with other endoscopic methods. The aim of the study was to estimate the safety and efficacy of ESTD as well as compare its efficacy with thoracoscopic enucleation for esophageal SMTs, which is used increasingly as a minimally invasive approach., Methods: We retrospectively collected the clinical data of patients with esophageal SMTs <40 mm who underwent ESTD or thoracoscopic enucleation at Nanfang Hospital between January 2008 and August 2016. Epidemiologic data (sex, age), tumor location, tumor size, en bloc resection rate, adverse events, pathologic results, length of postoperative hospital stay, and cost were compared between ESTD and thoracoscopic enucleation., Results: A total of 126 patients were included. A total of 74 patients underwent ESTD, and the other 52 underwent thoracoscopic enucleation. There was no significant difference between the 2 groups in sex, age, tumor size, hospitalization expense, infection, adverse events, and en bloc resection rate (P < .05). However, patients in the ESTD group had a shorter operating time, less estimated blood loss, shorter length of postoperative hospital stay, and lower chest pain level (P < .05). Kaplan-Meier curves for disease-free survival also showed no statistically significant difference between ESTD and thoracoscopic enucleation groups during the median follow-up of 19.5 and 42 months, respectively., Conclusions: The treatment efficacy was comparable between the ESTD and thoracoscopic enucleation for esophageal SMTs <40 mm. However, there was a significant advantage in the ESTD group for a shorter operating time, reduced postoperative chest pain, and shorter hospitalization., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and study aims  Submucosal tunneling endoscopic resection with double opening (DO-STER) was developed by our group for the resection of submucosal tumors in the esophagus and gastric fundus near the cardia. This study aimed to provide a preliminary evaluation of feasibility and safety of DO-STER. Methods  The key to DO-STER is the creation of a tunnel opening in the mucosa over the inferior border of the tumor. During resection, the tumor can be gradually pushed out of the submucosal tunnel through the opening, leaving enough space for operation within the tunnel. A total of 10 tumors resected by DO-STER were retrospectively reviewed. Results  All tumors were successfully resected by DO-STER. One tumor was located at the lower esophagus, four at the esophagogastric junction, and five at the gastric fundus near the cardia. Tumor size ranged from 1.0 × 1.2 cm to 3.5 × 5.0 cm, and all tumors originated from the muscularis propria. Operative times ranged from 45 to 150 minutes. No delayed bleeding or perforation occurred. Conclusion DO-STER seems to provide an alternative approach for resection of tumors in the esophagus and gastric fundus near the cardia., Competing Interests: Competing interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To investigate the clinical value of intraoperative radiofrequency ablation (RFA) in the treatment of colorectal liver metastasis (CLM). Methods: A retrospectively analysis of 187 patients with CLM who underwent liver resection with or without RFA from January 2009 to August 2016 in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences was performed. According to whether RFA was used intraoperatively, patients were divided into resection only group and combined treatment group. The clinical and pathological characteristics of the two groups were compared to explore factors influencing survival and recurrence. Imbalance of background characteristics between the two groups was further overcome by propensity score matching method (PSM). Results: The number of liver metastases (267), simultaneous liver metastases (100%), bilobar involvement (73.3%) and preoperative chemotherapy (93.3%) rates were significantly higher in the combined treatment group than those in the resection only group(471, 74.7%, 42.0% and 63.1%)(all P <0.05). In the combined treatment group, median overall survival (OS) was 25.7 months; and 3-year and 5-year OS were 47.9% and 28.8%, respectively. In the resection only group, the median survival time was 46.9 months; and 3-year and 5-year OS rate was 59.1% and 42.4%, respectively (χ(2)=4.579, P =0.034). Median disease-free survival (DFS) was 5.4 months in the combined treatment group, and 10.1 months in the resection only group (χ(2)=5.399, P =0.023). In multivariate analysis, intraoperative RFA was not an independent prognostic factor for OS and DFS ( HR =0.98, 95% CI: 0.47-2.08, P =0.965; HR =1.21, 95% CI: 0.71-2.07, P =0.465). After PSM, the median OS of the resection only and the combined treatment groups were 30.2 and 25.7 months (χ(2)=0.876, P =0.350). The median DFS in the two groups was 5.3 and 4.2 months, respectively (χ(2)=0.199, P =0.650). Conclusion: In patients with similar tumor burden, liver resection combined with intraoperative RFA for unresectable CLM can achieve long-term outcomes similar to hepatectomy alone for resectable CLM.

Aim: The prognostic value of the newly raised objective liver function assessment tool, the albumin-bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child-Pugh (C-P) score in predicting prognosis in this study., Methods: The clinical data of 491 C-P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C-P score in predicting the short- and long-term clinical outcomes were compared., Results: The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C-P score. With a median follow-up of 57 months, the 1-year, 3-year, and 5-year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C-P score in terms of both the Akaike information criterion value and χ 2 value of likelihood ratio test., Conclusions: The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C-P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well-designed studies with larger sample sizes are warranted., (© 2016 The Japan Society of Hepatology.)