Role of TRPC6 in apoptosis of skeletal muscle ischemia/reperfusion injury.

BACKGROUND: Skeletal muscle ischaemia-reperfusion injury (IRI) is a prevalent condition encountered in clinical practice, characterised by muscular dystrophy. Owing to limited treatment options and poor prognosis, it can lead to movement impairments, tissue damage, and disability. This study aimed to determine and verify the influence of transient receptor potential canonical 6 (TRPC6) on skeletal muscle IRI, and to explore the role of TRPC6 in the occurrence of skeletal muscle IRI and the signal transduction pathways activated by TRPC6 to provide novel insights for the treatment and intervention of skeletal muscle IRI. METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice. RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R. CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.

Targeting the STAT3/IL-36G signaling pathway can be a promising approach to treat rosacea.

BACKGROUND: Rosacea is an inflammatory skin disorder characterized by the release of inflammatory mediators from keratinocytes, which are thought to play a crucial role in its pathogenesis. Despite an incidence of approximately 5.5%, rosacea is associated with a poor quality of life. However, as the pathogenesis of rosacea remains enigmatic, treatment options are limited. OBJECTIVES: To investigate the pathogenesis of rosacea and explore new therapeutic strategies. METHODS: Transcriptome data from rosacea patients combined with immunohistochemical staining were used to investigate the activation of STAT3 in rosacea. The role of STAT3 activation in rosacea was subsequently explored by inhibiting STAT3 activation both in vivo and in vitro. The key molecules downstream of STAT3 activation were identified through data analysis and experiments. Dual-luciferase assay and ChIP-qPCR analysis were used to validate the direct binding of STAT3 to the IL-36G promoter. DARTS, in combination with experimental screening, was employed to identify effective drugs targeting STAT3 for rosacea treatment. RESULTS: STAT3 signaling was hyperactivated in rosacea and served as a promoter of the keratinocyte-driven inflammatory response. Mechanistically, activated STAT3 directly bind to the IL-36G promoter region to amplify downstream inflammatory signals by promoting IL-36G transcription, and treatment with a neutralizing antibody (α-IL36γ) could mitigate rosacea-like inflammation. Notably, a natural plant extract (pogostone), which can interact with STAT3 directly to inhibit its activation and affect the STAT3/IL36G signaling pathway, was screened as a promising topical medication for rosacea treatment. CONCLUSIONS: Our study revealed a pivotal role for STAT3/IL36G signaling in the development of rosacea, suggesting that targeting this pathway might be a potential strategy for rosacea treatment.

Dilemmas and prospects of artificial intelligence technology in the data management of medical informatization in China: A new perspective on SPRAY-type AI applications.

Objectives: This study aims to address the critical challenges of data integrity, accuracy, consistency, and precision in the application of electronic medical record (EMR) data within the healthcare sector, particularly within the context of Chinese medical information data management. The research seeks to propose a solution in the form of a medical metadata governance framework that is efficient and suitable for clinical research and transformation. Methods: The article begins by outlining the background of medical information data management and reviews the advancements in artificial intelligence (AI) technology relevant to the field. It then introduces the "Service, Patient, Regression, base/Away, Yeast" (SPRAY)-type AI application as a case study to illustrate the potential of AI in EMR data management. Results: The research identifies the scarcity of scientific research on the transformation of EMR data in Chinese hospitals and proposes a medical metadata governance framework as a solution. This framework is designed to achieve scientific governance of clinical data by integrating metadata management and master data management, grounded in clinical practices, medical disciplines, and scientific exploration. Furthermore, it incorporates an information privacy security architecture to ensure data protection. Conclusion: The proposed medical metadata governance framework, supported by AI technology, offers a structured approach to managing and transforming EMR data into valuable scientific research outcomes. This framework provides guidance for the identification, cleaning, mining, and deep application of EMR data, thereby addressing the bottlenecks currently faced in the healthcare scenario and paving the way for more effective clinical research and data-driven decision-making.

Integrated bioinformatics analysis and experimental validation identifies CPE as a potential biomarker and therapeutic target for skin aging.

Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.

Downregulated SPESP1-driven fibroblast senescence decreases wound healing in aged mice.

BACKGROUND: Human dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin. METHODS: The expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography-mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1-induced senescent HDFs in wound healing. RESULTS: Here, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl-binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin. CONCLUSIONS: Taken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti-ageing strategies and improve wound healing in the elderly.

Association of Biological Age Acceleration with Cardiac Morphology, Function, and Incident Heart Failure: Insights from UK Biobank Participants.

BACKGROUND: Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined. METHODS: Utilizing the UK Biobank cohort, we assessed biological age using the Klemera-Doubal and PhenoAge method. BAA was quantified by residual analysis compared to chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analyses was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations. RESULTS: A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF (26% per standard deviation [SD] increase in KDM-BA acceleration, 95% confidence intervals [CI]: 23%-28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32%-35%). Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk. CONCLUSIONS: In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions.

CT-based radiomics for predicting pathological grade in hepatocellular carcinoma.

Objective: To construct and validate radiomics models for hepatocellular carcinoma (HCC) grade predictions based on contrast-enhanced CT (CECT). Methods: Patients with pathologically confirmed HCC after surgery and underwent CECT at our institution between January 2016 and December 2020 were enrolled and randomly divided into training and validation datasets. With tumor segmentation and feature extraction, radiomic models were constructed using univariate analysis, followed by least absolute shrinkage and selection operator (LASSO) regression. In addition, combined models with clinical factors and radiomics scores (Radscore) were constructed using logistic regression. Finally, all models were evaluated using the receiver operating characteristic (ROC) curve with the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Results: In total 242 patients were enrolled in this study, of whom 170 and 72 formed the training and validation datasets, respectively. The arterial phase and portal venous phase (AP+VP) radiomics model were evaluated as the best for predicting HCC pathological grade among all the models built in our study (AUC = 0.981 in the training dataset; AUC = 0.842 in the validation dataset) and was used to build a nomogram. Furthermore, the calibration curve and DCA indicated that the AP+VP radiomics model had a satisfactory prediction efficiency. Conclusions: Low- and high-grade HCC can be distinguished with good diagnostic performance using a CECT-based radiomics model.

The underlying neuropsychological and neural correlates of the impaired Chinese reading skills in children with attention deficit hyperactivity disorder.

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance.

Efficacy of Dan'e Fukang Soft Extract in Moderate Ovarian Hyperstimulation Syndrome for Concurrent Treatment of Blood and Fluid Guided by the "Triple Prevention" Principle.

Objective: This study aimed to evaluate the therapeutic efficacy and safety of Dan'e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of "triple prevention". Methods: This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan'e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators. Results: There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group. Conclusion: Based on the traditional Chinese medicine principle of "triple prevention", the use of Dan'e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.

WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8.

N6-methyladenosine (m6A), the most prevalent posttranscriptional RNA modification, involved in various diseases and cellular processes. However, the underlying mechanisms of m6A regulation in skin aging are still not fully understood. In this study, proteomics analysis revealed a significant correlation between Wilms' tumor 1-associating protein (WTAP) expression and cellular senescence. Next, upregulated WTAP was detected in aging skin tissues and senescent human dermal fibroblasts (HDFs). Functionally, overexpressed WTAP induced senescence and knockdown of WTAP rescued senescence of HDFs. Mechanistically, WTAP directly targeted ELF3 and promoted its expression in an m6A-dependent manner. Exogenous-ELF3 overexpression evidently reversed shWTAP-suppressed fibroblast senescence. Furthermore, ELF3 induced IRF8-mediated senescence-associated secretory phenotype (SASP) by binding to the (-817 to -804) site of the IRF8 promoter directly. In vivo, overexpression of WTAP evidently increased senescence cells in skin and induced skin aging. In summary, these findings revealed the critical role of WTAP-mediated m6A modification in skin aging and identified ELF3 as an important target of m6A modification in HDFs senescence, providing a new idea for delaying the aging process.

Endoscopic resection for calcifying fibrous tumors of the gastrointestinal tract.

BACKGROUND: Calcifying fibrous tumors (CFTs) are rare mesenchymal lesions that can occur in various sites throughout the body, including the tubular gastrointestinal (GI) tract. AIM: To analyze the clinical findings of 36 patients with GI tract CFTs to provide guidance for diagnosis and treatment. METHODS: This retrospective study included 36 patients diagnosed with CFTs of the GI tract. We collected demographic and clinical information and conducted regular follow-ups to assess for local recurrence. RESULTS: The stomach was the most commonly involved site, accounting for 72.2% of the 36 CFTs. Endoscopic mucosal resection (n = 1, 2.8%), endoscopic submucosal dissection (n = 14, 38.9%), endoscopic full-thickness resection (n = 16, 44.4%), and submucosal tunneling endoscopic resection (n = 5, 13.9%) were used to resect calcifying fibrous tumors. Overall, 34 (94.4%) CFTs underwent complete endoscopic resections with a mean procedure time of 39.8 ± 29.8 min. The average maximum diameter of the tumors was 10.6 ± 4.3 cm. No complications, such as bleeding or perforation, occurred during an average hospital stay of 2.9 ± 1.2 d. In addition, two patients developed new growth of CFTs near the primary tumor sites, and none of the patients developed distant metastases during the follow-up period. CONCLUSION: GI tract CFTs are rare and typically benign tumors that can be effectively managed with endoscopic procedures.

Long-term outcomes of endoscopic resection for well-differentiated nonampullary duodenal neuroendocrine tumors.

BACKGROUND & AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare with limited evidence regarding endoscopic treatment. The study aimed to investigate the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluate long-term outcomes, including local recurrence and metastasis. METHODS: A total of 78 patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. The clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En bloc resection was achieved for 74 of the tumors (94.9%) and R0 resection was obtained in 68 of the tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥ 10 mm and muscularis propria invasion as risk factors for non-curative resection. Two patients with R1 resection (vertical margin involvement) and two patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including two cases of delayed bleeding and two cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in one patient with R1 resection 3 months after the original procedure. CONCLUSION: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.

The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study.

Background: Accumulating evidence shows that dysregulation of intestinal flora is associated with inflammatory skin diseases, specifically atopic dermatitis (AD), psoriasis (PSO), and rosacea (ROS). However, the causality is still unclear. Objectives: To study the underlying causality between gut microbiota (GM) and AD, PSO, and ROS, a bi-directional two-sample Mendelian randomization (2SMR) analysis was conducted. Methods: Summary statistics of gut microbiota, AD, PSO, and ROS were extracted from large-scale genome-wide association studies (GWASs). In 2SMR analysis, in addition to the inverse variance weighted as the principal method for evaluating causal association, four different methods were also used. Sensitivity analysis and reverse 2SMR study were implemented to evaluate the robustness of 2SMR results or reverse causal relationship, respectively. Results: A total of 24 specific gut microbiota species related to AD, PSO, and ROS were identified by 2SMR analysis. After using the Bonferroni method for multiple testing correction, family FamilyXIII (ID: 1957) [OR = 1.28 (1.13, 1.45), p = 9.26e-05] and genus Eubacteriumfissicatenagroup (ID: 14373) [OR = 1.20 (1.09, 1.33), p = 1.65e-04] were associated with an increased risk for AD and PSO, respectively. The genus Dialister showed a negative association, suggesting a protective role against both atopic dermatitis and rosacea. Our reverse 2SMR analysis indicated no reverse causality between these inflammatory skin diseases and the identified gut microbiota. Conclusions: In summary, this study provided evidence for the causality between GM and inflammatory skin diseases. These findings suggested that supplementing specific bacterial taxa may be an effective therapy for AD, PSO, and ROS.

Frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students.

AIM: To investigate the frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students. METHODS: Totally 158 student volunteers underwent routine vision examination in the optometry clinic of Guangxi Medical University. Their data were used to identify the different types of accommodation and non-strabismic binocular vision dysfunction and to determine their frequency. Correlation analysis and logistic regression were used to examine the factors associated with these abnormalities. RESULTS: The results showed that 36.71% of the subjects had accommodation and non-strabismic binocular vision issues, with 8.86% being attributed to accommodation dysfunction and 27.85% to binocular abnormalities. Convergence insufficiency (CI) was the most common abnormality, accounting for 13.29%. Those with these abnormalities experienced higher levels of eyestrain (χ2=69.518, P<0.001). The linear correlations were observed between the difference of binocular spherical equivalent (SE) and the index of horizontal esotropia at a distance (r=0.231, P=0.004) and the asthenopia survey scale (ASS) score (r=0.346, P<0.001). Furthermore, the right eye's SE was inversely correlated with the convergence of positive and negative fusion images at close range (r=-0.321, P<0.001), the convergence of negative fusion images at close range (r=-0.294, P<0.001), the vergence facility (VF; r=-0.234, P=0.003), and the set of negative fusion images at far range (r=-0.237, P=0.003). Logistic regression analysis indicated that gender, age, and the difference in right and binocular SE did not influence the emergence of these abnormalities. CONCLUSION: Binocular vision abnormalities are more prevalent than accommodation dysfunction, with CI being the most frequent type. Greater binocular refractive disparity leads to more severe eyestrain symptoms.

DNAzyme-based faithful probing and pulldown to identify candidate biomarkers of low abundance.

Biomarker discovery is essential for the understanding, diagnosis, targeted therapy and prognosis assessment of malignant diseases. However, it remains a huge challenge due to the lack of sensitive methods to identify disease-specific rare molecules. Here we present MORAC, molecular recognition based on affinity and catalysis, which enables the effective identification of candidate biomarkers with low abundance. MORAC relies on a class of DNAzymes, each cleaving a sole RNA linkage embedded in their DNA chain upon specifically sensing a complex system with no prior knowledge of the system's molecular content. We show that signal amplification from catalysis ensures the DNAzymes high sensitivity (for target probing); meanwhile, a simple RNA-to-DNA mutation can shut down their RNA cleavage ability and turn them into a pure affinity tool (for target pulldown). Using MORAC, we identify previously unknown, low-abundance candidate biomarkers with clear clinical value, including apolipoprotein L6 in breast cancer and seryl-tRNA synthetase 1 in polyps preceding colon cancer.

Validation and update of a clinical score model to predict technical difficulty of colorectal endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).

Feasibility and safety of endoscopic resection for the jejunoileal lesions.

BACKGROUND: Endoscopic resection (ER) for jejunoileal lesions (JILs) has been technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and safety of ER for JILs. METHOD: We retrospectively investigated 52 patients with JILs who underwent ER from January 2012 to February 2022. We collected and analyzed clinicopathological characteristics, procedure-related parameters, outcomes, and follow-up data. RESULTS: The mean age was 49.4 years. Of the 52 JILs, 33 ileal tumors within 20 cm from the ileocecal valve were resected with colonoscopy, while 19 tumors in the jejunum or the ileum over 20 cm from the ileocecal valve received enteroscopy resection. The mean procedure duration was 49.0 min. The en bloc resection and en bloc with R0 resection rates were 86.5% and 84.6%, respectively. Adverse events (AEs) included one (1.9%) major AE (delayed bleeding) and five (9.6%) minor AEs. During a median follow-up of 36.5 months, two patients had local recurrence (3.8%), while none had metastases. The 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 92.9% and 94.1%, respectively. Compared with the enteroscopy group, overall AEs were significantly lower in the colonoscopy group (P < 0.05), but no statistical differences were observed in RFS (P = 0.412) and DSS (P = 0.579). There were no significant differences in AEs, RFS, and DSS between the endoscopic submucosal dissection (ESD) and the endoscopic mucosal resection (EMR) group. CONCLUSIONS: ER of JILs has favorable short-term and long-term outcomes. Both ESD and EMR can safely and effectively resect JILs in appropriately selected cases.

Effect of tree height and spraying methods on Diaphorina citri kuwayama endosymbionts in the context of Huanglongbing disease management in citrus orchards.

BACKGROUND: Huanglongbing (HLB) (caused by Candidatus Liberibacter asiaticus) is the most damaging disease of citrus around the world. This study investigated the effects of citrus tree height on Diaphorina citri Kuwayama mortality, endosymbiont responses, and HLB distribution. RESULTS: The results reveal that the age of citrus trees plays a significant role in psyllid mortality. Interestingly, the cumulative mean mortality (%) of psyllids over the seven-day observation period was higher (31.50±0.03) when four-year-old (501A1, 502A2, 501A3) citrus trees were sprayed with a US-SMART mechanical sprayer. In contrast, the psyllids mortality was 0.09±0.23 for the 13-year-old citrus trees (104A2, 104A3, 104C1) sprayed with a US-SMART mechanical sprayer and 9.10±0.05 for 13-year-old (502A2, 502B2, 502D1) citrus trees sprayed with a fixed US-SMART mechanical sprayer. Our findings also revealed that psyllids from both four- and 13-year-old citrus trees carried Candidatus Carsonella ruddii species and Wolbachia, the primary and secondary endosymbionts, respectively. Surprisingly, infection rates of these endosymbionts remained consistent across different age groups, as confirmed by quantitative polymerase chain reaction analysis. Furthermore, our study highlights the significance of tree height as a proxy for tree age in influencing HLB occurrence. Specifically, four-year-old citrus trees subjected to the US-SMART mechanical sprayer for citrus psyllid control demonstrated effective disease management compared to 13-year-old (104A2, 104A3, 104C1) citrus trees sprayed with US-SMART mechanical sprayers. Additionally, the investigation explored the impact of tree height on HLB distribution. In four-year-old trees, no significant correlation between HLB disease and tree height was observed, potentially due to effective spray coverage with US-SMART mechanical sprayer. However, in 13-year-old (104A2, 104A3, 104C1) citrus tree sprayed with US-SMART mechanical sprayer, a positive correlation between tree height and HLB disease was evident. CONCLUSION: This research provides valuable insights into the complex interaction between citrus tree age, psyllid endosymbionts responses, and HLB distribution. These results emphasize effective HLB management strategies, especially in orchards with diverse tree age populations, ultimately contributing to the long-term sustainability of citrus cultivation. © 2023 Society of Chemical Industry.

Impact of Molecular Status on Cytoreductive Surgery for Peritoneal Metastases from Colorectal Cancer.

Colorectal cancer peritoneal metastases (CRC-PM) are present in 5 to 15% of instances of CRC, and the overall survival (OS) of patients with CRC-PM is much lower than that of patients with other isolated metastatic locations. In recent years, the introduction of cytoreductive surgery (CRS) in conjunction with hyperthermic intraperitoneal chemotherapy has resulted in a significant improvement in CRC-PM patients' OS. Despite this, a significant proportion of CRS patients continue to suffer complications of grades III to V or even die during the perioperative period. Early diagnosis, optimization of patient selection criteria, and refining of individualized combination therapy are necessary for these patients. In this review, we evaluate studies examining the relationship between molecular status and CRS in CRC-PM. Our objective is to gain a comprehensive understanding of how the altered molecular status of CRC-PM impacts CRS, which could increase the likelihood of tailored therapy in the future.

Management of delayed bleeding of upper gastrointestinal endoscopic submucosal tunneling procedures: a retrospective single-center analysis and brief meta-analysis.

OBJECTIVES: Delayed bleeding is a rare but important major adverse event (mAE) after endoscopic submucosal tunneling procedures (ESTP), which is scarcely reported. We aimed to characterize the clinical characteristics of delayed bleeding and provide better management of this mAE. METHOD: From August 2010 to October 2022, we reviewed 3852 patients with achalasia receiving peroral endoscopic myotomy (POEM) and 1937 patients with upper gastrointestinal tumors receiving submucosal tunneling endoscopic resection (STER). Among these, records of 22 patients (15 POEM, 7 STER) with delayed bleeding were collected. Clinical characteristics, treatment, and outcomes of delayed bleeding were analyzed. RESULTS: The mean age was 43.6 years. Ten patients (45.5%) were intratunnel bleeding, seven (31.8%) were intratunnel bleeding accompanied by mucosal bleeding, and five (22.7%) were mucosal bleeding. The most common accompanied symptoms were hematemesis, fever, and melena. The most common accompanied mAEs were fistula, pulmonary inflammation, and pleural effusion with atelectasis. The mean duration from ESTP to endoscopic intervention was 5.3 ± 4.9 days. Active bleeding was identified in 21 patients (95.5%). The bleeding was successfully controlled by electrocoagulation (19 cases), endoscopic clipping (six cases), and Sengstaken-Blakemore tube insertion (three cases), and no patient required surgical intervention. The mean hemostatic procedure duration was 61.8 ± 45.8 min. The mean post-bleeding hospital stay was 10.0 ± 6.2 days. A brief meta-analysis of previous studies showed the pooled estimate delayed bleeding rate after POEM, STER, and G-POEM was 0.4%. CONCLUSIONS: Delayed bleeding is uncommon and could be effectively managed by timely emergency endoscopic procedures without requiring subsequent surgical interventions.