Unveiling clinicopathologic features and outcomes for endoscopic submucosal dissection of early gastric cancer at gastric angulus in China.

BACKGROUND: With advances in endoscopic submucosal dissection (ESD) technique, an increasing number of the Chinese population are being diagnosed with early gastric cancers (EGCs) at gastric angulus. However, the relationship between gastric angulus and EGCs remains obscure. OBJECTIVES: We aimed to unveil the unreported location characteristics of gastric angulus in Chinese EGC patients and the correlation between the degree of submucosal fibrosis and ESD outcomes. METHODS: We retrospectively reviewed the medical records of EGC patients treated with ESD from January 2010 to March 2023. We retrospectively investigated and analyzed 740 EGC patients using multiple analyses. RESULTS: Following gastric antrum (53.1%), the gastric angulus (21.8%) emerged as the second-most prevalent site for EGCs. It had highest incidence of severe submucosal fibrosis and ulceration than the other parts. Multivariate analysis showed independent associations of submucosal fibrosis at the angulus with ulceration (OR: 3.714, 95% CI: 1.041-13.249), procedure duration (OR: 1.037, 95% CI: 1.014-1.061), and perforation complication (OR: 14.611, 95% CI: 1.626-131.277) (all P < 0.05). CONCLUSIONS: The gastric angulus demonstrates the highest incidence of severe submucosal fibrosis and ulceration for EGCs identified by ESD. This condition is linked to unfavorable outcomes, typically increased perforation risks and prolonged operation duration. Therefore, meticulous dissection is crucial for patients with EGCs in the gastric angulus.

Photoinduced Metal-Free Radical Addition/Cyclization of 2-Cyanoaryl Acrylamides to Prepare gem-Difluorinated Naphthyridinone Scaffolds.

Direct construction of gem-difluorinated heterocycles represents a long-standing challenge in organic chemistry. Herein, we developed a transition-metal-free photocatalytic radical addition/cyclization of BrCF2COR with 2-cyanoaryl acrylamides to give gem-difluorinated naphthyridinone scaffolds in moderate to good yields. Furthermore, some natural products were found to be suitable in the reaction system. The easily available substrates, mild reaction conditions, simple operation, and wide functionality tolerance show practical and environmental advantages in this method.

Visible-Light-Promoted Selenylation/Cyclization of o-Alkynyl Benzylazides/o-Propargyl Arylazides: Synthesis of Seleno-Substituted Isoquinolines and Quinolines.

A simple and efficient visible-light-promoted selenylation/cyclization of o-alkynyl benzylazides/o-propargyl arylazides have been realized for the practical synthesis of seleno-substituted isoquinolines and quinolines. This strategy provides the synthesis of valuable seleno-substituted isoquinoline and quinoline derivatives via the construction of one C(sp2)-Se bond and one C-N bond within one process.

Assessing anorectal function in patients with recurrent ulcerative colitis.

PURPOSE: Ulcerative colitis (UC) is an inflammatory bowel disease with an unclear etiology that can lead to irreversible changes in distal colonic function in chronic patients. This study investigated anorectal function in recurrent UC patients and identified influencing factors. METHODS: This prospective study enrolled 33 recurrent UC patients and 40 newly diagnosed patients from January 2019 to December 2022. Data collection included clinical records, scores, and anorectal function assessments. Regression analyses were used to identify factors impacting anorectal function. RESULTS: Recurrent UC patients had higher baseline CRP and fecal calprotectin levels, increased anxiety and depression, and more severe fecal incontinence. They also had lower BMIs, serum Hb and albumin (ALB) levels, and Inflammatory Bowel Disease Questionnaire scores than did initial-onset UC patients. Multivariate linear regression analysis revealed that long disease duration (coef. - 0.376, P < 0.001) and high fecal calprotectin level (coef. - 0.656, P < 0.001) independently influenced the initial sensation threshold in recurrent UC patients. Additionally, high fecal calprotectin (coef. - 0.073, P = 0.013) and high Zung Self-Rating Anxiety Scale score (coef. - 0.489, P = 0.001) were identified as two independent determinants of the defecation volume threshold. For the defecation urgency threshold, the independent factors included high disease duration (coef. - 0.358, P = 0.017) and high fecal calprotectin level (coef. - 0.499, P = 0.001). Similarly, the sole independent factor identified for the maximum capacity threshold was high fecal calprotectin (coef. - 0.691, P = 0.001). CONCLUSION: Recurrent UC patients had increased rectal sensitivity and compromised anorectal function, which significantly impacted quality of life. Proactively managing the disease, reducing UC relapses, and addressing anxiety are effective measures for improving anorectal function in these patients.

Visible-Light-Promoted bis(Difluoromethylation)/Cyclization of 2-Vinyloxy Arylalkynes to Prepare Benzofuran Derivatives.

A visible-light-promoted difluoromethylation/cyclization of 2-vinyloxy arylalkynes was developed, providing a variety of bis(difluoromethyl)-substituted benzofurans in moderate to good yields. A plausible mechanism involving difluoromethyl radical cascade cyclization and solvent-promoted ionic addition was proposed. This protocol has the advantages of having mild reaction conditions, simple operation, and good functional group tolerance.

Hyperspectral Imaging for the Nondestructive Quality Assessment of the Firmness of Nanguo Pears Under Different Freezing/Thawing Conditions.

Firmness changes in Nanguo pears under different freezing/thawing conditions have been characterized by hyperspectral imaging (HSI). Four different freezing/thawing conditions (the critical temperatures, numbers of cycles, holding time and cooling rates) were set in this experiment. Four different pretreatment methods were used: multivariate scattering correction (MSC), standard normal variate (SNV), Savitzky-Golay standard normal variate (S-G-SNV) and Savitzky-Golay multiplicative scattering correction (S-G-MSC). Combined with competitive adaptive reweighted sampling (CARS) to identify characteristic wavelengths, firmness prediction models of Nanguo pears under different freezing/thawing conditions were established by partial least squares (PLS) regression. The performance of the firmness model was analyzed quantitatively by the correlation coefficient (R), the root mean square error of calibration (RMSEC), the root mean square error of prediction (RMSEP) and the root mean square error of cross validation (RMSECV). The results showed that the MSC-PLS model has the highest accuracy at different cooling rates and holding times; the correlation coefficients of the calibration set (Rc) were 0.899 and 0.927, respectively, and the correlation coefficients of the validation set (Rp) were 0.911 and 0.948, respectively. The accuracy of the SNV-PLS model was the highest at different numbers of cycles, and the Rc and the Rp were 0.861 and 0.848, respectively. The RMSEC was 65.189, and the RMSEP was 65.404. The accuracy of the S-G-SNV-PLS model was the highest at different critical temperatures, with Rc and Rp values of 0.854 and 0.819, respectively, and RMSEC and RMSEP values of 74.567 and 79.158, respectively.

Transesophageal echocardiography guidance for percutaneous closure of PFO and a new method to improve the diagnosis and safety during the procedures.

Purpose: Percutaneous patent foramen ovale (PFO) closure is becoming more and more common for the treatment or prevention of PFO-associated right-to-left shunt (RLS). This study aims to investigate the value of transesophageal echocardiography (TEE) in percutaneous PFO closure, and to explore a new method that can improve intraoperative diagnosis and surgical safety. Materials and methods: Based on our inclusion and exclusion criteria, we enrolled 73 patients between 16 and 70 years old (average age 43.25 ± 14.87 years) who underwent percutaneous PFO closure at the Department of Cardiac Surgery, Zhongshan Hospital (Xiamen), Fudan University, from January 2022 to December 2023. Out of the 73 enrolled patients, there were 28 males (38.36%) and 45 females (61.64%), 29 migraine patients (39.73%), 14 patients (19.19%) with headache and dizziness, 14 patients (19.18%) with a history of cerebral infarction (CI), and 25 patients (34.25%) with CI, lacunar infarction or ischemic focus on magnetic resonance imaging (MRI). All patients received routine transthoracic echocardiography (TTE) and agitated saline contrast echocardiography (ASCE) before operations. Percutaneous closure of PFO was completed under the guidance of TEE. In 12 patients, the method of "injection of heparinized sterile saline through the delivery sheath" was used to observe their RLS, and the anatomical characteristics of the PFO according to the shunt path were monitored and evaluated. This method was also applied to some patients to guide the conveyor to pass through the foramen ovale (FO) channel safely and effectively, thereby improving the success rate of PFO closure. Results: The application of TEE during the procedure of percutaneous PFO closure, including preoperative evaluation, intraoperative guidance, and postoperative reevaluation, can offer further details about the anatomical and shunt characteristics of PFO, improve the diagnosis rate, and confirm the safety of the surgical path. It ensures the safety and reliability of the whole operation, greatly improving the success rate and reducing postoperative complications. Conclusions: TEE guidance of percutaneous PFO closure has the advantages of minimal trauma, no radiation and real-time visualization, while injecting heparinized sterile saline through the delivery sheath is safer and more effective in improving the success rate and reducing postoperative complications.

Application of myocardial work in predicting adverse events among patients with resistant hypertension.

BACKGROUND: Hypertension is the most common chronic disease and the leading risk factor for disability and premature deaths worldwide. Approximately 10-20% of all patients with hypertension and 15-18% of the general population who are treated for hypertension have resistant hypertension (RH). Patients with RH have a higher risk of end-organ damage, such as carotid intima-media thickening, retinopathy, left ventricular hypertrophy and heart failure, myocardial infarction, stroke, impaired renal function, and death than those with controlled blood pressure. In the present study, we applied echocardiography to patients with RH to evaluate myocardial work (MW) and determine whether it is predictive for the occurrence of adverse events within 3 years. METHODS: We included 283 outpatients and inpatients aged ≥ 18 years who met the clinical criteria for RH, without arrhythmia and severe aortic valve stenosis, between July 2018 and June 2019. The patients were followed up for 3 years from starting enrollment, and any adverse event that occurred during the period was used as the observation end point. Each enrolled patient underwent a complete transthoracic echocardiogram examination, blood pressure was measured and recorded, and MW was then analyzed. RESULTS: Eighty-two (28.98%) patients with RH had adverse events, such as myocardial infarction (n = 29, 35.36%), heart failure (n = 4, 0.05%), renal insufficiency (n = 40, 48.78%), renal failure (n = 2, 0.02%), cerebral infarction (n = 5, 0.06%), and cerebral hemorrhage (n = 2, 0.02%), and no death events occurred. In patients with RH and adverse events, global longitudinal strain (GLS) (- 16% vs. - 18%), the global work index (2079 mmHg% vs. 2327 mmHg%), global constructive work (2321 mmHg% vs. 2610 mmHg%), and global work efficiency (93% vs. 94%) were lower than those in patients without adverse events. However, global wasted work (GWW) was higher in patients with RH and adverse events than in those without adverse events (161 mmHg% vs. 127 mmHg%). GLS and GWW were the most significant in predicting adverse events. CONCLUSIONS: MW, especially GLS and GWW, is a good method to predict 3-year adverse events in patients with RH.

Ruxolitinib Alleviates Inflammation, Apoptosis, and Intestinal Barrier Leakage in Ulcerative Colitis via STAT3.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa with increasing prevalence and limited management. Ruxolitinib is a new anti- JAK/STAT3 biologic agent that has shown potential in protecting against colitis. METHODS: We first constructed an in vivo UC model and an in vitro colonic epithelial cell inflammation model. Ruxolitinib was administered via gavage in mice. After treatment, colon tissues, cells, and cell lysates were collected and prepared for histological evaluation, immunohistochemistry, immunofluorescence staining, quantitative reverse-transcriptase polymerase chain reaction, Western blotting, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining, and cytokine analysis. STAT3 expression was silenced and overexpressed via small interfering RNA and overexpression plasmid transfection, respectively, and quantitative reverse-transcriptase polymerase chain reaction was used to examine the downstream effects. RESULTS: Ruxolitinib administration significantly alleviated colitis both in vivo and in vitro, as manifested by reduced body weight loss, shortened colon lengths, relieved disease activity (measured by the disease activity index), and prolonged survival. A mechanistic study showed that ruxolitinib attenuated nuclear factor kappa B-induced inflammation, reduced apoptosis, and ameliorated epithelial barrier leakage, and thereby reduced colitis activity in vivo. STAT3 knockdown partially reversed the protective effect of ruxolitinib against colitis, while STAT3 overexpression exaggerated the reductions in proinflammatory cytokine levels upon ruxolitinib treatment. CONCLUSIONS: We demonstrate that ruxolitinib alleviates colitis by inhibiting nuclear factor kappa B-related inflammation and apoptosis in addition to restoring epithelial barrier function via STAT3, providing a new strategy for UC treatment.

We studied the effect and mechanism of ruxolitinib on ulcerative colitis. We discovered that ruxolitinib administration significantly alleviated murine colitis by relieving disease activity and prolonged survival through intestinal epithelial cell nuclear factor kappa B­induced inflammation, reduced apoptosis, and ameliorated epithelial barrier leakage via STAT3.

Microglial Dysfunction in Neurodegenerative Diseases via RIPK1 and ROS.

Microglial dysfunction is a major contributor to the pathogenesis of multiple neurodegenerative diseases. The neurotoxicity of microglia associated with oxidative stress largely depends on NF-κB pathway activation, which promotes the production and release of microglial proinflammatory cytokines and chemokines. In this review, we discuss the current literature on the essential role of the NF-κB pathway on microglial activation that exacerbates neurodegeneration, with a particular focus on RIPK1 kinase activity-dependent microglial dysfunction. As upregulated RIPK1 kinase activity is associated with reactive oxygen species (ROS) accumulation in neurodegenerative diseases, we also discuss the current knowledge about the mechanistic links between RIPK1 activation and ROS generation. Given RIPK1 kinase activity and oxidative stress are closely regulated with each other in a vicious cycle, future studies are required to be conducted to fully understand how RIPK1 and ROS collude together to disturb microglial homeostasis that drives neurodegenerative pathogenesis.

Comparisons of the therapeutic safety of seven oral antimuscarinic drugs in patients with overactive bladder: a network meta-analysis.

OBJECTIVES: This network meta-analysis aimed to assess the safety profiles of seven commonly used oral antimuscarinic drugs (darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, and tolterodine) in patients with overactive bladder (OAB). METHODS: PubMed, Cochrane Library, EMBASE, CNKI, and Wanfang databases were searched for randomized controlled trials (RCTs). Studies comparing one or more antimuscarinic drugs for treating OAB with reported adverse effects (AEs) were eligible. Data were extracted, and a network meta-analysis was performed by two authors independently. RESULTS: Forty-five RCTs and 124,587 patients were included. The results demonstrated that tolterodine had better safety outcomes for 7 out of 12 major AEs, including dry mouth, constipation, urinary retention, dizziness, urinary tract infection, dry eyes, and dry skin. Darifenacin, fesoterodine, imidafenacin, oxybutynin, and solifenacin presented comparable safety profiles. CONCLUSIONS: Tolterodine may be preferable as it showed a reduced association with important AEs. Darifenacin, fesoterodine, imidafenacin, oxybutynin, and solifenacin have similar safety profiles in treating patients with OAB. Taken together, this analysis provides a valuable overview of the therapeutic safety for oral antimuscarinic drugs and is useful for personalized medicine in patients with OAB.Trial registration: This trial was retrospectively registered at INPLASY (https://inplasy.com/) with the registration number 202170095.

Kidney Injury Molecule-1 and Periostin Urinary Excretion and Tissue Expression Levels and Association with Glomerular Disease Outcomes.

INTRODUCTIONS: Kidney injury molecule-1 (KIM-1) and periostin (POSTN) are proximal and distal tubule injury biomarkers. We tested whether baseline urine KIM-1/creatinine (uKIM-1/cr) and/or uPOSTN/cr correlated with disease severity or improved a remission prediction model. METHODS: Baseline uKIM1/cr and uPOSTN/cr were measured on spot urine samples from immunosuppression-free patients enrolled in Nephrotic Syndrome Study Network until December 15, 2014. Urine protein/creatinine (UPCR) and albumin/creatinine (UACR) were measured at baseline, 4 months, and until last follow-up. Glomerular and tubulointerstitial (TI) expression arrays were analyzed from a baseline research renal biopsy core collected during a clinically indicated biopsy.Renal diagnoses were centrally confirmed, sections scanned, and measured morphometrically. Correlations between baseline uKIM-1/cr and uPOSTN/cr and UPCR, UACR, histopathologic features, glomerular and TI KIM-1 and POSTN expression levels, and renal outcomes were assessed. RESULTS: Baseline uKIM-1/cr correlated with UPCR and UACR, and were associated with complete remission after adjustment for proteinuria, histopathologic diagnosis, and treatment. Baseline uKIM-1/cr also correlated with degree of foot process effacement and acute tubular injury. Glomerular and TI KIM-1 expression levels correlated with UPCR and UACR. Higher TI KIM-1 expression levels correlated with interstitial fibrosis, tubular atrophy, and global glomerulosclerosis, while glomerular KIM-1 expression correlated with time to remission. Findings for POSTN were of lesser statistical strength. DISCUSSION/CONCLUSION: Lower baseline uKIM-1/cr values were associated with more rapid time to complete remission after adjusting for proteinuria, histopathologic diagnosis, and treatment. Increased TI KIM-1 expression levels in proteinuric states were associated with chronic morphological injury; lower glomerular expression levels were associated with a greater potential for proteinuria reversibility.

[Development and inheritance of ZHENG's acupuncture school].

ZHENG's acupuncture school in Gansu,represented by ZHENG Yulin and ZHENG Kuishan,is of great influence in China. ZHENG's acupuncture school originated from Huangdi Neijing(Inner Canon of Yellow Emperor) and Nanjing(Classic of Questioning),and shaped around Yuan Dynasty and Ming Dynasty. Professor ZHENG Kuishan has formed a unique "ZHENG's acupuncture" diagnosis and treatment system by inheritance and innovation. He clinically paid attention to basic training,obtaining qi and keeping spirit,as well as syndrome differentiation,reinforcing and reducing. Also,he took the priority the pressing hand with bilaterally needle manipulation. Besides,he thought important simplicity,innovation and acupoints selecting according to time. We inherited ZHENG's acupuncture from his family,teachers'techniques,international communication,college and university education and scientific research. In this article we prescribe the development,the inheritance and the protection measures of ZHENG's acupuncture school in terms of its origination,academic thought,and inheritance research,etc.,so as to provide references for further study and inheritance.

[ApoE4 increases glycogen synthase kinase 3ß expression and Tau phosphorylation in U87 cells].

OBJECTIVE: To explore the relations among apolipoprotein E4, Tau protein and glycogen synthase kinase 3ß (GSK-3ß). METHODS: U87 cells were transfected with pIRES-EGFP (control) or the recombinant plasmids ApoE4/pIRES-EGFP or ApoE3/pIRES-EGFP, and the expression levels of p-Tau/Tau and GSK-3ß in the cells were examined with Western blotting. To further confirm the effect of ApoE on GSK-3ß and p-Tau expressions, a short interfering RNA (siRNA) targeting ApoE (ApoE-siRNA) was transfected into U87 cells via Lipofectamine 2000 and the protein expressions were examined 24 h later. RESULTS: Compared with those in the control group, the expressions levels of both GSK-3ß and p-Tau/Tau increased significantly in the cells transfected with ApoE4 and ApoE3 plasmids (P<0.01), and the ApoE4 plasmid produced a more potent effect than the ApoE3 plasmid on the protein expressions (P<0.01). ApoE knockdown resulted in significantly reduced expressions of GSK-3ß (P<0.001) and p-Tau (P<0.01) in the cells. CONCLUSION: ApoE4 can enhance Tau phosphorylation though upregulating GSK-3ß, which sheds light on a new role of ApoE4 in Alzheimer's disease.