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Background Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs). We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan. Methods Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported. Results All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI): 92.1%-99.0%) and 100% (95% CI: 96.4%-100%) in EP and PP populations. Three (2.8%) patients were lost to off-treatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred, but unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve. Conclusions SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs.

In this study, we implemented an artificial intelligence (AI) model—Convolutional Neural Network (CNN)—to help physicians classify colonic polyps into traditional adenoma (TA), sessile serrated adenoma (SSA), and hyperplastic polyp. We collected ordinary endoscopy images under both white and NBI lights. Under white light, we collected 257 images of hyperplastic polyp (HP), 423 images of SSA, and 60 images of TA. Under NBI light, were collected 238 images of HP, 284 images of SSA, and 71 images of TA. We implemented the artificial intelligence model to build a classification model for the types of colon polyps. Our final AI classification model is built only with white light images. Our classification prediction accuracy of colon polyp type is 94%, and the discriminability of the model (area under the curve) was 98%. Thus, we can conclude that our model can effectively help physicians distinguish between TA, SSA, and HPs, and correctly identify serrated-type colon polyps.

Background Fecal microbiota transplantation (FMT) has been shown to highly effective in the treatment of recurrent or refractory Clostridioides difficile infection (rCDI) in many countries of the world. Not until 2018, Ministry of Health and Welfare, Taiwan approved the application of FMT for rCDI under a special law. The study reported the first implementation of the technology in the medical center in Taiwan and the preliminary outcome. Methods FMT was used to treat patients with rCDI in Chang Gung Memorial Hospital. FMT was delivered by gastroenterologists using colonoscope. Strict donor screening was performed according to the guidelines. We followed up the clinical course of patients after FMT. 16S rRNA sequencing of fecal samples for donor, and also recipient before and after FMT was carried out. Results From September 2018 to June 2020, 39 patients with rCDI received FMT, with a successful rate of 89.7%. Two patients died due to causes unrelated to FMT, and two other cases showed no clinical improvement after the procedure. High school and college students showed the best pass rate during donor screening. The presence of multi-drug resistant pathogen was the most common cause for screening failure. We demonstrated in a case the use of rRNA sequencing as a biomarker indicating for the improvement of dysbiosis in a patient after FMT. Conclusions FMT was successfully implemented in a medical center in Taiwan and showed a comparable successful rate in treating rCDI, compared to other countries. Safety remains the most important issue when applying FMT in the clinical setting.

The prevalence of peptic ulcer diseases has decreased over the past decades. The contribution of Helicobacter pylori to these changes has not been clearly delineated. Two cohorts of patients receiving esophagogastroduodenoscopy examination together with urease test were enrolled, 1 from year 2001 (n = 1030), the other from year 2019 (n = 600). The prevalence changes of peptic ulcer diseases as well as the associated clinical factors were analyzed. An independent cohort of gastric biopsy samples (n = 151) positive for H. pylori were retrieved for ureC gene genotype analysis. Comparison between the patients recruited from 2001 and 2019 revealed significant decrease in H. pylori infection (P0.001), duodenal ulcer prevalence (P0.001) and gastric ulcer prevalence (P0.001). Multivariate analysis showed that the decreases of these factors were independent (adjusted P0.001 for all). Intriguingly, in H. pylori positive patients, the prevalence of duodenal ulcer still decreased with year (P0.001), which was not found in gastric ulcer (P = 0.345). Genetic analysis of H. pylori urease gene showed that MboI-restriction fragment length polymorphism-defined genotype 3 UreC was significantly more prevalent in gastric ulcer patients than in others (P = 0.022). Independent decreases of H. pylori infection, gastric ulcer and duodenal ulcer over decades were found. In H. pylori positive patients, duodenal ulcer prevalence decreased overtime while gastric ulcer prevalence remained unchanged. Gastric ulcer/cancer had a higher prevalence of MboI-defined genotype 3 UreC gene.

Ulcerative colitis (UC), a subtype of inflammatory bowel disease, is characterized by repetitive remission and relapse. Gut microbiome is critically involved in pathogenesis of UC. The shifts in microbiome profile during disease remission remain under-investigated. Recent studies revealed that UC pathogenesis is likely to originate in the mucosal barrier. Therefore, we investigated the effectiveness of mucosal tissue microbiomes to differentiate patients with subclinical UC from healthy individuals. The microbiomes of cecal and rectal biopsies and feces were characterized from 13 healthy individuals and 45 patients with subclinical UC. Total genomic DNA was extracted from the samples, and their microbial communities determined using next-generation sequencing. We found that changes in relative abundance of subclinical UC were marked by a decrease in Proteobacteria and an increase in Bacteroidetes phyla in microbiome derived from rectal tissues but not cecal tissue nor feces. Only in the microbiome of rectal tissue had significantly higher community richness and evenness in subclinical UC patients than controls. Twenty-seven operational taxonomic units were enriched in subclinical UC cohort with majority of the taxa from the Firmicutes phylum. Inference of putative microbial functional pathways from rectal biopsy microbiome suggested a differential increase in interleukin-17 signaling and T-helper cell differentiation pathways. Rectal biopsy tissue was suggested to be more suitable than fecal samples for microbiome assays to distinguish patients with subclinical UC from healthy adults. Assessment of the rectal biopsy microbiome may offer clinical insight into UC disease progression and predict relapse of the diseases.

Advanced cancer patients who are not expected to survive past the short term can benefit from early initiation of palliative care in the emergency department (ED). This discussion, however, requires accurate prognostication of their short-term survival. We previously found in our retrospective study that shock index (SI) is an ideal risk stratification tool in predicting the 60-day mortality risk of advanced cancer patients presenting to the ED. This study is a follow-up prospective validation study conducted from January 2019 to April 2021. A total of 410 advanced cancer patients who presented to the ED of a medical centre and could be followed-up feasibly were recruited. Univariate and multivariable logistic regression analyses were performed with receiver operator calibrating (ROC) curve analysis. Non-survivors had significantly lower body temperatures, higher pulse rates, higher respiratory rates, lower blood pressures, and higher SI. Each 0.1 increment of SI increased the odds of 60-day mortality by 1.591. Area under ROC curve was 0.7819. At optimal cut-off of 0.94, SI had 66.10% accuracy. These results were similar to our previous study, thus validating the use of SI in predicting the 60-day mortality of advanced cancer patients presenting to the ED. Identified patients may be offered palliative care.

Caustic substance ingestion is frequently life-threatening, and its pathological mechanisms of tissue damage are well documented. However, few studies have assessed the combined effects of pH and the ingested dose on patient outcomes. Additionally, the miscellaneous chemical properties are not immediately available for providing predictive insights to physicians. This study aimed to provide a new perspective of the risk assessment of caustic substance ingestion based on the pH and dose.The retrospective study analyzed adults treated for caustic substance ingestion at Chang Gung Memorial Hospital between January 1999 and December 2018. Uniformly strict inclusion/exclusion criteria and a double-checked process during chart review were adopted. All patients underwent urgent esophagogastroduodenoscopy (EGD) within 24 h. Caustic mucosal damage was graded using Zargar's modified endoscopic classification. The pH and ingested dose of caustic substances were clearly recorded. Statistical analyses were conducted using IBM SPSS, version 22.Based on the 468 enrolled cases, the pH and dose were valuable predictors of the extent of gastrointestinal tract injury, commonly encountered complications, and long-term overall survival outcomes. Risks of mortality and perforation were dose-dependent for acids and pH-dependent for alkalis. The severe EGD findings (grade ≥ 2b) in this study were pH-dependent for both substances and additionally dose-dependent for acids.Combining pH and dose, we proposed a new perspective for the risk assessment of caustic substance ingestion. Such findings may provide predictive insights for resolving clinical uncertainty before the availability of examination results. "Large doses of acids" and "high pH of alkalis" deserve special attention. This new perspective with a retrospective nature requires further validation.

Purpose High prevalence of psychiatric comorbidities (PCs) has been widely documented in caustic substance ingestion cases. However, their effect on the clinical features and prognostic outcomes remains unclear due to the paucity of discussion. We report on detailed clinical courses with long-term multifaceted outcomes and review the association between caustic ingestion and each specific PC. Patients and methods The retrospective chart review included 396 adults (median follow-up, 16.6 months) with and 377 without (control group) PCs treated between 1999 and 2018 at Chang Gung Memorial Hospital. All PCs were diagnosed/confirmed by psychiatrists through face-to-face interviews. Results The PCs predicted serious esophagogastroduodenoscopy grading, higher rates of admission/surgery/intensive care unit stay, increments of systemic/gastrointestinal complications, and poorer 5-year overall survival rates. The poor survival among patients with PCs was highly consistent with their baseline characteristics. Significantly advanced age, more non-PCs, alcoholism, illicit drug abuse, and baseline unhealthy status resulted in statistically higher risks of severe complications and limited recovery. Conclusion PCs changed clinical patterns and had critical roles in the survival outcomes of caustic injury victims. Clinical awareness achieves benefit by limiting injuries in mild cases or allowing emergent interventions in severe cases. Future studies based on worldwide populations are essential for realizing geographic differences.

Background There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin. Methods After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion. Results A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure. Conclusions Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.

Colorectal cancer is the leading cause of cancer-related deaths worldwide, and early detection has proven to be an effective method for reducing mortality. The machine learning method can be implemented to build a noninvasive stratifying tool that helps identify patients with potential colorectal precancerous lesions (polyps). This study aimed to develop a noninvasive risk-stratified tool for colorectal polyps in asymptomatic, healthy participants. A total of 20,129 consecutive asymptomatic patients who underwent a health checkup between January 2005 and August 2007 were recruited. Positive relationships between noninvasive risk factors, such as age, Helicobacter pylori infection, hypertension, gallbladder polyps/stone, and BMI and colorectal polyps were observed (p < 0.0001), regardless of sex, whereas significant findings were noted in men with tooth disease (p = 0.0053). A risk stratification tool was developed, for colorectal polyps, that considers annual checkup results from noninvasive examinations. For the noninvasive stratified tool, the area under the receiver operating characteristic curve (AUC) of obese females (males) aged 50 years old), the AUCs of the stratifying tools were >85%. Our results indicate that the risk stratification tool can be built by using random forest and serve as an efficient noninvasive tool to identify patients requiring colonoscopy.

Background: Totally laparoscopic surgery for early gastric cancer and subepithelial tumors has been popularized worldwide, yet localization of early or small-sized tumors is a persistent challenge due to difficulty being identified with the lack of manual tactile sensation. Thus, accurate localization with tattooing before the surgery would help improve efficiency during surgery. There are multiple methods to localize tumors before laparoscopy, each with varying advantages and disadvantages. The use of endoscopic tattooing with dye has been carried out for several decades due to its safety, lower cost, and convenience. However, there is a lack of studies on endoscopic tattooing before totally laparoscopic resection. Aims: To evaluate the effect of endoscopic tattooing with dye for gastric subepithelial tumors localization before laparoscopic resection and to evaluate the tattooing effect on different locations of tumors in stomach. Method: We retrospectively collected data of patients with gastric subepithelial tumors who underwent endoscopic tattooing before totally laparoscopic resection from 2017 to 2020 in a university affiliated medical center. All patients were analyzed for preoperative characteristics and then categorized into two groups based on tumor locations concerning the difficulty of laparoscopic surgery. The independent t test and Chi-square test were performed to compare perioperative outcome and complications between these two groups. Result: A total of 19 patients were included retrospectively at our center. The individuals were 5 male and 14 female patients with a mean age of 58.2 years old. Most patients had no symptoms, and the tumors were found incidentally in 12 patients (63%). All tumors were identified clearly during laparoscopic resection. The mean tumor size was 2.3 cm. The surgeries took an average of 111 min and a mean of 7 mL blood loss was found. All tumors had negative resection margins with no recurrence during follow-up. Gastrointestinal stromal tumor was the major pathologic diagnosis, found in 12 patients (63%), followed by the leiomyoma in 5 patients (26%). Only three patients had mild adverse effects after surgery and the symptoms were self-limited. Our analysis found no significant difference in preoperative patient characteristics and perioperative outcomes between patients with differing tumor locations. Conclusion: This study is the first and largest report on endoscopic tattooing with dye before laparoscopic resection of gastric subepithelial tumor resection. Our results emphasize that endoscopic tattooing with dye is a safe and reliable method for localizing subepithelial tumors in the stomach prior to totally laparoscopic resection, with no correlation to where the tumor is located.

Background: Caustic ingestion has gained increasing attention worldwide. However, the insight into whether to use esophagogastroduodenoscopy (EGD) or computed tomography (CT) for first-line investigation remains controversial. This study aimed to evaluate a diagnostic and management algorithm that combines EGD and CT for rapid triage. Methods: We established an algorithm for our hospital in 2013, aiming to maximize the benefits and minimize the limitations of EGD and CT. Then, we retrospectively analyzed the 163 enrolled patients treated between 2014 and 2019 and categorized them into 4 groups: A = 3 (1.8%): with perforation signs and directly confirmed by CT, B = 10 (6.1%): clinically suspected perforation but not initially proven by CT, C = 91 (55.8%): initial perforation less favored but with EGD grade ≥ 2b or GI/systemic complications, and D = 59 (36.2%): clinically stable with EGD grade ≤ 2a, according to initial signs/symptoms and EGD/CT grading. The morbidity and mortality of each group were analyzed. The predictive values of EGD and CT were examined by logistic regression analyses and receiver operating characteristic (ROC) curves. Results: The outcomes of such algorithm were reported. CT was imperative for patients with toxic signs and suspected perforation. For non-emergent operations, additional EGD was safe and helpful in identifying surgical necessity. For patients with an initially low perforation risk, EGD alone sufficiently determined admission necessity. Among inpatients, EGD provided excellent discrimination for predicting the risk for signs/symptoms’ deterioration. Routine additional CT was only beneficial for those with deteriorating signs/symptoms. Conclusions: According to the analyses, initial signs/symptoms help to choose EGD or CT as the first-line investigative tool in caustic patients. CT is necessary for seriously injured patients, but it cannot replace EGD for moderate/mild injuries. The severity stratification and patient categorization help to simplify complex scenarios, accelerate decision-making, and prevent unnecessary intervention/therapy. External validation in a larger sample size is further indicated for this algorithm.

Introduction Study of inflammatory cytokines in patients with caustic gastrointestinal tract injury is sketchy. This study investigated the cytokine profiling of patients with caustic substance ingestion, and analyzed the differences between patients with severe and mild injury. Methods This prospective, cross-sectional study enrolled 22 patients admitted to Chang Gung Memorial Hospital between March and October 2018. All patients underwent esophagogastroduodenoscopy in 24 hours. Patients were categorized into two subgroups, as mild ( Results The neutrophil count was higher in severe than mild group (P = 0.032). Patients in mild and severe groups exhibited significantly higher circulating inflammatory cytokines than healthy control, including interleukin (IL)-2, IL-5, IL-8, IL-9, IL-12, IL-13, interferon-gamma inducible protein-10, macrophage inflammatory protein-1 beta, regulated upon activation, normal T cell expressed and presumably secreted and tumor necrosis factor-alpha. Furthermore, the levels of IL-2 and tumor necrosis factor-alpha were significantly higher in patients with severe group than mild group. Although there was no difference in cumulative survival between both groups (P = 0.147), the severe group received more operations (P = 0.035) and suffered more gastrointestinal complications (P = 0.035) than mild group. Conclusion Caustic substance ingestion produces mucosal damages and leads to excessive neutrophils and inflammatory cytokines in peripheral blood.

Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values

What is known and objective Hexavalent (VI) chromium is a powerful oxidant that can produce cellular oxidative stress and multi-organ system dysfunction. The role of antioxidants such as N-acetylcysteine (NAC) and ascorbic acid in alleviating organ damage in humans remains unclear. Case description We present a 47-year-old male who ingested 30 mL of plating solution and developed hepatic injury. He was treated with NAC and ascorbic acid with improvement in hepatic function. However, his clinical conditions and jaundice worsened again after discontinuing these therapies. What is new and conclusion Our findings suggest a potential role for antioxidant therapy for acute hexavalent chromium poisoning.

MicroRNA-196a (miRNA-196a) is associated with the development of gastric cancer and metastasis. Intestinal metaplasia and low- or high-grade dysplasia are considered to be precursors of intestinal type gastric cancer. Accordingly, we investigated the expression of plasma miRNA-196a as an early detection biomarker in precancerous gastric lesions and early cancer (pT1a/b), which is otherwise treated with endoscopic submucosal dissection. Our data showed that levels of circulating (plasma) miRNA-196a were higher in patients with precancerous lesions/early gastric adenocarcinoma than in healthy controls. The area under the receiver operating characteristic curve (AUC) for healthy controls vs. intestinal metaplasia was 0.9736; healthy controls vs. low-grade/high-grade dysplasia 0.9495; and healthy controls vs. early gastric cancer 0.9318. These results indicate that circulating miRNA-196a is a novel biomarker for detection of early gastric cancer and its precursor.

BackgroundCritically-ill surgical patients are at higher risk for sarcopenia, which is associated with worse survival. Sarcopenia may impair the respiratory musculature, which can subsequently influence the outcome of ventilator weaning. Although there are a variety of weaning parameters predictive of weaning outcomes, none have tried to incorporate "muscle strength" or "sarcopenia". The aim of the current study was to explore the association between sarcopenia and difficult-to-wean (DtW) in critically-ill surgical patients. The influence of sarcopenia on ICU mortality was also analyzed.MethodsNinety-six patients undergoing mechanical ventilation in the surgical intensive care unit (ICU) were enrolled. Demographic data and weaning parameters were recorded from the prospectively collected database, and the total psoas muscle area (TPA) was determined at the level of the 3rd lumbar vertebra by computed tomography. Sarcopenia was defined by previously established cut-off points and its influence on clinical outcomes was examined. Receiver operating characteristic (ROC) curve analysis was conducted to investigate the predictive capability of TPA and weaning parameters for predicting weaning outcomes.ResultsThe median age of the studied patients was 73 years. Thirty patients (31.3%) were sarcopenic and 30 (31.3%) were defined as DtW. Eighteen patients (18.8%) had ICU mortality. Multivariate logistic regression analyses revealed that sarcopenia was an independent risk factor for DtW and ICU mortality. The area under the ROC curve (AUC) of TPA for predicting successful weaning was 0.727 and 0.720 in female and male patients, respectively. After combining TPA and conventional weaning parameters, the AUC for DtW increased from 0.836 to 0.911 and from 0.835 to 0.922 in female and male patients, respectively.ConclusionSarcopenia is an independent risk factor for DtW and ICU mortality. TPA has predictive value when assessing weaning outcomes and can be used as an effective adjunct predictor along with conventional weaning parameters.

Berberine is an isoquinoline alkaloid isolated from herb plants, such as Cortex phellodendri (Huangbai) and Rhizoma coptidis (Huanglian). Huanglian and Huangbai have been used as “heat-removing” agents. In addition, berberine has been reported to exert anti-inflammatory effect both in vivo and in vitro, where mitogen-activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) expressions are critically implicated. We herein tested the hypothesis that berberine exerts an anti-inflammatory effect through MAPK and COX-2 signaling pathway in T-cell acute lymphoblastic leukemia (T-ALL). In Jurkat cells, we found that PHA exposure caused elevation on interleukin-2 (IL-2) production in a time-dependent manner. PHA-stimulated reactions were steeply suppressed by berberine, such as IL-2 mRNA expression and protein secretion. However, berberine did not exert any cytotoxic effect at doses of 40 μg/ml. In addition, the possible molecular mechanism of anti-inflammation effect of berberine could be the inhibition of PHA-evoked phosphorylation of p38, since c-Jun N-terminal kinases (JNK) and extracellular signal-regulated kinase (ERK) expressions did not alter. Consistent with above results, berberine inhibition on PHA-induced IL-2 secretion could be reversed by treatment of SB203580, a specific inhibitor of p38-MAPK. Interestingly, upregulation of PHA-induced COX-2 expression was also observed following berberine treatment of Jurkat cells. Furthermore, flow cytometry analysis showed berberine-induced cell cycle arrest at G1 phase after PHA stimulation and decreased percentage of G2/M phase. In conclusion, our study demonstrated that the anti-inflammatory effect of berberine largely potentially results from its ability to attenuate p38 MAPK expression, and does not exclude a positive action of berberine on cell cycle arrest. These results provide an innovative medicine strategy to against or treat T-ALL patients.

Gossypol, a natural polyphenolic compound extracted from cottonseed oil, has been reported to possess pharmacological properties via modulation cell cycle and immune signaling pathway. However, whether gossypol has anti-inflammatory effects against phytohemagglutinin (PHA)-induced cytokine secretion in T lymphocytes through similar mechanism remains unclear. Using the T lymphocytes Jurkat cell line, we found that PHA exposure caused dramatic increase in interleukin-2 (IL-2) mRNA expression as well as IL-2 secretion. All of these PHA-stimulated reactions were attenuated in a dose-dependent manner by being pretreated with gossypol. However, gossypol did not show any in vitro cytotoxic effect at doses of 5–20 μM. As a possible mechanism underlying gossypol action, such as pronounced suppression IL-2 release, robust decreased PHA-induced phosphorylation of p38 and c-Jun N-terminal kinase expressions was found with gossypol pretreatment, but not significant phosphorylation of extracellular signal-regulated kinase expression. Furthermore, gossypol could suppress the Jurkat cells’ growth, which was associated with increased percentage of G1/S phase and decreased fraction of G2 phase in flow cytometry test. We conclude that gossypol exerts anti-inflammatory effects probably through partial attenuation of mitogen-activated protein kinase (phosphorylated JNK and p38) signaling and cell cycle arrest in Jurkat cells.

Background Despite melatonin treatment diminishes inflammatory mediator production and improves organ injury after acute pancreatitis (AP), the mechanisms remain unknown. This study explores whether melatonin improves liver damage after AP through protein kinase B (Akt)-dependent peroxisome proliferator activated receptor (PPAR)-γ pathway. Methods Male Sprague–Dawley rats were subjected to cerulein-induced AP. Animals were treated with vehicle, melatonin, and melatonin plus phosphoinositide 3-kinase (PI3K)/Akt inhibitor wortmannin 1 h following the onset of AP. Various indicators and targeted proteins were checked at 8 h in the sham and AP groups. Results At 8 h after AP, serum alanine aminotransferase/aspartate aminotransferase levels, histopathology score of hepatic injury, liver myeloperoxidase activity, and proinflammatory cytokine production were significantly increased and liver tissue adenosine triphosphate concentration was lower compared with shams. AP resulted in a marked decrease in liver Akt phosphorylation and PPAR-γ expression in comparison with the shams (relative density, 0.442 ± 0.037 versus. 1.098 ± 0.069 and 0.390 ± 0.041 versus ± 1.080 0.063, respectively). Melatonin normalized AP-induced reduction in liver tissue Akt activation (1.098 ± 0.054) and PPAR-γ expression (1.145 ± 0.083) as well as attenuated the increase in liver injury markers and proinflammatory mediator levels, which was abolished by coadministration of wortmannin. Conclusions Collectively, our findings suggest that melatonin improves AP-induced liver damage in rats, at least in part, via Akt-dependent PPAR-γ pathway.

Background Laparoscopic liver resection has been regarded as the standard treatment for liver tumors located at the left lateral liver sector. However, few studies have reported the results of laparoscopic left lateral sectionectomy (LLS) for HCC, not to mention the feasibility of this emerging technique for the less experienced liver surgeons. The current study would reappraise the Louisville statement by examining the outcome of LLS performed by a young liver surgeon. Methods We retrospectively reviewed two separate groups of patients who underwent open or laparoscopic left lateral sectionectomies at Chung Gung Memorial Hospital, Linkou. All laparoscopic hepatectomies were performed by the index young surgeon following a stepwise stapleless LLS. The surgical results and oncological outcomes of laparoscopic vs. open hepatectomies (LH and OH, respectively) with the surgical indication of HCC at left lateral liver sector were further compared and analyzed. Results 18 of 29 patients in the laparoscopic group and 75 patients in the conventional open group had primary HCC. The demographic data was essentially the same for the two groups. Statistical analysis revealed that the LH group had smaller tumor size, higher blood transfusion requirement, longer duration of inflow control and parenchymal transection, and longer operation time. However, no significant difference was observed in terms of complication rate, mortality rate, and hospital stay between the two groups. After adjusting for tumor size, LH and OH showed no statistical difference in the amount of blood transfusion, operation time and patient survival. Conclusions This study demonstrated that stapleless LLS is a safe and feasible procedure for less experienced liver surgeons to resect HCC located at the left lateral liver sector. This stepwise stapleless LSS can not only achieve surgical results comparable to OH but also can provide a platform for liver surgeons to apply laparoscopic technique before conducting more complicated liver resections.

Background Clostridium difficile infection (CDI) has high incidence in the United States, but less so in East Asian countries such as Taiwan. The reason for this is not understood, but microbial studies could reveal important epidemiologic insights. We hypothesized that the circulating strains of C. difficile and the gut microbiota differ between the United States and Taiwan. Methods Patients with diarrhea ± CDI from the University of Michigan and Chang Gung Memorial Hospital were included. CDI was defined by + enzyme immunoassay for the glutamate dehydrogenase gene and toxins A/B, with reflex to tcdB gene PCR for discordants. C. difficile was isolated by anaerobic culture and characterized by PCR ribotype. The fecal microbiota was assessed by sequence analysis of 16S rRNA-encoding gene amplicons targeting the V4 region. Amplicon sequences were processed using the mothur bioinformatics pipeline, with an operational taxonomic unit (OTU) defined by < = 3% sequence homology. Analysis was performed via logistic regression, principal coordinates (PCoA), and ANOVA. Results Community diversity by Shannon index of CDI- patients was lower (Figure 1); this difference was greater in Taiwan (P < .001, OR = 3.9 per unit Shannon). Taiwanese CDI- patients had lower Bacteroidetes relative abundance (RA) (Figure 2). The Taiwanese CDI- group also differed on PCoA and ANOVA (Figure 3, P < .001). OTU1 (genus Firmicutes) was depleted in CDI+ patients (P < .001, OR = 0.69 per 10% RA increase). Circulating ribotypes (Table 1) differ between countries, with no epidemic strains (R027/R078) present in Taiwan (P = .027). R027 and 014/020 comprised > 50% of US isolates while > 50% of Taiwanese isolates were R002. Conclusion Taiwan and US CDI+ patients differ in dominant ribotypes. It is overall difficult to differentiate diarrheal CDI+ and CDI- patients by the microbiome. Taiwanese CDI- patients are outliers, and possible reasons (e.g., differential burden of parasitic infection; diet) require further study. The increased diversity and lower Bacteroidetes in CDI+ vs. CDI- diarrheal patients contrast with prior studies that instead compared with CDI- non-diarrheal patients. Circulating strains in Taiwan include no epidemic variants; whether this explains the differential incidence needs further study. Disclosures All authors: No reported disclosures.

Gastric cancer is the second most common cause of cancer related death worldwide and lacks a highly effective treatment for the advanced disease. In this study, we have successfully demonstrated the preparation of core–shell type biopolymer based zein/chondroitin sulphate nanoparticles for the delivery of sorafenib in gastric cancers. The SRF-loaded zein/chondroitin sulphate nanoparticles (SZCS) were nanosized with a spherical morphology and exhibited a higher encapsulation of more than >90%. The biopolymer nanoparticles showed the ability to release the drug in a controlled manner for 120 h, indicating their potential application in systemic delivery. The nanoparticles showed a remarkable uptake in gastric cancer cells in a time-dependent manner. The SZCS displayed an improved cytotoxic effect compared to that of free SRF in the equivalent concentrations in SGC7901 cancer cells. Also, we demonstrated a higher apoptosis and caspase 3/7 activity for the SZCS nanoparticle system. Based on our results, we can conclude that SZCS might hold great potential in the treatment of gastric cancers.

How hepatatitis C virus (HCV) infection affects the interplay among abundant adipokines in the host remains unclear. A prospective study was conducted with 450 consecutive genotype 1 (G1) and G2 HCV patients who completed a course of anti-HCV therapy and underwent pre-therapy and 24-week post-therapy surveys to assess various profiles and levels of abundant adipokines, including leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1). Before anti-HCV therapy, multivariate analyses showed gender to be associated with leptin and adiponectin levels, and BMI with leptin and PAI-1 levels. Among patients with a sustained virological response (SVR, n = 372), associations at 24 weeks post-therapy were as follows: gender and BMI with all adipokine levels; hepatic steatosis and aspartate aminotransferase to platelet ratio index with adiponectin levels; and HOMA-IR and HCV genotype with PAI-1 levels. Paired t-tests revealed increased post-therapeutic PAI-1 levels in G1 SVR patients and decreased adiponectin levels in all SVR patients compared to pre-therapeutic levels. HCV infection may obscure associations between abundant adipokines and metabolic/hepatic profiles. In SVR patients, a higher hierarchical status of PAI-1 versus adiponectin in affecting glucose metabolism was noted at 24 weeks post-therapy. Such genotype-non-specific adiponectin decreases and G1-specific PAI-1 increases warrant careful follow-up of HCV patients after SVR according to viral genotype.

Background: Esophagogastroduodenoscopy (EGD) is a standard tool for detection of mucosal and submucosal lesions. However, identification of Helicobacter pylori (H. P) infection using EGD alone is limited in accuracy. Linked color imaging (LCI) is a novel tool to capture real-time image with sufficient contrast to observe mucosal microstructure. Methods: This study aims to evaluate the applicability of LCI in the identification of H. pylori infection. Consecutive 122 patients scheduled for EGD were included. They were examined with LCI and magnifying endoscopy. The classification of H. pylori was based on pathology results of biopsy and rapid urease test or urea breath test. Results: We compared the results based on LCI or magnifying endoscopy to reference classification. Of 122 patients, 36 had H. pylori infection (29.51%). The level of accuracy of diagnosis of H. pylori infections by LCI, magnifying endoscopy, and both LCI and magnifying endoscopy was 78.38%, 81.98%, and 78.38%, respectively. The sensitivity and specificity of each group were 70.97%, 81.25%, and 80.65% and 82.5%, 83.87%, and 76.25%, respectively. The positive predictive values were 59.46%, 64.10%, and 57.78%, respectively, and the negative predictive values were 87.84%, 91.67%, and 92.42%, respectively. Conclusion: LCI could be playing a valuable initial screen tool for real-time diagnosis of H. pylori infections. It has a high accuracy of diagnosis of H. pylori infections. Therefore, in patients suspected to have H. pylori infections using LCI, the infections need to be carefully diagnosed using appropriate methods because, as per the consensus, they should be eradicated as soon as possible before precancerous lesions develop. Keywords: H. pylori infection, Image-enhanced endoscopy, Linked color imaging, White light imaging

Biopsy of ulcer margin is routinely performed to exclude malignancy in patients with gastric ulcers, but its utility in diagnosing Helicobacter pylori infection has not yet been fully studied. A cohort of 50 patients with gastric ulcer was prospectively examined. Three tests including histology, rapid urease test, and urea breath test were performed in all patients for diagnosing H pylori infection. Six biopsied specimens from the margin of the gastric ulcer and 1 each specimen from antrum and body of non-ulcer part were obtained for histology using hematoxylin-eosin (H&E) stain. The criterion used for defining H pylori infection was a positive result in at least 2 of the 3 tests. H pylori infection was diagnosed in 27 (54%) of the patients. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the histological examination of the ulcer margin were 92.6%, 95.7%, 96.2%, 91.7%, and 94%, respectively. The addition of 1 specimen from the antrum or body or a combination of the 2 specimens did not increase the diagnostic yields of those for histological examination of ulcer margin alone. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the rapid urease test were 96.3%, 100%, 100%, 95.8%, and 98%, respectively, and the corresponding values for the urea breath test were 88.9%, 87%, 88.9%, 87%, and 88%. We performed Giemsa stain for the 3 patients with false-negative and false-positive results of histological examination of ulcer margin using H&E stain, and all were positive for H pylori infection. In conclusion, histological examination of the ulcer margin using hematoxylin-eosin stain was quite accurate and useful for diagnosing H pylori infection in patients with gastric ulcers. A special stain is required when the diagnosis of H pylori infection is questionable on routine H&E staining.