Impacts of Inflammatory Cytokines Variants on Systemic Inflammatory Profile and COVID-19 Severity.

BACKGROUND: Cytokine storm is known to impact the prognosis of coronavirus disease 2019 (COVID-19), since pro-inflammatory cytokine variants are associated with cytokine storm. It is tempting to speculate that pro-inflammatory cytokines variants may impact COVID-19 outcomes by modulating cytokine storm. Here, we verified this hypothesis via a comprehensive analysis. METHODS: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 15, 2023. Case-control or cohort studies that investigated the impacts of rs1800795 or rs1800629 on COVID-19 susceptibility, severity, mortality, IL-6, TNF-α, or CRP levels were included after an anonymous review by two independent reviewers and consultations of disagreement by a third independent reviewer. RESULTS: 47 studies (8305 COVID-19 individuals and 17,846 non-COVID-19 individuals) were analyzed. The rs1800629 A allele (adenine at the -308 position of the promoter was encoded by the A allele) was associated with higher levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). In contrast, the rs1800795 C allele (cytosine at the -174 position of the promoter was encoded by the C allele) was linked to higher levels of interleukin-6 (IL-6) and CRP. In addition, the A allele of rs1800629 increased the severity and mortality of COVID-19. However, the C allele of rs1800795 only increased COVID-19 susceptibility. CONCLUSIONS: rs1800629 and rs1800795 variants of pro-inflammatory cytokines have significant impacts on systemic inflammatory profile and COVID-19 clinical outcomes. rs1800629 may serve as a genetic marker for severe COVID-19.

The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study.

BACKGROUND: Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS: IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS: Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION: The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).

Case report: An unusual case of small bowel bleeding and common iliac artery pseudoaneurysm caused by an unnoticed swallowed toothpick.

Gastrointestinal (GI) bleeding is a common clinical condition that can be caused by a variety of reasons. Bleeding can occur anywhere in the GI tract, and it usually presents as vomiting of blood, melena or black stools. We herein present a case of a 48-year-old man who was ultimately diagnosed with perforation of the lower ileum, pseudoaneurysm of the right common iliac artery, lower ileum-right common iliac artery fistula, and pelvic abscess caused by accidental ingestion of a toothpick. This case suggests that accidental ingestion of a toothpick may also be the cause of GI bleeding in some patients. For patients with unexplained GI bleeding, especially those with small bowel bleeding, a rational and combined use of gastroduodenoscopy, colonoscopy, unenhanced and contrast-enhanced abdominal CT can help detect the causes of GI bleeding and improve diagnostic accuracy.

Cap-assisted endoscopic sclerotherapy is effective for rectal mucosal prolapse associated outlet obstructive constipation.

BACKGROUND AND STUDY AIMS: Outlet obstructive constipation (OOC) is a common type of chronic constipation that is usually caused by internal hemorrhoids (IH) and rectal mucosal prolapse (RMP). Cap-assisted endoscopic sclerotherapy (CAES) was demonstrated to be effective in the treatment of IH and RMP. This study explored the efficacy of CAES in treating OOC associated with IH and RMP. METHODS: Thirty-one patients (15 males and 16 females) were diagnosed with OOC after colonoscopy and anorectal manometry (AM). CAES was used to treat IH and RMP. The self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Wexner constipation score (WCS) were used to assess patients at baseline and at the end of follow-up. AM tests were performed before and after CAES. RESULTS: The mean age of patients was 56.19 ± 7.969 years, and the follow-up time was 2.875 ± 3.703 months. After CAES treatment, subjective indices, including frequency of bowel movements (p < 0.05), defecation time (p < 0.05), SAS (p < 0.05), SDS (p < 0.05), and WCS (p < 0.05), were significantly improved. AM showed that the anal relaxation rate (p < 0.05), maximum squeeze pressure (p < 0.05), and rectal residual pressure (p < 0.05) were significantly improved. The ratio of Bristol stool form scale typeIII-Vincreased from 12.5 % to 56.25 % (p < 0.05). CONCLUSIONS: CAES is effective for treating OOC caused by IH and RMP. The relief of OOC symptoms could improve anxiety and depression symptoms associated with the disease.

Acute myocardial infarction followed by radiofrequency therapy for gastroesophageal reflux disease in a man: A case report.

Coronary artery disease (CAD) is a common comorbidity of gastroesophageal reflux disease. Since the distal esophagus and heart share a common afferent vagal supply, the delivery of radiofrequency in the distal esophagus can stimulate the coronary artery and induce acute myocardial infarction in a patient with CAD.

The prevalence of coronary atherosclerosis in patients with refractory gastroesophageal reflux disease ready for antireflux surgery.

Coronary atherosclerosis (CAS) and gastroesophageal reflux disease (GERD) share common risk factors. The existing CAS may not only increase the possibility of GERD to be refractory GERD (RGERD), but also increase the risk of antireflux surgery for these patients. The aim of this study was to estimate the prevalence of CAS and its potential risk factors in patients with RGERD ready for antireflux surgery. The retrospective analysis was performed in the digestive disease center of Suining Central Hospital, a teritary hospital in Sichuan, China. Records of patients with RGERD admitted to the hospital for antireflux surgery between July 2018, and June 2021 were included. The included patients were divided into the RGERD group and RGERD-CAS group based on the coronary computed tomography angiography (CCTA) results, which were defined as no CAS and CAS (<50% mild stenosis or ≥50% significant stenosis). In total, 448 patients with RGERD qualified for the study. The prevalence of CAS in these patients was 45.1%. Specifically, 246 patients (54.9%) were in the RGERD group, and 202 patients (45.1%) were in the RGERD-CAS group. Among these 202 patients with CAS, 120 patients (59.4%) had mild CAS (<50% stenosis), 82 patients (40.6%) had significant CAS (≥50% stenosis). Five independent risk factors, including male sex, high blood pressure (HBP), diabetes mellitus (DM), Barrett's esophagus (BE) and family history of coronary artery disease were identified for the occurrence of CAS in patients with RGERD ready for antireflux surgery after adjusting for other factors. CAS is prevalent in patients with RGERD ready for antireflux surgery. Routing CTTA was suggested to exclude potential coronary artery disease in RGERD patients ready for antireflux surgery with independent risk factors.

Minimally invasive treatment of cirrhotic secondary hypersplenism with high-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) has been reported to be a minimally invasive effective method for the treatment of secondary hypersplenism. However, neither the short-term efficacy nor the indications and/or contraindications have been described in patients with cirrhosis. From October 2019 to May 2021, eleven cases of patients with cirrhotic secondary hypersplenism were enrolled. The blood counts, liver function tests and abdominal ultrasound and/or MRI scans of all patients were closely evaluated. Among these 11 patients, eight (72.7%) patients were classified as Child-Pugh A, and the other 3 (27.3%) patients were Child-Pugh B; Five (45%) patients were diagnosed with gallstone, including multiple small stones in 2 patients and single stone in 3 patients. HIFU was performed successfully in all 11 patients. After HIFU, hematologic parameters and liver function were significantly improved in all 11 patients (p < 0.05). The HIFU ablated volume to spleen volume rate was 35-61%. Complications were ecchymosis of the waist in 7 (63.3%) patients, ablated area pain in 3 (27.3%) patients, and choledocholithiasis in 2 (18.2%) patients with multiple small gallstones. All of them recovered smoothly without additional treatment except for 2 patients with choledocholithiasis recovered with risky endoscopic retrograde cholangiopancreatography (ERCP) treatment. This series suggested that HIFU is an effective and safe treatment for cirrhotic secondary hypersplenism in patients classified as Child-Pugh A or B. However, multiple small gallstones could be a relative contraindication for it.

Gastroesophageal reflux disease and salivary pepsin in patients with heterotopic gastric mucosa in the upper esophagus.

BACKGROUND: Heterotopic gastric mucosa in the upper esophagus (HGMUE) is reported to be related to gastroesophageal reflux disease (GERD). This study investigated the prevalence of GERD and the use of salivary pepsin to diagnose gastroesophageal reflux, especially proximal reflux, in HGMUE patients. METHODS: One hundred and fifty-three HGMUE patients and 50 healthy volunteers were studied. All subjects took a reflux symptom index questionnaire (RSI); underwent endoscopy, barium esophagogram, high-resolution manometry (HRM), and 24-hour multichannel intraluminal impedance-pH-metry (MII-pH); and salivary pepsin test. RESULTS: Ninety-five (62.1%) HGMUE patients but no control subjects were diagnosed with GERD. The salivary pepsin concentration, RSI score, DeMeester score, acid exposure time (AET), total reflux episodes, proximal acidic reflux episodes, and proximal weakly acidic reflux episodes were significantly higher in the HGMUE group than in the control group (P < 0.05). The salivary pepsin test showed a sensitivity of 85.9% and specificity of 56.9% for diagnosing GERD using the optimal cut-off value of 75 ng/mL. One hundred and seven (69.9%) and 46 (30.1%) HGMUE patients were categorized as pepsin (+) and pepsin (-), respectively when 75 ng/mL was used as a cut-off value. Male sex, RSI, AET, and proximal acid reflux episodes were positive predictive factors for the occurrence of pepsin (+) in HGMUE patients. CONCLUSIONS: GERD, especially GERD with proximal acid reflux and related symptoms, was common in HGMUE patients. The salivary pepsin test could be an additional useful test for testing reflux in HGMUE patients, but it will not replace the MII-pH.

Chloride intracellular channels as novel biomarkers for digestive system tumors (Review).

Digestive system malignant tumors are common tumors, and the traditional treatment methods for these tumors include surgical resection, radiotherapy, chemotherapy, and molecularly targeted drugs. However, diagnosis remains challenging, and the early detection of postoperative recurrence is complicated. Therefore, it is necessary to explore novel biomarkers to facilitate clinical diagnosis and treatment. Accumulating evidence supports the crucial role of chloride channels in the development of multiple types of cancers. Given that chloride channels are widely expressed and involved in cell proliferation, apoptosis and cell cycle, among other processes, they may serve as a promising diagnostic and therapeutic target. Chloride intracellular channels (CLICs) are a class of chloride channels that are upregulated or downregulated in certain types of cancer. Furthermore, in certain cases, during cell cycle progression, the localization and function of the cytosolic form of the transmembrane proteins of CLICs are also altered, which may provide a key target for cancer therapy. The aim of the present review was to focus on CLICs as biomarkers for digestive system tumors.

Roles of Cl­/HCO3­ anion exchanger 2 in the physiology and pathophysiology of the digestive system (Review).

Cl­/HCO3­ anion exchangers (AEs), which are members of the solute carrier 4 family, contribute to the exchange of one intracellular HCO3­ for one extracellular Cl­. AE2, a vital subtype of the Cl­/HCO3­ exchangers, is expressed widely in various cells and tissues in mammals and serves essential roles in the pathophysiological processes of the cardiovascular system and renal tubular reabsorption. Recently, research on the function of AE2 in the digestive system shed new light on its roles in the regulation of cellular and organ physiology. AE2 not only participates in gastric acid secretion, but also mediates bile secretion and digestive cancer development. The aim of the present review was to describe the role of AE2 in the physiology and pathophysiology of the digestive system, with the aim of guiding clinical diagnosis and treatment.

Transient delayed gastric emptying following laparoscopic Nissen fundoplication for gastroesophageal reflux disease.

PURPOSE: Although laparoscopic Nissen fundoplication (LNF) is a kind of minimally invasive surgery, some transition time may still be required to allow the fundoplicated stomach to adapt to the new anatomical position. We observed transient delayed gastric emptying (DGE) post-LNF in our preliminary study. This study aimed to investigate the occurrence rate and development of transient DGE post-LNF. METHODS: Patients who underwent LNF for gastroesophageal reflux disease (GERD) at our institution were recruited consecutively. They were treated with standardized LNF and prospectively followed up for 2 months. Proper diet guidance and/or pharmacologic therapy were given during these 2 months. GERD Health-Related Quality of Life (GERD-HRQL), DGE symptoms, and DGE status were evaluated preoperatively and postoperatively. RESULTS: Fifty-one patients underwent LNF and completed a 2-month follow-up. LNF succeeded in all patients. Prior to LNF, no DGE was identified. At the 1-month follow-up, LNF led to a significant reduction in the GERD-HRQL total score but a significantly increased DGE score. Endoscopically, DGE was identified in forty-seven (n = 47, 92.2%) patients. At the 2-month follow-up, the GERD-HRQL scores continued to show decreases compared to the 1 month. The DGE score returned to the baseline value. Endoscopically, no DGE was identified in any patients (n = 0, 0.0%). CONCLUSIONS: Transient DGE is a very common one-month post-LNF but can recover quickly in the second month following LNF.

A case report of eosinophilic gastroenteritis misdiagnosed as cholelithiasis.

Eosinophilic gastroenteritis is not only easy to ignore in clinical practice, but also easy to miss in the process of pathological diagnosis. There is a need to consider it in the differential diagnosis of alimentary disease.

Cap-assisted endoscopic sclerotherapy for internal hemorrhoids: technique protocol and study design for a multi-center randomized controlled trial.

BACKGROUND: Cap-assisted endoscopic sclerotherapy is a new interventional therapy for internal hemorrhoids and rectal prolapse under colonoscopy. The proper length of the endoscopic injection needle is the core for performing cap-assisted endoscopic sclerotherapy well with more benefits and less complications. However, no data are currently available to guide endoscopists to consider the length of injection needle before cap-assisted endoscopic sclerotherapy. This study is designed to evaluate the efficacy and safety of cap-assisted endoscopic sclerotherapy with long or short injection needle in the treatment of internal hemorrhoids. METHODS: This is a nationwide multi-center, prospective, single-blind and randomized controlled trial. Patients with grade I-II internal hemorrhoids who have failed to conservative treatments and grade III internal hemorrhoids who are not suitable for surgery or refuse surgery will be included. Participants will be randomized 1:1 into either long or short injection needle group. The primary outcome is the recurrence rate of internal hemorrhoids 24 weeks after cap-assisted endoscopic sclerotherapy. The secondary outcomes are as follows: (1) symptom severity score, (2) three-level EuroQoL five dimensions health scale scores, (3) occurrence of adverse events and severe adverse events, and (4) patients' attitudes toward cap-assisted endoscopic sclerotherapy. Data collection will be conducted before and during operation, the 1st day, 1st week, 2nd week, and 24th week after cap-assisted endoscopic sclerotherapy. DISCUSSION: The outcome of this study is expected to provide a practical clinical protocol of cap-assisted endoscopic sclerotherapy for patients with internal hemorrhoids and promote the use of this new endoscopic technique. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03917056. Registered on 12 April 2019.

Stretta procedure versus proton pump inhibitors for the treatment of nonerosive reflux disease: A 6-month follow-up.

To compare the Stretta procedure with proton pump inhibitors for the treatment of nonerosive reflux disease (NERD).From July 2018 to April 2019, patients diagnosed with NERD and referred for treatment were enrolled. They were treated with either Stretta procedure or proton pump inhibitor (PPI) medication and followed-up for 6 months. The symptom control, quality of life, lower esophageal sphincter (LES) pressure, 24-hour pH parameters, PPI usage and satisfaction rate were evaluated. The complications were assessed. The outcomes of the 2 groups were analyzed and compared.Twenty-eight patients in the Stretta group and 21 patients in the PPI group completed the 6-month follow-up. No severe adverse events occurred in both groups. Both interventions were effective in improvement of symptom and quality of life. The symptom score improvement was significantly superior in the Stretta group compared to the PPI group (6.3 ±â€Š3.4 vs 8.5 ±â€Š4.1, P = .03). LES pressure increased significantly in the Stretta group compared to the PPI group (14.2 ±â€Š4.4 mm Hg vs 10.0 ±â€Š4.0 mm Hg, P < .01). Although both interventions improved 24-hour pH parameters, including number of acid episodes (P = .27), acid exposure time (P = .39), and DeMeester score (P = .28), no difference was found between the 2 groups. Complete PPI cessation rate (82% vs 52%, P = .03) as well as satisfaction rate (89% vs 57%, P = .02) was much higher in Stretta group than those in the PPI groupThe Stretta procedure was safe and effective in the short term for the management of NERD. The Stretta procedure resulted in higher LES pressure and achieved better improvement of symptom control and PPI cessation than did PPI in the short term.

Effect of VIATORR stent in early ultrasound evaluation after transjugular intrahepatic portosystemic shunt (TIPS): A case report.

Shunt dysfunction is a major complication of transjugular intrahepatic portosystemic shunt (TIPS). Ultrasonography is a preferred method of shunt follow-up after TIPS, but some misjudgments can occur in cases of shunt dysfunction due to peculiarities of the VIATORR stent. Here we report one case and suggest that the first ultrasound evaluation for patients who received TIPS procedure with VIATORR stent should be performed one month after the procedure.

24-hour monitoring of transient lower esophageal sphincter relaxation events by long-term high-resolution impedance manometry in normal volunteers: The "mirror phenomenon".

BACKGROUND: The aim of this study was to investigate the frequency and circadian changes in transient lower esophageal sphincter relaxations (TLESRs) in normal volunteers using 24-hour high-resolution impedance manometry (HRIM). METHODS: Fifteen volunteers underwent HRIM. TLESRs were recorded during the mealtime, 2-hour postprandial, daytime, and supine periods. The catheter was firmly secured to the nose, and subjects went home, ate normal meals, and continued routine daily activities. KEY RESULTS: Successful recordings were obtained in 11 volunteers. Overall, 1083 TLESRs were documented; the average occurrence was 4.2/h, and the duration was 21.0 ± 5.2 seconds. The majority of the TLESRs occurred during the 2-hour postprandial (42.7%) and daytime (31.5%) periods, while 10.2% and 15.6% occurred during the mealtime and supine periods, respectively. Eight hundred and eighty-six (81.8%) TLESRs were associated with reflux. Overall, 25.5% of TLESRs were preceded by partial secondary peristalsis (PSP), while 74.5% were preceded by nothing. Terminating events included primary peristalsis (PP; 40.3%), PSP (42.8%), full secondary peristalsis (FSP; 8.2%), or nothing (8.7%). Both preceding and terminating events periodically changed throughout the four periods. One hundred and twelve (10.3%) TLESRs with both preceding and terminating events of PSP, presenting as a "mirror phenomenon," were documented. The majority of these TLESRs occurred during the supine (70.5%). CONCLUSIONS & INFERENCES: Transient lower esophageal sphincter relaxations are common physiological motor events in normal volunteers; these events have certain circadian rhythms, as do the events that precede and terminate TLESR events. A special "mirror phenomenon" is observed when both the preceding and terminating events are PSP.

Visfatin increases miR-21 to promote migration in HCC.

Hepatocellular carcinoma (HCC) is a common human malignancy. In this study, we aimed to investigate the serum levels of visfatin and miR-21 in HCC patients, to analysis the relationship between the pathological features and the plasma level of visfatin or miR-21, and to explore the roles of visfatin and miR-21 in migration of HCC cells. Our results showed that the serum levels of visfatin and miR-21 were significant higher in HCC patients than healthy subjects. The diagnostic sensitivity of serum visfatin was 82.5% and the specificity was 65.0%. The serum visfatin was significantly associated with the histology and metastasis. Visfatin induced miR-21 expression and cell migration in HepG2 cells. Transfection of miR-21 inhibitor suppressed the visfatin-induced migration in HCC cells. These results suggested that visfatin induced HCC cell migration via upregulation of miR-21, which provides a novel basis for the diagnosis of HCC.

Endoluminal Sphincter Augmentation with the MUSE™ System and GERDX™ System in the Treatment of Gastroesophageal Reflux Disease: A New Impact?

To bridge the gap between the long-term intake of proton pump inhibitors (PPIs) and the potential risks of laparoscopic fundoplication, a number of endoscopic procedures for the treatment of gastro-esophageal reflux disease (GERD) have been developed over the past 30 years. Because of the minimally invasive approach, short operative time, and efficacy in selected patients, endoluminal sphincter augmentation appears to be highly attractive. However, most early devices have proven to be unsafe or failed to provide long-term symptom relief. Accordingly, products for endoluminal sphincter augmentation have undergone several modifications to achieve an increased lower esophageal sphincter (LES) baseline pressure to re-establish the LES as an efficacious anti-reflux barrier. This paper reviews and discusses the two latest products for endoluminal sphincter augmentation, the MUSE™ device (Medigus, Ltd., Omer, Israel) and the GERDX™ system (G-SURG GmbH, Seeon-Seebruck, Germany). While the currently available literature has proven their effectiveness in principle, long-term results are lacking. Further studies and developments are necessary to determine whether these two new devices will truly impact GERD therapy.

Graphene oxide directed in-situ deposition of electroactive silver nanoparticles and its electrochemical sensing application for DNA analysis.

The development of high-performance biosensing platform is heavily dependent on the recognition property of the sensing layer and the output intensity of the signal probe. Herein, we present a simple and highly sensitive biosensing interface for DNA detection on the basis of graphene oxide nanosheets (GONs) directed in-situ deposition of silver nanoparticles (AgNPs). The fabrication process and electrochemical properties of the biosensing interface were probed by electrochemical techniques and scanning electron microscopy. The results indicate that GONs can specifically adsorb at the single-stranded DNA probe surface, and induces the deposition of highly electroactive AgNPs. Upon hybridization with complementary oligonucleotides to generate the duplex DNA on the electrode surface, the GONs with the deposited AgNPs will be liberated from the sensing interface due to the inferior affinity of GONs and duplex DNA, resulting in the reduction of the electrochemical signal. Such a strategy combines the superior recognition of GONs toward single-stranded DNA and double-stranded DNA, and the strong electrochemical response of in-situ deposited AgNPs. Under optimal conditions, the biosensor can detect target DNA over a wide range from 10 fM to 10 nM with a detection limit of 7.6 fM. Also, the developed biosensor shows outstanding discriminating ability toward oligonucleotides with different mismatching degrees.