Meta-analysis: Over-the-scope clips in patients at high risk of re-bleeding following upper gastrointestinal tract bleeding.

BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (UGIB) is challenging in patients at high risk of re-bleeding in whom standard endoscopic treatment (ST) has limited effectiveness. Over-the-scope clips (OTSC) have shown promise in these patients although their precise role remains uncertain. AIMS: To confirm the role of OTSC in patients with UGIB at high risk of re-bleeding. METHODS: We systematically searched CENTRAL, MEDLINE and Embase from January 1st, 1970 to April 24, 2024 for randomised controlled trials (RCTs) comparing OTSC and ST in acute non-variceal UGIB with high re-bleeding risk. The GRADE framework assessed evidence certainty, while trial sequential analysis (TSA) controlled random errors and evaluated conclusion validity. RESULTS: We analysed four RCTs (319 patients); pooled risk ratio (RR) for clinical success at initial endoscopy favoured OTSC (RR = 1.30, 95% CI = 1.08-1.56, p = 0.006, I2 = 58%, moderate certainty of evidence). TSA showed the desired sample size was 410 and the cumulative Z curve crossing the trial sequential monitoring boundary. The pooled RR for re-bleeding within 30 days favoured OTSC (RR = 0.53, 95% CI = 0.30-0.94, p = 0.03, I2 = 0%, moderate certainty of evidence). There was no significant difference in 30-day mortality, or length of hospital or ICU stay. CONCLUSIONS: Moderate certainty evidence supports OTSC as a superior initial treatment for acute non-variceal UGIB with high re-bleeding risk. Further large-scale studies are needed to confirm OTSCs' role by exploring other prognostic outcomes and assessing cost-effectiveness and potential complications.

Efficacy and safety of thalidomide in gastrointestinal angiodysplasias: systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Background: Gastrointestinal (GI) angiodysplasias is a potential cause of life-threatening bleeding. Thalidomide may have a certain effect on the treatment. Objectives: We aim to evaluate the efficacy and safety of thalidomide and used trial sequential analysis (TSA) to assess the need for further randomized controlled trials (RCTs). Design: Meta-analysis of RCTs. Data sources and methods: We systematically searched Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, WanFang, and China National Knowledge Infrastructure databases for RCTs evaluating thalidomide in GI angiodysplasias without language restrictions. We used a random-effects model to obtain pool data and followed Grading of Recommendations Assessment, Development and Evaluation framework. TSA was employed to control the risk of random errors and to evaluate the validity of our conclusions. Results: Three RCTs were included involving 279 patients with the proportion of small intestinal angiodysplasias of 87.1%. Thalidomide led to improved mean change of hemoglobin level [mean difference (MD): 3.06, 95% confidence interval: 2.66-3.46] without severe adverse effects occurring. Other secondary endpoints, including effective response rate, cessation of bleeding after treatment, hospitalization rate because of bleeding, change in duration of hospital stays for bleeding, transfused red cell requirements, and overall adverse effects, also showed significantly better outcomes in the thalidomide group compared to the control group. TSA for all outcomes exceeded required information sizes, and cumulative Z curve all traverse trial sequential monitoring boundary. Conclusion: Almost all of the evidence was of moderate quality, suggesting that thalidomide holds promise for treating GI angiodysplasias, with favorable safety profiles. TSA suggests that conducting large-scale real-world research is recommended over relying solely on RCTs conducted within the same population and trial design. Trial registration: This meta-analysis protocol was registered on PROSPERO (CRD42023480621).

Bilateral Inferior Petrosal Sinus Sampling Without Lateralization Is Less Accurate for the Diagnosis of Cushing Disease.

Context: During bilateral inferior petrosal sinus sampling (BIPSS), the side-to-side adrenocorticotropic hormone (ACTH) ratio, referred to as sampling lateralization, was used to predict pituitary adenoma localization. Objective: To investigate the potential different diagnostic accuracy of BIPSS for differentiating Cushing disease (CD) and ectopic ACTH secretory syndrome (EAS) patients with low lateralization (inferior petrosal sinus [IPS]:IPS ≤ 1.4) and high lateralization (IPS:IPS > 1.4). Methods: This single-center retrospective study (2011-2021) included (all patients had BIPSS results and confirmed pathologic diagnoses) 220 consecutive CD patients (validation set), 30 EAS patients, and 40 of the CD patients who had digital subtraction angiography (DSA) videos (discovery set). Results: In the discovery set, the low-lateralization CD group (n = 11) had a higher median plasma ACTH concentration (62.2, IQR 44.7-181.0 ng/L) than the high-lateralization CD group (n = 29) (33.0, IQR 18.5-59.5, P = .013). Lower IPS to peripheral ratios were observed in the low-lateralization group during BIPSS, both before and after stimulation (P = .013 and P = .028). The sensitivity of BIPSS before stimulation in differentiating CD from EAS was lower in the low-lateralization group than the high-lateralization group (54.6% vs 93.1%, P = .003), as validated in the validation set. DSA videos revealed higher vascular area difference visible in the 2 sides of the pituitary in low lateralization (median 1.2 × 105 pixels, IQR 0.5-1.8) than the high-lateralization group (0.4 × 105 pixels, IQR 0.1-0.7, P = .008). The vascular area ratio of the 2 sides was also significantly higher in low (1.55, IQR 1.31-2.20) than high lateralization (1.19, IQR 1.07-1.35, P = .010). Conclusion: Our study suggested that low lateralization in CD patients may reduce the diagnostic sensitivity of BIPSS, which might be potentially associated with peripituitary vascular anatomy.

Exploring Advanced Therapies for Primary Biliary Cholangitis: Insights from the Gut Microbiota-Bile Acid-Immunity Network.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the effectiveness of conventional immunosuppressive therapy is disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and evidence is increasing that gut microbiota and bile acids play an important role in the pathogenesis of cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Autoimmune cholangitis has the potential to be improved through immune system modulation. Considering the failure of conventional immunotherapies and the involvement of gut microbiota and bile acids in the pathogenesis, targeting immune factors associated with them, such as bile acid receptors, microbial-derived molecules, and related specific immune cells, may offer breakthroughs. Understanding the gut microbiota-bile acid network and related immune dysfunctions in PBC provides a new perspective on therapeutic strategies. Therefore, we summarize the latest advances in research of gut microbiota and bile acids in PBC and, for the first time, explore the possibility of related immune factors as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine.

Bile acid diarrhea (BAD) is a multifaceted intestinal disorder involving intricate molecular mechanisms, including farnesoid X receptor (FXR), fibroblast growth factor receptor 4 (FGFR4), and Takeda G protein-coupled receptor 5 (TGR5). Current diagnostic methods encompass bile acid sequestrants (BAS), 48-h fecal bile acid tests, serum 7α-hydroxy-4-cholesten-3-one (C4), fibroblast growth factor 19 (FGF19) testing, and 75Selenium HomotauroCholic acid test (75SeHCAT). Treatment primarily involves BAS and FXR agonists. However, due to the limited sensitivity and specificity of current diagnostic methods, as well as suboptimal treatment efficacy and the presence of side effects, there is an urgent need to establish new diagnostic and treatment methods. While prior literature has summarized various diagnostic and treatment methods and the pathogenesis of BAD, no previous work has linked the two. This review offers a molecular perspective on the clinical diagnosis and treatment of BAD, with a focus on FXR, FGFR4, and TGR5, emphasizing the potential for identifying additional molecular mechanisms as treatment targets and bridging the gap between diagnostic and treatment methods and molecular mechanisms for a novel approach to the clinical management of BAD.

Factors affecting the transmission of dengue fever in Haikou city in 2019.

In this study, due to multiple cases of dengue fever in two locations in Haikou, Hainan, several factors affecting the transmission of dengue fever in Haikou in 2019 were analyzed. It was found that dengue fever spread from two sites: a construction site, which was an epidemic site in Haikou, and the university, where only four confirmed cases were reported. Comparative analysis revealed that the important factors affecting the spread of dengue fever in Haikou were environmental hygiene status, knowledge popularization of dengue fever, educational background, medical insurance coverage and free treatment policy knowledge and active response by the government.

Effects of reciprocal hybridization on cadmium accumulation in F1 hybrids of two Solanum photeinocarpum ecotypes.

In this study, farmland and mining ecotypes of Solanum photeinocarpum (a potential cadmium (Cd) hyperaccumulator plant) were reciprocally hybridized each other, and the Cd accumulation characteristics of the F1 hybrids were studied. In pot experiments, higher biomasses and Cd extraction abilities were found for two S. photeinocarpum F1 hybrids than for the parents, but the Cd contents in various organs were lower in the hybrids than the parents. However, the differences between the Cd contents in the two hybrids were not significant. The antioxidant enzyme (superoxide dismutase and peroxidase) activities were higher for the S. photeinocarpum F1 hybrids than the parents. Less DNA methylation was found in the hybrids than the parents because more demethylation occurred in the hybrids than the parents. The biomass, Cd content, and Cd extraction ability effects in field experiments were similar to the effects in the pot experiments. It was concluded that reciprocally hybridizing different S. photeinocarpum ecotypes improved the ability of S. photeinocarpum to be used to phytoremediate contaminated land.

Effects of grafting on the cadmium accumulation characteristics of the potential Cd-hyperaccumulator Solanum photeinocarpum.

The effects of grafting on the cadmium (Cd) accumulation characteristics of the potential Cd-hyperaccumulator Solanum photeinocarpum were studied under Cd stress in our experiment. Four treatments were used in the experiment: ungrafted (UG), self-rooted grafting by the same S. photeinocarpum seedling (SG), self-rooted grafting by two different development stages of S. photeinocarpum seedlings (DG), and grafting on the rootstock of wild potato (PG). SG and DG decreased the root, scion stem, leaf, whole shoot, and whole plant biomasses compared with UG, but increased the rootstock stem biomass, while only PG increased the root and whole plant biomasses. SG and DG increased the Cd contents in the different organs of S. photeinocarpum compared with UG, while PG decreased the Cd content compared with UG. The Cd extraction by the whole plant of S. photeinocarpum was ranked as DG > SG > UG > PG. Additionally, the antioxidant enzyme activities in SG and DG were enhanced compared with UG, while that of PG was reduced compared with UG. The grafting increased the DNA methylation levels and changed the methylation patterns of S. photeinocarpum compared with UG. Therefore, SG and DG can increase the Cd accumulation in S. photeinocarpum, which can be used for the phytoremediation of Cd-contaminated soil.

Effects of mulching tolerant plant straw on soil surface on growth and cadmium accumulation of Galinsoga parviflora.

Pot and field experiments were conducted to study the effects of mulching with straw of cadmium (Cd) tolerant plants (Ranunculus sieboldii, Mazus japonicus, Clinopodium confine and Plantago asiatica) on growth and Cd accumulation of Galinsoga parviflora in Cd-contaminated soil. In the pot experiment, mulching with M. japonicus straw increased the root biomass, stem biomass, leaf biomass, shoot biomass, plant height and activities of antioxidant enzymes (superoxide dismutase, peroxidase and catalase) of G. parviflora compared with the control, whereas mulching with straws of R. sieboldii, C. confine and P. asiatica decreased these parameters. Straws of the four Cd-tolerant plants increased the Cd content in roots of G. parviflora compared with the control. However, only straws of M. japonicus and P. asiatica increased the Cd content in shoots of G. parviflora, reduced the soil pH, and increased the soil exchangeable Cd concentration. Straw of M. japonicus increased the amount of Cd extraction in stems, leaves and shoots of G. parviflora by 21.11%, 29.43% and 24.22%, respectively, compared with the control, whereas straws of the other three Cd-tolerant plants decreased these parameters. In the field experiment, the M. japonicus straw also increased shoot biomass, Cd content in shoots, and amount of Cd extraction in shoots of G. parviflora compared with the control. Therefore, straw of M. japonicus can be used to improve the Cd extraction ability of G. parviflora from Cd-contaminated soil.