The canonical Hippo pathway components modulate the differentiation of lamina propria regulatory T cells and T helper 17-like regulatory T cells in mouse colitis.

Regulatory T cells (Tregs) ameliorate inflammatory bowel diseases. However, their plasticity is not completely understood. In this study using a mouse colitis model, Tregs and T helper 17 (Th17)-like Tregs were detected and sorted using flow cytometry, followed by transcriptome sequencing, real-time RT-PCR, and flow cytometry to analyze the mRNA profiles of these cells. Treg plasticity was evaluated by in vitro differentiation assays. The immunosuppressive activities of Tregs and Th17-like Tregs were assessed in an adoptive transfer assay. We found Tregs-derived Th17-like Tregs in inflamed colonic lamina propria (LP). LP Th17-like Tregs expressed higher Th17-related cytokines and lower immunosuppressive cytokines compared with LP Tregs. Notably, Tregs expressed higher Yes-associated protein 1 (YAP1) but lower transcriptional coactivator with PDZ­binding motif (TAZ) than Th17-like Tregs. Verteporfin-mediated inhibition of YAP1 activity enhanced Th17-like Treg generation, whereas IBS008739-induced TAZ activation did not affect Th17-like Treg generation. Besides, verteporfin enhanced while IBS008739 suppressed the differentiation of Th17-like Tregs into Th17 cells. Furthermore, YAP1 activated STAT5 signaling in Tregs, whereas YAP1 and TAZ activated STAT3 and STAT5 signaling in Th17-like Tregs. Compared with Tregs, Th17-like Tregs were less efficacious in ameliorating colitis. Therefore, YAP1 suppressed Treg differentiation into Th17-like Tregs. Both YAP1 and TAZ inhibited the differentiation of Th17-like Tregs into Th17 cells. Therefore, YAP1 and TAZ probably maintain the immunosuppressive activities of Tregs and Th17-like Tregs in colitis.

Nomogram for Predicting Postoperative Pulmonary Metastasis in Hepatocellular Carcinoma Based on Inflammatory Markers.

BACKGROUND: Uncertainty surrounds the usefulness of inflammatory markers in hepatocellular carcinoma (HCC) patients for predicting postoperative pulmonary metastasis (PM). The purpose of this study was to assess the predictive value of inflammatory markers as well as to create a new nomogram model for predicting PM. METHODS: Cox regression was utilized to identify independent prognostic variables and to create a nomogram that predicted PM for comparison with a validation cohort and other prediction systems. We retrospectively analyzed a total of 1109 cases with HCC were included. RESULTS: The systemic inflammatory response index (SIRI) and aspartate aminotransferase-to-platelet ratio index (APRI) were independent risk factors for PM, with a concordance index of .78 (95% CI: .74-.81) for the nomogram. The areas under the curve of the nomograms for PM predicted at 1-, 3-, and 5-year were .82 (95% CI: .77-.87), .82 (95% CI: .78-.87) and .81 (95% CI: .75-.86), respectively, which were better than those of Barcelona Clinic Liver Cancer and China liver cancer stage. Decision curve analyses demonstrated a broader range of nomogram threshold probabilities. CONCLUSION: A nomogram based on SIRI and APRI can accurately predict postoperative PM in HCC.

Efficacy, safety and prognostic factors of camrelizumab plus carboplatin and pemetrexed chemotherapy in advanced lung adenocarcinoma patients.

WHAT IS KNOWN AND OBJECTIVE: Camrelizumab is a recently developed PD-1 inhibitor in China applied in treating different cancers including lung cancer. This study is designed to evaluate the efficacy, safety and prognostic factors for camrelizumab plus carboplatin and pemetrexed (CP) chemotherapy in treating patients with advanced lung adenocarcinoma. METHODS: Of 51 advanced lung adenocarcinoma patients with negative driver genes who received camrelizumab plus CP chemotherapy were recruited. These patients received four cycles of camrelizumab plus CP chemotherapy in a 21-day cycle. Then, camrelizumab, pemetrexed or camrelizumab plus pemetrexed was administered as maintenance therapy. RESULTS AND DISCUSSION: The rates of complete response, partial response, stable disease and progressive disease were 2.0%, 56.8%, 19.6% and 5.9%, respectively; while treatment response of 15.7% of patients was missing or not evaluable. The objective response and disease control rates were 58.8% and 78.4%, respectively. With a median follow-up period of 14.9 months (the follow-up duration ranged from 3.9 months to 24.3 months), 41 (83.4%) cases of disease progression and 22 (43.1%) cases of death were recorded. The median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI): 8.4-12.6 months) with a 1-year PFS rate of 36.3% and a 2-year PFS rate of 7.5%. In addition, the median overall survival (OS) was 18.7 months (95% CI: 16.4-21.0 months) with a 1-year OS rate of 79.1% and a 2-year OS rate of 30.4%. In consideration of safety, the most frequent adverse events were peripheral neuropathy (37.3%), neutropenia (37.3%), alopecia (35.3%), etc. and most of them were grade 1-2 and could be controlled. WHAT IS NEW AND CONCLUSION: Camrelizumab plus CP chemotherapy achieves favourable efficacy and tolerable adverse events in advanced lung adenocarcinoma patients.

Development and Validation of a Novel Diagnostic Nomogram to Differentiate Between Intestinal Tuberculosis and Crohn's Disease: A 6-year Prospective Multicenter Study.

OBJECTIVES: Differentiating Crohn's disease (CD) from intestinal tuberculosis (ITB) remains a diagnostic challenge. Misdiagnosis carries potential grave implications. We aimed to develop and validate a novel diagnostic nomogram for differentiating them. METHODS: In total, 310 eligible patients were recruited from 6 tertiary inflammatory bowel disease centers. Among them, 212 consecutive patients (143 CD and 69 ITB) were used in the derivation cohort for the establishment of diagnostic equation and nomogram; 7 investigative modalities including clinical manifestations, laboratory results, endoscopic findings, computed tomography enterography features, and histology results were used to derive the diagnostic model and nomogram. Ninety-eight consecutive patients (76 CD and 22 ITB) were included for validation of the diagnostic model. RESULTS: Eight out of total 79 parameters were identified as valuable parameters used for establishing diagnostic equations. Two regression models were built based on 7 differential variables: age, transverse ulcer, rectum involvement, skipped involvement of the small bowel, target sign, comb sign, and interferon-gamma release assays (for model 1) or purified protein derivative (for model 2), respectively. Accordingly, 2 nomograms of the above 2 models were developed for clinical practical use, respectively. Further validation test verified the efficacy of the nomogram 1 with 90.9% specificity, 86.8% sensitivity, 97.1% PPV, 66.7% negative predictive value (NPV), and 87.8% accuracy for identifying CD, and the efficacy of the nomogram 2 with 100% specificity, 84.2% sensitivity, 100% positive predictive value, 64.7% NPV, and 87.8% accuracy for diagnosing CD. CONCLUSIONS: The derivation and validation cohorts identified and validated 2 highly accurate and practical diagnostic nomograms for differentiating CD from ITB. These diagnostic nomograms can be conveniently used to identify some difficult CD or ITB cases, allowing for decision-making in a clinical setting.

Current diagnosis and management of Crohn's disease in China: results from a multicenter prospective disease registry.

BACKGROUND: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China. METHODS: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD. RESULTS: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission. CONCLUSIONS: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

Identification of Two Additional Susceptibility Loci for Inflammatory Bowel Disease in a Chinese Population.

BACKGROUND/AIMS: To investigate the associations between the rs1250569 (zinc finger MIZ-type containing 1, ZMIZ1), rs1042522 (tumour protein p53, TP53), and rs10114470 (tumour necrosis factor-like cytokine 1A, TL1A) polymorphisms and the development of inflammatory bowel disease (IBD) in a Chinese (Han) population. We analysed the expression of genes that predispose patients to Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A total of 381 IBD patients and 517 healthy controls were recruited into our study. Polymorphisms at the three loci were genotyped using polymerase chain reaction-ligation detection reactions (PCR-LDR). Genotype-phenotype correlations were analysed. Blood and gut samples were obtained and analysed using quantitative real-time PCR (qRT-PCR), western blot analysis, and immunohistochemistry to investigate the mRNA and protein levels and in situ expression of genes found to predispose patients to IBD. Furthermore, the expression of susceptible genes was further verified using a mouse dextran sulphate sodium (DSS)-induced acute colitis model. RESULTS: No significant association was detected between rs1250569 and rs1042522 genotypes and CD or UC susceptibility. However, the frequency of allele A of rs1250569 was much higher in CD patients than that in healthy controls (55.03% vs. 48.48%, respectively; p = 0.044). The mutation rates at rs10114470 were dramatically lower at both the genotype and allele level in patients than those in healthy controls (p = 0.002 at both the genotype and allele level). Additionally, increased ZMIZ1 and TL1A levels were detected in intestinal samples obtained from both IBD patients and DSS-treated mice. CONCLUSION: rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two novel loci that indicate susceptibility to IBD in Han-Chinese patients. Consistent with previous studies, TL1A expression levels were higher in Chinese Han IBD patients and DSS-treated mice. Most importantly, we found that ZMIZ1 expression was markedly higher in both IBD patients and mice with experimentally induced colitis, suggesting that ZMIZ1 plays important roles in the pathogenesis of IBD.

Risk factors for initial surgery in patients with Crohn's disease in Central China.

PURPOSES: To establish the risk factors for initial surgery in patients with Crohn's disease (CD) in Central China. METHODS: The subjects of this study were patients with CD treated at Zhongnan Hospital of Wuhan University, an IBD center in Wuhan City, Central China, between January, 1992 and June, 2012. We conducted uni- and multivariate analyses of the risk factors for initial surgery for CD in these patients. RESULTS: A total of 197 patients with CD were included in this study. The cumulative incidence of initial surgery was 21.8, 28.9, and 32.5%, at 1, 5, and 10 years, respectively, after the onset of symptoms. Analysis using multivariate Cox models showed that the relative risk for initial surgery was lower in patients who were younger than 16 years at diagnosis (HR = 0.57, 95% CI 0.34-0.96, P = 0.034). The risk increased in patients with stricturing (HR = 4.75, 95% CI 2.48-9.11), those with CD showing penetrating behavior at diagnosis (HR = 5.14, 95% CI 2.54-10.39), and those with a history of appendectomy (HR = 1.87, 95% CI 1.03-3.40). Azathioprine (AZA) treatment appeared to decrease the risk for initial surgery in patients with non-penetrating and non-stricturing CD (HR = 0.14, 95% CI 0.13-3.10). CONCLUSION: Age at diagnosis, disease behavior, and a history of appendectomy appeared to have an impact on the risk for initial surgery. AZA treatment might be helpful for decreasing the risk of needing initial surgery for patients in whom stricturing or fistulizing disease has not yet developed.

Downregulation of MMP-9 by epicatechin can improve the radiosensitivity of non-small cell lung cancer.

BACKGROUND AND PURPOSE: Radiation therapy is a crucial treatment for nonsmall cell lung cancer (NSCLC), but its effectiveness is limited by the resistance of tumor cells to radiation. This study aimed to evaluate the effect of epicatechin (EC) on radiosensitivity in NSCLC and to determine its relationships with matrix metalloproteinase (MMP)-9. METHODS: MMP-9 expression was detected by Western blotting, and the expression of the DNA damage marker protein was detected by immunofluorescence. Cell viability was assessed using the CCK-8 assay, and cell proliferation was evaluated using the clonogenesis assay. Flow cytometry was used to determine the cell apoptosis, whereas cell migration and invasion were detected using the transwell assays. The cells were treated with ionizing radiation (IR) and EC to verify the sensitizing effect of EC on radiation therapy. RESULTS: MMP-9 expression was elevated in the NSCLC cells and tissues. DNA damage and cell apoptosis were increased, whereas cell vigor, proliferation, migration, and invasion were significantly decreased after IR. MMP-9 knockdown strengthened the impact of IR on the biological behaviors of the cells. EC + IR had the best effect on promoting DNA damage and the biological behaviors of the NSCLC cells; alternatively, the overexpression of MMP-9 weakened the role of EC. CONCLUSIONS: This study shows that EC can downregulate MMP-9 expression, promote DNA damage, reduce cell viability, proliferation, migration, and invasion, and facilitate cell apoptosis, thus, showing potential as a radiosensitizer for NSCLC.

Sirtuin2 suppresses the polarization of regulatory T cells toward T helper 17 cells through repressing the expression of signal transducer and activator of transcription 3 in a mouse colitis model.

INTRODUCTION: Regulatory T cells (Tregs) play an important role in inflammatory bowel diseases (IBDs) through modulating intestinal inflammation. However, the factors affecting Treg function and plasticity during IBD progression are not thoroughly disclosed. The current study aims to reveal new molecular mechanisms affecting Treg plasticity. METHODS: A mouse strain, in which tdTomato and enhanced green fluorescent protein were under the control of the Foxp3 promoter and Il17a promoter, was established and subjected to colitis induction with dextran sulfate sodium. The existence of Tregs and IL-17-expressing Tregs (i.e., Treg/T helper 17 [Th17] cells) were observed and sorted from the spleen, mesenteric lymph nodes, and lamina propria by flow cytometry, followed by measuring Sirtuin2 (Sirt2) expression using quantitative reverse transcription polymerase chain reaction and Immunoblotting. Lentivirus-induced Sirt2 silencing was applied to determine the impact of Sirt2 on Treg polarization to Treg/Th17 cells and even Th17 cells. The effect of Sirt2 on Stat3 was analyzed by flow cytometry and immunoblotting. RESULTS: Sirt2 was highly expressed in lamina propria Tregs and it moderately suppressed Foxp3 expression as well as the immunosuppressive function of Tregs. Surprisingly, lentivirus-mediated Sirt2 silencing promoted the generation of Treg/Th17 cells out of Tregs. Sirt2 silencing also enhanced the generation of Th17 cells out of Tregs under the Th17 induction condition. Furthermore, Sirt2 inhibited Th17 induction by suppressing the protein level of the signal transducer and activator of transcription 3. CONCLUSION: Sirt2 suppresses Treg function but also inhibits Treg polarization toward Treg/Th17 cells and Th17 cells. The ultimate effect of Sirt2 on colitis might depend on the balance among Tregs, Treg/Th17 cells, and Th17 cells.

(-) - Epicatechin regulates LOC107986454 by targeting the miR-143-3p/EZH2 axis to enhance the radiosensitivity of non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a pernicious tumor with high incidence and mortality rates. The incidence rate of NSCLC increases with age and poses a serious danger to human health. The aim of this study was to determine the mechanism by which (-)-epicatechin (EC) alleviates NSCLC. METHODS: Twenty-four pairs of NSCLC tissues and cancer-adjacent tissues were collected, and A549 and H460 radiotherapy-resistant strains were generated by repeatedly irradiating A549 and H460 cells with dose-gradient X-rays. Radiotherapy-resistant H460 cells were successfully injected subcutaneously into the left dorsal side of nude mice at a dose of 1 × 105 to establish an NSCLC animal model. The levels of interrelated genes and proteins were detected by RT‒qPCR and Western blotting, and cell proliferation and apoptosis were evaluated by CCK‒8 assay, Transwell assay, flow cytometry, and TUNEL staining. RESULTS: LOC107986454 was highly expressed in NSCLC patients, while miR-143-3p was expressed at low levels and was negatively correlated with LOC107986454. Functionally, EC promoted autophagy and apoptosis induced by radiotherapy, restrained cell proliferation and migration, and ultimately enhanced the radiosensitivity of NSCLC cells. A downstream mechanistic study showed that EC facilitated miR-143-3p expression by inhibiting LOC107986454 and then restraining the expression of EZH2, which ultimately facilitated autophagy and apoptosis in cancer cells, inhibited proliferation and migration, and enhanced the radiosensitivity of NSCLC cells. CONCLUSION: EC can enhance the radiosensitivity of NSCLC cells by regulating the LOC107986454/miR-143-3p/EZH2 axis.

(-)-Epicatechin regulates endoplasmic reticulum stress and promotes ferroptosis in lung cancer cells via the PERK/eIF2α/ATF4 signaling pathway.

OBJECTIVE: (-)-Epicatechin (EC) is an active ingredient of Fagopyrum dibtrys (D. Don) Hara and can regulate lung cancer progression. However, the specific regulatory mechanism is poorly understood. This study explored the specific mechanism of EC in the treatment of lung cancer. METHODS: H460 cells were injected subcutaneously into the left dorsal sides of nude mice to establish an animal model of lung cancer. H460 and H1299 cells and nude mice were treated with different concentrations of EC. The expression levels of related proteins were detected by Western blotting. Cell proliferation, migration, and invasion were detected by CCK-8, colony formation, and Transwell assays. Flow cytometry was used to detect the Ca2+ level in lung cancer cells. Immunohistochemistry was used to detect the expression of Ki-67 in tumor tissues. RESULTS: This study revealed that ferroptosis in lung cancer cells was inhibited during lung cancer development. EC treatment promotes ferroptosis, inhibits the proliferation, migration and invasion of lung cancer cells, and inhibits the formation of tumors in vivo. Ferroptosis inhibitors (Fer-1) weaken the effects of EC on lung cancer cells, whereas a ferroptosis inducer (erastin) further promotes the effects of EC. In addition, endoplasmic reticulum (ER) stress is involved in the EC-induced ferroptosis of lung cancer cells, and treatment with GSK, an inhibitor of the ER stress protein PERK, can reverse the effect of EC. CONCLUSION: EC therapy activates the PERK-eIF2α-ATF4 signaling pathway to increase ER stress, thereby promoting ferroptosis in lung cancer cells and inhibiting the occurrence and development of lung cancer. Our research suggests that EC may become a drug candidate for treating lung cancer.

Elevated risk of opportunistic viral infection in patients with Crohn's disease during biological therapies: a meta analysis of randomized controlled trials.

BACKGROUND: Biological agents have been widely used in the treatment of Crohn's disease (CD). These drugs carry the risk of excessive immunosuppression, indicating possible opportunistic infections including opportunistic viral infections, but no meta analysis has ever focused on this issue. PURPOSE: To evaluate whether there is an association between biological agents therapy and the risk of opportunistic viral infections and serious infections in patients with CD. METHODS: A search of online databases was performed and literature selection was carried out according to the inclusion and exclusion criteria by reading titles, abstracts and full texts. Study heterogeneity and publication bias were assessed. Whether to choose a fixed effects model or a random effects model depended on the result of heterogeneity test. RESULTS: There was a statistical significance in opportunistic viral infection events between the biological agents group and the placebo group. However, our analysis didn't observe statistically significant differences between the two groups when combined analyses were carried out for herpes zoster and herpes simplex separately. A risk trend in the biological agents group was observed in the analysis for herpes zoster. More analyses aimed at the outcome measures and including influenza and serious infection were carried out separately, but no statistical significance was found in them. CONCLUSION: Biological agents use might increase the risk of opportunistic viral infections in patients with CD, but not the risk of herpes simplex and serious infections. More randomized controlled trials (RCTs) are needed to draw the conclusion of whether they could elevate the risk of herpes zoster.

[The clinical, endoscopic and pathologic features of Crohn's disease in the differentiation from intestinal tuberculosis].

OBJECTIVE: To investigate the clinical, endoscopic and pathologic features in the differential diagnosis between Crohn's disease(CD) and intestinal tuberculosis (ITB). METHODS: The complete clinical data of 107 patients with CD and 69 patients with ITB in our hospital from January 2011 to January 2012 were retrospectively analyzed. The diagnostic value of the clinical and endoscopic scoring system was evaluated. RESULTS: CD occurred mainly in male. The salient features of CD included long duration of disease high incidence of colectomy. Comparing with patients with ITB, patients with CD have more cases of diarrhea, hematochezia, abdominal mass, intestinal obstruction, intestinal hemorrhage, perianal lesions, and extraintestinal manifestations (all P < 0.05).It's more frequent to have positive results of anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear antineutrophil cytoplasmic antibody (pANCA) and fecal occult blood in CD patients, as well as low albumin, high C-reactive protein ( CRP), elevated platelet count and hematocrit (P < 0.05 or P < 0.01). The salient features of ITB included low fever, night sweats, active parenteral tuberculosis, increased erythrocyte sedimentation rate (ESR), chest X-ray abnormalities, the positive PPD (purified protein derivatives tuberculin) and T-SPOT (P < 0.05 or P < 0.01). Based on the imaging, CD often involved the small intestine, such as the intestinal stricture and abdominal abscess (P < 0.05), while mesenteric lymphadenopathy was more common in ITB (P < 0.05). The endoscopic examination showed that some patterns of disease involvement such as fissure-shape ulcer [41.12% (44/107) vs 5.80% (4/69)], cobblestone sign[15.89% (17/107) vs 4.35% (3/69)], lesions over four segment [24.30% (26/107) vs 7.25% (5/69)], rectum involvement [17.76% (19/107) vs 5.80% (4/69)], ileocecal valve stenosis [21.50% (23/107) vs 8.70% (6/69)] and mucosal bridge[5.61% (6/107) vs 0(0/69)] were more frequent in CD patients than those in ITB patients(P < 0.01 or P < 0.05). However circular ulcers[37.68% (26/69) vs 9.35% (10/107)], rat-bite-like ulcers[24.64% (17/69) vs 12.15% (13/107)], persistent open ileocecal valves [39.13% (27/69) vs 19.63% (21/107)], tuberous and polypoid lesions[36.23% (25/69) vs 20.56% (22/107), 37.68% (26/69) vs 22.43% (24/107)] were more common in ITB (P < 0.01 or P < 0.05). In terms of pathological findings, certain characteristic features such as transmural inflammation [5.61% (6/107) vs 0(0/69)], fissure-liked ulcers [14.02% (15/107) vs 4.35% (3/69)], non-caseous granulomas [5.61% (6/107) vs 0(0/69)], lymphoid hyperplasia [16.82% (18/107) vs 5.80% (4/69)] and crypt abscess [9.35% (10/107) vs 1.45% (1/69)] were more common in CD than those in ITB(P < 0.05). According to the clinical and endoscopic scoring system, the positive diagnostic rate of CD was 50.47% (54/107) and of ITB was 66.67% (46/69) (P < 0.05) . CONCLUSIONS: The differential diagnosis between CD and ITB should be considered carefully based on clinical, endoscopic, pathological characteristics. The clinical and endoscopic scoring system may contribute to distinguish CD and ITB.

Novel Long Noncoding RNAs, LINC01093 and MYLK-AS1, Serve as Potential Diagnostic and Prognostic Biomarkers or Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies worldwide. In this research, we aimed to identify long noncoding RNAs (lncRNAs) as biomarkers for HCC diagnosis and prognosis. lncRNA expression profiles were obtained from Gene Expression Omnibus and The Cancer Genome Atlas databases. The differentially expressed lncRNAs between HCC and adjacent tissues were analyzed with bioinformatic tools. Four lncRNAs with area under the curve of the receiver operating characteristic curve >0.9 were selected from both datasets. Univariate and Kaplan-Meier analyses were performed to obtain LINC01093, MYLK-AS1, and MCM3AP-AS1 as the optimal diagnostic and prognostic biomarkers. Finally, qPCR confirmed that LINC01093 and MYLK-AS1 were significantly differentially expressed in HCC and adjacent normal tissues. In general, we demonstrated that novel lncRNAs, LINC01093 and MYLK-AS1, could be used as potential diagnostic and prognostic biomarkers for HCC.

Constructing abundant interfaces by decorating MoP quantum dots on CoP nanowires to induce electronic structure modulation for enhanced hydrogen evolution reaction.

Interface engineering is a method of enhancing catalytic activity while maintaining a material's surface properties. Thus, we explored the interface effect mechanism via a hierarchical structure of MoP/CoP/Cu3P/CF. Remarkably, the heterostructure MoP/CoP/Cu3P/CF demonstrates an outstanding overpotential of 64.6 mV at 10 mA cm-2 with a Tafel slope of 68.2 mV dec-1 in 1 M KOH. DFT calculations indicate that the MoP/CoP interface in the catalyst exhibited the most favorable H* adsorption characteristics (-0.08 eV) compared to the pure phases of CoP (0.55 eV) and MoP (0.22 eV). This result can be attributed to the apparent modulation of electronic structures within the interface domains. Additionally, the CoCH/Cu(OH)2/CF‖MoP/CoP/Cu3P/CF electrolyzer demonstrates excellent overall water splitting performance, achieving 10 mA cm-2 in 1 M KOH solution with a modest voltage of only 1.53 V. This electronic structure adjustment via interface effects provides a new and efficient approach to prepare high-performance hydrogen production catalysts.

Indolent T-cell lymphoproliferative disorder of gastrointestinal tract with unusual clinical courses: report of 6 cases and literature review.

Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (iTLPD-GI) is a rare neoplasm usually having an indolent clinical course and easily misdiagnosed as inflammatory bowel disease or other T-cell lymphomas. A subset of the disorders that progressed to overt peripheral T-cell lymphoma have been reported, and the etiology and pathogenesis are poorly understood. The current study retrospectively examined the pathological, molecular, and clinical features of 6 cases of iTLPD-GI. Hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, T-cell receptor gene rearrangement, and next-generation sequencing (NGS) were performed with the diseased tissues. All the 6 patients were immunocompetent Chinese men, who presented with recurrent abdominal pain and diarrhea for 4 to 13 years. Histologically, the intestinal tissue was expanded by lymphoid infiltration, composed of small-to-medium-sized lymphocytes with gland intact. The neoplastic cells were CD4 - /CD8 + with expression of TIA1 and variable granzyme B in five cases, and the other one was CD4 + /CD8 - . Two of the 5 patients progressed to more aggressive T-cell lymphoma and died of disease with complications. NGS identified TET2 and DDX3X mutations in patient 1, and BIRC6 and REV3L mutations in patient 2. Literature review indicated that iTLPD-GI with CD4 - /CD8 + immunophenotype was more commonly reported in Chinese cases. Our limited data indicated CD4-/CD8 + iTLPD-GI have similar potential to progress to more aggressive T-cell lymphoma as that of CD4 + /CD8 - , and gradually increased expression of granzyme B and Ki-67 may be early signs of the disease progression. Gain of novel gene mutations may be indicators of the pathogenesis.

Knockdown of LINC00511 enhances radiosensitivity of lung adenocarcinoma via regulating miR-497-5p/SMAD3.

As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used in LUAD cases, and radiosensitivity is vital for LUAD therapy. This research sought to explore the genetic factors affecting radiosensitivity in LUAD and inner mechanisms. LINC00511, miR-497-5p, and SMAD3 expression in LUAD cells were detected via qRT-PCR and western blot. CCK-8 assays, colony formation, and flow cytometry assays were employed to explore the cell viability, apoptosis, and radiosensitivity in PC-9 and A549 cells. The targeting relationship between LINC00511, miR-497-5p, and SMAD3 was verified by dual luciferase reporter assay. Furthermore, xenograft experiments were performed for the in vivo verification. In conclusion, LINC00511 was overexpressed in LUAD cells, which downregulated downstream miR-497-5p expression and mediately led to SMAD3 activation. LINC00511 downregulation suppressed cell viability while enhanced apoptosis rate in LUAD cells. Also, LINC00511 and SMAD3 were overexpressed, while miR-497-5p was downregulated in LUAD cells exposed to 4Gy irradiation treatment. Moreover, LINC00511 inhibition could block SMAD3 expression and promoted the radiosensitivity both in vitro and in vivo. These findings uncover LINC00511 knockdown promoted miR-497-5p expression and subsequently led to lower SMAD3 level, which enhanced radiosensitivity in LUAD cells. LINC00511/miR-497-5p/SMAD3 axis could be of considerable potential to enhance radiosensitivity in LUAD.

Pretreatment Fibrinogen-Albumin Ratio (FAR) Associated with Treatment Response and Survival in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Anti-PD-1 Therapy Plus Platinum-Based Combination Chemotherapy.

PURPOSE: PD-1 inhibitors have been routinely used to treat advanced non-small cell lung cancer (NSCLC) and have significantly improved clinical outcomes. In this study, we aimed to explore the influence of pretreatment fibrinogen-albumin ratio (FAR) on treatment response and survival in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. PATIENTS AND METHODS: A total of 91 patients with advanced NSCLC were included in the study. All patients received at least two cycles of systemic first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. Receiver operating characteristics analysis was performed to determine the optimal cutoff values of FAR. Univariate and multivariate analyses were used to identify independent prognostic factors, and the Kaplan-Meier method was used to estimate survival curves. RESULTS: Multivariate logistic regression analysis showed that N stage (N2-3) and high FAR (≥0.175, optimal cutoff value) were independent predictors for objective response rate (P = 0.0002, P = 0.0005, respectively). Multivariate Cox regression analysis of progression-free survival and overall survival showed that high FAR (≥0.145) was independent prognostic factors (P = 0.0061, P = 0.0024, respectively). Progression-free survival and overall survival were significantly shorter in the high FAR (≥0.145) group than those in the low FAR (<0.145) group (P = 0.0024, P = 0.0024, respectively). CONCLUSION: Pretreatment FAR was an independent predictor for treatment response and independent prognostic factors in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy.

A Retrospective Analysis of Clinical Features and Treatment of the Inflammatory Bowel Disease in China.

Purpose: To retrospectively collect and analyze demographic information as well as symptoms, laboratory results, endoscopic and pathologic findings, and treatment of ulcerative colitis (UC) and Crohn's disease (CD) patients in Wuhan, China. Methods: Patients who were diagnosed as inflammatory bowel disease (IBD) and hospitalized from January 2012 to December 2017 were enrolled in this study. The clinical characteristics including symptoms, laboratory results, and treatment were reviewed and analyzed. Results: Totally 821 cases were screened, and finally 430 UC patients and 286 CD patients were selected and enrolled in this study. The most common symptom in UC patients was bloody stool (90.7%) followed by diarrhea (87.7%), mucus in stool (72.1%), and abdominal pain (66.3%), which were significantly different from those of CD patients (P < 0.01). In contrast, the most common symptom in CD patients was abdominal pain (80.0%) followed by diarrhea (58.4%), bloody stool (27.6%), and fever (18.2%). Erythrocyte sedimentation, C-reactive protein, and platelets were significantly increased, while hemoglobin was decreased, in the moderately or highly active IBD. The percentage of positive perinuclear anti-neutrophil cytoplasmic antibody was significantly higher in UC patients (31.1%) than that in CD patients (4.8%, P < 0.001), while the percentage of positive anti-intestinal goblet cell antibody was significantly higher in CD patients (23.1%) than that in UC patients (14.9%, P = 0.037). Conclusion: The findings of the current study may provide evidence-based information for Chinese gastroenterologists to treat IBD more effectively in the future.

Safety and Efficacy of CT-Guided Central Venous Catheter Gastric Insufflation in Percutaneous Gastrostomy.

Gastric insufflation for computed tomography (CT)-guided percutaneous gastrostomy is currently performed via a nasogastric tube or a Chiba needle. However, nasogastric tube placement requires patient pharynx and esophagus, and Chiba needle use is associated with an increased risk of organ damage and prolonged operation time. Herein, we introduce a new method of gastric insufflation via a central venous catheter and explore its safety and efficacy by retrospective analysis of the clinical data of patients who underwent percutaneous gastrostomy using this method in our hospital from April 2021 to March 2022. The extracted data included the following: success rate, operation time, gastric insufflation time, radiation dose, postoperative pain score, and complications. We also compared the preoperative levels of several nutritional indicators (body mass index, hemoglobin, albumin, creatinine, and blood urea nitrogen) with those obtained 1 month postoperatively. A total of 12 patients underwent percutaneous gastrostomy under CT guidance using central venous catheter gastric insufflation. The surgery and gastric insufflation success rates were 100% both. The average operation time, gastric insufflation time, and effective radiation dose were 24.08 ± 5.25 min, 5.08 ± 2.50 min, and 14.16 ± 3.63 mSv, respectively. Based on the World Health Organization scale for pain assessment, five patients reported no postoperative pain and seven patients had mild pain. There were no serious complications, such as stoma infection, peritonitis, gastrointestinal perforation and bleeding, or embedding syndrome. All evaluated nutritional indicators showed improvement at 1 month postoperatively, with statistically significant differences compared to the preoperative values (p < 0.05 for all). In conclusion, CT-guided percutaneous gastrostomy with central venous catheter gastric insufflation is a safe, effective, and feasible minimally invasive treatment.