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Intestinal fibrosis and subsequent stricture formation are major clinical challenges in inflammatory bowel disease, resulting in an increased rate of operation and poor prognosis compared with those without. With the changing perception that intestinal fibrosis is irreversible to the point of view that it is reversible in recent years, various candidate serum biomarkers have been studied over the past decades, which may stratify patients based on their risks of developing stenosis and enable the detection of early stages of fibrosis. However, reliable and accurate biomarkers are still unavailable due to conflicting results and the lack of high-quality evidence. In this review we summarized the serum biomarkers that have been proposed for intestinal fibrosis in recent years, which includes gene polymorphisms or variants, epigenetic markers, extracellular matrix components, growth factors, and antibodies, aiming to provide clues for future research.

Background Infliximab levels have been reported to be associated with mucosal healing (MH) in Crohn’s disease (CD). However, whether the association differs between postinduction (week 14) and maintenance (week 30) has seldom been investigated. We aimed to analyze the association between serum infliximab trough levels and MH at the 2 different time points. Methods A retrospective study of CD patients treated with infliximab in a tertiary referral center between January 2012 and May 2018 was conducted. MH was defined as absence of ulceration by endoscopy. Correlations between infliximab level and MH were investigated at 2 specific time points, weeks 14 and 30. Results Median infliximab levels were higher in patients with MH than those without at weeks 14 (7.5 vs 1.5 μg/mL; P < 0.001) and 30 (5.9 vs 0.5 μg/mL; P < 0.001). The median levels in patients with MH at week 14 were higher than at week 30 (7.5 vs 5.9 μg/mL; P < 0.05). Multivariate analysis showed that infliximab level was independently associated with MH (both P < 0.001 at weeks 14 and 30). Infliximab level above 4.85 μg/mL and 2.85 μg/mL identified patients with MH at week 14 (area under the curve [AUC], 0.796; P < 0.001) and week 30 (AUC, 0.780; P < 0.001) with 80% specificity. The rates of MH reached a plateau (>85%) when infliximab levels were above 10 and 6 μg/mL at weeks 14 and 30, respectively. Conclusions Infliximab levels correlated with MH at weeks 14 and 30 in CD patients. Higher levels might be required to achieve MH at postinduction than during maintenance treatment.

Background Telemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear. Objective This systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD. Methods We systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis. Results A total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference −0.71, 95% CI −1.07 to −0.36; P Conclusions Telemedicine intervention showed a promising role in improving IBD-specific QoL among adolescents and decreased the number of clinic visits among patients with IBD. Further research is warranted to identify the group of patients with IBD who would most benefit from telemedicine.

Background and Aims Epidemics pose a great challenge to health care of patients. However, the impact of unprecedented situation of COVID‐19 outbreak on health care of inflammatory bowel disease (IBD) patients in real‐world setting has seldom been investigated. Methods We performed an observational study in a tertiary referral IBD center in China. The mode of health care and medication use was compared before and after COVID‐19 outbreak. Electronic questionnaire surveys were performed among gastroenterologists and IBD patients to investigate the impact of COVID‐19 outbreak on their attitudes towards telemedicine. Results COVID‐19 outbreak resulted in substantial decrease of patients participating in standard face‐to‐face visit during 1 month post‐outbreak (n = 51) than pre‐outbreak (n = 249), whereas the participation in telemedicine was significantly higher than comparable period in 2019 (414 vs 93). During the 1 month after COVID‐19 outbreak, 39 (39/56, 69.6%) patients had their infliximab infusion postponed with the mean delay of 3 weeks. The immunomodulator use was similar between pre‐outbreak and post‐outbreak. Six elective surgeries were postponed for a median of 43 days. In post‐outbreak period, 193 (193/297, 64.98%) of the surveyed physicians have used telemedicine with an increase of 18.9% compared with 46.13% (137/292) in the pre‐outbreak period (P

Summary Background The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. Methods In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series ( Findings We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2–5; range 0–15; I2=74%). The pooled prevalence of digestive symptoms was 15% (10–21; range: 2–57; I2=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9–32; range 1–53; I2=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of abdominal pain (odds ratio [OR] 7·10 [95% CI 1·93–26·07]; p=0·003; I2=0%) and abnormal liver function including increased ALT (1·89 [1·30–2·76]; p=0·0009; I2=10%) and increased AST (3·08 [2·14–4·42]; p Interpretation Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. Funding None.

The ATPase H+/K+ Transporting Beta Subunit (ATP4B) encodes the β subunit of the gastric H+, K+-ATPase, which controls gastric acid secretion and is therefore a target for acid reduction. Downregulation of ATP4B was recently observed in human gastric cancer (GC) without known mechanisms. In the present study, we demonstrated that ATP4B expression was decreased in human GC tissues and cell lines associated with DNA hypermethylation and histone hypoacetylation of histone H3 lysine 9 at its intragenic region close to the transcriptional start site. The expression of ATP4B was restored in GC cell lines by treatment with the DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-AZA), or histone deacetylase inhibitor, trichostatin A (TSA), with further enhancement by combined treatment with both drugs. In contrast, 5-AZA had no effect on ATP4B expression in human hepatocellular carcinoma (HCC) and pancreatic cancer cell lines, in which ATP4B was silenced and accompanied by intragenic methylation. Chromatin immunoprecipitation (ChIP) showed that, in BGC823 GC cells, histone H3 lysine 9 acetylation (H3K9ac) was enhanced in the intragenic region of ATP4B upon TSA treatment, whereas 5-AZA showed a minimal effect. Additionally, ATP4B expression enhanced the inhibitory effects of chemotherapeutic mediation docetaxel on GC cell growth. Thus, as opposed to HCC and pancreatic cancer cells, the silencing of ATP4B in GC cells is attributable to the interplay between intragenic DNA methylation and histone acetylation of ATP4B, the restoration of which is associated with a favorable anticancer effect of docetaxel. These results have implications for targeting epigenetic alteration at the intragenic region of ATP4B in GC cells to benefit diagnosis and treatment of GC.

Eighty eight surface soil samples were collected from the Qinghai-Tibetan Plateau (QTP) for determination of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs), including dichlorodiphenyltrichloroethane and metabolites (DDXs) and hexachlorocyclohexane isomers (HCHs). The measured concentrations were 51.8 ± 38.5 ng g(-1), 0.329 ± 0.818 ng g(-1), and 0.467 ± 0.741 ng g(-1) as means and standard deviations of PAHs, DDXs, and HCHs, respectively, which were 1-2 orders of magnitude lower than those reported for eastern China. Significant differences were also revealed among four sub-areas within QTP. PAHs detected in the samples from the remote sub-areas of T'ang-ku-la/Hoh Xil Mountains and along the Qinghai-Tibet highway in the west and northwest of QTP were 1 order of magnitude lower than those from Lhasa and east Qinghai. The differences in soil OCPs among the sub-areas were 2-7 times. Soil PAHs were significantly correlated with emission density and soil organic carbon content (SOC), while OCPs were correlated significantly with the population density and SOC. Based on the calculated backward air mass trajectories and geographical distributions of emission and population, it was revealed that PAHs and OCPs accumulated in the soils in the west and northwest QTP were primarily from long-range transport and may represent the background levels of East Asia. This part of QTP can also serve as an important receptor area for regional or even global long-range transport study. The elevated concentrations of PAHs and OCPs in Lhasa and east Qinghai were mainly from local sources, while PAHs from adjacent Lanzhou area also contributed considerably to the accumulation of PAHs in east Qinghai.

Ras-association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene and its expression is lost in numerous types of cancer cells, including primary osteosarcoma cells. However, its functional significance in osteosarcoma has not been well defined. The messenger RNA (mRNA) expression of RASSF1A in osteosarcoma tissues and corresponding non-tumoral tissues was measured by real-time PCR. Overexpression of RASSF1A was established by an adenoviral vector expressing RASSF1A. Cell migration and invasion were analyzed in transwells. Apoptosis and cell cycle were analyzed using flow cytometry. Wnt/β-catenin activity was measured by TCF reporter dual-luciferase assay. Cell viability was measured by MTT assay. Protein expression was detected by Western blot. RASSF1A mRNA expression was significantly lower in osteosarcoma tissues than that in the corresponding non-tumoral tissues. The lowered RASSF1A expression correlated with the clinical severity of osteosarcoma. rAd-RASSF1A injection significantly inhibited the growth of xenograft MNNG/HOS tumors in mice. Overexpression of RASSF1A resulted in significant inhibition of the proliferation, migration, and invasion; induced apoptosis; and arrested cell cycle at G0/G1 phase in both the MNNG/HOS and SaOS2 cells. Overexpression of RASSF1A inhibited the Wnt/β-catenin activity, decreased phosphorylation of Akt/glycogen synthase kinase-3-β (GSK3-β), and increased phosphorylation of mammalian sterile 20-like kinase 1 (MST1). Overexpression of RASSF1A downregulated the cyclin D1, c-Myc, and matrix metalloproteinase-7 (MMP-7) protein levels. RASSF1A functions as a tumor suppressor in osteosarcoma and exerts anti-cancer roles through regulating Akt/GSK-3-Wnt/β-catenin signaling.