Association of circulating inflammatory proteins with type 2 diabetes mellitus and its complications: a bidirectional Mendelian randomization study.

Background: Increasing evidence indicates that immune response underlies the pathology of type 2 diabetes (T2D). Nevertheless, the specific inflammatory regulators involved in this pathogenesis remain unclear. Methods: We systematically explored circulating inflammatory proteins that are causally associated with T2D via a bidirectional Mendelian randomization (MR) study and further investigated them in prevalent complications of T2D. Genetic instruments for 91 circulating inflammatory proteins were derived from a genome-wide association study (GWAS) that enrolled 14,824 predominantly European participants. Regarding the summary-level GWASs of type 2 diabetes, we adopted the largest meta-analysis of European population (74,124 cases vs. 824,006 controls) and a prospective nested case-cohort study in Europe (9,978 cases vs. 12,348 controls). Summary statistics for five complications of T2D were acquired from the FinnGen R9 repository. The inverse variance-weighted method was applied as the primary method for causal inference. MR-Egger, weighted median and maximum likelihood methods were employed as supplementary analyses. Results from the two T2D studies were combined in a meta-analysis. Sensitivity analyses and phenotype-wide association studies (PheWAS) were performed to detect heterogeneity and potential horizontal pleiotropy in the study. Results: Genetic evidence indicated that elevated levels of TGF-α (OR = 1.16, 95% CI = 1.15-1.17) and CX3CL1 (OR = 1.30, 95% CI = 1.04-1.63) promoted the occurrence of T2D, and increased concentrations of FGF-21 (OR = 0.87, 95% CI = 0.81-0.93) and hGDNF (OR = 0.96, 95% CI = 0.95-0.98) mitigated the risk of developing T2D, while type 2 diabetes did not exert a significant influence on said proteins. Elevated levels of TGF-α were associated with an increased risk of ketoacidosis, neurological complications, and ocular complications in patients with T2D, and increased concentrations of FGF-21 were potentially correlated with a diminished risk of T2D with neurological complications. Higher levels of hGDNF were associated with an increased risk of T2D with peripheral vascular complications, while CX3CL1 did not demonstrate a significant association with T2D complications. Sensitivity analyses and PheWAS further ensure the robustness of our findings. Conclusion: This study determined four circulating inflammatory proteins that affected the occurrence of T2D, providing opportunities for the early prevention and innovative therapy of type 2 diabetes and its complications.

Unsupervised Clustering-Assisted Method for Consensual Quantitative Analysis of Methanol-Gasoline Blends by Raman Spectroscopy.

Methanol-gasoline blends have emerged as a promising and environmentally friendly bio-fuel option, garnering widespread attention and promotion globally. The methanol content within these blends significantly influences their quality and combustion performance. This study explores the qualitative and qualitative analysis of methanol-gasoline blends using Raman spectroscopy coupled with machine learning methods. Experimentally, methanol-gasoline blends with varying methanol concentrations were artificially configured, commencing with initial market samples. For qualitative analysis, the partial least squares discriminant analysis (PLS-DA) model was employed to classify the categories of blends, demonstrating high prediction performance with an accuracy of nearly 100% classification. For the quantitative analysis, a consensus model was proposed to accurately predict the methanol content. It integrates member models developed on clustered variables, using the unsupervised clustering method of the self-organizing mapping neural network (SOM) to accomplish the regression prediction. The performance of this consensus model was systemically compared to that of the PLS model and uninformative variable elimination (UVE)-PLS model. Results revealed that the unsupervised consensus model outperformed other models in predicting the methanol content across various types of methanol gasoline blends. The correlation coefficients for prediction sets consistently exceeded 0.98. Consequently, Raman spectroscopy emerges as a suitable choice for both qualitative and quantitative analysis of methanol-gasoline blend quality. This study anticipates an increasing role for Raman spectroscopy in analysis of fuel composition.

Safety and efficacy of ESD for laterally spreading tumors with hemorrhoids close to the dentate line.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a curative treatment for laterally spreading tumors (LSTs). However, the outcomes of ESD for LSTs with hemorrhoids remain largely unknown. Our study aimed to evaluate the usefulness of ESD in managing LSTs with hemorrhoids. MATERIAL AND METHODS: We retrospectively collected 418 consecutive LST patients treated with ESD between 2011 and 2023. A retrospective comparative analysis was conducted. RESULTS: There were 85 patients included in the hemorrhoids group and 333 patients included in the other group. The en-bloc resection rate, R0 resection rate, and curative resection rate were comparable in these two groups (p > 0.05). The LSTs with hemorrhoids have a significantly higher intraoperative bleeding rate during ESD when compared to the other group (12.9% vs. 5.4%, p = 0.028). Rates of intraoperative perforation and anal pain in the hemorrhoid group were significantly higher than those in the no-hemorrhoid group (2.4% vs. 0%, p = 0.041; 9.4% vs.0.6%, p < 0.001; respectively). Moreover, most of the related manifestations caused by hemorrhoids were relieved to various degrees after ESD. CONCLUSIONS: ESD is a safe and effective treatment strategy for LSTs with hemorrhoids. A multi-center and prospective study should be conducted in the future to validate our results.

Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors.

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

Lesion size affects the risk of technical difficulty in gastric endoscopic submucosal dissection.

Current evidence shows an inter-country inconsistency in the effect of lesion size on the technical difficulty of gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the specific correlation and quantify the ensuing risks. This retrospective study consisted of 405 ESD cases with gastric single lesion from April 2015 to April 2023. The correlation and risk prediction of lesion size with technical difficulty was explored to provide further clinical evidence. An additive generalized model and recursive algorithm were used to describe the non-linear association, and a linear two-piece regression was constructed to analyze the inflection point. Subgroup analysis and interaction were used to explore intergroup characteristics. Overall, difficult cases had larger lesion sizes, and the more significant the increase, the higher the risk of technical difficulty. In the full model, after adjusting for all covariates, each 1 mm, 3 mm, 5 mm, 7 mm, and one standard increase in lesion size increased the risk of technical difficulty by 8%, 26%, 42%, 72%, and 125%, respectively. There is a nonlinear positive correlation between lesion size and risk of technical difficulty, and the premeditated inflection point was 40 (mm) via two-piecewise linear regression and recursive algorithm. Subgroup analysis showed a stronger correlation between lesion size and difficult ESD in the upper site and submucosal fibrosis groups. Available evidence suggests that lesion size as a risk signal nonlinearly increases the technical difficulty of gastric ESD procedure, especially in cases of upper site and submucosal fibrosis, which deserves further investigation.

Complex duodenal fistula after cholecystectomy successfully treated with endoscopic suturing.

We reported a 47-year-old female with a history of laparoscopic cholecystectomy presented with a complex duodenal fistula. The bleeding artery embolization and endoscopic suture of the duodenal fistula were performed successfully. We highlight the endoscopic tissue clip suture as a safe and feasible option when surgery is too risky.

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.

Development of a novel cholesterol tag-based system for trans-membrane transport of protein drugs.

The main technological difficulties of developing an intracellular (transmembrane) transport system for protein drugs lie in two points: i) overcoming the barriers in the cellular membrane, and ii) loading enough protein drugs, and particularly high-dose proteins, into particles. To address these two technological problems, we recently developed a novel cholesterol tag (C-Tag)-based transmembrane transport system. This pilot study found that the C-Tag dramatically improved the cellular uptake of Fab (902-fold, vs. Fab alone) into living cells, indicating that it successfully achieved transmembrane transport. Moreover, C-Tag-mediated membrane transport was verified using micron-scale large unilamellar vesicles (LUVs, approximately 1.5 µm)-based particles. The C-Tagged Fab was able to permeate the liposomal bilayer and it greatly enhanced (a 10.1-fold increase vs. Fab alone) internalization of proteins into the LUV-based particles, indicating that the C-Tag loaded enough proteins into particles for use of high-dose proteins. Accordingly, we established a novel C-Tag-based transport system that has overcome the known technological difficulties of protein transmembrane delivery, and this might be a useful technology for drug development in the future.

Research progress in cuproptosis in liver cancer. / é“œæ­»äº¡åœ¨è‚ç™Œä¸­çš„ç ”ç©¶è¿›å±•.

Copper, like iron, is an essential trace metal element for human cells. The role of iron overload and ferroptosis has been gradually clarified in tumors, but the role of copper overload and cuproptosis is still being explored. Cuproptosis is a novel mode of cell death, secondary to impaired mitochondrial function induced by copper overload, and characterized by copper-dependent and programmed. The excessive copper leads to protein toxicity stress by binding to sulfhydryl proteins in the tricarboxylic acid (TCA) cycle of mitochondria, disrupting cellular homeostasis and triggering cuproptosis. Copper accumulation has carcinogenic effects on normal cells, dual effects on tumor cells. Liver cancer is one of the most common malignant tumors in China and even globally, with hepatocellular carcinoma (HCC) being the most common histological subtype. Copper exhibits dualism in HCC, as it both contributes to the growth and invasion of HCC cells, and exerts anticancer effects by inducing cuproptosis. Also, cuproptosis-related genes can be the evaluation of immunotherapy effect and the construction of prognostic models. Clarifying the role of copper death in liver cancer can help explore new methods for liver cancer screening, treatment, and prognosis evaluation.

An update: is there a relationship between H. pylori infection and nonalcoholic fatty liver disease? why is this subject of interest?

Helicobacter pylori (H. pylori) infection is thought to impact various extragastric diseases, including nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease. Meanwhile, the pathogenesis of NAFLD needs further research, and effective treatment for this disease remains elusive. In this mini-review, we enumerate and ponder on the evidence demonstrating an association between H. pylori infection and NAFLD. Primarily, we delve into high-quality meta-analyses and clinical randomized controlled trials focusing on the association studies between the two. We also discuss clinical studies that present opposite conclusions. In addition, we propose a mechanism through which H. pylori infection aggravates NAFLD: inflammatory cytokines and adipocytokines, insulin resistance, lipid metabolism, intestinal barrier and microbiota, H. pylori outer membrane vesicles and H. pylori-infected cell-extracellular vesicles. This mini-review aims to further explore NAFLD pathogenesis and extragastric disease mechanisms caused by H. pylori infection.

Association between the Systemic Immune-Inflammation Index and Thyroid Function in U.S. Adults.

Background: The systemic immune-inflammation index (SII) is used as an indicator of prognosis for a wide range of diseases. Thyroid function has been found to be strongly associated with inflammation. The purpose of this investigation was to analyze the correlation between SII and various thyroid functions. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. The association between SII and thyroid function was analyzed using weighted univariate and multivariate linear regression analyses. Subgroup analyses, interaction tests, and weighted restricted cubic spline (RCS) regression analyses were also employed to test this correlation. Results: Of the 6,875 participants (age ≥ 20 years), the mean age was 46.87 ± 0.40 years. The adjusted model showed that lnSII was negatively correlated with FT3 (ß = -0.0559, 95% CI -0.1060 to -0.0059,) and FT3/FT4 (ß = -0.0920, 95% CI -0.1667 to -0.0173,). There was a positive correlation between lnSII and TT4 (ß = 0.1499, 95% CI 0.0722-0.2276,). In subgroup analyses, lnSII still independently affected a wide range of thyroid functions. Weighted RCS analysis showed a nonlinear relationship between FT3 and lnSII. Conclusion: Close relationships exist between SII and a variety of thyroid functions. SII can be used as an indicator to predict thyroid dysfunction. Control of inflammatory activity may be a protective measure against thyroid dysfunction. More large-scale prospective studies are necessary to further explore the correlation between SII and thyroid function and the role of obesity in this.

Endoscopic Submucosal Dissection for Treatment of Early-Stage Cancer or Precancerous Lesion in the Upper Gastrointestinal Tract in Patients with Liver Cirrhosis.

(1) Background: Endoscopic submucosal dissection (ESD) has been widely accepted as the standard method for treating early-stage cancer or precancerous lesions in the upper gastrointestinal tract; however, it may be difficult in patients with liver cirrhosis due to clinical challenges such as coagulation dysfunction, presence of gastroesophageal varices, etc. We aimed to demonstrate the safety and efficacy of ESD in these populations. (2) Methods: The clinical data of patients were retrospectively collected and analyzed. Inclusion criteria of the study were: a. patients with liver cirrhosis; b. patients who underwent ESD; c. patients who were diagnosed with early-stage cancer or precancerous lesions in the upper gastrointestinal tract. (3) Results: Eight patients were enrolled from April 2019 to April 2023, of whom three were male and five were female, with ages ranging from 43 to 70 years old. Seven lesions were located in the stomach and one other lesion was in the esophagus. ESD was performed successfully in all eight patients, and the resected lesion size ranged from 2 to 6 cm. Only one patient encountered postoperative complications, namely, chest pain and fever. No recurrence was noticed during a follow-up of 3 to 45 months. (4) Conclusions: ESD may serve as a safe and effective method for treating upper gastrointestinal early-stage cancer or precancerous lesions in patients with liver cirrhosis.

The feasibility of endoscopic resection for colorectal laterally spreading tumors.

The present study aimed to investigate the feasibility and safety of endoscopic resection for colorectal laterally spreading tumors (LSTs) in different size groups. This retrospective study included 2699 patients with LSTs who underwent endoscopic treatment at the Second Xiangya Hospital of Central South University from May 2012 to February 2022. The patient baseline and procedure outcomes were compared between the < 5 cm group, 5-10 cm group, and ≥ 10 cm group. Meanwhile, lesions larger than 5 cm in diameter were longitudinally compared for endoscopic safety using ESD with surgical operation outcomes. There were 2105 patients in the < 5 cm group, 547 patients in the 5-10 cm group, and 47 patients in the ≥ 10 cm group. En bloc resection and R0 resection rates, the incidence of adverse events, length of stay (LOS), and medical costs significantly differed between the groups (P < 0.01). Comorbidity of diabetes or hypertension, history of antithrombotic drug use, lesion size, location, gross type, endoscopic procedures selection, and circumferential extent of the mucosal defect were independent risk factors for delayed bleeding (P < 0.05). En bloc resection, R0 resection, and lesion canceration were associated with local recurrence. For lesions larger than 5 cm in diameter, ESD had similar R0 resection and local recurrence rates compared with a surgical operation but a lower en bloc rate, LOS, and medical costs. Expert endoscopists can significantly increase en bloc and R0 resection rates and reduce the incidence of adverse events. Endoscopic resection results distinguish in different size groups of colorectal LSTs, yet its safety and feasibility are not inferior to a surgical operation.

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.

Efficacy of scalp acupuncture combined with conventional therapy in the intervention of post-stroke depression: A systematic review and meta-analysis.

BACKGROUND: Post-stroke depression (PSD) is a common complication following a stroke, significantly impacting patients' quality of life and mental well-being. Currently, two primary approaches are employed to treat PSD: drug therapy and non-drug therapy. Among these, acupuncture, specifically scalp acupuncture (SA), has gained attention due to its cost-effectiveness and broad social benefits. SA is a precise and direct form of acupuncture that has been utilized in the treatment of PSD. Although several randomized controlled trials (RCTs) have demonstrated the efficacy of SA in treating PSD, there is a lack of comprehensive systematic reviews. Given the limitations of existing evidence, we conducted a systematic evaluation to assess the effectiveness of SA in combination with conventional therapy (CT) for intervening in PSD. METHODS: We systematically searched five databases for articles published up until May 31, 2023, pertaining to SA treatment of PSD. A team of researchers meticulously screened and assessed these articles to identify the final included studies. After extracting relevant information and outcome indicators from the selected articles, we employed RevMan5.3 software to evaluate their quality and perform statistical analysis. Throughout our research, we strictly adhered to the PRISMA 2020 guidelines. RESULTS: A total of 11 articles were included, and a meta-analysis was conducted to evaluate the effectiveness of SA combined with CT for treating PSD. The results revealed that SA combined with CT can effectively improve the treatment's success rate for PSD and reduce the severity of depressive symptoms measured by the Self-Rating Depression Scale. However, SA combined with CT did not show significant reductions in depressive symptoms assessed by the Hamilton Rating Scale for Depression, which may be related to the inclusion of high heterogeneity articles. Importantly, the combination treatment did not lead to an increase in adverse reactions among PSD patients. CONCLUSION: While the effectiveness of SA combined with CT in treating PSD still requires further validation through rigorous randomized double-blind trials, this study provides a comprehensive collection of studies that meet the criteria for SA combined with CT in PSD treatment. It objectively and systematically evaluated the impact of SA combined with CT on PSD. Consequently, the findings of this study hold certain clinical significance.

The correlation of two bone turnover markers with bone mineral density: a population-based cross-sectional study.

OBJECTIVE: Exploring the correlation between bone turnover marks (BTMs) with lumbar BMD in middle-aged populations. METHODS: The cross-sectional analysis fetched data came from NHANES. The level of serum bone alkaline phosphatase (sBAP) and urinary N-telopeptide (uNTx) were regarded as representative of bone turnover. Lumbar BMD was the outcome of the study. Multivariable linear regression models were utilized to detect the correlation of sBAP and uNTx with Lumbar BMD. RESULTS: The level of sBAP and uNTx was negatively correlated with lumbar BMD in every multivariable linear regression. For sBAP, this inverse correlation was stable in both men and women (P < 0.01). uNTx indicated a negative association after all relevant covariables were adjusted (P < 0.01). The men group remained the negative correlation in gender subgroup analysis (P < 0.01). CONCLUSION: This study indicated that the increased level of sBAP and uNTx associated with lumbar BMD decreased among middle-aged adults. This correlation could prompt researchers to explore further the relationship between bone turnover rate and BMD, which may provide information for the early detection of BMD loss and provide a new strategy for clinical practice.

Identification and validation of aging-related gene signatures and their immune landscape in diabetic nephropathy.

Background: Aging and immune infiltration have essential role in the physiopathological mechanisms of diabetic nephropathy (DN), but their relationship has not been systematically elucidated. We identified aging-related characteristic genes in DN and explored their immune landscape. Methods: Four datasets from the Gene Expression Omnibus (GEO) database were screened for exploration and validation. Functional and pathway analysis was performed using Gene Set Enrichment Analysis (GSEA). Characteristic genes were obtained using a combination of Random Forest (RF) and Support Vector Machine Recursive Feature Elimination (SVM-RFE) algorithm. We evaluated and validated the diagnostic performance of the characteristic genes using receiver operating characteristic (ROC) curve, and the expression pattern of the characteristic genes was evaluated and validated. Single-Sample Gene Set Enrichment Analysis (ssGSEA) was adopted to assess immune cell infiltration in samples. Based on the TarBase database and the JASPAR repository, potential microRNAs and transcription factors were predicted to further elucidate the molecular regulatory mechanisms of the characteristic genes. Results: A total of 14 differentially expressed genes related to aging were obtained, of which 10 were up-regulated and 4 were down-regulated. Models were constructed by the RF and SVM-RFE algorithms, contracted to three signature genes: EGF-containing fibulin-like extracellular matrix (EFEMP1), Growth hormone receptor (GHR), and Vascular endothelial growth factor A (VEGFA). The three genes showed good efficacy in three tested cohorts and consistent expression patterns in the glomerular test cohorts. Most immune cells were more infiltrated in the DN samples compared to the controls, and there was a negative correlation between the characteristic genes and most immune cell infiltration. 24 microRNAs were involved in the transcriptional regulation of multiple genes simultaneously, and Endothelial transcription factor GATA-2 (GATA2) had a potential regulatory effect on both GHR and VEGFA. Conclusion: We identified a novel aging-related signature allowing assessment of diagnosis for DN patients, and further can be used to predict immune infiltration sensitivity.

Alterations in the gut microbiota and the efficacy of adjuvant probiotic therapy in liver cirrhosis.

Background: Liver cirrhosis is the end stage of various chronic liver diseases (CLDs). The gut microbiota can impact the liver environment and trigger chronic liver inflammation through the gut-liver axis. Alteration of the gut microbiota has become an effective strategy in the biological treatment of cirrhosis. Methods: Twenty-eight patients with liver cirrhosis and 16 healthy individuals were included, and fresh stool samples were collected. We analyzed changes in the gut microbiota between groups by 16S rRNA sequencing and evaluated the association between microbiota alterations and hepatic function. Additionally, 102 cirrhotic patients were retrospectively enrolled and divided into a probiotic group (n=44) and a nonprobiotic group (n=58) in addition to standard treatment for cirrhosis. Patients were monitored for hematological parameters and hepatic function during the six-month follow-up. Results: The gut microbiota profile of patients with cirrhosis was greatly different from that of healthy individuals, presenting with significantly reduced α diversity and decreased abundance of representative SCFA-producing bacteria including Firmicutes, Coprococcus and Clostridium IV. The pathogenic bacteria Gammaproteobacteria, Veillonella, and Bacilli were greatly enriched in cirrhotic patients. Additionally, patients with decompensated cirrhosis (DCPC) had a significantly reduced abundance of Oscillibacter compared to compensated cirrhosis (CPC), which is also a SCFA-producing bacteria, and the lower Firmicutes to Bacteroidetes ratio and enhanced MDR values were also shown in DCPC patients compared to CPC patients. In addition, the abundance of Firmicutes was negatively related to hepatic function in cirrhotic patients, including the levels of ALT, AST, and DBIL. From the retrospective study, we found that biochemical improvements in alanine transaminase (ALT) and total bilirubin (TBIL) were obtained in DCPC patients who received oral probiotic therapy compared with the nonprobiotic group. Conclusion: Severe microbial dysbiosis existed in patients with liver cirrhosis, especially patients who reached the decompensatory stage. SCFA-producing bacteria were significantly reduced in cirrhosis. Altered gut microbiota cause changes in functional modules, which may contribute to cirrhosis progression and are associated with clinical prognosis. Adjuvant probiotic supplementation to enhance SCFA-producing bacteria can be a prospective therapy for patients with cirrhosis.

Coexisting achalasia and leiomyoma misdiagnosed as the submucosal tumor, successfully treated by simultaneous peroral endoscopic myotomy and submucosal tunneling endoscopic resection in the same tunnel.

Peroral endoscopic myotomy (POEM) is a safe and effective method in the treatment of achalasia. Meanwhile, submucosal tunneling endoscopic resection (STER) is a common endoscopic method for the treatment of submucosal tumors (SMT) in the upper digestive tract. However simultaneous POEM and STER for coexisting achalasia and esophageal SMT is rarely reported. A 40-year-old woman underwent esophagoscopy after dysphagia and vomiting for 20 years. The protruding submucosal lesion with normal overlying mucosa was found in the lower part of the esophagus, nearing cardia. Considering the persistent swallowing discomfort and vomiting symptoms, the patient underwent esophageal manometry and barium esophagram, and was finally diagnosed as achalasia with esophageal submucosal tumor. Finally, POEM and STER were performed simultaneously on the patient in the same tunnel. The patient was followed up for 4 months without recurrence or complaints. We herein report a case of achalasia with esophageal leiomyoma who underwent POEM and STER in the same tunnel to remove the mass and relieve the symptoms.