A Mendelian randomization study on the effects of plasma lipids on irritable bowel syndrome and functional dyspepsia.

Although functional gastrointestinal disorder (FGID) is a common clinical condition, its risk factors remain unclear. We performed a Mendelian randomization study to explore the association between plasma lipids and the risk of FGID. Instrumental variables closely related to six plasma lipids were obtained from the corresponding genome-wide association studies, and summary-level data on FGID, including irritable bowel syndrome (IBS) and functional dyspepsia (FD), were extracted from the FinnGen study. The primary inverse variance weighted method and other supplementary analyses were used to evaluate the causal relationship between diverse plasma lipids and FGID. For each increase in the standard deviation of triglyceride levels, there was a 12.0% increase in the risk of IBS rather than that of FD. Low- and high-density lipoprotein cholesterol, total cholesterol, apolipoprotein A, and apolipoprotein B levels were not associated with the risk of IBS or FD. Through this study, we identified the causal role of triglycerides in the pathogenesis of IBS, which could benefit further basic and clinical research.

Systemic immune-inflammation index as a potential biomarker to monitor ulcerative colitis.

OBJECTIVE: The treat-to-target strategy is recommended by Selecting Therapeutic Targets in Inflammatory Bowel Disease II (STRIDE-II) for treating ulcerative colitis (UC), and monitoring remission status is crucial during this management. The systemic immune-inflammation index (SII), defined as platelet * neutrophil/lymphocyte, is a complete blood count-based index reflecting the balance of immune and inflammatory status. This study aims to investigate the feasibility of SII for diagnosing UC and monitoring UC disease activity. METHODS: This study retrospectively analyzed patients with UC and controls. Relationships between SII and Mayo clinical score, Mayo Endoscopic Score (MES), and Nancy Histological Index (NHI) were evaluated. RESULTS: 167 patients with UC and 106 controls were included. SII significantly increased in patients with UC and was closely correlated with the Mayo clinical score, MES, and NHI. SII diagnosed UC with a cut-off value of 619.1 × 109/L (area under the curve = 0.861, p < 0.0001, sensitivity 79.64%, specificity 77.36%), evaluated clinical remission status with a cut-off value of 1068 × 109/L (area under the curve = 0.691, p < 0.05, sensitivity 55.71%, specificity 81.48%), endoscopic improvement with a cut-off value of 981.3 × 109/L (area under the curve = 0.819, p < 0.0001, sensitivity 65.22%, specificity 89.66%), and histological healing with a cut-off value of 689.3 × 109/L (area under the curve = 0.898, p < 0.0001, sensitivity 88.89%, specificity 95.83%). CONCLUSION: SII is a potential biomarker for diagnosing UC and monitoring UC disease severity, especially in evaluating mucosal and histological healing during the long-term management in treat-to-target strategy. However, further research is needed to confirm its usefulness and optimize its clinical application.

Researchers studied an index calculated from a blood test, named the "systemic immune-inflammation index" (SII), to see if it can identify and track the activity of a bowel condition called ulcerative colitis (UC).They reviewed health records of UC patients and compared them to people without this condition. They specifically checked if the SII test's results aligned with other common tests that show the severity of UC.People with UC tended to have higher SII results. The SII test results were consistent with other tests for UC. Specific scores from the SII test, like 619.1 × 10⁹/L, can indicate someone might have UC. What's more, this test can give clues about inflammation in the bowel, saving some from more invasive tests like a colonoscopy or biopsy.The SII test could be a promising way for doctors to diagnose UC and gauge its activity without needing more intrusive tests. However, more studies are required to fully trust this approach.

Identification of the Roles of Coagulation-Related Signature and its Key Factor RABIF in Hepatoma Cell Malignancy.

BACKGROUND: Hepatoma is a high morbidity and mortality cancer, and coagulation is a potential oncogenic mechanism for hepatoma development. OBJECTIVE: In this study, we aimed to reveal the role of coagulation in hepatoma. METHODS: We applied the LASSO to construct a coagulation-related risk score (CRS) and a clinical nomogram with independent validation. The heterogeneity of various aspects, including functional enrichment, SNV, CN, immunocyte infiltration, immune pathways, immune checkpoint, and genomic instability indexes, was evaluated. Besides, the prognostic value of the CRS genes was tested. We selected the critical risky gene related to coagulation from the LASSO coefficients, for which we applied transwell and clone formation assays to confirm its roles in hepatoma cell migration and clone formation ability, respectively. RESULTS: The CRS and the nomogram predicted patients' survival with good accuracy in both two datasets. The high-CRS group was associated with higher cell cycle, DNA repair, TP53 mutation rates, amplification, and lower deletion rates at chromosome 1. For immunocyte infiltration, we noticed increased Treg infiltration and globally upregulated immune checkpoints and genomic instability indexes. Additionally, every single CRS gene affected the patient's survival. Finally, we observed that RABIF was the riskiest gene in the CRS. Its knockdown suppressed hepatoma cell migration and clone formation capability, which could be rescued by RABIF overexpression. CONCLUSION: We built a robust CRS with great potential as a prognosis and immunotherapeutic indicator. Importantly, we identified RABIF as an oncogene, promoting hepatoma cell migration and clone formation, revealing underlying pathological mechanisms, and providing novel therapeutic targets for hepatoma treatment.

Highly Chemoselective Synthesis of Azaarene-Equipped CF3-Tertiary Alcohols under Metal-Free Conditions and Their Fungicidal Activities.

A highly chemoselective reaction between α,ß-unsaturated trifluoromethyl ketones with azaarenes under metal-free conditions was carried out, affording a range of valuable azaarene-equipped CF3-tertiary alcohols in moderate to excellent yields (up to 95% yield) with good tolerance of functional groups, and their structures were confirmed by NMR, HRMS, and X-ray diffraction for validation. This method features simple reaction conditions (only solvent), high atom- and step-economy, and broad substrate scope. Moreover, most of the target products exhibited promising fungicidal activities, and compound 3al exhibited 91.65% fungicidal activity against R. solani, with an EC50 value of 0.18 mg/mL.

Endoscopic Treatment for Pediatric Esophageal Stenosis Induced by Chemical Burn, Congenitally, or After Surgical Repair of Esophageal Atresia.

Objectives: To evaluate the safety and efficacy of endoscopic treatment for congenital pediatric esophageal stenosis or pediatric stenosis that develops after a chemical burn or surgical repair of esophageal atresia. Methods: We retrospectively reviewed the medical records of 15 pediatric patients who underwent endoscopic treatments (dilation and/or stenting and/or incision) for congenital esophageal stenosis or esophageal stenosis that developed after a chemical burn or surgical repair of esophageal atresia, between January 2010 and January 2019. The patients were periodically followed-up to assess the safety and efficacy of treatment by comparing the diameter of stricture and dysphagia score before and after procedures, and complications or recurrence. Results: All children successfully underwent the procedures. Fourteen of the 15 patients received endoscopic balloon dilation (EBD) as the first step of treatment, but EBD alone only resolved the symptoms in two patients. The remaining patients received other comprehensive treatments, such as EBD with endoscopic incision (EI), EBD with stent replacement, or a combination of EBD, stent replacement, and EI. Eleven (11/15, 73.3%) patients experienced symptomatic relief after endoscopic treatment, and recurrence was noted in four patients on 3-36 months after the final endoscopic treatment. All four patients underwent esophageal surgery to relieve their symptoms. Until October 2021, all patients experienced symptom relief, and their dysphagia scores decreased from 3-4 to 0-1 during the follow-up period of 8-121 months. The average diameter of stenosis was increased from 0.34 cm (range 0.2-0.7 cm) to 1.03 cm (range 0.8-1.2 cm). No severe complications occurred during endoscopic treatment and follow-up. Conclusions: Endoscopic treatment is safe and effective for pediatric esophageal stenosis that is congenital or induced by chemical burns or surgical repair of esophageal atresia. Comparative large-scale studies are required to confirm our findings.

Single nucleotide polymorphisms in binding site of miRNA-135a and targeted gene IRS2 are correlated with multiple clinical features of PCOS: A study in Chinese women.

BACKGROUND: The etiology of polycystic ovary syndrome (PCOS) remains unclear with highly heterogeneous clinical manifestations, recently growing evidence revealing genetic variants play a crucial part in its pathogenesis. OBJECTIVE: This study aimed to examine the correlation between SNPs in miRNA-135a's binding site of targeted gene IRS2 and clinical manifestations of PCOS in Chinese females. METHOD: A total of 126 Chinese women with PCOS and 109 healthy women were enrolled, divided into 4 groups based on different clinical features of hyperandrogenemia (HA), insulin resistance (IR), polycystic ovary morphology (PCOM) and obesity. We analyzed 2 single nucleotide polymorphisms (SNPs) of the IRS2 gene (rs2289046 and rs1865434) and clinical features' laboratory measurements such as sex hormone, fasting plasma glucose (FPG), fasting plasma insulin (FINS). RESULTS: Located in miRNA-135a binding site of IRS2 gene, the rs2289046's triple genotypes distribution showed a significant difference between PCOS/control group and PCOM/non-PCOM group (P< 0.05) while the rs1865434's triple genotype distribution showed a significant difference between obesity/non-obesity group (P< 0.05). CONCLUSION: The results revealed the two SNPs as rs2289046 and rs1865434 in the IRS-2 binding region of miRNA-135a have correlations with the clinical features of PCOS in Chinese population.

Design, Catalyst-Free Synthesis of New Novel α-Trifluoromethylated Tertiary Alcohols Bearing Coumarins as Potential Antifungal Agents.

A new method for the synthesis of α-trifluoromethylated tertiary alcohols bearing coumarins is described. The reaction of 3-(trifluoroacetyl)coumarin and pyrrole provided the target compounds with high yields under catalyst-free, mild conditions. The crystal structure of compound 3fa was investigated by X-ray diffraction analysis. The biological activities, such as in vitro antifungal activity of the α-trifluoromethylated tertiary alcohols against Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Rhizoctonia solani Kuhn, and Phytophthora parasitica var nicotianae, were investigated. The bioassay results indicated that compounds 3ad, 3gd, and 3hd showed broad-spectrum antifungal activity in vitro. Compound 3cd exhibited excellent fungicidal activity against Rhizoctonia solani Kuhn, with an EC50 value of 10.9 µg/mL, which was comparable to that of commercial fungicidal triadimefon (EC50 = 6.1 µg/mL). Furthermore, molecular docking study suggested that 3cd had high binding affinities with 1W9U, like argifin.

Combustion Kinetics of Coal Treated by Microwave Irradiation Combined with Hydrochloric Acid Pickling.

The desulfurization efficiency, combustion properties, combustion kinetics, and structural changes of Kentucky coal under microwave irradiation (MI) combined with hydrochloric acid solution pickling were investigated and compared using a thermogravimetric analyzer coupled to a Fourier transform infrared spectrometer. The results show that the desulfurization rate increases with the concentration of hydrochloric acid solution. The introduction of MI can effectively improve the desulfurization efficiency. After desulfurization, the ignition temperature and burnout temperature of coal samples increase, the combustion index decreases, and the combustion performance deteriorates. The maximum weight loss rate decreases with the increase of the concentration of hydrochloric acid solution, and the activation energy of the coal sample after microwave treatment increases, and the reaction difficulty increases. The infrared analysis results show that MI and hydrochloric acid pickling treatment have little effect on the functional group structure of coal samples.

Role of HDAC6 and Its Selective Inhibitors in Gastrointestinal Cancer.

Worldwide, cancer is the second leading cause of mortality after cardiovascular diseases. Among the numerous malignant tumors in human, digestive system cancers are the primary cause of morbidity and mortality. Acetylation and deacetylation are crucially involved in cancer occurrence and development; in addition, the deacetylation process is regulated by histone deacetylases (HDACs). Among the 18 human HDACs that have been reported, HDAC6 has been widely studied. There is upregulated HDAC6 expression in numerous types of tumor tissues and is closely associated with clinicopathological characteristics. Moreover, several HDAC6 inhibitors have been identified; furthermore, there has been extensive research on their ability to inhibit the growth of many tumors. This review summarizes the roles of HDAC6 in different primary digestive system malignancies.

SET7 interacts with HDAC6 and suppresses the development of colon cancer through inactivation of HDAC6.

SET7 is the first lysine methyltransferase and plays vital roles in tumorigenesis. This study aims to seek clinical value of SET7 in colorectal cancer (CRC) patients, along with its biological impact on cell proliferation and migration. In patients with CRC, the expression of SET7 in cancer tissue was significantly lower than that in adjacent tissue, and down-regulated SET7 was closely correlated with poor prognosis. Loss-of-function and gain-of-function studies indicated that SET7 inhibited cell proliferation and migration by acting on HDAC6 substrate in colon cancer cells. Besides, the co-immunoprecipitation assay showed that SET7 and HDAC6 can interact reciprocally. The interaction effect between SET7 and HDAC6 could significantly reduce cell viability, scratch healing rate, and migrated cells in colon cancer cells. Instead of acting on each endogenous expression, the results demonstrated that the level of acetylated α-tubulin was greatly decreased in HDAC6 overexpression group, while significantly increased in SET7 overexpressed group. However, changes were partly restored in both SET7 and HDAC6-transfected group. On the contrary, the expression of acetylated α-tubulin protein was significantly increased in HDAC6 knockdown group, but higher in both HDAC6 and SET7 silencing group. These results indicated that SET7 played a role in tumor suppression via increasing levels of acetylated-α-tubulin mediated by HDAC6. In addition, the interaction effect significantly decreased the ratios of p-ERK/ERK, which indicated that it may partly suppress ERK signaling pathway. In conclusion, SET7 is a promising therapeutic target for preventing metastasis and improving prognosis in colon cancer.

Gastric per-oral endoscopic myotomy (G-POEM) is a promising treatment for refractory gastroparesis: a systematic review and meta-analysis

AIM: to evaluate the efficacy and safety of gastric per-oral endoscopic myotomy (G-POEM) for the treatment of refractory gastroparesis. METHODS: PubMed, Embase and Cochrane databases were searched and used for study inclusion. Clinical studies since January 2013 to October 2019 were identified as suitable for inclusion. Conference papers, review articles, case reports, animal studies, letters, studies with repetitive data, studies that did not mention the Gastroparesis Cardinal Symptom Index (GCSI) score/gastric emptying scintigraphy (GES) hours or were not indicated in the standard form were excluded. GCSI score, GCSI reduction, gastric emptying scintigraphy at four hours (GES-4h) and GES time (GET) reduction were considered as major indexes and the meta-analysis was achieved using Review Manager 5.3. Research bias was measured according to Cochrane handbook. RESULTS: nine studies were included with a total of 235 patients that underwent G-POEM, and the technical success rate was 100%. After G-POEM, patients reported changes in GCSI score (6/9 studies, mean difference 1.41 [CI: 0.93, 1.88], p < 0.0001), GCSI reduction (8/9 studies, odds ratio 3.00 [CI: 2.24, 4.03], p < 0.0001), GES-4h (8/9 studies, mean difference 23.78 [CI: 19.88, 27.68], p < 0.00001) and GET reduction (6/9 studies, odds ratio 3.50 [CI: 2.12, 5.78], p < 0.00001). The intra-procedure complication rate was 5.1% (12/235), including capnoperitoneum (seven cases) and accidental mucotomy (five cases). The post-procedure complication rate was 6.8% (16/235), including abdominal pain (three cases), bleeding (three cases), ulcer (one case), difficulty swallowing (one case) and others (eight cases). Both per- and post-procedure complications were easily managed by conservative or endoscopic treatments. CONCLUSION: the results show that gastroparesis patients can benefit from G-POEM, the success rate was impressive and the complication rate was relatively low. However, caution is necessary when interpreting the results, primarily due to the limitations of uncontrolled studies. Randomized control studies are still needed for further evaluations

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Gastric per-oral endoscopic myotomy (G-POEM) is a promising treatment for refractory gastroparesis: a systematic review and meta-analysis.

AIM: to evaluate the efficacy and safety of gastric per-oral endoscopic myotomy (G-POEM) for the treatment of refractory gastroparesis. METHODS: PubMed, Embase and Cochrane databases were searched and used for study inclusion. Clinical studies since January 2013 to October 2019 were identified as suitable for inclusion. Conference papers, review articles, case reports, animal studies, letters, studies with repetitive data, studies that did not mention the Gastroparesis Cardinal Symptom Index (GCSI) score/gastric emptying scintigraphy (GES) hours or were not indicated in the standard form were excluded. GCSI score, GCSI reduction, gastric emptying scintigraphy at four hours (GES-4h) and GES time (GET) reduction were considered as major indexes and the meta-analysis was achieved using Review Manager 5.3. Research bias was measured according to Cochrane handbook. RESULTS: nine studies were included with a total of 235 patients that underwent G-POEM, and the technical success rate was 100%. After G-POEM, patients reported changes in GCSI score (6/9 studies, mean difference 1.41 [CI: 0.93, 1.88], p < 0.0001), GCSI reduction (8/9 studies, odds ratio 3.00 [CI: 2.24, 4.03], p < 0.0001), GES-4h (8/9 studies, mean difference 23.78 [CI: 19.88, 27.68], p < 0.00001) and GET reduction (6/9 studies, odds ratio 3.50 [CI: 2.12, 5.78], p < 0.00001). The intra-procedure complication rate was 5.1% (12/235), including capnoperitoneum (seven cases) and accidental mucotomy (five cases). The post-procedure complication rate was 6.8% (16/235), including abdominal pain (three cases), bleeding (three cases), ulcer (one case), difficulty swallowing (one case) and others (eight cases). Both per- and post-procedure complications were easily managed by conservative or endoscopic treatments. CONCLUSION: the results show that gastroparesis patients can benefit from G-POEM, the success rate was impressive and the complication rate was relatively low. However, caution is necessary when interpreting the results, primarily due to the limitations of uncontrolled studies. Randomized control studies are still needed for further evaluations.

Histone deacetylase 6 is overexpressed and promotes tumor growth of colon cancer through regulation of the MAPK/ERK signal pathway.

Purpose: To investigate the expression of histone deacetylase 6 (HDAC6) in colon cancer and its role in colon cancer cell growth and migration. Materials and methods: We detected the expression of HDAC6 in a colon cancer tissue chip using immunochemical staining, and analyzed the difference in HDAC6 expression between cancer and adjacent noncancerous tissues. Then, we explored the relationship between HDAC6 expression and patients' clinicopathological characteristics and prognoses. In adidition, the role of HDAC6 in colon cancer cell growth and migration, as well as its potential related signal pathway, through HDAC6 knockdown was explored. Results: The immunochemical score of HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (4.54 vs 3.08, P<0.005); similarly, as well as the rate of high HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (71.1% vs 40.9%, P<0.001). Patients showing high HDAC6 expression had a shorter overall survival time. Additionally, Cox regression analysis showed that high HDAC6 expression was an independent risk factor for poor prognosis. HDAC6 knockdown decreased cell viability, colony formation, and number of migrated colon cancer cells (HCT116 and HT29); the expression of p-MEK, p-ERK, and p-AKT was also decreased, but had no influence on MEK, ERK, and AKT expression. Conclusion: HDAC6 is highly expressed in colon cancer and associated with a poor prognosis. HDAC6 knockdown inhibits colon cancer cell growth and migration, partly through the MAPK/ERK pathway.

Submucosal Tunneling Endoscopic Resection for Gastric Submucosal Tumors: a Comparison Between Cardia and Non-cardia Location.

BACKGROUND AND PURPOSE: Submucosal tunneling endoscopic resection (STER) was initially used to remove submucosal tumors (SMTs) located at the esophagus and cardia; only few researchers have reported the feasibility of STER for gastric SMTs beyond cardia due to the technical difficulty, and little is known about the comparison of STER for cardia and non-cardia gastric SMTs. The purpose was to compare the feasibility and efficacy of STER for cardia and non-cardia gastric SMTs, as well as to explore the risk factors for failure of en bloc resection. METHODS: We retrospectively collected the clinical data about patients with gastric SMTs who received STER at our hospital from June 2012 to June 2018. Demographics, tumor size, procedure-related parameters, complications, hospital stay, and follow-up data were compared between cardia and non-cardia SMTs. And multivariate analyses were conducted to look for the risk factors for failure of en bloc resection. RESULTS: A total of 46 SMTs were removed, and 25 of them were located at cardia, while the other 21 at non-cardia position. There was no significant difference between the two groups in terms of gender, age, tumor size, en bloc resection rate, operation time, complications, and hospital stay (p > 0.05). No recurrence was noticed in all the cases. Multivariate analyses revealed that irregular shape was an independent risk factor for failure of en bloc resection. CONCLUSION: STER is feasible for both cardia and non-cardia gastric SMTs, and the efficacy between cardia and non-cardia location is comparable. Irregular shape was an independent risk factor for failure of en bloc resection.

An esophageal cyst containing heterotopic gastric glands

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An esophageal cyst containing heterotopic gastric glands.

A 71-year-old man came to our hospital for endoscopic treatment of a suspicious early gastric carcinoma. A 0.6×0.4 cm protrusive esophageal lesion with smooth surface was found accidentally, located at about 20 cm from the incisors. The lesion was successfully resected by endoscopic mucosal resection, which was esophageal cyst containing heterotopic gastric glands.

Dysphagia and hematemesis caused by an intramural esophageal dissection

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Dysphagia and hematemesis caused by an intramural esophageal dissection.

We report the case of a 60-year-old male with aggravated dysphagia and hematemesis. Severe esophageal mucosa defects and two 'submucosal tunnels'were found.Diagnosis was intramucosal esophageal dissection. After 2 weeks' conservative treatment failed, we tired implantation of a covered mental stent, which worked well.

[Unexpected discovery of a fetus with DMD gene deletion using single nucleotide polymorphism array].

OBJECTIVE: To investigate the value of single nucleotide polymorphism array (SNP array) for the identification of de novo mutations in the DMD gene among fetuses. METHODS: G-banded karyotyping and SNP array were performed on a fetus with intrauterine growth restriction but without family history of Duchenne/Becker muscular dystrophy (DMD/BMD). Multiplex ligation-dependent probe amplification (MLPA) was subsequently applied on amniocytes and maternal peripheral blood sample to detect DMD gene deletion/duplication mutations. RESULTS: Karyotyping of amniocytes showed a normal 46, XY karyotype. SNP array on amniocytes detected a 116 kb deletion (chrX: 32 455 741-32 571 504) at Xp21.1 with breakpoints at introns 16 and 30 respectively, encompassing exons 17-29 of the DMD gene. In addition, MLPA analysis of the DMD gene on amniocytes confirmed the deletion of exons 17 to 29 identified by SNP array. However, no deletion/duplication mutation was detected by MLPA in the mother. CONCLUSION: The de novo deletion of exons 17 to 29 of the DMD gene detected in the fetus may result in BMD or DMD. SNP array can improve the efficiency for detecting genomic disorders in fetuses with unidentified pathogenic genes, negative family history and nonspecific phenotypes.