Identification of a novel hypoglycemic small molecule, trans-2, 4-dimethoxystilbene by rectifying gut microbiota and activating hepatic AMPKα-PPARγ pathway through gut-liver axis.

With the increasing prevalence of metabolic disorders, hyperglycemia has become a common risk factor that endangers people's lives and the need for new drug solutions is burgeoning. Trans-2, 4-dimethoxystilbene (TDMS), a synthetic stilbene, has been found as a novel hypoglycemic small molecule from glucose consumption test. Normal C57BL/6 J mice, mouse models of type 1 diabetes mellitus and diet-induced obesity subjected to TDMS gavage were found with lower glycemic levels and better glycemic control. TDMS significantly improved the symptoms of polydipsia and wasting in type 1 diabetic mice, and could rise their body temperature at the same time. It was found that TDMS could promote the expression of key genes of glucose metabolism in HepG2, as do in TDMS-treated liver, while it could improve the intestinal flora and relieve intestinal metabolic dysbiosis in hyperglycemic models, which in turn affected its function in the liver, forming the gut-liver axis. We further fished PPARγ by virtual screening that could be promoted by TDMS both in-vitro and in-vivo, which was regulated by upstream signaling of AMPKα phosphorylation. As a novel hypoglycemic small molecule, TDMS was proven to be promising with its glycemic improvements and amelioration of diabetes symptoms. It promoted glucose absorption and utilization by the liver and improved the intestinal flora of diabetic mice. Therefore, TDMS is expected to become a new hypoglycemic drug that acts through gut-liver axis via AMPKα-PPARγ signaling pathway in improving glycemic metabolism, bringing new hope to patients with diabetes and glucose metabolism disorders.

Cold Snare Polypectomy With or Without Submucosal Injection for Endoscopic Resection of Colorectal Polyps: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: The impact of submucosal injection during cold snare polypectomy (CSP) remains uncertain. We conducted an evidence-based comparison of conventional CSP (C-CSP) and CSP with submucosal injection (SI-CSP) for colorectal polyp resection. METHODS: PubMed, Embase, and the Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing C-CSP with SI-CSP. Major outcomes included the rates of complete resection, en bloc resection, polyp retrieval, and adverse events, as well as the duration of polypectomy. Data were analyzed by using a random-effects model. RESULTS: A total of seven RCTs were included. Complete resection rates for all polyps (RR 0.98; 95% CI 0.93-1.03), polyps ≤ 10 mm (RR 0.99; 95% CI 0.96-1.02) and polyps > 10 mm (RR 0.92; 95% CI 0.69-1.12) were not substantially different between C-CSP and SI-CSP groups. En bloc resection rate (RR 0.93; 95% CI 0.79-1.09) and polyp retrieval rate (RR 1.00; 95% CI 0.99-1.01) were also not significantly different between the two groups. The SI-CSP group required a prolonged polypectomy time than the C-CSP group (SMD - 0.89; 95% CI -1.29 to -0.49). Adverse events were rare in both groups. CONCLUSIONS: SI-CSP is not an optimal substitute for CSP in the resection of colorectal polyps, particularly diminutive and small polyps.

Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics.

Lipid metabolic reprogramming is an emerging hallmark of cancer. In order to sustain uncontrolled proliferation and survive in unfavorable environments that lack oxygen and nutrients, tumor cells undergo metabolic transformations to exploit various ways of acquiring lipid and increasing lipid oxidation. In addition, stromal cells and immune cells in the tumor microenvironment also undergo lipid metabolic reprogramming, which further affects tumor functional phenotypes and immune responses. Given that lipid metabolism plays a critical role in supporting cancer progression and remodeling the tumor microenvironment, targeting the lipid metabolism pathway could provide a novel approach to cancer treatment. This review seeks to: (1) clarify the overall landscape and mechanisms of lipid metabolic reprogramming in cancer, (2) summarize the lipid metabolic landscapes within stromal cells and immune cells in the tumor microenvironment, and clarify their roles in tumor progression, and (3) summarize potential therapeutic targets for lipid metabolism, and highlight the potential for combining such approaches with other anti-tumor therapies to provide new therapeutic opportunities for cancer patients.

Development and validation of a model to determine the risk of esophageal strictures after endoscopic submucosal dissection for esophageal neoplasms.

BACKGROUND: Currently, endoscopic submucosal dissection (ESD) is widely used as therapeutic methods for superficial esophageal neoplasms (SENs). However, patients are likely to develop esophageal strictures after ESD. Our study aims to explore the possible risk factors for esophageal strictures after ESD and develop and validate a risk model for predicting the progression of postoperative esophageal strictures. METHODS: Clinical data of patients who underwent ESD in our hospital for suspected early esophageal squamous cell carcinoma were collected from January 2014 to March 2020. The possible risk factors for postoperative esophageal strictures were analyzed by univariate and multivariate logistic regression analysis. Eventually, a risk-scoring model was built, in which 70% of patients were used to develop the model and the remaining 30% were used for validation. RESULTS: A total of 553 patients who received ESD were involved, and the incidence of esophageal strictures after ESD was 16.6% (92/553). In our study, the operating time, circumferential range, lesion location, depth of infiltration, and R0 resection were independent risk factors for esophageal strictures after ESD. According to the risk of postoperative esophageal stenosis, a risk-scoring model for esophageal strictures prediction was developed. The risk score ranged from 0 to 11 points, and the risk scores were divided into low risk (0-3 points), intermediate risk (4-7 points), and high risk (8-11 points). The proportions of esophageal stenosis progression in the corresponding risk categories were 6.33%, 29.14%, and 100%. CONCLUSIONS: We developed a risk-scoring model based on factors including circumferential range, lesion location, depth of infiltration, and R0 resection. It stratified patients into low-, intermediate-, and high-risk groups for postoperative esophageal strictures development. This scoring model may have the potential to guide the management of patients after ESD in the future.

Bioremediation of selenium-contaminated soil using earthworm Eisenia fetida: Effects of gut bacteria in feces on the soil microbiome.

Selenium (Se) contamination in the soil poses a food safety risk to humans. The present study was to investigate the role of earthworm Eisenia fetida in soil Se remediation. When exposed to selenite at 4 mg Se/kg, E. fetida efficiently concentrated Se in tissues (24.53 mg Se/kg dry weight), however, only accounting for a minor portion of the added Se. Microbial analysis shows 12 out of 15 functional genera became more abundant in the worm-inhabited soil when exposed to Se, suggesting E. fetida contributed to Se remediation mainly by introducing Se-reducing bacteria to the soil via feces, which were dominated by the genera Pseudomonas (∼62.65%) and Aeromonas (∼29.99%), whose abundance was also significantly boosted in the worm-inhabited soil. However, when isolated from worm feces at 200 mg Se/L, Pseudomonas strains only displayed a high tolerance to Se rather than removal capacity. In contrast, among 4 isolated Aeromonas strains, A. caviae rapidly removing 85.74% of the added selenite, mainly through accumulation (67.38%), while A. hydrophila and A. veronii were more effective at volatilizing Se (27.77% and 24.54%, respectively), and A. media performed best by reducing Se by ∼49.00% under anaerobic conditions. Overall, our findings have highlighted the importance of E. fetida as a key contributor of functional bacteria to the soil microbiome, building a strong foundation for the development of an earthworm-soil system for Se bioremediation.

The value of contrast-enhanced ultrasound for the diagnosis of metastatic cervical lymph nodes of papillary thyroid carcinoma: A systematic review and meta-analysis.

To investigate the diagnostic efficiency of contrast-enhanced ultrasound (CEUS) for the diagnosis of cervical lymph nodes metastasis (CLNM) of papillary thyroid carcinoma (PTC), eight available datasets of seven qualified articles before March 31, 2021 were included after a comprehensive search. Meta-analysis results showed that CEUS demonstrated acceptable diagnostic performance in the diagnosis of CLNM of PTC. Furthermore, meta-regression analysis was conducted to identify the reasons for heterogeneity and the results indicated that the criteria of CEUS for the diagnosis of CLNM in PTC need to be unified.

Se transformation and removal by a cattail litter treatment system inoculated with sulfur-based denitrification sludge: Role of the microbial community composition under various temperature and aeration conditions.

With a narrow margin between deficiency and toxicity, rising levels of selenium (Se) are threatening aquatic ecosystems. To investigate the role of microorganisms in Se bioremediation, a cattail litter system inoculated with the sulfur-based denitrification sludge was conducted. The results show the litter, as a carrier and nutrient source for bacteria, efficiently removed Se by ~ 97.0% during a 12-d treatment with water circulating. As the major removal pathways, immobilization rates of selenite were ~ 2.9-fold higher than selenate, and the volatilization, contributing to ~ 87.7% of the total Se removal, was significantly correlated with temperature (positively) and oxidation-reduction potential (ORP; negatively). Using X-ray absorption spectroscopy to speciate litter-borne Se, more Se0 formed without aeration due to abundant Se-reducing bacteria, among which Azospira and Azospirillum were highly related to the removal of both Se oxyanions, while Desulfovibrio, Azoarcus, Sulfurospirillum, Thauera, Geobacter, Clostridium, and Pediococcus were the major contributors to selenate removal. Overall, our study suggests microbial Se metabolism in the litter system was significantly affected by temperature and ORP, which could be manipulated to enhance Se removal efficiency and the transformation of selenate/selenite into low toxic Se0 and volatile Se, reducing risks posed by the residual Se in the system.

Salinity-driven nitrogen removal and its quantitative molecular mechanisms in artificial tidal wetlands.

The present study investigated the performance in nitrogen removal and associated nitrogen transformation processes in seven mesocosms fed with saline water (0‰ to 30‰) to simulate tidal flow constructed wetlands (TF CWs). The highly effective and steady removal of NH4+-N (84.74% averagely) was obtained at various salinities, while the rates varied from 6.34% to 89.19% and 22.54% to 87.48% for NO3--N and total nitrogen (TN), respectively. Overall, nitrogen removal efficiencies were greater at lower salinities. Molecular biological analyses verified the co-occurrence of dissimilatory nitrate reduction to ammonium (DNRA), denitrification, anaerobic ammonium oxidation (anammox) and nitrification in the mesocosms, reportedly contributing to nitrogen removal in TF CWs. The absolute copy numbers of nitrogen functional genes and total bacterial 16S rRNA were 2.54 × 103-7.35 × 107 and 3.21 × 107-7.82 × 109 copies g-1 dg (dry gravel), respectively, with the dominant phyla, i.e., Chloroflexi, Proteobacteria, Actinobacteriota, Cyanobacteria, and Firmicutes, accounting for over 80% of the sequences. The relative abundances of the genera related to nitrification and dissimilatory nitrate reduction processes, i.e., denitrification, anammox and DNRA, varied from 0.16% to 0.89% and from 3.66% to 11.59%, respectively, while quantitative relationships confirmed NH4+-N transformation rate was jointly controlled by amoA, hzsB, nxrA and nrfA, and NO3--N removal rate by nirS, nosZ, narG, qnorB and nxrA. These findings may shed light on quantitative molecular mechanisms for nitrogen removal in TF CWs for the saline water treatment, providing a sustainable solution to nitrogen pollution problem in the estuary ecosystem.

Healthcare Costs Associated with Complications in Patients with Type 2 Diabetes among 1.85 Million Adults in Beijing, China.

We aimed to provide reliable regression estimates of expenditures associated with various complications in type 2 diabetics in China. In total, 1,859,039 type 2 diabetes patients with complications were obtained from the Beijing Medical Claim Data for Employees database from 2008 to 2016. We estimated costs for complications using a generalized estimating equation model adjusted for age, sex, and the incidence of various complications. The average total cost for diabetic patients with complications was 17.12 thousand RMB. Prescribed drugs accounted for 63.4% of costs. We observed a significant increase in costs in the first year after the onset of complications. Compared with costs before the incidence of complications, the additional costs per person in the first year and >1 year after the event would be 10,631.16 RMB and 1150.71 RMB for cardiovascular disease, 1017.62 RMB and 653.82 RMB for cerebrovascular disease, and 301.14 RMB and 624.00 RMB for kidney disease, respectively. The estimated coefficients for outpatient visits were relatively lower than those of inpatient visits. Complications in diabetics exert a significant impact on total healthcare costs in the first year of their onset and in subsequent years. Our estimates may assist policymakers in quantifying the economic burden of diabetes complications.

Interobserver agreement for contrast-enhanced ultrasound of liver imaging reporting and data system: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma is the most common primary liver malignancy. From the results of previous studies, Liver Imaging Reporting and Data System (LI-RADS) on contrast-enhanced ultrasound (CEUS) has shown satisfactory diagnostic value. However, a unified conclusion on the interobserver stability of this innovative ultrasound imaging has not been determined. The present meta-analysis examined the interobserver agreement of CEUS LI-RADS to provide some reference for subsequent related research. AIM: To evaluate the interobserver agreement of LI-RADS on CEUS and analyze the sources of heterogeneity between studies. METHODS: Relevant papers on the subject of interobserver agreement on CEUS LI-RADS published before March 1, 2020 in China and other countries were analyzed. The studies were filtered, and the diagnostic criteria were evaluated. The selected references were analyzed using the "meta" and "metafor" packages of R software version 3.6.2. RESULTS: Eight studies were ultimately included in the present analysis. Meta-analysis results revealed that the summary Kappa value of included studies was 0.76 [95% confidence interval, 0.67-0.83], which shows substantial agreement. Higgins I 2 statistics also confirmed the substantial heterogeneity (I 2 = 91.30%, 95% confidence interval, 85.3%-94.9%, P < 0.01). Meta-regression identified the variables, including the method of patient enrollment, method of consistency testing, and patient race, which explained the substantial study heterogeneity. CONCLUSION: CEUS LI-RADS demonstrated overall substantial interobserver agreement, but heterogeneous results between studies were also obvious. Further clinical investigations should consider a modified recommendation about the experimental design.

[Changes in serum cortisol and adrenocorticotropic hormone in children with sepsis shock and their clinical significance].

OBJECTIVE: To study the changes in serum levels of cortisol and adrenocorticotropic hormone (ACTH) in children with septic shock (SS) and to explore their relationship with the disease severity and prognosis. METHODS: Twenty-five children with decompensated SS and 24 children with early SS were enrolled. Serum cortisol and ACTH levels were determined on admission and days 3 and 8 after admission. Twenty-five healthy children were used as the control group. The children with decompensated SS were further divided into death group (n=5) and survival group (n=20) based on their clinical outcome. RESULTS: On admission, the decompensated SS and early SS groups had significantly higher serum cortisol and ACTH levels than the control group (P<0.05), and the decompensated SS group had significantly higher serum cortisol and ACTH levels than the early SS group. On day 3 after admission, the decompensated SS group had significantly higher serum cortisol and ACTH levels than the early SS and control groups (P<0.05), and the early SS group had a significantly higher serum ACTH level than the control group (P<0.05). Among the children with decompensated SS, the death group had significantly higher serum cortisol and ACTH levels than the survival group on admission (P<0.01); on day 3 after admission, the death group still had a significantly higher serum cortisol level than the survival group (P<0.01). CONCLUSIONS: Children with SS have increased serum cortisol and ACTH levels, which are associated with the disease severity. A persistent high serum cortisol level indicates a poor prognosis. Dynamic monitoring of serum cortisol and ACTH levels in children with SS is of great significance in evaluating the disease severity and prognosis.

Intestinal histoplasmosis in immunocompetent adults.

AIM: To present a retrospective analysis of clinical and endoscopic features of 4 cases of immunocompetent hosts with intestinal histoplasmosis (IH). METHODS: Four immunocompetent adults were diagnosed with IH between October 2005 and March 2015 at West China Hospital of Sichuan University. Clinical and endoscopic characteristics were summarized and analyzed retrospectively. GMS (Gomori methenamine silver), PAS (periodic acid-Schiff) and Giemsa staining technique were used to confirm Histoplasma capsulatum(H. capsulatum). The symptoms, signs, endoscopic presentations, radiographic imaging, pathological stain results and follow-up are presented as tables and illustrations. RESULTS: The cases were male patients, ranging from 33 to 61 years old, and primarily presented with non-specific symptoms such as irregular fever, weight loss, abdominal pain and distention. Hepatosplenomegaly and lymphadenopathy were the most common signs. Endoscopic manifestations were localized or diffuse congestion, edema, ulcers, and polypoid nodules with central erosion involving the terminal ileum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum, similar to intestinal tuberculosis, tumor, and inflammatory bowel disease. Numerous yeast-like pathogens testing positive for PAS and GMS stains but negative for Giemsa were detected in the cytoplasm of the histiocytes, which were highly suggestive of H. capsulatum. CONCLUSION: Immunocompetent individuals suffering from histoplasmosis are rarely reported. It is necessary that gastroenterologists and endoscopists consider histoplasmosis as a differential diagnosis, even in immunocompetent patients.

Distribution of metastatic disease in the brain in relation to the hippocampus: a retrospective single-center analysis of 6064 metastases in 632 patients.

This study aimed to investigate the patterns of brain metastasis and to explore the risk factors affecting hippocampus metastasis (HM). We retrospectively analyzed the clinical information of patients with metastatic disease in the brain. The associations between clinicopathologic variables with HM and peri-hippocampal metastasis (PHM) were evaluated in univariate and multivariate regression analyses. A total of 632 patients with 6064 metastatic lesions were recruited into the present study. Of these, 4.1% (26/632) of patients developed HM, and 5.5% (35/632) of patients developed PHM. Only 0.5% (31/6064) of metastatic lesions were located in the hippocampus and 0.6% (37/6064) were in the PHM. Age ≤60 years was an independent risk factor for HM (odds ratio [OR]: 2.602, 95% confidence interval [CI]: 1.115-6.076, P = 0.027) and PHM (OR: 2.555, 95%CI: 1.229-5.310, P = 0.012) in univariate and multivariate analyses. The hippocampus is a rare site of brain metastasis. Younger patients (age ≤60 years) had increased risk of developing HM and PHM. The current study provides the opportunity to investigate the clinical feasibility of hippocampal sparing whole brain radiation therapy, especially in older patients.

Decreased histone H2B monoubiquitination in malignant gastric carcinoma.

AIM: To investigate H2B monoubiquitination (uH2B) and H3K4 di- and tri-methylation (H3K4-2me, H3K4-3me) levels and their clinical significance in gastric cancer (GC). METHODS: Immunohistochemistry (IGC) was used to detect the differential levels of uH2B, H3K4-2me and H3K4-3me modifications in GC specimens from chemo/radiotherapy-naïve patients who underwent potentially curative surgical resection (n = 159) and in a random sampling of non-tumor gastric epithelium specimens (normal controls, n = 20). The immunohistochemistry (IHC)-detected modifications were classified as negative, low-level, or high-level using a dual-rated (staining intensity and percentage of positively-stained cells) semi-quantitative method. The relationships between uH2B modification levels and clinicopathological parameters of GC were assessed by a Wilcoxon rank sum test (pairwise comparisons) and the Kruskal-Wallis H test (multiple comparisons). The correlation between uH2B modification and survival was estimated by Kaplan-Meier analysis, and the role of uH2B as an independent prognostic factor for survival was assessed by multivariate Cox regression analysis. RESULTS: The presence and level of H3K4-2me and H3K4-3me IHC staining was similar between the normal controls and GC specimens. In contrast, the level of uH2B was significantly lower in the malignant gastric tissues (vs normal control tissues) and decreased along with increases in dedifferentiation (well differentiated > moderately differentiated > poorly differentiated). The level of uH2B correlated with tumor differentiation (P < 0.001), Lauren's diffuse- and intestinal-type classification (P < 0.001), lymph node metastasis (P = 0.049) and tumor-node-metastasis stage (P = 0.005). Patients with uH2B+ staining had higher 5-year survival rates than patients with uH2B-staining (52.692 ± 2.452 vs 23.739 ± 5.207, P < 0.001). The uH2B level was an independent prognostic factor for cancer-specific survival (95%CI: 0.237-0.677, P = 0.001). CONCLUSION: uH2B displays differential IHC staining patterns corresponding to progressive stages of GC. uH2B may contribute to tumorigenesis and could be a potential therapeutic target.