Discovery of ciliary G protein-coupled receptors regulating pancreatic islet insulin and glucagon secretion.

Multiple G protein-coupled receptors (GPCRs) are expressed in pancreatic islet cells, but the majority have unknown functions. We observed specific GPCRs localized to primary cilia, a prominent signaling organelle, in pancreatic α and ß cells. Loss of cilia disrupts ß-cell endocrine function, but the molecular drivers are unknown. Using functional expression, we identified multiple GPCRs localized to cilia in mouse and human islet α and ß cells, including FFAR4, PTGER4, ADRB2, KISS1R, and P2RY14. Free fatty acid receptor 4 (FFAR4) and prostaglandin E receptor 4 (PTGER4) agonists stimulate ciliary cAMP signaling and promote glucagon and insulin secretion by α- and ß-cell lines and by mouse and human islets. Transport of GPCRs to primary cilia requires TULP3, whose knockdown in primary human and mouse islets relocalized ciliary FFAR4 and PTGER4 and impaired regulated glucagon or insulin secretion, without affecting ciliary structure. Our findings provide index evidence that regulated hormone secretion by islet α and ß cells is controlled by ciliary GPCRs providing new targets for diabetes.

Increased Attenuation of Intestinal Contents at CT Indicates Bowel Necrosis in Closed-Loop Small Bowel Obstruction.

Background Preoperative recognition of irreversible bowel necrosis is important, as it provides valuable guidance for surgical strategy selection but also may inform perioperative risk assessment and communication. Few studies have focused on the association between CT signs and bowel necrosis. Purpose To assess the diagnostic accuracy of CT signs to predict bowel necrosis in patients with closed-loop small bowel obstruction (CL-SBO). Materials and Methods This retrospective single-center study included patients who were surgically confirmed to have CL-SBO caused by adhesion or internal hernia between January 2016 and May 2022. Necrosis was determined based on surgical exploration and postoperative pathologic examination. Two radiologists independently reviewed CT signs by both subjective visual assessment and objective measurement. Disagreements were resolved in consensus with a third gastrointestinal radiologist. Univariable and multivariable analyses were used to assess the association between CT signs and bowel necrosis, and Cohen κ was used to assess interobserver agreement. Sensitivity and specificity were calculated for each CT sign. Results This study included 145 patients: 61 (42.1%) in the necrotic group (median age, 62 years [IQR, 51-71.5 years]; 37 [60.7%] women) and 84 (57.9%) in the nonnecrotic group (median age, 61.5 years [IQR, 51-68.8 years]; 51 [60.7%] women). Univariable analysis and multivariable analysis showed that increased attenuation of intestinal contents and increased attenuation of intestinal wall were independent predictors for bowel necrosis (odds ratio = 45.3 and 15.1; P = .001 and P < .001, respectively). Increased attenuation of intestinal contents and increased attenuation of intestinal wall had similar sensitivity (64% and 67%, respectively) and specificity (99% and 92%, respectively) for predicting bowel necrosis. However, interobserver agreement was better for assessing the contents than the wall (κ = 0.84 and 0.59, respectively). Conclusion Increased attenuation of intestinal contents was a highly specific CT sign with good reproducibility to predict bowel necrosis in CL-SBO. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Taourel and Zins in this issue.

Cascade Reactions of Alkynyl Ketones and Amides to Generate Unsaturated Oxacycles and Aromatic Carbocycles.

We describe novel amine-mediated transformation of alkynyl ketones and amides to generate 2-methylene-2H-pyrans, substituted 3-hydroxy-9H-fluoren-9-ones, and amine-incorporated arenes. These cascade processes are initiated by conjugate addition of secondary amine followed by hydrolysis of the enamine/vinylogous amide intermediates. The product distribution is highly sensitive to the steric and electronic effects of the substituents on both the alkyne moieties, the tether structure connecting them, and the nature of the amine. Alkynyl amide participates in the Alder-ene reaction favorably to generate more reactive allene amide that reacts with amine to generate amine-incorporated arene products. These metal-free cascade reactions are a useful synthetic method that can be exploited for the construction of various hetero- and carbocyclic systems.

[Research Progress on End-Tidal Carbon Dioxide Detection Technology Based on Non-Dispersive Infrared Method].

The concentration of end-tidal carbon dioxide is one of the important indicators for evaluating whether the human respiratory system is normal. Accurately detecting of end-tidal carbon dioxide is of great significance in clinical practice. With the continuous promotion of the localization of end-tidal carbon dioxide monitoring technology, its application in clinical practice in China has become increasingly widespread in recent years. The study is based on the non-dispersive infrared method and comprehensively elaborates on the detection principle, gas sampling methods, key technologies, and technological progress of end-tidal carbon dioxide detection technology. It comprehensively introduces the current development status of this technology and provides reference for application promotion and further improvement.

[Wireless Pulse Wave Monitoring System Based on Reflective Flexible Probe and AFE4490].

Pulse rate and blood oxygen levels are crucial physiological parameters that reflect physiological and pathological information within the human body. The system designs a wireless pulse wave monitoring system utilizing a flexible reflective probe and the AFE4490, which is capable of monitoring pulse wave and blood oxygen levels on the human forehead. The system is predominantly based on a reflective flexible probe, the AFE4490, a power supply module, a control microcontroller unit (MCU), and a Wi-Fi module. Post-processing by a slave computer, the collected pulse wave data is wirelessly transmitted to a smartphone. The real-time pulse waveform, pulse rate, and blood oxygen levels are displayed on an application. Following relevant tests and verifications, the system can accurately detect pulse wave signals, meet the requirements for wearable technology, and possesses significant market application potential.

Correlation between Apolipoprotein A1 and the Occurrence and Prognosis of Cardiovascular Events in Peritoneal Dialysis Patients.

BACKGROUND: This study investigates the value of apolipoprotein A1 in assessing the occurrence and prognosis of cardiovascular events in peritoneal dialysis patients. METHODS: A retrospective analysis was conducted based on the clinical information of 80 end-stage renal disease patients who underwent peritoneal dialysis at Zhuji People's Hospital Zhejiang Province from January 2015 to December 2016. Based on the median value of apolipoprotein A1, patients were evenly distributed as either High Apolipoprotein A1 Group (H-ApoA1, > 1.145g/L, n = 40) or Low Apolipoprotein A1 Group (L-ApoA1, < 1.145g/L, n = 40). RESULTS: When compared with the H-ApoA1 group, the L-ApoA1 group patients were observed to have higher BMI, total Kt/V, hemoglobin, AKP, glycated hemoglobin, HOMA-IR, HDL levels, while simultaneously having lower total Ccr, triglycerides, total cholesterol, LDL, CRP levels (p < 0.05). Further analysis found that the all-cause mortality rate, cardiovascular death rate, and cardiovascular event rates were significantly higher in L-ApoA1 group patients than the H-ApoA1 group (p < 0.05); no statistical significance was found for mortality rates due to infection, abandon treatment, tumor, failure, gastrointestinal bleeding or undetermined reasons between the two groups (p > 0.05). In addition, the median all-cause mortality and median occurrence of cardiovascular events of L-ApoA1 group patients were observed to be shorter than the H-ApoA1 group (p < 0.05), and apolipoprotein A1 is a risk factor for all-cause mortality rate and cardiovascular occurrence end-point events (p < 0.05). CONCLUSIONS: Peritoneal dialysis patients with a reduced level of apolipoprotein A1 have a poorer prognosis and more severe cardiovascular events.

Single-Nucleus and In Situ RNA-Sequencing Reveal Cell Topographies in the Human Pancreas.

BACKGROUND & AIMS: Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been yet established because of the local concentration and cascade of hydrolytic enzymes that can rapidly degrade cells and RNA upon pancreatic resection. We sought to better understand the heterogeneity and cellular composition of the pancreas in neonates and adults in healthy and diseased conditions using single-cell sequencing approaches. METHODS: We innovated single-nucleus RNA-sequencing protocols and profiled more than 120,000 cells from pancreata of adult and neonatal human donors. We validated the single-nucleus findings using RNA fluorescence in situ hybridization, in situ sequencing, and computational approaches. RESULTS: We created the first comprehensive atlas of human pancreas cells including epithelial and nonepithelial constituents, and uncovered 3 distinct acinar cell types, with possible implications for homeostatic and inflammatory processes of the pancreas. The comparison with neonatal single-nucleus sequencing data showed a different cellular composition of the endocrine tissue, highlighting the tissue dynamics occurring during development. By applying spatial cartography, involving cell proximity mapping through in situ sequencing, we found evidence of specific cell type neighborhoods, dynamic topographies in the endocrine and exocrine pancreas, and principles of morphologic organization of the organ. Furthermore, similar analyses in chronic pancreatitis biopsy samples showed the presence of acinar-REG+ cells, a reciprocal association between macrophages and activated stellate cells, and a new potential role of tuft cells in this disease. CONCLUSIONS: Our human pancreas cell atlas can be interrogated to understand pancreatic cell biology and provides a crucial reference set for comparisons with diseased tissue samples to map the cellular foundations of pancreatic diseases.

Application of Magnetic Resonance Imaging in Neoadjuvant Treatment of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors of the human digestive system. Due to its insidious onset, many patients have already lost the opportunity for radical resection upon tumor diagnosis. In recent years, neoadjuvant treatment for patients with borderline resectable PDAC has been recommended by multiple guidelines to increase the resection rate of radical surgery and improve the postoperative survival. However, further developments are required to accurately assess the tumor response to neoadjuvant therapy and to select the population suitable for such treatment. Reductions in drug toxicity and the number of neoadjuvant cycles are also critical. At present, the clinical evaluation of neoadjuvant treatment is mainly based on several serological and imaging indicators; however, the unique characteristics of PDAC and the insufficient sensitivity and specificity of the markers render this system ineffective. The imaging evaluation system, magnetic resonance imaging (MRI), has its own unique imaging advantages compared with computed tomography (CT) and other imaging examinations. One key advantage is the ability to reflect the changes more rapidly in tumor tissue components, such as the degree of fibrosis, microvessel density, and tissue hypoxia. It can also perform multiparameter quantitative analysis of tumor tissue and changes, attributing to its increasingly important role in imaging evaluation, and potentially the evaluation of neoadjuvant treatment of pancreatic cancer, as several current articles have studied. At the same time, owing to the complexity of MRI and some of its limitations, its wider application is limited. Compared with CT imaging, few relevant studies have been conducted. In this review article, we will investigate and summarize the advantages, limitations, and future development of MRI in the evaluation of neoadjuvant treatment of PDAC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Shark mouth pancreaticojejunostomy reduced the rate of clinically related pancreatic fistula: a historic cohort comparative analysis.

BACKGROUND: A novel procedure called shark mouth pancreaticojejunostomy (SMP) was developed, for the reconstruction of the pancreatic stump which has a theoretical advantage for anastomosis healing and wide applicability. METHODS: A comparative study of the patients who underwent SMP (SMP cohort) and those who underwent end-to-end dunking pancreaticojejunostomy (historic cohort) at Peking University Third Hospital was conducted. Each group was analyzed for the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) and morbidities. RESULTS: The clinicopathological data of 151 patients from the SMP cohort and 82 patients from the historic cohort were analyzed. In the SMP group, the rate of CR-POPF was 7.3% (11/151), which was significantly lower than the rate of CR-POPF in the historic group as 19.5% (16/82) (P = 0.005). The primary results were unaffected by sensitivity analyses based on several risk factors for CR-POPF. The rates of morbidities besides CR-POPF were 15.9% (24/151) in the SMP group and 17.1% (14/82) in the historic cohort (P = 0.194). The principal results were not changed by the propensity score matched (PSM) analysis. CONCLUSION: SMP is a safe and simple surgical procedure for the reconstruction of the pancreatic stump compared with end-to-end dunking pancreticojejunostomy.

KLHDC7B-DT aggravates pancreatic ductal adenocarcinoma development via inducing cross-talk between cancer cells and macrophages.

Tumor microenvironment (TME) exerts key roles in pancreatic ductal adenocarcinoma (PDAC) development. However, the factors regulating the cross-talk between PDAC cells and TME are largely unknown. In the present study, we identified a long noncoding RNA (lncRNA) KLHDC7B divergent transcript (KLHDC7B-DT), which was up-regulated in PDAC and correlated with poor survival of PDAC patients. Functional assays demonstrated that KLHDC7B-DT enhanced PDAC cell proliferation, migration, and invasion. Mechanistically, KLHDC7B-DT was found to directly bind IL-6 promoter, induce open chromatin structure at IL-6 promoter region, activate IL-6 transcription, and up-regulate IL-6 expression and secretion. The expression of KLHDC7B-DT was positively correlated with IL-6 in PDAC tissues. Via inducing IL-6 secretion, KLHDC7B-DT activated STAT3 signaling in PDAC cells in an autocrine manner. Furthermore, KLHDC7B-DT also activated STAT3 signaling in macrophages in a paracrine manner, which induced macrophage M2 polarization. KLHDC7B-DT overexpressed PDAC cells-primed macrophages promoted PDAC cell proliferation, migration, and invasion. Blocking IL-6/STAT3 signaling reversed the effects of KLHDC7B-DT on macrophage M2 polarization and PDAC cell proliferation, migration, and invasion. In conclusion, KLHDC7B-DT enhanced malignant behaviors of PDAC cells via IL-6-induced macrophage M2 polarization and IL-6-activated STAT3 signaling in PDAC cells. The cross-talk between PDAC cells and macrophages induced by KLHDC7B-DT represents potential therapeutic target for PDAC.

Nomogram and competing risk model to predict recurrence after curative surgical resection of PDAC.

BACKGROUND: Surgical resection remains the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, a number of patients get disease recurred in a short time post-operation. Few studies have focused on the predictors of different recurrence patterns of PDAC. OBJECTIVE: To try to establish and verify a nomogram to predict recurrence free survival (RFS) in PDAC patients, and to distinguish the risk factors of local recurrence first and distant metastasis first via competing risk model. METHODS: Patients who underwent radical pancreatectomy for PDAC in our center from 2010 to 2018 were reviewed retrospectively. Kaplan-Meier methods and multivariate Cox regression analyses were used to identify the clinicopathological predictors of recurrence post-operation. And then, a nomogram was constructed and validated. Competing risk regression model was used to compare the predictors between local recurrence group and distant metastasis group. RESULTS: A total of 200 patients were included into the final analysis, and 153 patients got disease relapsed post-operation. CA19-9 level, vascular resection, tumor differentiation, lymph node ratio (LNR) and adjuvant chemotherapy were identified as independent risk factors for recurrence free survival (RFS) and incorporated into the nomogram. The C-index of the nomogram was 0.650. Competing risk model indicated that the status of lymph-node metastasis was significantly associated the patterns of first relapse. CONCLUSIONS: Nomogram and competing risk model were constructed to quantify the risk of recurrence following surgery for PDAC. Our findings may be useful for predicting RFS and recurrence pattern in clinical work.

Does Prior Cancer Have an Influence on the Survival Outcomes of Patients with Localized Pancreatic Neuroendocrine Tumors?

Objective To investigate the impact of prior non-pancreatic cancer on the survival outcomes of patients with localized pancreatic neuroendocrine tumors (PanNETs). Methods We reviewed the Surveillance, Epidemiology, and End Results database and selected patients with localized PanNETs diagnosed between 1973 and 2015. We divided the patients into two groups according to the presence or absence of prior non-pancreatic malignancy. Before and after propensity score matching, we compared the clinicopathological characteristics and studied the overall survival and cancer-specific survival. Results A total of 357 (12.9%) of 2778 patients with localized PanNETs had prior cancer. A total of 1211 cases with only a localized PanNET and 133 cases with a localized PanNET and prior cancer had complete data and met the inclusion criteria of the current study. Patients with prior cancer were associated with advanced age (>65 years, 57.9% prior cancer vs. 31.0% no prior cancer, P<0.001), later year of diagnosis (87.2% vs. 80.2%, P=0.049), a higher proportion of poorly differentiated/undifferentiated grade tumors (4.5% vs. 1.5%, P=0.025), and a higher proportion of no primary site surgery (19.5% vs. 10.4%, P=0.003). Prostate (29.32%), breast (18.05%), other genitourinary and retroperitoneal (16.54%), and gastrointestinal (12.78%) cancers were the most common prior cancer types. Most of the prior cancers (95.49%) were localized and regional, and only 4.51% of the prior cancers were distant. Patients with interval periods between the prior cancer and PanNET of ≤36 months, 36-60 months, 60-120 months, and >120 months accounted for 33.08%, 13.53%, 24.06%, and 29.32% of all cases with prior cancers, respectively. Univariate and multivariate Cox proportional hazards analyses were performed. The presence/absence of prior cancers did not impact survival outcomes of patients with localized PanNETs before and after propensity score matching (PSM). Further subgroups analysis showed that, patients with localized PanNETs and prior distant cancer had worse cancer-specific survival than patients with prior local/regional cancer or patients without prior cancer (P<0.001). No significant differences in cancer-specific survival were observed in terms of the different sites of the prior cancers and the different interval periods of prior cancers and PanNETs (P<0.05). Conclusions Patients with localized PanNETs and a history of prior cancer had survival outcomes that were comparable to those of patients with no history of prior cancer. Patients with localized PanNETs and prior cancer could be candidates for clinical trials if they satisfy all other conditions; aggressive and potentially curative therapies should be offered to these patients.

[Active components and mechanism of Taohong Siwu Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking technology].

This paper aimed to investigate the active components and mechanism of Taohong Siwu Decoction in the treatment of primary dysmenorrhea(PD) based on network pharmacology and molecular docking technology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to search the chemical compositions and targets of six herbs in Taohong Siwu Decoction. The targets for PD treatment were selected through the databases of DrugBank, OMIM, TTD and CTD, and gene annotation of the targets was conducted with UniProt database. Cytoscape 3.7.2 was then used to construct the drug-compound-target network. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Taohong Siwu Decoction in the treatment of PD were selected according to the topological parameters. David database was used for GO enrichment analysis and KOBAS 3.0 was used for KEGG enrichment analysis. The molecular docking technology was used to connect the components with higher medium values in the network with core targets. The results showed that the network contained 36 compounds such as quercetin, kaempferol, luteolin, myricanone and ferulic acid, and 99 targets such as PTGS2, PTGS2, PGR and PPARG. Totally 102 GO terms were obtained by GO functional enrichment analysis(P<0.01), and 228 signal pathways were obtained by KEGG pathway enrichment(P<0.05), mainly involving inflammatory factors, hormone regulation, central analgesia, amino acid metabolism and spasmolysis. The results of molecular docking showed that the main active components can spontaneously bind to the targets. This study preliminarily revealed the mechanism of Taohong Siwu Decoction for treatment of primary dysmenorrheal through multi-components, multi-targets and multi-pathways, providing theoretical references for further researches on mechanism of Taohong Siwu Decoction.

Spinal cord injury effectively ameliorated by neuroprotective effects of rosmarinic acid.

OBJECTIVE: Pathophysiology of spinal cord injury (SCI) causes primary and secondary effects leading to loss of neuronal function. The aim of the present study was to investigate the role of rosmarinic acid (RA) in protection against SCI. METHODS: The experimental study was carried out in male wistar rats categorized into three groups. Group I - sham operated rats; Group II - SCI; Group III - SCI followed by RA treatment (10 mg/kg). The spinal tissues after treatment schedule were analyzed for oxidative stress status through determination of reactive oxygen species (ROS), lipid peroxidation, protein damage (carbonyl and sulfhydryl contents), and antioxidant enzyme activities. The expression of oxidative stress factors NF-κB and Nrf-2 was determined by Western blot analysis. Further pro-inflammatory cytokines (TNF-α, IL-6, MCP-1, and IL-1ß) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results show that treatment with RA significantly enhances the antioxidant status and decrease the oxidative stress in wistar rats post-SCI. RA effectively ameliorated inflammatory mechanisms by downregulation of NF-κB and pro-inflammatory cytokines post-SCI. CONCLUSION: The study demonstrates for the first time on the role of RA in protecting the spinal cord from injury and demonstrates its neuroprotection in wistar rats.

[Clinical analyses of fungal pleurisy: a report of 4 cases].

OBJECTIVE: To explore the clinical features of fungal pleurisy. METHODS: Four cases of fungal pleurisy diagnosed by medical thoracoscopy at Beijing Chaoyang Hospital from April 2005 to December 2012 were retrospectively studied. RESULTS: There were 3 males and 1 female with an age range of 43-73 years. The time from initial onset to definite diagnosis was 17 days to 4 months. Among them, two were previously healthy while another two had underlying diseases. The diagnoses were mucor pleuritis (n = 1) and aspergillus (n = 3). There was one case of empyema. One case was diagnosed as non-Hodgkin lymphoma two years ago and had pleural metastasis during hospitalization. And another one suffered concurrently from diabetes mellitus and hypoproteinemia. The primary clinical manifestations included fever (n = 2), cough and sputum (n = 3), breathlessness (n = 4) and weight loss (n = 2). The major chest computed tomography (CT) scan revealed pleural effusion with thickening. All cases had an elevated plasma level of C-reactive protein (CRP). The characteristics of pleural effusion were empyema (n = 1) and exudates (n = 3). Pleural fluid smear and culture tests for bacteria and fungi were negative, so were pleural fluid smear tests for mycobacteria. All cases were confirmed through histopathological examination of pleural biopsies and cured after systemic antifungal therapy and pleural irrigation. CONCLUSIONS: Fungal pleurisy is infrequent. Early thoracoscopy is vital because of a low positive yield of microbiologic testing of pleural fluid specimens. Systemic antifungal therapy and pleural irrigation improve the prognosis.

[Molecular typing of 12 Brucella strains isolated in Guizhou province in 2010-2013].

OBJECTIVE: To identify and characterize the Brucella strains from Guizhou province in 2010-2013. METHODS: A total of 12 strains of Brucella suspicious bacteria were isolated in Guizhou province from 2010 to 2013. Four strains (GZLL3, GZLL4, GZLL11 and SH2) were isolated from goat blood samples and eight strains (SH4, GZZY, GZSQ, GZZA, BR13001, BR13004, BR13005 and BR13006) were isolated from blood samples of patient 12 Brucella suspicious strains were identified and characterized using conventional methods. Brucella genus specific gene BCSP31-based PCR (BCSP31-PCR) was used to identify the genus of Brucella and IS711 insert sequence-based PCR (AMOS-PCR) was applied to identify the species of Brucella strains. Goats and patients originated Brucella strains were comparatively analysed using Pulse-field Gel Electrophoresis (PFGE). RESULTS: Both of conventional methods and PCR identified the 12 Brucella suspicious strains as B. melitensis biotype 3. BCSP31-PCR identification results showed that a specific DNA bands (223 bp) were detected in all the 12 strains and positive control samples with no DNA band in negative samples. AMOS-PCR amplified a 731 bp-DNA bands in all the 12 strains, with 731 bp, 498 bp and 275 bp in M5, S2 and A19 strains, respectively, and no DNA band was detected in the negative control samples. PFGE analysis showed that 12 Brucella isolates from patients and goats showed consistent PFGE patterns with the digestion of restriction enzyme Xba I. CONCLUSION: The epidemic species/type of Brucella in both human and animal in Guizhou province was B. melitensis biotype 3 and goat was the main animal source of infection of brucellosis in Guizhou province.

Stromal KITL/SCF promotes pancreas tissue homeostasis and restrains tumor progression.

Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and non-immune stromal elements enable loss of homeostasis during tumor evolution. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown. Here we show that healthy pancreatic mesenchyme expresses the paracrine signaling molecule KITL, also known as stem cell factor, and identify loss of stromal KITL during tumorigenesis as tumor-promoting. Genetic inhibition of mesenchymal KITL in the contexts of homeostasis, injury, and cancer together indicate a role for KITL signaling in maintenance of pancreas tissue architecture, such that loss of the stromal KITL pool increased tumor growth and reduced survival of tumor-bearing mice. Together, these findings implicate loss of mesenchymal KITL as a mechanism for establishing a tumor-permissive microenvironment.

RFX6 Maintains Gene Expression and Function of Adult Human Islet α-Cells.

Mutations in the gene encoding the transcription factor regulatory factor X-box binding 6 (RFX6) are associated with human diabetes. Within pancreatic islets, RFX6 expression is most abundant in islet α-cells, and α-cell RFX6 expression is altered in diabetes. However, the roles of RFX6 in regulating gene expression, glucagon output, and other crucial human adult α-cell functions are not yet understood. We developed a method for selective genetic targeting of human α-cells and assessed RFX6-dependent α-cell function. RFX6 suppression with RNA interference led to impaired α-cell exocytosis and dysregulated glucagon secretion in vitro and in vivo. By contrast, these phenotypes were not observed with RFX6 suppression across all islet cells. Transcriptomics in α-cells revealed RFX6-dependent expression of genes governing nutrient sensing, hormone processing, and secretion, with some of these exclusively expressed in human α-cells. Mapping of RFX6 DNA-binding sites in primary human islet cells identified a subset of direct RFX6 target genes. Together, these data unveil RFX6-dependent genetic targets and mechanisms crucial for regulating adult human α-cell function.

Prediction of bowel necrosis by reduced bowel wall enhancement in closed-loop small bowel obstruction: Quantitative methods.

PURPOSE: To assess diagnostic performance and reproducibility of reduced bowel wall enhancement evaluated by quantitative methods using CT to identify bowel necrosis among closed-loop small bowel obstruction (CL-SBO) patients. METHODS: This retrospective single-center study included patients who diagnosed with CL-SBO caused by adhesion or internal hernia during January 2016 and May 2022. Patients were divided into necrotic group (n = 41) and non-necrotic group (n = 67) according to surgical exploration and postoperative pathology. Two doctors independently measured the attenuation of bowel wall and consensus was reached through panel discussion with a third gastrointestinal radiologist. Reduced bowel wall enhancement was assessed by four quantitative methods. Univariate analyses were used to evaluate the association between each method and bowel necrosis, and kappa/intraclass correlation coefficient values were used to assess interobserver agreement. Diagnostic performance parameters were calculated for each method. RESULTS: Reduced bowel wall enhancement in arterial phase (OR 8.98, P < 0.0001), reduced bowel wall enhancement in portal phase (OR 16.84, P < 0.001), adjusted reduced bowel wall enhancement in arterial phase (OR 29.48, P < 0.001), adjusted reduced bowel wall enhancement in portal phase (OR 145.69, P < 0.001) were significantly associated with bowel necrosis. Adjusted reduced bowel wall enhancement in portal phase had the best diagnostic performance (AUC: 0.92; Youden index: 0.84; specificity: 94.03 %) and interobserver agreement (kappa value of 0.59-0.73) to predict bowel necrosis. CONCLUSION: When assessing reduced bowel enhancement to predict bowel necrosis among CL-SBO patients, using unenhanced CT images and proximal dilated loop as standard references in portal phase is the most accurate quantitative method among those tested.