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Rationale: Failure to recognize intestinal malrotation in adults can cause complications during surgeries, especially those with a limited operative field. We report a case of short bowel syndrome caused by mistaken creation of a loop enterostomy in the jejunum due to undiagnosed intestinal malrotation., Patient Concerns: A 72-year-old man underwent a laparoscopic right hemicolectomy and ileocolostomy because of complicated diverticulitis. Six days after the surgery, he received laparoscopic exploration because of anastomotic leak, and a laparoscopic loop ileostomy was also performed as a protective diversion stoma. One month after surgery, he complained of severe diarrhea from the enterostomy after food and water intake. An upper gastrointestinal and small bowel series revealed that the duodenojejunal junction (DJJ) did not cross the midline and there was a short distance between the DJJ and the enterostomy in the right lower quadrant., Diagnoses: Short bowel syndrome caused by mistaken creation of a loop enterostomy in the jejunum due to undiagnosed intestinal malrotation., Interventions: Total parental nutrition was used and the loop enterostomy was closed 3 months after the initial surgery., Outcomes: The patient was discharged uneventfully 2 weeks after the loop enterostomy., Lessons: Intestinal malrotation in adults is often encountered during routine radiological examinations. However, it may cause complications during surgery if ignored. Radiologists should keep in mind that complications may occur if a complete presurgical evaluation of intestinal malrotation is not performed, and surgeons should take caution when performing surgeries, especially those with a limited operative field.

In pharmaceutical-related research, we usually use clinical trials methods to identify valuable treatments and compare their efficacy with that of a standard control therapy. Although clinical trials are essential for ensuring the efficacy and postmarketing safety of a drug, conducting clinical trials is usually costly and time-consuming. Moreover, to allocate patients to the little therapeutic effect treatments is inappropriate due to the ethical and cost imperative. Hence, there are several 2-stage designs in the literature where, for reducing cost and shortening duration of trials, they use the conditional power obtained from interim analysis results to appraise whether we should continue the lower efficacious treatments in the next stage. However, there is a lack of discussion about the influential impacts on the conditional power of a trial at the design stage in the literature. In this article, we calculate the optimal conditional power via the receiver operating characteristic curve method to assess the impacts on the quality of a 2-stage design with multiple treatments and propose an optimal design using the minimum expected sample size for choosing the best or promising treatment(s) among several treatments under an optimal conditional power constraint. In this paper, we provide tables of the 2-stage design subject to optimal conditional power for various combinations of design parameters and use an example to illustrate our methods., (Copyright © 2018 John Wiley & Sons, Ltd.)

Several studies suggested a relationship between stress and related mental illnesses, such as depression and osteoporosis. However, it was unclear whether patients with post-traumatic stress disorder (PTSD) were at risk of developing osteoporosis in later life. In this study, 6,041 patients with PTSD and 24,164 age- or sex-matched controls were enrolled between 2002 and 2009 in our study and followed up to the end of 2011. Cases of osteoporosis were identified during the follow-up. Patients with PTSD had an elevated likelihood of developing osteoporosis (HR: 2.66, 95% CI [1.91, 3.71]) in later life compared with the controls. Sensitivity tests after excluding the first year observation (HR: 2.46, 95% CI [1.72, 3.53]) and the first 3-year observation (HR: 1.88, 95% CI [1.18, 3.01]) were consistent. Patients with PTSD had a higher risk of developing osteoporosis at an earlier age compared with those without PTSD. Further studies would be necessary to clarify the pathophysiology between PTSD and osteoporosis., (Copyright © 2018 John Wiley & Sons, Ltd.)

Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide. Chemotherapy has been the major strategy for treating patients with advanced CRC. Oxaliplatin (OXA) is used as both an adjuvant and neoadjuvant anticancer agent available to treat advanced CRC. High-mobility group box 1 protein (HMGB1) is a critical regulator of cell death and survival. HMGB1 overexpression has been shown to be resistant to cytotoxic agents. In addition, Metformin, a widely used drug for diabetes, has emerged as a potential anticancer agent. In this study, we examined whether HMGB1 plays a role in the OXA- and/or metformin-induced cytotoxic effect on CRC cells. The results showed that treatment with OXA increased HMGB1 expression in the ERK1/2- and Akt-dependent manners in DLD-1 cells. HMGB1 gene knockdown enhanced the cytotoxicity and cell growth inhibition of OXA. Moreover, OXA-increased HMGB1 expression was by inducing NF-κB-DNA-binding activity to in DLD-1 cells. Compared to a single agent, OXA combined with metformin administration resulted in cytotoxicity and cell growth inhibition synergistically, accompanied with reduced HMGB1 level. These findings may have implications for the rational design of future drug regimens incorporating OXA and metformin for the treatment of CRC., (© 2018 Wiley Periodicals, Inc.)

BH3 domains, classified initially as BCL2 homology domains, participate in both apoptosis and autophagy. Beclin‑1 contains a BH3 domain, which is required for binding to antiapoptotic BCL2 homologs and BCL2‑mediated inhibition of autophagy. BCL2‑like 12 (BCL2L12) also harbors a BH3‑like domain, which is 12 residues long and contains a LXXXAE/D motif. In a yeast two‑hybrid system performed in the present study, BCL2L12 shared similar binding partnerships to antiapoptotic BCL2 homologs, such as Beclin‑1. In addition, this BH3‑like domain was involved in anti‑apoptosis and drug‑induced autophagy in glioma cell lines. Mutations in S156 and hydrophobic L213 to alanine counteracted the antiapoptotic properties of BCL2L12 and downregulated the activation of microtubule associated protein 1 light chain 3B (LC3B), autophagy‑related (ATG)12‑ATG5 conjugates and Beclin‑1, compared with a BCL2L12 wild‑type group. Molecular dynamics simulations revealed that phosphorylation at Ser156 of BCL2L12 (within α‑6 and α‑7 helices) influenced the BH3‑like domain conformation (α‑9 helix), indicating that glycogen synthase kinase (GSK) 3β‑mediated Ser156 phosphorylation modulated a BH3‑like domain in BCL2L12. Altogether, the present findings indicated that BCL2L12 may participate in anti‑apoptosis and autophagy via a BH3‑like domain and GSK3β‑mediated phosphorylation at Ser156. Furthermore, blockade of temozolomide (TMZ)‑induced autophagy by 3‑methyladenine (3‑MA) resulted in enhanced activation of apoptotic markers, as well as tumor suppresor protein p53 (p53) expression in U87MG cells. The present results suggested that p53 and O6‑methylguanine DNA methyltransferase activation, and BCL2, BCL‑extra large, Beclin‑1 and BCL2L12 expression may be used as a detection panel to determine which patients can benefit from TMZ and ABT‑737 combination treatment.

An efficient catalytic enantioselective access to chiral functionalized trifluoromethyl cyclopropanes from two classes of diazo compounds and α-trifluoromethyl styrenes using Rh 2 ((S)-BTPCP) 4 as a catalyst is described. This method provides an efficient and practical strategy for the synthesis of highly functionalized CF 3 -cyclopropanes with excellent diastereoselectivities (up to 20:1) and enantioselectivities (up to 99 % ee). The depicted methodology represents, to date, the most efficient catalytic enantioselective method to access highly decorated chiral CF 3 -cyclopropanes. Extension to chiral monohalomethyl cyclopropanes in high ee is also reported., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To investigate the expression of miR-134 and the change of inflammatory cytokines in seizure rats and to explore its relationship., Materials and Methods: A rat model of seizures was made by an intraperitoneal injection with kainic acid. ELISA kit for detection of seizures in rats was used. The changes of inflammatory cytokines (IL-1, IL-2, IL-6, TNF-α, IFN-γ) and the hippocampal neuronal cell growth were observed. The expression of miR-134 in brain tissue and serum samples of model group and control group was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) quantitative determination., Results: After the intraperitoneal injection of kainic acid, the rat model of seizure was successfully established. Compared with the control group, the neuronal cells in the hippocampus of the model group showed evident pathological changes. Inflammatory cytokines in seizures rats showed that the increase of IL-2, IL-6, and TNF-α were larger, but the increase of IL-1 and IFN-γ was not obvious. The results of the RT-PCR quantitative analysis showed that the expression of miR-134 in brain tissue and serum of epilepsy rats was lower than that of the control group (p<0.05)., Conclusions: The expression of miR-134 would be down by the increasing of inflammatory cytokines in the epileptic seizure.

Background: To treat skin color disorders, such as vitiligo or burns, melanocytes are transplanted for tissue regeneration. However, melanocyte distribution in the human body varies with age and location, making it difficult to select the optimal donor skin to achieve a desired color match. Determining the correlations with the desired skin color measurement based on CIELAB color, epidermal melanocyte numbers, and melanin content of individual melanocytes is critical for clinical application., Method: Fifteen foreskin samples from Asian young adults were analyzed for skin color, melanocyte ratio (melanocyte proportion in the epidermis), and melanin concentration. Furthermore, an equation was developed based on CIELAB color with melanocyte ratio, melanin concentration, and the product of melanocyte ratio and melanin concentration. The equation was validated by seeding different ratios of keratinocytes and melanocytes in tissue-engineered skin substitutes, and the degree of fitness in expected skin color was confirmed., Results: Linear regression analysis revealed a significant strong negative correlation ( r  =  - 0.847, R 2  = 0.717) between CIELAB L * value and the product of the epidermal melanocyte ratio and cell-based melanin concentration. Furthermore, the results showed that an optimal skin color match was achieved by the formula., Discussion: We found that L * value was correlated with the value obtained from multiplying the epidermal melanocyte ratio (R) and melanin content (M) and that this correlation was more significant than either L * vs M or L * vs R. This suggests that more accurate prediction of skin color can be achieved by considering both R and M. Therefore, precise skin color match in treating vitiligo or burn patients would be potentially achievable based on extensive collection of skin data from people of Asian descent., Competing Interests: The authors declare there are no competing interests.

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an emerging surgical procedure for peritoneal carcinomatosis (PC). CRS/HIPEC is a complicated treatment that requires multi-disciplinary teamwork (MDT), which may be lacking when establishing a CRS/HIPEC programme. Herein, we report our preliminary treatment outcomes with the early implementation of an MDT model for CRS/HIPEC., Methods: From April 2015 to December 2016, 45 patients with a diagnosis of PC who received CRS/HIPEC were reviewed retrospectively in a single institution in Taiwan., Results: Among the 45 patients, CRS was mainly performed by laparotomy (n = 42), and only three patients with limited PC underwent laparoscopic CRS. The first 13 patients received treatment before the MDT had been established (group 1), and the other 32 patients were treated after the MDT had been established (group 2). The highest peri-HIPEC body temperature in group 2 was significantly lower than that in group 1 (36.8 °C vs. 37.5 °C, p < 0.001). Overall, eight patients experienced major complications. The trend of a lower major complication rate was observed after the MDT model had been implemented (30.7% in group 1 vs. 12.4% in group 2, p = 0.202). Pre-CRS/HIPEC abdominal pain significantly increased the risk of post-operative major complications (p = 0.017)., Conclusions: Our experience suggests that the early implementation of an MDT model when establishing a CRS/HIPEC programme at a single institution may result in a higher complete cytoreduction rate and lower major complication rate, and also shorten the learning curve of this complicated procedure.

Background: A satisfactory bolus injection is essential for a successful first-pass radionuclide angiography (FPRNA). Rescheduling the FPRNA study is usually needed due to high background interference caused by an unsatisfactory bolus injection. We developed a protocol to correct the pre-existing background activity subsequent to immediately repeating the study., Methods: Seventy-four consecutive patients who had their bone scan and FPRNA scheduled on the same day were included for analysis. The initial 51 cases constituted the "validation-only" group. In the other 23 cases, the "validation plus clearance constants" group, a 5-min dynamic acquisition was performed during the 5-min equilibrium to obtain the background clearance curve and the clearance constants. For all included 74 cases ejection fraction (EF) analysis was proceeded using the images from the first injection, second injection, and second injection with the corrected background to yield EF1, EF2, and EF2', respectively. EF2 and EF2' were then compared to the ejection fraction without background interference, the EF1., Results: For the LV, the mean difference between the EF1 and the uncorrected EF2 (|LVEF1-LVEF2| in mean ± SD) was 3.1 ± 2.0% and the difference between the EF1 and the corrected EF2' (|LVEF1-LVEF2'|) was 1.6 ± 2.1%, while the mean differences for RV are 2.2 ± 1.9% and 1.8 ± 1.8%, respectively. A significant difference (p < 0.05) was observed between the uncorrected and the corrected data for both the LV and RV., Conclusion: In FPRNA, when a bolus injection is immediately readministered, both LVEF and RVEF can be underestimated. With our correction method, the results are superior to those without correction., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Black garlic has been reported to show multiple bioactivities against the development of different diseases. In the present study, the hepatoprotective effect of black garlic on injured liver cells was investigated. Rat clone-9 hepatocytes were used for all experiments; tert-Butyl hydroperoxide (tBHP) was used to induce injury of rat clone-9 hepatocytes. The contents of malondialdehyde (MDA) and glutathione (GSH); anti-oxidative enzyme activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx); and mRNA expression levels of interleukin (IL)-6 and IL-8 in rat clone-9 hepatocytes were determined to evaluate the level of cell damage. Black garlic extracts were demonstrated to significantly attenuate tBHP-induced cell death of rat clone-9 hepatocytes (P<0.05). Pretreatment with black garlic extracts antagonized GSH depletion, tBHP-increased MDA accumulation and the mRNA expression level of IL-6/IL-8, and tBHP-decreased antioxidative enzyme activities (all P<0.05). Moreover, the present study revealed that c-Jun N-terminal kinase signaling regulated black garlic-inhibited tBHP effects in rat clone-9 hepatocytes. Our findings demonstrate that black garlic has the hepatoprotective potential to block tBHP-damaged effects on cell death, lipid peroxidation, oxidative stress, and inflammation in rat clone-9 hepatocytes. Thus, the present study indicates that black garlic may be an excellent natural candidate in the development of adjuvant therapy and healthy foods for liver protection.

Background: Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- 11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1- 11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear., Methods: [1- 11 C]-acetate positron emission tomography (PET) with dynamic measurement of K 1 and k 2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication., Results: PET imaging demonstrated decreased [1- 11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K 1 and clearance rate constant k 2 were decreased in acutely intoxicated rats. No significant change was noted in K 1 and k 2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k 2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect., Conclusions: In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- 11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- 11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain., (Copyright © 2017 by the Research Society on Alcoholism.)

Hypomagnesemia is a recognized side-effect of cetuximab- or panitumumab-based chemotherapy for metastatic colorectal cancer (mCRC). The clinical relevance of hypomagnesemia is under debate. Thus, a systematic review and meta-analysis of retrospective studies and randomized clinical trials (RCTs) comparing hypomagnesemia with normal magnesium levels in wild-type KRAS mCRC was performed. One RCT, two retrospective studies, and two American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) conference presentations from phase III RCTs involving 1723 patients were included in this study. Patients with hypomagnesemia demonstrated better progression-free survival (PFS) (Hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.47-0.88), overall survival (OS) (HR: 0.72; 95% CI: 0.53-0.92), and objective response rate (ORR) (Risk ratio [RR]: 1.81; 95% confidence interval [CI]: 1.30-2.52). By subgroup analysis, frontline, later lines or combination therapy with hypomagnesemia were associated with PFS benefits (HR: 0.78; 95% CI: 0.62-0.98; HR: 0.60; 95% CI: 0.40-0.90; HR: 0.62; 95% CI: 0.41-0.94, respectively). In patients with wild-type KRAS mCRC, hypomagnesemia is associated with better clinical benefits of PFS, OS and ORR when treated with cetuximab- or panitumumab-based chemotherapy. Future clinical trials should corroborate its predictive role.

Aim: To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization combined with sorafenib (TACE-S)., Methods: We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S (median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors (mRECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival., Results: Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate (DCR) of 63.2%. Patients who got sorafenib at the first TACE (no previous TACE) and patients without portal vein tumor thrombus (PVTT) had a higher DCR than those who underwent previous TACE before TACE-S (72.4% vs 48.6%, P = 0.019) and those with PVTT (75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni- and multivariate analyses., Conclusion: The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with mRECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to declare.

Anti-predator strategies are significant components of adaptation in prey species. Aposematic prey are expected to possess effective defences that have evolved simultaneously with their warning colours. This study tested the hypothesis of the defensive function and ecological significance of the hard body in aposematic Pachyrhynchus weevils pioneered by Alfred Russel Wallace nearly 150 years ago. We used predation trials with Japalura tree lizards to assess the survivorship of 'hard' (mature) versus 'soft' (teneral) and 'clawed' (intact) versus 'clawless' (surgically removed) weevils. The ecological significance of the weevil's hard body was evaluated by assessing the hardness of the weevils, the local prey insects, and the bite forces of the lizard populations. The existence of toxins or deterrents in the weevil was examined by gas chromatography-mass spectrometry (GC-MS). All 'hard' weevils were instantly spat out after being bitten once and survived attacks by the lizards. In contrast, the 'soft' weevils were chewed and subsequently swallowed. The results were the same regardless of the presence or absence of the weevil's tarsal claws. The hardness of 'hard' Pachyrhynchus weevils was significantly higher than the average hardness of other prey insects in the same habitat and the mean bite forces of the local lizards. The four candidate compounds of the weevil identified by GC-MS had no known toxic or repellent functions against vertebrates. These results reveal that the hardness of aposematic prey functions as an effective secondary defence, and they provide a framework for understanding the spatio-temporal interactions between vertebrate predators and aposematic insect prey., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Background/aims: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear., Methods: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins., Results: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, β-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways., Conclusion: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: Oxidants are important human toxicants. They have been implicated in the occurrence and development of liver diseases. Increased intracellular tert-butylhydroperoxide (t-BHP) may be critical for oxidant toxicity, and is commonly used for evaluating mechanisms involving oxidative stress, but the method remains controversial., Methods: Primary cultures of hepatocytes as well as human Hep G2 and mouse FL83B liver cells were obtained. Cell viability was measured by annexin V-FITC/propidium iodide and DAPI staining to determine the effects of t-BHP treatment on acute liver injury. A proteomic assay provided information that was used to identify the differentially expressed proteins following t-BHP treatment; immunohistochemistry and western blotting were performed to detect the expression of PDIA6 activity in apoptotic and endoplasmic reticulum (ER) stress pathways., Results: Our results demonstrate that t-BHP treatment of liver cells increased cell cytotoxicity and the generation of reactive oxygen species. This treatment also increased the level of PDIA6; this was validated in vitro and in vivo based on a comparison of t-BHP-treated and -untreated groups. Treatment of mouse liver FL83B cells with t-BHP activated caspase 3, increased the expression of apoptotic molecules, caused cytochrome c release, and induced Bcl-2, Bax and IRE1α/TRAF2 complex formation. t-BHP-dependent induction of apoptosis was accompanied by sustained phosphorylation of the IRE1α/ASK1/JNK1/2/p38 pathways and PDIA6 expression. Furthermore, t-BHP induced liver FL83B cell viability and apoptosis by upregulating the levels of PDIA6; this process could be involved in the activation of the IRE1α/ASK1/JNK1/2/p38 signalling pathways., Conclusions: We conclude that t-BHP induced an apoptosis cascade and ER stress in hepatocytes by upregulation of PDIA6, providing a new mechanism underlying the effects of t-BHP on liver injury., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The Republic of China Navy instituted the pressure test as one of the selection tools for diving troops and submarine crews. We analyzed factors associated with failure in the pressure test., Methods: This was a retrospective cohort study designed to investigate pressure test failure in Navy recruits between January 2010 and August 2015. The recruits received pressurization in a hyperbaric chamber to a simulated depth of 112 feet of seawater (fsw) at a rate of 25 fsw/minute. Data describing trainee demographics, disease history, causes and depth of failure, as well as type of injury, were extracted from case notes and facility databases for statistical analysis., Results: Of 3,608 trial cohorts, there were 435 failures, with an overall failure rate of 12.06%. About 95% of these failure trials were within a simulated depth of 60 fsw. Fifty-seven (57) failures did not record causes of failure. Among the other 378 failures, the most commonly identified causes were ear barotrauma (365 trials, 96.56%) and sinus barotrauma (10 trials, 2.65%). Statistical analysis revealed that recent upper respiratory tract infection, allergic rhinitis, and cigarette smoking were all significantly associated with higher incidence of middle ear barotrauma., Conclusions: Our results suggest that pressure testing to a depth of 60 fsw is effective in disqualifying personnel entering diving and submarine service. Recent infection of the upper respiratory tract, allergic rhinitis and cigarette smoking are risk factors for middle ear barotrauma, resulting in failure of the pressure test., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the dependent variable. The total positive predictive value was 64.7%(77/119), with 66.7% for bacterial infection, 78.0% for viral infection and 33.3% for the mixed infection. Conclusions: The mostly detected pathogens were Pseudomonas aeruginosa, atypitcal pathogens, Klebsiella pneumoniae, influenza A virus and human cytomegalovirus in hospitalized patients with LRTI in this hospital. The discriminant diagnostic model established by clinical features may contribute to predict the pathogens of LRTI.

Colorectal cancer (CRC) is one of the leading causes of cancer mortality and 5-Fluorouracil (5-FU) is the most common chemotherapy agent of CRC. A high level of X-ray repair cross complementing group 1 (XRCC1) in cancer cells has been associated with the drug resistance occurrence. Moreover, the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been indicated to regulate the cancer cell survival. Thus, this study was aimed to examine whether XRCC1 plays a role in the 5-FU/AMPK agonist (AICAR)-induced cytotoxic effect on CRC and the underlying mechanisms. Human HCT-116 colorectal cells were used in this study. It was shown that 5-FU increases the XRCC1 expression in HCT-116 cells and then affects the cell survival through CXCR4/Akt signaling. Moreover, 5-FU combined with AICAR further result in more survival inhibition in HCT-116 cells, accompanied with reduced CXCR4/Akt signaling activity and XRCC1 expression. These results elucidate the role and mechanism of XRCC1 in the drug resistance of HCT-116 cells to 5-FU. We also demonstrate the synergistic inhibitory effect of AMPK on 5-FU-inhibited HCT-116 cell survival under the 5-FU and AICAR co-treatment. Thus, our findings may provide a new notion for the future drug regimen incorporating 5-FU and AMPK agonists for the CRC treatment., Competing Interests: The authors declare no conflicts of interest.

The first catalytic asymmetric synthesis of highly functionalized difluoromethylated cyclopropanes is described. The method, based on a rhodium-catalyzed cyclopropanation of difluoromethylated olefins, gives access to a broad range of cyclopropanes bearing ester, ketone, or nitro functional groups. By using Rh 2 ((S)-BTPCP) 4 as a catalyst, the corresponding products were obtained in high yields and high diastereo- and enantioselectivities (up 20:1 d.r. and 99 % ee). This methodology allowed preparation of enantioenriched difluoromethylcyclopropanes for the first time., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Radiation-related sarcoma is a rare but serious complication for patients after receiving radiation therapy initially for their primary malignancy. However, it usually takes several years and needs enough in-field radiation dose to develop this sarcoma. We describe a 60-year-old man with right axillary sarcoma revealed by whole-body F-FDG PET/CT 1 year after chemoradiotherapy, which presented ultrashort latency period and did not match the consensus definition of radiation-related sarcoma. Besides, metastatic sarcoma to small intestine was accidentally noted in the F-FDG PET/CT image.

Boron neutron capture therapy (BNCT) is a binary therapy that employs neutron irradiation on the boron agents to release high-energy helium and alpha particles to kill cancer cells. An optimal response to BNCT depends critically on the time point of maximal 10 B accumulation and highest tumor to normal ratio (T/N) for performing the neutron irradiation. The aggressive cholangiocarcinoma (CCA) representing a liver cancer that overexpresses COX-2 enzyme is aimed to be targeted by COX-2 selective boron carrier, fenbufen boronopinacol (FBPin). Two main works were performed including: 1) chemical synthesis of FBPin as the boron carrier and 2) radiochemical labeling with F-18 to provide the radiofluoro congener, m-[ 18 F]fluorofenbufen ester boronopinacol (m-[ 18 F]FFBPin), to assess the binding affinity, cellular accumulation level and distribution profile in CCA rats. FBPin was prepared from bromofenbufen via 3 steps with 82% yield. The binding assay employed [ 18 F]FFBPin to compete FBPin for binding to COX-1 (IC 50 =0.91±0.68μM) and COX-2 (IC 50 =0.33±0.24μM). [ 18 F]FFBPin-derived 60-min dynamic PET scans predict the 10 B-accumulation of 0.8-1.2ppm in liver and 1.2-1.8ppm in tumor and tumor to normal ratio=1.38±0.12. BNCT was performed 40-55min post intravenous administration of FBPin (20-30mg) in the CCA rats. CCA rats treated with BNCT display more tumor reduction than that by NCT with respect of 2-[ 18 F]fluoro-2-deoxy glucose uptake in the tumor region of interest, 20.83±3.00% (n=12) vs. 12.83±3.79% (n=10), P=0.05. The visualizing agent [ 18 F]FFBPin resembles FBPin to generate the time-dependent boron concentration profile. Optimal neutron irradiation period is thus determinable for BNCT. A boron-substituted agent based on COX-2-binding features has been prepared. The moderate COX-2/COX-1 selectivity index of 2.78 allows a fair tumor selectivity index of 1.38 with a mild cardiovascular effect. The therapeutic effect from FBPin with BNCT warrants a proper COX-2 targeting of boron NSAIDs., (Copyright © 2017. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it's definite clinical effect and mechanism on colon carcinoma is unclear., Aim of the Study: To test the hypothesis that the protective effect of danshen on colon cancer and discover the bioactive compounds through in vitro study., Materials and Methods: We conducted a nationwide cohort study by using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). The study cohort comprised patients diagnosed with malignant neoplasm of colon (ICD-9-CM codes:153) in catastrophic illness database between January 1, 2000, and December 31, 2010. We used the Kaplan-Meier method to estimate colon [corrected] cancer cumulative incidences. Next, human colon cancer cells (HCT 116 cells and HT29 cells) were used to investigate the effect of dihydroisotanshinone I (DT) on the proliferation and apoptosis of human colon cancer cells and the underlying mechanism through XTT assay and flow cytometry. The in vivo effect of DT treatment was investigated through a xenograft nude mouse model., Results: In our study, the in vivo protective effect of danshen in the different stage of colon cancer patients was validated through data from the National Health Insurance Research Database in Taiwan. In vitro, we found that dihydroisotanshinone I (DT), a bioactive compound present in danshen, can inhibit the proliferation of colon carcinoma cells, HCT 116 cells and HT-29 cells. Moreover, DT induced apoptosis of colorectal cancer cells. DT also repressed the protein expression of Skp2 (S-Phase Kinase Associated Protein 2) and the mRNA levels of its related gene, Snail1 (Zinc finger protein SNAI1) and RhoA (Ras homolog gene family, member A). In addition, DT also blocked the colon cancer cells recruitment ability of macrophage by decreasing CCL2 secretion in macrophages. DT treatment also significantly inhibited the final tumor volume in a xenograft nude mouse model., Conclusion: Danshen has protective effects in colon cancer patients, which could be attributed to DT through blocking the proliferation of colon cancer cells through apoptosis., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

The data presented in this article are related to the research article entitled "Synthesis and Characterization of Boron Fenbufen and its F-18 Labeled Homolog for Boron Neutron Capture Therapy of COX-2 Overexpressed Cholangiocarcinoma". The contents of the data article include 1) the set up for performing in vitro binding assay, 2) 1 H-, 13 C- and 19 F-NMR of compounds described in main text, 3) HPLC chromatogram of the fluorination mixtures, 4) data of in vitro stability test, cell survival assay, western blot and PCR analysis, 5) the modules for fixing the two CCA rats for BNCT, and 6) bar diagram for tumor reduction using [ 18 F]FDG-PET 24 h post treatment with BNCT.

Background and Purpose: Inflammation comprises important aspects of large-artery atherosclerosis (LAA) stroke pathophysiology. YKL-40 is a new and emerging biomarker that is associated with both acute and chronic inflammations. Elevated serum concentrations of YKL-40 have been reported in patients with atherosclerosis and other cardiovascular diseases. This study investigates whether serum YKL-40 concentrations on admission can predict 3-month clinical outcomes after LAA stroke., Methods: We recruited control patients (n=85) and those with LAA stroke (n=141) according to the TOAST classification system. The modified Rankin scale at 3 months after stroke was used to evaluate the prognosis. The prognostic accuracy was assessed by the receiver operating characteristic curve., Results: Serum YKL-40 level was significantly higher for LAA patients than for controls (P<.001). Patients with poor outcomes (n=36) had significantly increased serum YKL-40 concentrations on admission (P=.01). High YKL-40 levels predicted poor functional outcome (OR=6.47, P=.02). Moreover, the combination of YKL-40 level and the NIHSS score could improve the prognostic accuracy of the NIHSS in predicting functional outcome (combined areas under the curve, 0.87; 95% CI, 0.80-0.94; P<.001)., Conclusions: The level of serum YKL-40 is a significant and independent biomarker to predict the clinical outcome of LAA stroke., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cerenkov luminescence imaging (CLI) has been an evolutional and alternative approach of nuclear imaging in basic research. This study aimed to measure the 131 I thyroid uptake of mouse using CLI for assessment of thyroid function. Quantification of 131 I thyroid uptake of mice in euthyroid, hypothyroid and hyperthyroid status was performed by CLI and γ-scintigraphy at 24 hours after injection of 131 I. The 131 I thyroid uptake was calculated using the equation: (thyroid counts - background counts)/(counts of injected dose of 131 I) × 100%. Serum T4 concentration was determined to evaluate the thyroid function. The radioactivity of 131 I was linearly correlated with the CL signals in both in vitro and in vivo measurements. CLI showed a significant decrease and increase of 131 I thyroid uptake in the mice in hypo- and hyperfunctioning status, respectively, and highly correlated with that measured by γ-scintigraphy. However, the percent thyroid uptake measured by CLI were one-fifth of those measured by γ-scintigraphy due to insufficient tissue penetration of CL. These results indicate that CLI, in addition to nuclear imaging, is able to image and evaluate the 131 I thyroid uptake function in mice in preclinical and research settings.

Objective: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem., Methods: Nuclear and cytoplasmic protein extraction and immuno？uorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody. The gene expression of XIAP was tested by quantitative RT-PCR., Results: Previously, we reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of PKC-mediated GSK3β phosphorylation. In this study, we further demonstrate that TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells. The hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL-induced apoptosis. Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor-site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK induced by TRAIL. Moreover, we show that XIAP is involved in hnRNPK-mediated TRAIL resistance in H1299 cells., Conclusion: Taken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma., (Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Recently, multi-regional clinical trials (MRCTs), which incorporate subjects from many countries/regions around the world under the same protocol, have been widely conducted by many global pharmaceutical companies. The objective of such trials is to accelerate the development process for a drug and shorten the drug's approval time in key markets. Several statistical methods have been purposed for the design and evaluation of MRCTs, as well as for assessing the consistency of treatment effects across all regions with one primary endpoint. However, in some therapeutic areas (e.g., Alzheimer's disease), the clinical efficacy of a new treatment may be characterized by a set of possibly correlated endpoints, known as multiple co-primary endpoints. In this paper, we focus on a specific region and establish three statistical criteria for evaluating consistency between the specific region and overall results in MRCTs with multiple co-primary endpoints. More specifically, two of those criteria are used to assess whether the treatment effect in the region of interest is as large as that of the other regions or of the regions overall, while the other criterion is used to assess the consistency of the treatment effect of the specific region achieving a pre-specified threshold. The sample size required for the region of interest can also be evaluated based on these three criteria.

Background/purpose: The aims of the current study were to determine whether patients with conduct disorder (CD) showed an abnormal availability of serotonin reuptake transporter (SERT), and if their hyperkinetic symptoms, impulsivity, and quality of life were correlated with the availability of SERT., Methods: We recruited 14 drug-naïve patients with CD and eight age-matched healthy controls (HCs). The adult attention-deficit/hyperactivity disorder (ADHD) self-report scale (ASRS), Barrett impulsivity scale (BIS), and the World Health Organization quality of life-brief version (WHOQOL-BREF) scale were administered. Positron emission tomography (PET) of the brain with 4-[ 18 F]-ADAM was arranged for SERT imaging., Results: SERT availability was significantly reduced in the striatum and midbrain of patients with CD. Quality of life and inattention symptoms were also significantly correlated with the availability of SERT in the prefrontal cortex., Conclusion: The study suggested that a reduction in the availability of SERT might be associated with CD and could potentially predict poor quality of life or symptoms of inattention for these patients. The implications of our results might be limited to individuals with CD; a future study with a larger sample to validate our preliminary results is warranted., (Copyright © 2016. Published by Elsevier B.V.)

Photochemically induced cerebral ischemia is an easy-manipulated, reproducible, relatively noninvasive, and lesion controllable model for translational study of ischemic stroke. In order to longitudinally investigate the characterization of the model, magnetic resonance imaging, 18 F-2-deoxy-glucose positron emission tomography, fluorescence, and bioluminescence imaging system were performed in correlation with triphenyl tetrazolium chloride (TTC), hematoxylin-eosin staining, and immunohistochemistry examinations of glial fibrillary acidic protein, CD68, NeuN, von willebrand factor, and α-smooth muscle actin in the infarct zone. The results suggested that the number of inflammatory cells, astrocytes, and neovascularization significantly elevated in peri-infarct region from day 7 and a belt of macrophage/microglial and astrocytes was formed surrounding infarct lesion at day 14. Both vasogenic and cytotoxic edema, as well as blood brain-barrier leakage, occurred since day 1 after stroke induction and gradually attenuated with time. Numerous cells other than neuronal cells infiltrated into infarct lesion, which resulted in no visible TTC negative regional existence at day 14. Furthermore, recovery of cerebral blood flow and glucose utilization in peri-infarct zone were noted and more remarkably than that in infarct core following the stroke progression. In conclusion, these characterizations may be highly beneficial to the development of therapeutic strategies for ischemic stroke.

Age-related hearing loss (ARHL) is postulated to affect dementia. Our study aims to investigate the relationship between ARHL and the prevalence, and 10-year incidence of dementia in the Taiwan National Health Insurance Research Database (NHIRD). We selected patients diagnosed with ARHL from the NHIRD. A comparison cohort comprising of patients without ARHL was frequency-matched by age, sex, and co-morbidities, and the occurrence of dementia was evaluated in both cohorts. The ARHL cohort consisted of 4108 patients with ARHL and the control cohort consisted of 4013 frequency-matched patients without ARHL. The incidence of dementia [hazard ratio (HR), 1.30; 95% confidence interval (CI 1.14-1.49); P = 0.002] was higher among ARHL patients. Cox models showed that being female (HR, 1.34; 95% CI 1.07-1.68), as well as having co-morbidities, including chronic liver disease and cirrhosis, rheumatoid arthritis, hypertension, diabetes mellitus, stroke, head injury, chronic kidney disease, coronary artery disease, alcohol abuse/dependence, and tobacco abuse/dependence (HR, 1.27; 95% CI 1.11-1.45), were independent risk factors for dementia in ARHL patients. We found ARHL may be one of the early characteristics of dementia, and patients with hearing loss were at a higher risk of subsequent dementia. Clinicians should be more sensitive to dementia symptoms within the first 2 years following ARHL diagnosis. Further clinical studies of the relationship between dementia and ARHL may be necessary.

Objectives: This study was conducted to evaluate the safety and efficacy of single sebacoyl dinalbuphine ester (SDE) injection (150 mg/2 mL) when administered intramuscularly to patients who underwent hemorrhoidectomy for postoperative long-acting analgesia., Methods: A total of 221 patients scheduled for hemorrhoidectomy from 6 centers in Taiwan were randomly divided into SDE group and placebo group, and received the treatment, vehicle or SDE, 1 day before the surgery. Visual analogue scale (VAS) was recorded up to 7 to 10 days. Pain intensity using VAS AUC through 48 hours after surgery was calculated as the primary efficacy endpoint., Results: Area under the curve of VAS pain intensity scores (VAS AUC) through 48 hours after hemorrhoidectomy was significantly less in SDE group than those in placebo group (209.93 vs. 253.53). VAS AUC from the end of surgical procedure to day 7 was also significantly different between SDE and placebo group (630.79 vs. 749.94). SDE group consumed significantly less amount of other analgesics, such as PCA ketorolac and oral ketorolac. Median time from the end of surgery to the first use of pain relief medication was also shortened in the placebo group than in the SDE group. Most adverse events were assessed as mild and tolerable in both groups., Discussion: SDE injection demonstrated an extended analgesia effect, with a statistically significant reduction in pain intensity through 48 hours and 7 days after hemorrhoidectomy.

Despite standard treatment, about 70% of ovarian cancer will recur. Cancer stem cells (CSCs) have been implicated in the drug-resistance mechanism. Several drug resistance mechanisms have been proposed, and among these, autophagy plays a crucial role for the maintenance and tumorigenicity of CSCs. Compared to their differentiated counterparts, CSCs have been demonstrated to display a significantly higher level of autophagy flux. Moreover, mitophagy, a specific type of autophagy that selectively degrades excessive or damaged mitochondria, is shown to contribute to cancer progression and recurrence in several types of tumors. Nanomedicine has been shown to tackle the CSCs problem by overcoming drug resistance. In this work, we developed a nanomedicine, 188 Re-liposome, which was demonstrated to target autophagy and mitophagy in the tumor microenvironment. Of note, the inhibition of autophagy and mitophagy could lead to significant tumor inhibition in two xenograft animal models. Lastly, we presented two cases of recurrent ovarian cancer, both in drug resistance status that received a level I dose from a phase I clinical trial. Both cases developing drug resistance showed drug sensitivity to 188 Re-liposome. These results suggest that inhibition of autophagy and mitophagy by a nanomedicine may be a novel strategy to overcome drug resistance in ovarian cancer.

Background: We previously identified 25 intraoperative findings during laparoscopic cholecystectomy (LC) as potential indicators of surgical difficulty per nominal group technique. This study aimed to build a consensus among expert LC surgeons on the impact of each item on surgical difficulty., Methods: Surgeons from Japan, Korea, and Taiwan (n = 554) participated in a Delphi process and graded the 25 items on a seven-stage scale (range, 0-6). Consensus was defined as (1) the interquartile range (IQR) of overall responses ≤2 and (2) ≥66% of the responses concentrated within a median ± 1 after stratification by workplace and LC experience level., Results: Response rates for the first and the second-round Delphi were 92.6% and 90.3%, respectively. Final consensus was reached for all the 25 items. 'Diffuse scarring in the Calot's triangle area' in the 'Factors related to inflammation of the gallbladder' category had the strongest impact on surgical difficulty (median, 5; IQR, 1). Surgeons agreed that the surgical difficulty increases as more fibrotic change and scarring develop. The median point for each item was set as the difficulty score., Conclusions: A Delphi consensus was reached among expert LC surgeons on the impact of intraoperative findings on surgical difficulty., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Erinacine A, a major active component of a diterpenoid derivative isolated from Hericium erinaceus mycelium, has been demonstrated to exert anticancer effects. Herein, we present an investigation of the molecular mechanism of erinacine A induction associated with cancer cells' aggressive status and death. A proteomic approach was used to purify and identify the differentially expressed proteins following erinacine A treatment and the mechanism of its action in apoptotic and the targets of erinacine A. Our results demonstrate that erinacine A treatment of HCT-116 and DLD-1 cells increased cell cytotoxicity and reactive oxygen species (ROS) production as well as decreased cell proliferation and invasiveness. Ten differentially displayed proteins were determined and validated in vitro and in vivo between the erinacine A-treated and untreated groups. In addition, erinacine A time-dependent induction of cell death and inhibitory invasiveness was associated with sustained phosphorylation of the PI3K/mTOR/p70S6K and ROCK1/LIMK2/Cofilin pathways. Furthermore, we demonstrated that erinacine A-induced HCT-116 and DLD-1 cells viability and anti-invasion properties by up-regulating the activation of PI3K/mTOR/p70S6K and production of ROS. Experiments involving specific inhibitors demonstrated that the differential expression of cofilin-1 (COFL1) and profilin-1 (PROF1) during erinacine A treatment could be involved in the mechanisms of HCT-116 and DLD-1 cells death and decreased aggressiveness, which occurred via ROCK1/LIMK2/Cofilin expression, with activation of the PI3K/mTOR/p70S6K signalling pathway. These findings elucidate the mechanism of erinacine A inhibiting the aggressive status of cells by activating PI3K/mTOR/p70S6K downstream signalling and the novel protein targets COF1 and PROF1; this could be a good molecular strategy to limit the aggressiveness of CRC cells., (© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in Taiwan. Multiple risk factors, such as chronic hepatitis B or C virus infection, carcinogen exposure, cirrhosis, and various single-nucleotide polymorphisms (SNPs), are considered to contribute to hepatocarcinogenesis. Chitinase-3-like protein 1 (CHI3L1), a biomarker implicated in inflammation and tissue remodeling, plays a promoting role in angiogenesis, antiapoptosis, and cell proliferation. This study investigated the role of CHI3L1 SNPs in HCC susceptibility and clinicopathology. Real-time polymerase chain reaction was used to analyze four SNPs of CHI3L1 in 343 patients with HCC and 686 cancer-free controls. We found associations with HCC susceptibility in CHI3L1 rs880633 polymorphism carriers with genotypes (TC+CC). We observed that HCC patients had lower frequencies of CHI3L1 rs6691378 polymorphisms with the variant genotype GA+AA than the wild-type carriers with distant metastasis and positive HBsAg did. In 200 HBsAg negative HCC patients, we observed that the CHI3L1 rs4950928 polymorphisms carriers with the variant genotype CG+GG had higher frequencies of vascular invasion. Finally, carriers of CHI3L1 rs6691378 and 10399805 polymorphisms with the variant genotypes GA+AA showed lower levels of alpha-fetoprotein in HCC laboratory status. In conclusion, our results indicate that patients with CHI3L1 rs880633 variant genotypes TC+CC are at a higher risk of HCC. CHI3L1 polymorphisms rs880633 or rs4950928 may be potential candidates for predicting poor HCC prognosis and clinical status., Competing Interests: Competing Interests: The authors have declared that no competing interests exist.