Performance of Baveno VII criteria for the screening of varices needing treatment in patients with biliary atresia.

OBJECTIVE: Biliary atresia (BA) is the leading cause of liver cirrhosis and chronic liver insufficiency in children in the world. Gastroesophageal varices bleeding is an ominous complication of cirrhosis in BA patients and is associated with high morbidity and mortality. In this study, we aimed to investigate the utility of noninvasive Baveno VI and Baveno VII criteria for the screening of varices need treatment (VNT) and the need for liver transplantation in BA patients. METHODS: This study enrolled 48 BA patients (23 females and 25 males) who underwent an esophagogastroduodenoscopy (EGD) and transient elastography at a mean age of 11.18 ± 1.48 years; the clinical data were surveyed in a retrospective design. RESULTS: The sensitivity and negative predictive value of Baveno VI and Baveno VII criteria for the prediction of VNT in BA patients are both 100% and 100%, respectively. The VNT missing rate of Baveno VI and Baveno VII criteria are both 0% in our cohort. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are also predictive of the need for liver transplantation in our cohort (OR = 10.33, 4.24, and 21.33; p = 0.009, 0.03, and 0.007, respectively). CONCLUSION: The Baveno VI and Baveno VII criteria are useful for the screening of VNT and minimize non-necessary invasive EGD in BA patients with low VNT missing rates. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are associated with the need for liver transplantation.

Prevalence of functional esophageal disorders and associated clinical characteristics in patients with proton-pump-inhibitor-unresponsive reflux symptoms.

BACKGROUND AND AIM: Patients with proton-pump-inhibitor (PPI)-unresponsive reflux symptoms, often caused by functional esophageal disorders (FED), are frequently encountered in clinical practice. We aimed to investigate the prevalence of FED and its associated clinical characteristics in patients with PPI-unresponsive reflux symptoms. METHODS: We retrospectively identified patients who were evaluated for persistent typical reflux symptoms, despite ≥8 weeks of PPI treatment, at the National Taiwan University Hospital from 2014 to 2023. All patients underwent a comprehensive evaluation comprising validated gastroesophageal reflux disease (GERD) symptom questionnaires, 5-item Brief Symptom Rating Scale (BSRS-5), Pittsburgh Sleep Quality Index (PSQI), esophagogastroduodenoscopy, high-resolution impedance manometry, and 24-h impedance-pH monitoring off PPI therapy. Diagnosis of FED and non-erosive reflux disease (NERD) was based on the Rome IV criteria. RESULTS: We analyzed 190 patients [46.8% male, median age 52 (interquartile range, 42-61) years], of whom 32 (16.8%) had NERD and 158 (83.2%) had FED (57.9% with functional heartburn and 25.3% with reflux hypersensitivity). Patients with FED had a lower body mass index than those with NERD and a higher prevalence of psychological comorbidities and poor sleep quality than healthy volunteers. The severity of reflux symptoms among FED patients was significantly associated with the severity of psychological comorbidities and sleep quality. CONCLUSIONS: A notably high prevalence (83.2%) of FED was observed among patients experiencing PPI-unresponsive reflux symptoms. Patients with FED had a higher level of psychological distress and diminished sleep quality, both of which were associated with reflux symptom severity.

Bilirubin Elevation During Hospitalization Post Radiofrequency Catheter Ablation of Persistent Atrial Fibrillation: Variation Trend, Related Factors, and Relevance to 1-Year Recurrence.

Background: The role of total bilirubin (TBIL) in cardiovascular disease has been increasingly recognized in recent decades. Studies have shown a correlation between total bilirubin levels and the prognosis of patients after heart surgery. This study aimed to investigate the clinical significance of bilirubin elevation in persistent atrial fibrillation (PAF) patients who received radiofrequency catheter ablation (RFCA). Methods and Results: A total of 184 patients with PAF who received RFCA were retrospectively studied. Laboratory examinations and demographic data were analyzed to identify independent predictors of TBIL elevation. The relationship between TBIL and prognosis was further investigated. Our results indicated that TBIL increased significantly after RFCA. Multiple linear regression analysis showed that TBIL elevation owned a negative correlation with the percentile of low voltage areas (LVAs) in left atria (ß=-0.490, P<0.001). In contrast, a positive correlation was observed with the white blood cell (WBC) ratio (ß=0.153, P=0.042) and left atrial diameter (LAD) (ß=0.232, P=0.025). It was found that postoperative TBIL levels increased and then gradually decreased to baseline within 5 days without intervention. The bilirubin ratio <1.211 indicated the possibility of 1-year AF recurrence after ablation with a predictive value of 0.743 (specificity = 75.00%, sensitivity = 66.67%). Conclusion: Bilirubin elevation post PAF RFCA was a common phenomenon and was associated with 1-year recurrence of AF in PAF patients after RFCA.

Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

The Emerging Role of Ubiquitin-Specific Protease 36 (USP36) in Cancer and Beyond.

The balance between ubiquitination and deubiquitination is instrumental in the regulation of protein stability and maintenance of cellular homeostasis. The deubiquitinating enzyme, ubiquitin-specific protease 36 (USP36), a member of the USP family, plays a crucial role in this dynamic equilibrium by hydrolyzing and removing ubiquitin chains from target proteins and facilitating their proteasome-dependent degradation. The multifaceted functions of USP36 have been implicated in various disease processes, including cancer, infections, and inflammation, via the modulation of numerous cellular events, including gene transcription regulation, cell cycle regulation, immune responses, signal transduction, tumor growth, and inflammatory processes. The objective of this review is to provide a comprehensive summary of the current state of research on the roles of USP36 in different pathological conditions. By synthesizing the findings from previous studies, we have aimed to increase our understanding of the mechanisms underlying these diseases and identify potential therapeutic targets for their treatment.

Survey of hepatitis B virus infection status after 35 years of universal vaccination implementation in Taiwan.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. METHODS: A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. RESULTS: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. CONCLUSION: The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

Non-contact wide-field viewing system-assisted scleral buckling surgery for retinal detachment in silicone oil-filled eyes.

AIM: To evaluate scleral buckling (SB) surgery using a non-contact wide-field viewing system and 23-gauge intraocular illumination for the treatment of rhegmatogenous retinal detachment in silicone oil (SO)-filled eyes. METHODS: Totally 9 patients (9 eyes) with retinal detachment in SO-filled eyes were retrospectively analyzed. All patients underwent non-contact wide-field viewing system-assisted buckling surgery with 23-gauge intraocular illumination. SO was removed at an appropriate time based on recovery. The patients were followed up for at least 3mo after SO removal. Retinal reattachment, complications, visual acuity and intraocular pressure (IOP) before and after surgery were observed. RESULTS: Patients were followed up for a mean of 8.22mo (3-22mo) after SO removal. All patients had retinal reattachment. At the final follow-up, visual acuity showed improvement for 8 patients, and no change for 1 patient. The IOP was high in 3 patients before surgery, but it stabilized after treatment; it was not affected in the other patients. None of the patients had infections, hemorrhage, anterior ischemia, or any other complication. CONCLUSION: This new non-contact wide-field viewing system-assisted SB surgery with 23-gauge intraocular illumination is effective and safe for retinal detachment in SO-filled eyes.

[Spectral Characteristics and Sources of Dissolved Organic Matter in Inflow Rivers of Baiyangdian Lake Water in Summer Flood Season].

DOM is the largest reservoir of organic carbon in the world, and it plays a crucial role in the biogeochemical cycles of natural water bodies. A river is a transition area connecting source water and receiving water that controls the DOM exchange between them. Therefore, in this study, ultraviolet visible spectroscopy (UV-vis) and three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC) were used to analyze the spectral characteristics and sources of dissolved organic matter in the Fuhe River, Xiaobai River, Baigouyin River, and Puhe River of Baiyangdian. The results showed that a245 and a355 in the Fuhe River and Xiaobai River were significantly higher than those in the Baigouyin River and Puhe River. E2/E3 showed that the DOM relative molecular mass of the inflow river water body was Puhe River > Baigouyin River > Fuhe River > Xiaobai River. Three components, tyrosine-like (C1), terrigenous humus (C2), and tryptophan-like (C3), were determined using three-dimensional fluorescence through PARAFAC. There was no difference among the fluorescence components (P>0.05), but there were differences among the C2 and C3 components (P<0.05). The proportion of easily degradable protein-like components (C1+C3) was higher than that of humus-like components (C2). The autogeny index BIX was greater than 1, and the humification index HIX was less than 4, indicating that the autogeny characteristics of the river bodies were obvious, and the humification degree was weak. The FI index was the highest (1.96±0.25), and the HIX index was the lowest (0.46±0.08), and the self-generated source characteristics gradually strengthened along the direction of the river entering the lake, indicating that the water body of the Fuhe River showed higher endogenous and autogenic characteristics. Based on the correlation analysis of fluorescence components and characteristic parameters of DOM, the correlations between the Fuhe River and Xiaobaihe River and between the Baigouyin River and Puhe River bodies were similar. The correlation between fluorescence components of DOM and water quality parameters of each lake was significantly different, and it was strongly correlated with nitrogen and phosphorus in water. According to multiple linear regression analysis, there was no significant difference among C1 components, but there was a significant difference between C2 and C3 components. In summary, the carbon cycle process of Baiyangdian Lake was further understood through the study on the DOM spectral characteristics and sources of the inflow river waters in the summer flood season.

LncRNA RGMB-AS1 inhibits HMOX1 ubiquitination and NAA10 activation to induce ferroptosis in non-small cell lung cancer.

Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non-coding RNA RGMB-AS1 as a key regulator of ferroptosis in NSCLC. Mechanistically, RGMB-AS1 interacted with heme oxygenase 1 (HMOX1) and prevented its ubiquitination by the E3 ligase TRC8, leading to increased HMOX1 stability and enhanced ferroptosis. Additionally, RGMB-AS1 bound to the 82-87 amino acid region of N-alpha-acetyltransferase 10 (NAA10), stimulating its acetyltransferase activity and promoting the conversion of acetyl-CoA to HMG-CoA, further contributing to ferroptosis. The RGMB-AS1-HMOX1 and RGMB-AS1-NAA10 axes synergistically inhibited NSCLC growth both in vitro and in vivo. Clinically, low RGMB-AS1 expression was associated with advanced tumor stage and poor overall survival in NSCLC patients. Furthermore, adeno-associated virus-mediated RGMB-AS1 overexpression significantly suppressed tumor growth in mouse xenograft models. Our findings uncover a novel lncRNA-mediated regulatory mechanism of ferroptosis and highlight the potential of RGMB-AS1 as a prognostic biomarker and therapeutic target in NSCLC.

The Role of m6A-Mediated DNA Damage Repair in Tumor Development and Chemoradiotherapy Resistance.

Among the post-transcriptional modifications, m6A RNA methylation has gained significant research interest due to its critical role in regulating transcriptional expression. This modification affects RNA metabolism in several ways, including processing, nuclear export, translation, and decay, making it one of the most abundant transcriptional modifications and a crucial regulator of gene expression. The dysregulation of m6A RNA methylation-related proteins in many tumors has been shown to lead to the upregulation of oncoprotein expression, tumor initiation, proliferation, cancer cell progression, and metastasis.Although the impact of m6A RNA methylation on cancer cell growth and proliferation has been extensively studied, its role in DNA repair processes, which are crucial to the pathogenesis of various diseases, including cancer, remains unclear. However, recent studies have shown accumulating evidence that m6A RNA methylation significantly affects DNA repair processes and may play a role in cancer drug resistance. Therefore, a comprehensive literature review is necessary to explore the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.In conclusion, m6A RNA methylation is a crucial regulator of gene expression and a potential player in cancer development and drug resistance. Its dysregulation in many tumors leads to the upregulation of oncoprotein expression and tumor progression. Furthermore, the impact of m6A RNA methylation on DNA repair processes, although unclear, may play a crucial role in cancer drug resistance. Therefore, further studies are warranted to better understand the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.

Correlation Between Anesthesia Methods and Adverse Short-Term Postoperative Outcomes Depending on Frailty: A Prospective Cohort Study.

Purpose: This study aims to investigate how the type of anesthesia used during major orthopedic surgery may impact adverse short-term postoperative outcomes depending on frailty. Methods: To conduct this investigation, we recruited individuals aged 65 years and older who underwent major orthopedic surgery between March 2022 and April 2023 at a single institution. We utilized the FRAIL scale to evaluate frailty. The primary focus was on occurrences of death or the inability to walk 60 days after the surgery. Secondary measures included death within 60 days; inability to walk without human assistance at 60 days; death or the inability to walk without human assistance at 30 days after surgery, the first time out of bed after surgery, postoperative blood transfusion, length of hospital stay, hospital costs, and the occurrence of surgical complications such as dislocation, periprosthetic fracture, infection, reoperation, wound complications/hematoma. Results: In a study of 387 old adult patients who had undergone major orthopedic surgery, 41.3% were found to be in a frail state. Among these patients, 262 had general anesthesia and 125 had neuraxial anesthesia. Multifactorial logistic regression analyses showed that anesthesia type was not linked to complications. Instead, frailty (OR 4.04, 95% CI 1.04 to 8.57, P< 0.001), age (OR 1.05, 95% CI 1.00-1.10, P= 0.017), and aCCI scores, age-adjusted Charlson Comorbidity Index, (OR 1.36, 95% CI 1.12 to 1.66, P= 0.002) were identified as independent risk factors for death or new walking disorders in these patients 60 days after surgery. After adjusting for frailty, anesthesia methods was not associated with the development of death or new walking disorders in these patients (P > 0.05). Conclusion: In different frail populations, neuraxial anesthesia is likely to be comparable to general anesthesia in terms of the incidence of short-term postoperative adverse outcomes.

The incidence of Clostridium difficile infection in children with and without inflammatory bowel diseases: A single-center study in Taiwan from 2006 to 2019.

BACKGROUND: The incidence of Clostridium difficile infection (CDI) is increasing around the world, and patients with inflammatory bowel disease (IBD) have a higher risk of obtaining CDI. The data on the incidence rate of CDI in the Asian pediatric IBD population was lacking. METHODS: We retrospectively collected data from a tertiary medical center in Taipei, Taiwan. All patients aged 1-18 years old who visited the outpatient department or were admitted to our hospital between 2006 and 2019 were included. CDI was defined as positive stool C. difficile toxin or C. difficile culture results with appropriate antibiotic use within the range of 7 days prior or 14 days after the result. RESULTS: We compared the average annual incidence of CDI before and after 2013. The average incidence of community-acquired CDI (CA-CDI) increased from 0.063 to 0.564 cases per 1,000 visits, with a rate ratio (RR) of 8.82 (95% CI 5.74-14.38). In patients with IBD, the rate increased from 26.738 to 278.873 cases per 1,000 visits (RR=10.12, 95% CI: 4.57-29.02). The average incidence rate increased from 0.685 to 1.874 cases per 1,000 admissions in pediatric general patients (RR = 2.72, 95% CI 1.82-4.20) and from 14.706 to 62.500 cases per 1,000 admissions in pediatric IBD patients (RR = 3.77, 95% CI 0.71-93.53). CONCLUSIONS: Both CA-CDI and healthcare facility-onset CDI (HO-CDI) were increasing substantially in the pediatric population over the past decade in Taiwan. Compared to the general pediatric population, pediatric IBD patients had a much higher incidence of CDI.

CTLA-4 haplotype predicts HBsAg and HBcrAg levels and HBeAg seroconversion age in children with chronic HBV infection.

Background & Aim: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between CTLA-4 genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection. Methods: We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the CTLA-4 gene single nucleotide polymorphisms rs4553808 (-A1661G)/rs5742909 (-C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort. Results: CTLA-4 promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the CTLA-4 AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; p = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 vs. 0.03 log10 IU/ml/year, p = 0.02). The CTLA-4 AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (p = 0.01). Conclusions: Chronic HBV-infected patients with a CTLA-4 AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion. Impact and implications: The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that CTLA-4 haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

Molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania based on network pharmacology and molecular docking: Evidence from computational biology.

BACKGROUND: Quetiapine monotherapy is recommended as the first-line option for acute mania and acute bipolar depression. However, the mechanism of action of quetiapine is unclear. Network pharmacology and molecular docking were employed to determine the molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania. METHODS: Putative target genes for quetiapine were collected from the GeneCard, SwissTargetPrediction, and DrugBank databases. Targets for bipolar depression and bipolar mania were identified from the DisGeNET and GeneCards databases. A protein-protein interaction (PPI) network was generated using the String database and imported into Cytoscape. DAVID and the Bioinformatics platform were employed to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the top 15 core targets. The drug-pathway-target-disease network was constructed using Cytoscape. Finally, molecular docking was performed to evaluate the interactions between quetiapine and potential targets. RESULTS: Targets for quetiapine actions against bipolar depression (126 targets) and bipolar mania (81 targets) were identified. Based on PPI and KEGG pathway analyses, quetiapine may affect bipolar depression by targeting the MAPK and PI3K/AKT insulin signaling pathways via BDNF, INS, EGFR, IGF1, and NGF, and it may affect bipolar mania by targeting the neuroactive ligand-receptor interaction signaling pathway via HTR1A, HTR1B, HTR2A, DRD2, and GRIN2B. Molecular docking revealed good binding affinity between quetiapine and potential targets. LIMITATIONS: Pharmacological experiments should be conducted to verify and further explore these results. CONCLUSIONS: Our findings suggest that quetiapine affects bipolar depression and bipolar mania through distinct biological core targets, and thus through different mechanisms. Furthermore, our results provide a theoretical basis for the clinical use of quetiapine and possible directions for new drug development.

Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from taiwan.

BACKGROUND/PURPOSE: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. METHODS: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. RESULTS: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2-10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). CONCLUSIONS: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

Potential drug targets for gastroesophageal reflux disease and Barrett's esophagus identified through Mendelian randomization analysis.

Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett's esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA expression quantitative trait loci (eQTL) data from another GWAS encompassing four different tissues to identify additional drug targets. Meanwhile, we searched drug databases to evaluate these targets. Under Bonferroni correction (P < 4.8 × 10-5), we identified 11 plasma proteins significantly associated with GERD. Among these, 7 are protective proteins (MSP, GPX1, ERBB3, BT3A3, ANTR2, CCM2, and DECR2), while 4 are detrimental proteins (TMEM106B, DUSP13, C1-INH, and LINGO1). Ultimately, C1-INH and DECR2 successfully passed the screening process and exhibited similar directional causal effects on BE. Further analysis of eQTLs highlighted 4 potential drug targets, including EDEM3, PBX3, MEIS1-AS3, and NME7. The search of drug databases further supported our conclusions. Our study indicated that the plasma proteins C1-INH and DECR2, along with 4 genes (EDEM3, PBX3, MEIS1-AS3, and NME7), may represent potential drug targets for GERD and BE, warranting further investigation.