Search

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

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.

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.)

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.)

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.)

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 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 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.

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.)

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.

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: Obesity is a growing epidemic around the world, and obese patients are generally regarded as high risk for surgery compared with normal weight patients. The purpose of this study was to evaluate the influence of obesity on the surgical outcomes of laparoscopic gastrectomy (LG) for gastric cancer., Methods: We reviewed data for all patients undergoing LG for gastric cancer at our institute between October 2004 and December 2016. Patients were divided into non-obese and obese groups and the perioperative outcomes were compared. Furthermore, a subgroup analysis was conducted to evaluate which of the two commonly used methods of LG, laparoscopic-assisted gastrectomy (LAG) and totally laparoscopic gastrectomy (TLG), is more suitable for obese patients., Results: A total of 1691 patients, 1255 non-obese and 436 obese or overweight patients, underwent LG during the study period. The mean operation time was significantly longer in the obese group than in the non-obese group (209.9 ± 29.7 vs. 227.2 ± 25.7 min, P < 0.01), and intraoperative blood loss was significantly lower in the non-obese group (113.4 ± 34.1 vs. 136.9 ± 36.7 ml, P < 0.01). Time to first flatus, time to oral intake, and postoperative hospital stay were significantly shorter in the non-obese group than in the obese group (3.3 ± 0.8 vs. 3.6 ± 0.9 days; 4.3 ± 1.0 vs. 4.6 ± 1.0 days; and 9.0 ± 2.2 vs. 9.6 ± 2.2 days, respectively; P < 0.01). 119 (9.5%) of the non-obese patients had postoperative complications as compared to 44 (10.1%) of the obese patients (P = 0.71). In the subgroup analysis of all patients, TLG showed improved results for early surgical outcomes compared to LAG, mainly due to its advantages in obese patients., Conclusions: Obesity is associated with long operation time, increased blood loss, and slow recovery after laparoscopic gastric resection but does not affect intraoperative security or effectiveness. TLG may have less negative results in obese patients than LAG due to a variety of reasons. Our analysis shows that TLG is more advantageous, with regard to early surgical outcomes, for obese patients.

Objective: To investigate the influence of different anesthetic techniques on the prognosis of hepatocellular carcinoma (HCC)after hepatectomy. Methods: A total of 185 consecutive patients with HCC confirmed underwent surgery in Cancer Hospital, Chinese Academy of Medical Sciences were recruited from January 2006 to January 2008. The patients were assessed as American Society of Anesthesiologists (ASA)Ⅰ-Ⅲ, with body mass index (BMI) (22.8±4.6)kg/m(2). There were 169 males, with an average age of 56 years old and 16 females, with an average age of 53 years old. According to the different anesthesia methods, 185 patients were divided into two groups: total intravenous anesthesia group (TIVA) ( n =53) and intravenous-inhalation combined anesthesia group ( n =132). Postoperative pain and adverse reactions were compared in recent follow-up, prognosis were compared in long-term follow-up. Results: Recent follow-up showed that the NRS scores 2 hours after operation in TIVA group was 2.0 (0-2.0), whereas those in intravenous-inhalation combined anesthesia group was 3.0 (1.0-3.0). The pain in TIVA groups was significantly lower than that in intravenous-inhalation combined anesthesia group ( Z =-3.261, P =0.001). But for 24 hours after operation, the NRS scores in these two groups were 3.0 (2.0-5.0) and 3.0 (3.0-4.0), respectively. There was no significant difference in the two groups ( Z =-0.035, P =0.972). In addition, there was no significant difference between the two groups in the incidence of sedation, nausea/vomiting, restlessness and other adverse reactions (all P >0.05). Long-term follow-up indicated that anesthetic techniques have no correlation with HCC prognosis in Kaplan-Meier analysis and Cox's regression analysis. Conclusion: There is no significant effect of two anesthesia methods on the long-term prognosis of HCC.

Background: The liver is the most common site for colorectal cancer (CRC) metastases. Their removal is a critical and challenging aspect of CRC treatment. We investigated the prognosis and risk factors of patients with CRC and liver metastases (CRCLM) who underwent simultaneous resections for both lesions., Methods: From January 2009 to August 2016, 102 patients with CRCLM received simultaneous resections of CRCLM at our hospital. We retrospectively analyzed their clinical data and analyzed their outcomes. Overall survival (OS) and disease-free survival (DFS) were examined by Kaplan-Meier and log-rank methods., Results: Median follow-up time was 22.7 months; no perioperative death or serious complications were observed. Median OS was 55.5 months; postoperative OS rates were 1-year: 93.8%, 3-year: 60.7%, and 5-year: 46.4%. Median DFS was 9.0 months; postoperative DFS rates were 1-year: 43.1%, 3-year: 23.0%, and 5-year 21.1%. Independent risk factors found in multivariate analysis included carcinoembryonic antigen ≥100 ng/ml, no adjuvant chemotherapy, tumor thrombus in liver metastases, and bilobar liver metastases for OS; age ≥60 years, no adjuvant chemotherapy, multiple metastases, and largest diameter ≥3 cm for DFS., Conclusions: Simultaneous surgical resection is a safe and effective treatment for patients with synchronous CRCLM. The main prognostic factors are pathological characteristics of liver metastases and whether standard adjuvant chemotherapy is performed.

Background and Aims: EGFRvIII is the most prevalent glioblastoma mutation, occurring in more than 25% of glioblastomas. EGFRvIII cells release microvesicles that contain proteins, miRNAs, and mRNAs that enhance the growth and survival of surrounding tumor cells. However, little is known about the maturation process and regulatory mechanisms of secreted vesicles in EGFRvIII cells., Methods: Signal peptide peptidase (SPP) provides a fascinating mechanism for protein cleavage and subsequent dislocation in the endoplasmic reticulum transmembrane domain., Results: In this study, we reported that SPP facilitates the secretion of cytokines in vitro and promotes tumor progression in mice. Human cytokine antibody arrays revealed that EGFRvIII secreted higher levels of cytokines, but these levels were significantly reduced following SPP knockdown, suggesting that cytokines in EGFRvIII secretion profiles play important roles in GBM development. Identical results were confirmed in intracellular maturation tracking of TGF-β1 in mouse serum. Clinically, analyses of GBM patient data from the database revealed that HM13 expression was closely related to patient prognosis and survival, suggesting an influence by the secreted vesicles of EGFRvIII tumor cells., Conclusions: Collectively, our study identifies that SPP affects EGFRvIII secretion profiles and thus promotes tumor progression, providing further understanding of the formation of secreted vesicles and driving role of EGFRvIII in GBM., (© 2017 John Wiley & Sons Ltd.)

Background: Lymph node status is crucial to determining treatment for early gastric cancer (EGC). We aim to establish a nomogram to predict the possibility of lymph node metastasis (LNM) in EGC patients., Methods: Medical records of 952 EGC patients with curative resection, from 2002 to 2014, were retrospectively retrieved. Univariate and multivariate analysis were performed to examine risk factors associated with LNM. A nomogram for predicting LNM was established and internally validated., Results: Five variables significantly associated with LNM were included in our model, these are sex (Odd ratio [OR] = 1.961, 95% confidence index [CI], 1.334 to 2.883; P = 0.001), depth of tumor (OR = 2.875, 95% CI, 1.872 to 4.414; P = 0.000), tumor size (OR = 1.986, 95% CI, 1.265 to 3.118; P = 0.003), histology type (OR = 2.926, 95% CI, 1.854 to 4.617; P = 0.000) and lymphovascular invasion (OR = 4.967, 95% CI, 2.996 to 8.235; P = 0.000). The discrimination of the prediction model was 0.786., Conclusions: A nomogram for predicting lymph node metastasis in patients with early gastric cancer was successfully established, which was superior to the absolute endoscopic submucosal dissection (ESD) indication in terms of the clinical performance.

Background/aim: Endoscopic tunneling resection is a relatively novel endoscopic technology for removing gastric submucosal tumors. Our study aimed to compare the differences between tunneling and nontunneling resection for gastric submucosal tumors., Materials and Methods: Resections of gastric submucosal tumors (n = 97) performed from 2010 to 2015 at our endoscopy center were reviewed, and PubMed was searched for clinical studies on gastric submucosal tumor resection by endoscopic nontunneling and tunneling techniques., Results: At our endoscopy center, nontunneling (Group 1) and tunneling resection (Group 2) were performed for 78 and 19 submucosal tumors, respectively; median tumor diameters were 15 and 20 mm (P = 0.086), median procedural times were 50 and 75 min (P = 0.017), successful resection rates were 94.9% (74/78) and 89.5% (17/19) (P = 0.334), and en bloc resection rates were 95.9% (71/74) and 94.1% (16/17) (P = 0.569) in the Groups 1 and 2, respectively. Postoperative fever, delayed hemorrhage and perforation, hospitalization time, and hospitalization expense were statistically similar between the 2 groups. A literature review on gastric submucosal tumor resection suggested that the en bloc resection rates of the two methods for tumors with a median diameter of 15-30 mm were also high, and there were no relapses during the follow-up period., Conclusions: Both endoscopic nontunneling and tunneling resection seem to be effective and safe methods for removing relatively small gastric submucosal tumors. Compared with endoscopic nontunneling, tunneling resection does not seem to have distinct advantages for gastric submucosal tumors, and has a longer mean operative time.

Purpose: Lactate dehydrogenase (LDH), which was an indirect marker of hypoxia, was a potentially prognostic factor in several malignancies. There is a lack of evidence about the prognostic value of serum LDH level in patients with hepatocellular carcinoma (HCC) receiving sorafenib treatment from hepatitis B virus endemic areas., Materials and Methods: A total of 119 HBV-related HCC patients treated by sorafenib from a Chinese center were included into the study. They were categorized into 2 groups according to the cut-off value of pre-treatment LDH, which was determined by the time dependent receiver operating characteristics (ROC) curve for the overall survival. The prognostic value of LDH was evaluated. The relationships between LDH and other clinicopathological factors were also assessed., Results: The cut-off value was 221 U/L. With a median follow up of 15 (range, 3-73) months, 91 patients reached the endpoint. Multivariate analysis proved that pre-treatment serum LDH level was an independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). For patients whose pre-treatment LDH ≥ 221 U/L, increased LDH value after 3 months of sorafenib treatment predicted inferior OS and PFS. And patients with elevated pre-treatment LDH level predisposed to be featured with lower serum albumin, presence of macroscopic vascular invasion, advanced Child-Pugh class, advanced T category, higher AFP, and higher serum total bilirubin., Conclusions: Serum LDH level was a potentially prognostic factor in HCC patients treated by sorafenib in HBV endemic area. More relevant studies with reasonable study design are needed to further strengthen its prognostic value.

Background: Controversial results about the therapeutic value of radiofrequency ablation (RFA) and liver resection (LR) in the treatment of colorectal cancer liver metastasis (CRCLM) have been reported. Thus, we performed the present meta-analysis to summarize the related clinical evidences., Methods: A systematic literature search was conducted using PubMed (Medline), EMBASE, Cochrane Library, and Web of Science, for all years up to April 2016. Pooled analyses of the overall survival (OS), progression-free survival (PFS), and morbidity rates were performed., Results: A total of 14 studies were finally enrolled in the meta-analysis. Patients treated by LR gained a longer OS and PFS than those of patients treated by RFA. Patients in the RFA group had lower morbidity rates than those of patients in the LR group. Publication bias analysis revealed that there was no significant publication bias in the meta-analysis., Conclusions: Patients with CRCLM gained much more survival benefits from LR than that from RFA. RFA rendered lower rates of morbidities. More well-designed randomized controlled trails comparing the therapeutic value of LR and RFA are warranted., Competing Interests: There are no conflicts of interest.

Background: Totally laparoscopic gastrectomy (TLG) using intracorporeal anastomosis has gradually become mature thanks to the advancements of laparoscopic surgical instruments and the accumulation of operative experience. The goal of this study is to review our institution's experience with TLG for the treatment of gastric cancer., Methods: A retrospective study was conducted to examine the short-term outcomes of TLG using intracorporeally stapler or hand-sewn anastomosis performed at Sir Run Run Shaw Hospital between March 2007 and June 2015. The details of intracorporeal anastomosis were described, and the clinicopathological data, surgical outcomes, and postoperative complications were evaluated., Results: Four hundred seventy-eight patients were included in the study. Generally speaking, the patients could be divided into stapler or hand-sewn groups according to whether intracorporeal anastomosis was performed by only hand-sewn technique (n = 97) or only stapling devices (n = 381). For overall patients, the mean operation time and anastomotic time were 225.7 and 30.0 min, respectively. Postoperative complications were observed in 65 patients. All of the patients recovered well without perioperative death by conservative or surgical management., Conclusions: TLG using intracorporeally stapler or hand-sewn anastomosis is a reasonable option for the treatment of gastric cancer, with early data showing acceptable perioperative outcomes.

The purpose of this study was to evaluate the prognostic value of lymph node ratio (LNR) in patients with gastric cancer liver metastasis (GCLM) who received combined surgical resection. A retrospective analysis of 46 patients from two hospitals was conducted. Patients were dichotomized into two groups (high LNR and low LNR) by the median value of LNR. The overall survival (OS) and recurrence-free survival (RFS) were analyzed by the Kaplan-Meier method with the log-rank test. The Cox proportional hazard model was used to carry out the subsequent multivariate analyses. And the relationship between LNR and clinicopathological characteristics was assessed. The cut-off value defining elevated LNR was 0.347. With a median follow-up of 67.5 months, the median OS and RFS of the patients were 17 and 9.5 months, respectively. Six patients survived for >5 years after surgery. Patients with higher LNR had significantly shorter OS and RFS than those with lower LNR. In the multivariate analyses, higher LNR and multiple liver metastatic tumors were identified as the independent prognostic factors for both OS and RFS. Elevated LNR was significantly associated with advanced pN stage (P <0.001), larger primary tumor size (P = 0.046), the presence of microvascular invasion (P = 0.008), and neoadjuvant chemotherapy (P = 0.004). LNR may be prognostic indicator for patients with GCLM treated by synchronous surgical resection. Patients with lower LNR and single liver metastasis may gain more survival benefits from the surgical resection. Further prospective studies with reasonable study design are warranted.

Background: Laparoscopic-assisted total gastrectomy (LATG) is the most commonly used methods of laparoscopic gastrectomy for upper and middle gastric cancer. However, totally laparoscopic total gastrectomy (TLTG) is unpopular because reconstruction is difficult, especially for the intracorporeal esophagojejunostomy. We adopted TLTG with various types of intracorporeal esophagojejunostomy. In this study, we compared LATG and TLTG to evaluate their outcomes., Methods: From March 2006 to September 2015, 253 patients with upper and middle gastric cancer underwent laparoscopic total gastrectomy (LTG), 145 patients underwent LATG, and 108 patients underwent TLTG. The clinicopathological characteristics and postoperative outcomes were retrospectively compared between the two groups. Furthermore, a systematic review and meta-analysis were conducted., Results: The operation time and estimated blood loss were similar between the groups. There were no significant differences in first flatus, diet initiation, and postoperative hospital stay. The surgical complication rates were 17.2% (25/145) and 13.9% (15/108) in the LATG and TLTG groups, respectively. The meta-analysis also revealed no significant differences in the operation time, estimated blood loss, time to first flatus, length of hospital stay, overall, and anastomosis-related complications among the groups., Conclusions: TLTG is a feasible choice for gastric cancer patients, with comparable results to the LATG approach.

Aim: To assess the efficacy and safety of intracorporeal esophagojejunostomy in patients undergoing laparoscopic total gastrectomy (LTG) for gastric cancer., Methods: A retrospective review of 81 consecutive patients who underwent LTG with the same surgical team between November 2007 and July 2014 was performed. Four types of intracorporeal esophagojejunostomy using staplers or hand-sewn suturing were performed after LTG. Data on clinicopatholgoical characteristics, occurrence of complications, postoperative recovery, anastomotic time, and operation time among the surgical groups were obtained through medical records., Results: The average operation time was 288.7 min, the average anastomotic time was 54.3 min, and the average estimated blood loss was 82.7 mL. There were no cases of conversion to open surgery. The first flatus was observed around 3.7 d, while the liquid diet was started, on average, from 4.9 d. The average postoperative hospital stay was 10.1 d. Postoperative complications occurred in 14 patients, nearly 17.3%. However, there were no cases of postoperative death., Conclusion: LTG performed with intracorporeal esophagojejunostomy using laparoscopic staplers or hand-sewn suturing is feasible and safe. The surgical results were acceptable from the perspective of minimal invasiveness.

Background: Totally laparoscopic distal gastrectomy (TLDG) using intracorporeal anastomosis has gradually developed due to advancements in laparoscopic surgical instruments. However, totally laparoscopic total gastrectomy (TLTG) with intracorporeal esophagojejunostomy (IE) is still uncommon because of technical difficulties. Herein, we evaluated various types of IE after TLTG in terms of the technical aspects. We compared the short-term operative outcomes between TLTG with IE and laparoscopy-assisted total gastrectomy (LATG) with extracorporeal esophagojejunostomy (EE)., Methods: Between March 2006 and December 2014, a total of 213 patients with gastric cancer underwent TLTG and LATG. Overall, 92 patients underwent TLTG with IE, and 121 patients underwent LATG with EE. Generally, there are two methods of IE: mechanical staplers (circular or linear staplers) and hand-sewn sutures. Surgical efficiencies and outcomes were compared between two groups. We also described various types of IE using a subgroup analysis., Results: The mean operation times were similar in the two groups, as was the number of retrieved lymph nodes. However, the mean estimated blood loss of TLTG was statistically lower than LATG. There were no significant differences in time to first flatus, the time to restart oral intake, the length of the hospital stay after operation, and postoperative complications. Four types of IE have been applied after TLTG, including 42 cases of hand-sewn IE. The overall mean operation time and the mean anastomotic time in TLTG were 279.5 ± 38.4 min and 52.6 ± 18.9 min respectively. There was no case of conversion to open procedure. Postoperative complication occurred in 16 patients (17.4%) and no postoperative mortality occurred., Conclusions: IE is a feasible procedure and can be safely performed for TLTG with the proper laparoscopic expertise. It is technically feasible to perform hand-sewn IE after TLTG, which can reduce the cost of the laparoscopic procedure.

Background: Conflicting results about the association between expression level of excision repair cross-complementation group 1 (ERCC1) and clinical outcome in patients with colorectal cancer (CRC) receiving chemotherapy have been reported. Thus, we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC., Methods: A thorough literature search using PubMed (Medline), Embase, Cochrane Library, Web of Science databases, and Chinese Science Citation Database was conducted to obtain the relevant studies. Pooled hazard ratios (HR s) or odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the results., Results: A total of 11 studies were finally enrolled in this meta-analysis. Compared with patients with lower ERCC1 expression, patients with higher ERCC1 expression tended to have unfavorable overall survival (OS) (HR = 2.325, 95% CI: 1.720-3.143, P < 0.001), progression-free survival (PFS) (HR = 1.917, 95% CI: 1.366-2.691, P < 0.001) and poor response to chemotherapy (OR = 0.491, 95% CI: 0.243-0.990, P = 0.047). Subgroup analyses by treatment setting, ethnicity, HR extraction, detection methods, survival analysis, and study design demonstrated that our results were robust., Conclusions: ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy, OS, and PFS. Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC1's prognostic value.

To better understand the molecular mechanisms responsible for light-induced damage in retinal pigmented epithelial (RPE) cells, we developed an automated device to recapitulate intense light exposure. When compared with human fibroblasts, ARPE-19 cells that had been exposed to blue-rich light-emitting diode-light of 10 000 Lux at 37 °C for 9 h displayed dramatic cellular apoptosis. Collectively, gene expression profiling and qPCR demonstrated that growth arrest and DNA damage-45α (GADD45α) expression was markedly upregulated. Transient knockdown of GADD45α partially attenuated light-damage-induced apoptosis in ARPE-19 cells, whereas GADD45α overexpression dramatically increased it. These results demonstrate the critical function of GADD45α in light-induced RPE cellular apoptosis. Quantitative reverse transcription-PCR and western blotting revealed that the upregulation of GADD45α was under direct control of p53. Moreover, treatment with Ly294002, an inhibitor of AKT phosphorylation, further promoted GADD45α gene transcription in both non-light and light-damaged ARPE-19 cells. Treatment also exacerbated RPE cellular apoptosis after light exposure, confirming that inhibition of Akt phosphorylation increases GADD45α expression. Collectively, our findings reveal that light irrigation induces human RPE cellular apoptosis through upregulation of GADD45α expression mediated through both the p53 and phosphatidylinositol 3-kinase-AKT signaling pathways. These results provide new insights into human retinal diseases elicited by light damage and open a new avenue for disease prevention and treatment.

Objective: To summary the recent advances in molecular research of glioblastoma (GBM) and current trends in personalized therapy of this disease., Data Sources: Data cited in this review were obtained mainly from PubMed in English up to 2015, with keywords "molecular", "genetics", "GBM", "isocitrate dehydrogenase", "telomerase reverse transcriptase", "epidermal growth factor receptor", "PTPRZ1-MET", and "clinical treatment"., Study Selection: Articles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed., Results: There is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations. Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations. These differences are important, especially because they may affect sensitivity to radio- and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches., Conclusion: This review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM.

Conflicting results about the prognostic value of Glasgow Prognostic Score (GPS) in hepatocellular carcinoma (HCC) patients have been reported. We searched the available articles and performed the meta-analysis to clarify the predictive value of GPS in HCC patients' outcome.A systematic literature search was conducted using PubMed (Medline), Embase, Cochrane Library, Web of Science, ChinaInfo, and Chinese National Knowledge Infrastructure for all years up to September 2015. Studies analyzing the relationship of GPS and survival outcome were identified. Hazard ratio (HR) with 95% confidence interval (CI) was calculated to assess the risk.A total of 10 studies were finally enrolled in the meta-analysis. The pooled estimates demonstrated a significant relationship between elevated GPS and inferior overall survival in patients with HCC (HR = 2.156, 95% CI: 1.696-2.740, P < 0.001). Patients with increased GPS had a tendency toward shorter progression-free survival (HR = 1.755, 95% CI: 0.943-3.265, P = 0.076). And elevated GPS was found to be significantly associated with advanced Child-Pugh class (odds ratio = 25.979, 95% CI: 6.159-109.573, P < 0.001). The publication bias analysis revealed that there was publication bias in the meta-analysis.Glasgow Prognostic Score may be an independent prognostic factor in patients with HCC. More well-designed studies with adequate follow-up duration are warranted., Competing Interests: The authors have no conflicts of interest to disclose.

Anaplastic gliomas are characterized by variable clinical and genetic features, but there are few studies focusing on the substratification of anaplastic gliomas. To identify a more objective and applicable classification of anaplastic gliomas, we analyzed whole genome mRNA expression profiling of four independent datasets. Univariate Cox regression, linear risk score formula and receiver operating characteristic (ROC) curve were applied to derive a gene signature with best prognostic performance. The corresponding clinical and molecular information were further analyzed for interpretation of the different prognosis and the independence of the signature. Gene ontology (GO), Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were performed for functional annotation of the differences. We found a three-gene signature, by applying which, the anaplastic gliomas could be divided into low risk and high risk groups. The two groups showed a high concordance with grade II and grade IV gliomas, respectively. The high risk group was more aggressive and complex. The three-gene signature showed diagnostic and prognostic value in anaplastic gliomas.

Background: Glioma is the most common malignant primary brain tumor among adults, among which glioblastoma (GBM) exhibits the highest malignancy. Despite current standard chemoradiation, glioma is still invariably fatal. A further insight into the molecular background of glioma is required to improve patient outcomes., Method: Previous studies evaluated molecular genetic differences through comparing different grades of glioma. Here, we integrated DNA methylation, RNA sequencing and protein expression data sets of WHO grade II to IV gliomas, to screen for dysregulated genes in subtypes during malignant progression of glioma., Results: We propose a list of universal genes (UG) as novel glioma biomarkers: 977 up-regulated genes and 114 down-regulated genes, who involved in cell cycle, Wnt receptor signaling pathway and fatty acid metabolic process. Poorer survival was associated significantly with the high expression of 977 up-regulated genes and low expression of 114 down-regulated in UG (P <0.001)., Conclusion: To our knowledge, this was the first study that focused on subtypes to detect dysregulated genes that could contribute to malignant progression. Furthermore, the differentially expressed genes profile may lead to the identification of new therapeutic targets for glioma patients.

Aim: To investigate the expression characteristics of peroxiredoxin 1 (PRDX1) mRNA and protein in liver cancer cell lines and tissues., Methods: The RNA sequencing data from 374 patients with liver cancer were obtained from The Cancer Genome Atlas. The expression and clinical characteristics of PRDX1 mRNA were analyzed in this dataset. The Kaplan-Meier and Cox regression survival analysis was performed to determine the relationship between PRDX1 levels and patient survival. Subcellular fractionation and Western blotting were used to demonstrate the expression of PRDX1 protein in six liver cancer cell lines and 29 paired fresh tissue specimens. After bioinformatics prediction, a putative post-translational modification form of PRDX1 was observed using immunofluorescence under confocal microscopy and immunoprecipitation analysis in liver cancer cells., Results: The mRNA of PRDX1 gene was upregulated about 1.3-fold in tumor tissue compared with the adjacent non-tumor control (P = 0.005). Its abundance was significantly higher in men than women (P < 0.001). High levels of PRDX1 mRNA were associated with a shorter overall survival time (P = 0.04) but not with recurrence-free survival. The Cox regression analysis demonstrated that patients with high PRDX1 mRNA showed about 1.9-fold increase of risk for death (P = 0.03). In liver cancer cells, PRDX1 protein was strongly expressed with multiple different bands. PRDX1 in the cytosol fraction existed near the theoretical molecular weight, whereas two higher molecular weight bands were present in the membrane/organelle and nuclear fractions. Importantly, the theoretical PRDX1 band was increased, whereas the high molecular weight form was decreased in tumor tissues. Subsequent experiments revealed that the high molecular weight bands of PRDX1 might result from the post-translational modification by small ubiquitin-like modifier-1 (SUMO1)., Conclusion: PRDX1 was overexpressed in the tumor tissues of liver cancer and served as an independent poor prognostic factor for overall survival. PRDX1 can be modified by SUMO to play specific roles in hepatocarcinogenesis.

Isocitrate dehydrogenase 1 gene mutations are found in most World Health Organization grade II and III gliomas and secondary glioblastomas. Isocitrate dehydrogenase 1 mutations are known to have prognostic value in high-grade gliomas. However, their prognostic significance in low-grade gliomas remains controversial. We determined the predictive and prognostic value of isocitrate dehydrogenase 1 status in low-grade gliomas. The association of isocitrate dehydrogenase 1 status with clinicopathological and genetic factors was also evaluated. Clinical information and genetic data including isocitrate dehydrogenase 1 mutation, O 6-methylguanine DNA methyltransferase promoter methylation, 1p/19q chromosome loss, and TP53 mutation of 417 low-grade gliomas were collected from the Chinese Glioma Genome Atlas database. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the prognostic effect of clinical characteristics and molecular biomarkers. Isocitrate dehydrogenase 1 mutation was identified as an independent prognostic factor for overall, but not progression-free, survival. Notably, isocitrate dehydrogenase 1 mutation was found to be a significant prognostic factor in patients with oligodendrogliomas, but not in patients with astrocytomas. Furthermore, O 6-methylguanine DNA methyltransferase promoter methylation (p = 0.017) and TP53 mutation (p < 0.001), but not 1p/19q loss (p = 0.834), occurred at a higher frequency in isocitrate dehydrogenase 1-mutated tumors than in isocitrate dehydrogenase 1 wild-type tumors. Younger patient age (p = 0.041) and frontal lobe location (p = 0.010) were significantly correlated with isocitrate dehydrogenase 1 mutation. Chemotherapy did not provide a survival benefit in patients with isocitrate dehydrogenase 1-mutated tumors. Isocitrate dehydrogenase 1 mutation was an independent prognostic factor in low-grade gliomas, whereas it showed no predictive value for chemotherapy response. Isocitrate dehydrogenase 1 mutation was highly associated with O 6-methylguanine DNA methyltransferase promoter methylation and TP53 mutation.

Objective: The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with digestive system cancers., Methods: We searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) of overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic role of p-STAT3 expression level in cancer tissues. And the association between p-STAT3 expression and clinicopathological characteristics was evaluated., Results: A total of 22 studies with 3585 patients were finally enrolled in the meta-analysis. The results showed that elevated p-STAT3 expression level predicted inferior OS (HR = 1.809, 95% CI: 1.442-2.270, P < 0.001) and DFS (HR = 1.481, 95% CI: 1.028-2.133, P = 0.035) in patients with malignant cancers of the digestive system. Increased expression of p-STAT3 is significantly related with tumor cell differentiation (Odds ratio (OR) = 1.895, 95% CI: 1.364-2.632, P < 0.001) and lymph node metastases (OR = 2.108, 95% CI: 1.104-4.024, P = 0.024). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger's tests revealed there was no significant publication bias in the meta-analysis., Conclusion: Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers. More well designed studies with adequate follow-up are needed to gain a thorough understanding of the prognostic role of p-STAT3.

Background: The aim of this study was to compared laparoscopic (LWR) and open wedge resection (OWR) for the treatment of gastric gastrointestinal stromal tumors (GISTs)., Methods: The data of 156 consecutive GISTs patients underwent LWR or OWR between January 2006 and December 2013 were collected retrospectively. The surgical outcomes and the long-term survival rates were compared. Besides, a rapid systematic review and meta-analysis were conducted., Results: Clinicopathological characteristics of the patients were similar between the two groups. The LWR group was associated with less intraoperative blood loss (67.3 vs. 142.7 ml, P < 0.001), earlier postoperative flatus (2.3 vs. 3.2 days, P < 0.001), earlier oral intake (3.2 vs. 4.1 days, P < 0.001) and shorter postoperative hospital stay (6.0 vs. 8.0 days, P = 0.001). The incidence of postoperative complications was lower in LWR group but did not reach statistical significance (4/90, 4.4% vs. 8/66, 12.1%, P = 0.12). No significant difference was observed in 3-year relapse-free survival rate between the two groups (98.6% vs. 96.4%, P > 0.05). The meta-analysis revealed similar results except less overall complications in the LWR group (RR = 0.49, 95% CI, 0.25 to 0.95, P = 0.04). And the recurrence risk was similar in two group (RR = 0.80, 95% CI, 0.28 to 2.27, P > 0.05)., Conclusions: LWR is a technically and oncologically safe and feasible approach for gastric GISTs compared with OWR. Moreover, LWR appears to be a preferable choice with mini-invasive benefits.

Culture of hippocampal neurons in low-Mg(2+) medium (low-Mg(2+) neurons) results in induction of continuous seizure activity. However, the underlying mechanism of the contribution of low Mg(2+) to hyperexcitability of neurons has not been clarified. Our data, obtained using the patch-clamp technique, show that voltage-gated Na(+) channel (VGSC) activity, which is associated with a persistent, noninactivating Na(+) current (INa,P), was modulated by calmodulin (CaM) in a concentration-dependent manner in normal and low-Mg(2+) neurons, but the channel activity was more sensitive to Ca(2+)/CaM regulation in low-Mg(2+) than normal neurons. The increased sensitivity of VGSCs in low-Mg(2+) neurons was partially retained when CaM12 and CaM34, CaM mutants with disabled binding sites in the N or C lobe, were used but was diminished when CaM1234, a CaM mutant in which all four Ca(2+) sites are disabled, was used, indicating that functional Ca(2+)-binding sites from either lobe of CaM are required for modulation of VGSCs in low-Mg(2+) neurons. Furthermore, the number of neurons exhibiting colocalization of CaM with the VGSC subtypes NaV1.1, NaV1.2, and NaV1.3 was significantly higher in low- Mg(2+) than normal neurons, as shown by immunofluorescence. Our main finding is that low-Mg(2+) treatment increases sensitivity of VGSCs to Ca(2+)/CaM-mediated regulation. Our data reveal that CaM, as a core regulating factor, connects the functional roles of the three main intracellular ions, Na(+), Ca(2+), and Mg(2+), by modulating VGSCs and provides a possible explanation for the seizure discharge observed in low-Mg(2+) neurons., (Copyright © 2015 the American Physiological Society.)

Background: Hepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients., Methods: This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic., Results: The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7 th (TNM 7 th ) (AIC = 2899.980), TNM 6 th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389)., Conclusions: BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

Aim: To analyze the clinicopathologic characteristics and prognostic factors of rectal neuroendocrine tumors., Methods: The records of 48 patients with rectal neuroendocrine tumors who were treated at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, from March 2004 to September 2009 were retrospectively reviewed. The clinicopathological data were extracted and analyzed, and patients were followed-up by telephone or follow-up letter to determine their survival status. Follow-up data were available for all 48 patients. Uni- and multivariate Cox regression analyses were performed to determine the prognostic factors significantly associated with overall survival., Results: The tumors occurred mostly in the middle and lower rectum, and the most prominent symptoms experienced by patients were hematochezia and diarrhea. The median distance between the tumors and the anal edges was 5.0 ± 2.257 cm, and the median diameter of the tumors was 0.8 ± 1.413 cm. The major pathological type was a typical carcinoid tumor, which accounted for 93.8% (45/48) of patients. Tumor-node-metastasis (TNM) stages I, II, III and IV tumors accounted for 78.8%, 3.9%, 9.6% and 7.7% of patients, respectively. The main treatment method, in 72.9% (35/48) of patients, was transanal extended excision. The 1-, 3- and 5-year survival rates of the whole group of patients were 100%, 93.7%, and 91.3%, respectively. Univariate analysis showed that age (P = 0.032), tumor diameter (P < 0.001), histological type (P < 0.001), TNM stage (P < 0.001), and surgical approach (P = 0.002) were all prognostic factors. On multivariate analysis, only the pathological type was shown to be an independent prognostic factor (HR = 2.797, 95%CI: 1.676-4.668, P = 0.004)., Conclusion: In patients with rectal neuroendocrine tumors, TNM stage I is the most common stage found, and lymph node or distant metastases are rarely seen. The pathological type of the tumor is an independent prognostic factor.

Aim: To systematically review the surgical outcomes of totally laparoscopic gastrectomy (TLG) vs open gastrectomy (OG) for gastric cancer., Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted. All original studies comparing TLG with OG were included for critical appraisal. Data synthesis and statistical analysis were carried out using RevMan 5.1 software., Results: One RCT and 13 observational studies involving 1532 patients were included (721 TLG and 811 OG). TLG was associated with longer operation time [weighted mean difference (WMD) = 58.04 min, 95%CI: 37.77-78.32, P < 0.001], less blood loss [WMD = -167.57 min, 95%CI: -208.79-(-126.34), P < 0.001], shorter hospital stay [WMD = -3.75 d, 95%CI: -4.88-(-2.63), P < 0.001] and fewer postoperative complications (RR = 0.71, 95%CI: 0.58-0.86, P < 0.001). The number of harvested lymph nodes, surgical margin, mortality and cancer recurrence rate were similar between the two groups., Conclusion: TLG may be a technically safe, feasible and favorable approach in terms of better cosmesis, less blood loss and faster recovery compared with OG.

Gastric cancer in remnant stomach is a rare tumor but with poor prognosis. Compared with conventional open surgery, laparoscopic gastrectomy has potential benefits for these patients due to advantages resulting from its minimally invasive approach. Herein, we report on three patients with gastric cancer in remnant stomach who underwent laparoscopic total gastrectomy with intracorporeal esophagojejunostomy successfully. The operative time was 280, 250 and 225 minutes, the estimated blood loss was 100, 80 and 50 ml and the length of postoperative hospital stay was seven, eight and nine days respectively. Our experience has suggested that laparoscopic total gastrectomy with intracorporeal esophagojejunostomy can be a safe, feasible and promising option for patients with gastric cancer in remnant stomach.