Early Identification of Sepsis-Induced Acute Kidney Injury by Using Monocyte Distribution Width, Red-Blood-Cell Distribution, and Neutrophil-to-Lymphocyte Ratio.

Sepsis-induced acute kidney injury (AKI) is a common complication in patients with severe illness and leads to increased risks of mortality and chronic kidney disease. We investigated the association between monocyte distribution width (MDW), red-blood-cell volume distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), sepsis-related organ-failure assessment (SOFA) score, mean arterial pressure (MAP), and other risk factors and sepsis-induced AKI in patients presenting to the emergency department (ED). This retrospective study, spanning 1 January 2020, to 30 November 2020, was conducted at a university-affiliated teaching hospital. Patients meeting the Sepsis-2 consensus criteria upon presentation to our ED were categorized into sepsis-induced AKI and non-AKI groups. Clinical parameters (i.e., initial SOFA score and MAP) and laboratory markers (i.e., MDW, RDW, and NLR) were measured upon ED admission. A logistic regression model was developed, with sepsis-induced AKI as the dependent variable and laboratory parameters as independent variables. Three multivariable logistic regression models were constructed. In Model 1, MDW, initial SOFA score, and MAP exhibited significant associations with sepsis-induced AKI (area under the curve [AUC]: 0.728, 95% confidence interval [CI]: 0.668-0.789). In Model 2, RDW, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.712, 95% CI: 0.651-0.774). In Model 3, NLR, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.719, 95% CI: 0.658-0.780). Our novel models, integrating MDW, RDW, and NLR with initial SOFA score and MAP, can assist with the identification of sepsis-induced AKI among patients with sepsis presenting to the ED.

Role of STAT3 in cancer cell epithelial­mesenchymal transition (Review).

Since its discovery, the role of the transcription factor, signal transducer and activator of transcription 3 (STAT3), in both normal physiology and the pathology of numerous diseases, including cancer, has been extensively studied. STAT3 is aberrantly activated in different types of cancer, fulfilling a critical role in cancer progression. The biological process, epithelial­mesenchymal transition (EMT), is indispensable for embryonic morphogenesis. During the development of cancer, EMT is hijacked to confer motility, tumor cell stemness, drug resistance and adaptation to changes in the microenvironment. The aim of the present review was to outline recent advances in knowledge of the role of STAT3 in EMT, which may contribute to the understanding of the function of STAT3 in EMT in various types of cancer. Delineating the underlying mechanisms associated with the STAT3­EMT signaling axis may generate novel diagnostic and therapeutic options for cancer treatment.

A nomogram for prediction of ERCP success in patients with bile duct leaks: a multicenter study.

BACKGROUND: Bile duct leaks (BDLs) are serious complications that occurs after hepatobiliary surgery and trauma, leading to rapid clinical deterioration. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for BDLs, but it is not clear which patients will respond to this therapy and which patients will require additional surgical intervention. The aim of our study was to explore the predictors of successful ERCP for BDLs. METHODS: A retrospective analysis was conducted using data from six centers' databases. All consecutive patients who were clinically confirmed as BDLs were included in the study. Collected data were demographics, disease severity, and ERCP procedure characteristics. Univariate and multivariate analysis were used to select independent predictive factors that affect the outcome of ERCP for BDLs, and a nomogram was established. Calibration and ROC curves were used to evaluate the models. RESULTS: Four hundred and forty-eight consecutive patients were clinically confirmed as BDLs and 347 were excluded. In the 101 patients included patients, clinical success was achieved in 78 patients (77.2%). In logistic multivariable regression, two independent factors were negatively associated with the success of ERCP: SIRS (OR, 0.183; 95% CI 0.039-0.864; P = 0.032) and high-grade leak (OR 0.073; 95% CI 0.010-0.539; P = 0.010). Two independent factors were positively associated with the success of ERCP: leak-bridging drainage (OR 4.792; 95% CI 1.08-21.21; P = 0.039) and cystic duct leak (OR 6.193; 95% CI 1.03-37.17; P = 0.046). The prediction model with these four factors was evaluated using a receiver-operating characteristic (ROC) curve, which demonstrated an area under the curve of 0.9351. The calibration curve showed that the model had good predictive accuracy. CONCLUSION: Leak-bridging drainage and cystic duct leak are positive predictors for the success of ERCP, while SIRS and high-grade leak are negative predictors. This prediction model with nomogram has good predictive ability and practical clinical value, and may be helpful in clinical decision-making and prognostication.

Fournier's gangrene due to rectal cancer: A case report.

Fournier's gangrene (FG) is an extremely rare necrotizing fasciitis that is insidious, rapidly spreading and life-threatening. FGs due to rectal cancer occur rarely and there is a lack of clinical reference. In the present study, a severe FG due to rectal cancer perforation was described and the features of this rare disease were summarized with a literature review. A 57-year-old man was admitted because of rectal cancer-induced FG. The patient was misdiagnosed with extensive perianal abscess until the intraoperative biopsy confirmed that rectal cancer was the culprit. Incision, debridement and drainage were carried out to reduce infectious burdens. After that, the patient was transferred to Peking University People's Hospital for the subsequent therapy. Empirical broad-spectrum antibiotic therapy was used at the initial stage. Diversional transverse loop colostomy was performed to control infection and resume oral feeding. After four rounds of vacuum-assisted closure (VAC) therapy, radical resection and wound closure were accomplished. The scrotal defect was repaired by a skin flap. Pathological results indicated a moderately differentiated adenocarcinoma with perforation. The patient was discharged from the hospital on postoperative day 15 without any post-operative complications. No signs of recurrence were observed during a 22-month follow-up. In the setting of rectal cancer-induced FGs, the liquid resuscitation, broad-spectrum antibiotic therapy, and prompt debridement are the cornerstones of the initial management. Diversional colostomy and VAC therapy were effective in the management of severe infection and large wounds. The present case report also provided a clinical reference for the implementation of staged surgeries and the perioperative multidisciplinary management of FGs.

The mediating and moderating effects of resilience on the relationship between sleep quality and psychological distress in Chinese women with infertility.

BACKGROUND: Research has widely indicated that the psychological distress experienced by infertile patients during fertility treatments may have a negative effect on the results of assisted reproduction. Although numerous studies have shown that psychological resilience and sleep quality are important influencing factors for psychological distress, the mediating mechanisms of psychological resilience in the relationship between sleep quality and psychological distress for Chinese women in particular remain unclear. Therefore, the current study investigates the association between sleep quality, resilience, and psychological distress in Chinese women with infertility and examines the mediating and moderating roles of resilience on the relationship between sleep quality and psychological distress. METHODS: In this cross-sectional study, a total of 595 women with infertility who were undergoing IVF-ET were recruited at the Reproductive Medicine, Shandong University, from April to November 2019. Participants were instructed to complete four questionnaires, including a questionnaire about socio-demographic and clinical-related information, the Pittsburgh Sleep Quality Index (PSQI), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and the Kessler-10 (K10). Pearson's correlation analysis was conducted preliminarily to describe the relationships between sleep quality, resilience, and psychological distress. A mediation model and a moderated model were constructed and analyzed using the PROCESS macro for SPSS. The Johnson-Neyman (J-N) technique was then used to identify the regions of significance across the levels of moderator values. RESULTS: Patients in the sample had a high prevalence of psychological distress (48.6%, K10 scores > 22), and mediation analysis indicated that resilience played a partially mediating role in the relationship between sleep quality and psychological distress (indict effect = 0.072, P < 0.001). Moderation analysis indicated that resilience also moderated the association between sleep quality and psychological distress. CONCLUSIONS: Resilience may play a key role in the relationship between sleep quality and psychological distress. Our findings imply that resilience training may therefore be an effective component of psychological distress intervention in women with infertility.

Potential crosstalk between SPP1 + TAMs and CD8 + exhausted T cells promotes an immunosuppressive environment in gastric metastatic cancer.

BACKGROUND: Immunotherapy brings new hope to patients with advanced gastric cancer. However, liver metastases can reduce the efficacy of immunotherapy in patients. Tumor-associated macrophages (TAMs) may be the cause of this reduction in efficacy. SPP1 + TAMs are considered to have immunosuppressive properties. We aimed to investigate the involvement of SPP1 + TAMs in the metastasis of gastric cancer. METHODS: The single-cell transcriptome was combined with batched BULK datasets for analysis. Animal models were used to verify the analysis results. RESULTS: We reveal the interaction of SPP1 + TAMs with CD8 + exhausted T cells in metastatic cancer. Among these interactions, GDF15-TGFBR2 may play a key immunosuppressive role. We constructed an LR score to quantify interactions based on ligands and receptors. The LR score is highly correlated with various immune features and clinical molecular subtypes. The LR score may also guide the prediction of the efficacy of immunotherapy and prognosis. CONCLUSIONS: The crosstalk between SPP1 + TAMs and CD8 + exhausted T cells plays a key immunosuppressive role in the gastric metastatic cancer microenvironment.

EUS-guided bridging technique for treatment of biliary-enteric anastomotic stenosis after pancreaticoduodenectomy.

Biliary-enteric anastomotic stenosis is one of the main long-term complications after pancreaticoduodenectomy, with an incidence of 2%-8%. Although the relevant reports and studies are relatively few, the consequences such as biliary obstruction and refractory cholangitis seriously affect the quality of life of patients. In this case, the patient is not willing to receive conventional surgery again. This paper provides a bridge technique of EUS-guided Biliary Drainage (EUS-BD) to treat biliary-enteric anastomotic stenosis and solve the problem of obstructive jaundice in the patient.

Stomatin-like protein 2 promotes cell proliferation and survival under 5-Fluorouracil stress in hepatocellular carcinoma.

BACKGROUND: The crucial role of STOML2 in tumor progression has been documented recently in various cancers. Previous studies have shown that STOML2 promoted cancer cell proliferation, but the underlying mechanism is not fully illustrated. METHODS AND RESULTS: The expression and clinical relevance of STOML2 in pan-cancer was analyzed by TIMER2 web platform in pan-cancer. The prognostic significance of STOML2 in HCC was evaluated utilizing KM curve and a nomogram model. Signaling pathways associated with STOML2 expression were discovered by GSEA. CCK-8 assay was performed to evaluate the proliferative capacity of HCC cells after manipulating STOML2 expression. Flow cytometry was utilized to analyze cell cycle progression. Results indicated that increased STOML2 expression in HCC linked to unfavorable clinical outcomes. Cell cycle and cell division related terms were enriched under conditions of elevated STOML2 expression via GSEA analysis. A notable decrease in cell proliferation was observed in MHCC97H with STOML2 knocked-down, accompanied by G1-phase arrest, up-regulation of p21, down-regulation of CyclinD1 and its regulatory factor MYC, while STOML2 overexpression in Huh7 showed the opposite results. These results indicated that STOML2 was responsible for HCC proliferation by regulating the expression level of MYC/cyclin D1 and p21. Furthermore, an inverse correlation was found between STOML2 expression and 5-FU sensitivity. CONCLUSIONS: STOML2 promotes cell cycle progression in HCC which is associated with activation of MYC/CyclinD1/p21 pathway, and modulates the response of HCC to 5-FU.

Transduodenal accessory papillary Rendezvous technique assisted ERCP in the treatment of severe pancreatic duct stenosis caused by chronic pancreatitis in children.

Chronic pancreatitis in children is an irreversible inflammatory disease, which can cause intractable abdominal pain and abnormal internal and external secretion function of the pancreas, seriously affecting the growth and development of children and the quality of life. ERCP has become the first choice because of its good effect and less trauma. However, the severe stenosis of pancreatic duct caused by chronic pancreatitis may make ERCP more difficult. Here we used the rendezvous technique to assist ERCP to complete the treatment of severe pancreatic duct stenosis and abdominal pain.

ABHD6 suppresses colorectal cancer progression via AKT signaling pathway.

Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.

A whole new challenge: EUS-guided transhepatic antegrade stone removal (TASR) for the treatment of multiple choledocholithiasis after total gastrectomy.

EUS-TASR is a derivative of EUS-BD and serves as a remedy when ERCP fails. EUS-BD technology is commonly used in the diagnosis and treatment of biliary tract and pancreatic diseases with anatomical changes of the digestive tract. This article provides an experience of EUS-TASR and a new challenge in the treatment of common bile duct stones after total gastrectomy.

Functional identification of the calcineurin B-like protein PavCBL4 in modulating salt tolerance in sweet cherry.

Abiotic stresses, such as high salinity, pose a significant threat to plant growth and development, reducing crop yield and quality. Calcineurin B-like (CBL) proteins serve as crucial calcium sensors in plant responses to diverse environmental stresses. However, the CBL family in sweet cherry has not been identified at the genome-wide level, and the regulatory role of CBL proteins in cherry plants' salt response is unclear. Here, we identified 10 CBL family genes (PavCBLs) from the Prunus avium genome and cloned seven of them. We comprehensively analyzed PavCBL genes for collinearity, phylogenetic relationships, gene structure, and conserved motifs. Expression analysis revealed significant induction of transcription under abiotic stress, with PavCBL4 displaying the most substantial expression change. Additionally, we identified PavCBL4 as a PavSOS2 (Salt Overly Sensitive 2)-interacting protein through Y2H and Split-LUC assays. Subcellular localization analysis indicated that PavCBL4 is present in both the cytoplasm and nucleus. Functional assessment of PavCBL4 in the PavCBL4-overexpressing transgenic 'Gisela 6' plants showed its positive role in enhancing salt tolerance in cherry plants. Measurements of Na+ content and antioxidant enzyme activity under salt stress indicated that PavCBL4 functions positively by inhibiting Na+ accumulation and promoting ROS scavenging in response to salt stress. These findings lay the groundwork for a deeper understanding of the molecular mechanisms underlying PavCBL-mediated salt tolerance in sweet cherry.

The combination of EyeMax direct visualization system, EUS and ERCP for the precise treatment of intraductal papillary mucinous neoplasm / La combinación de EyeMax sistema de visualización directa, EUS y CPRE para la precisión tratamiento de intraductal neoplasia papilar mucinosa

Intraductal papillary mucinous neoplasm (IPMN) accounted for 5.0%~7.5% of pancreatic tumors and 21%~33% of cystic tumors. It usually occurs in people aged 60 to 70. The main treatment is surgical excision. The operation method is different according to the location of lesion, so we try our best to achieve accurate treatment. Here, we provide endoscopic ultrasonography combined with ERCP and eyeMax three endoscopic systems, so as to achieve accurate treatment of IPMN, which is recommended to the majority of endoscopists.(AU)

The combination of eyeMax direct visualization system, EUS and ERCP for the precise treatment of intraductal papillary mucinous neoplasm.

Intraductal papillary mucinous neoplasm (IPMN) accounted for 5.0%~7.5% of pancreatic tumors and 21%~33% of cystic tumors. It usually occurs in people aged 60 to 70. The main treatment is surgical excision. The operation method is different according to the location of lesion, so we try our best to achieve accurate treatment. Here, we provide endoscopic ultrasonography combined with ERCP and eyeMax three endoscopic systems, so as to achieve accurate treatment of IPMN, which is recommended to the majority of endoscopists.

Efficacy and safety of tirofiban in patients with acute ischemic stroke treated with endovascular thrombectomy: A frequentist and Bayesian meta-analysis.

BACKGROUND: Tirofiban is an antiplatelet treatment approved for acute coronary syndrome, but it has not been rigorously evaluated for efficacy and safety in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). METHODS: Electronic databases were systematically searched for studies conducted from January 1, 2015, to July 31, 2021, that evaluated tirofiban administration for patients with AIS treated with EVT in comparison with control. Risk ratios (RRs) and confidence intervals (CIs) were estimated for favorable functional outcomes (FFOs), mortality, and symptomatic intracranial hemorrhage (SICH), each 90 days after AIS. Bayesian hierarchical modeling was performed to obtain posterior RR and its 95% highest posterior density (HPD) for validation. RESULTS: Compared with controls, tirofiban users exhibited increased FFOs (RR, 1.18; 95% CI, 1.08-1.30), decreased mortality (RR, 0.77; 95% CI, 0.64-0.92), and no difference in SICH (RR, 0.97; 95% CI, 0.77-1.23). Tirofiban users in the postbolus infusion subgroup exhibited increased FFOs (RR, 1.20; 95% CI, 1.07-1.35), decreased mortality (RR, 0.71; 95% CI, 0.58-0.88), and no increase in SICH (RR, 0.97; 95% CI, 0.72-1.29). The bolus-only subgroup showed no differences in FFO, mortality, or SICH between the tirofiban and control groups. Consistent results were obtained for posterior density of FFO (posterior RR, 1.20; 95% HPD, 1.06-1.34), mortality (posterior RR, 0.77; 95% HPD, 0.63-0.92), and SICH (posterior RR, 0.98; 95% HPD, 0.71-1.26). CONCLUSION: For patients with AIS treated with EVT, tirofiban improved FFOs, decreased mortality, and did not increase SICH compared with controls; postbolus infusion for administering tirofiban was more favored than the bolus-only regimen.

Two-step approach for recurrent pancreatic pseudocysts: endoscopic ring drainage of the stent transpapillary combined with the posterior gastric wall.

Pancreatic pseudocyst is a complication of pancreatitis, with an incidence of about 5-16% and a incidence of about 20-40% in chronic pancreatitis. There are various ways to treat pancreatic pseudocysts, but the recurrence rate of cysts is as high as 23.9%. There are not many clinical options for the treatment of recurrent pseudocysts, and there is still a high recurrence of pseudocysts after EUS guided drainage alone. We present here a promising endoscopic treatment for patients with recurrent pancreatic pseudocyst.

EUS-guided Rendezvous technique for the treatment of choledocholithiasis with difficult cannulation.

It is not uncommon to encounter difficult cannulation during endoscopic retrograde cholangiopancreatography (ERCP), most of which can be performed by double-guide wire, pre-cut and other techniques. Endoscopic ultrasound-guided biliary drainage (EUS-BD) can be used as a remedial solution for ERCP failure. This article provides a very well experience in ERCP combine with EUS-RV technique in cases where the duodenal papilla is located above the medial diverticulum. At the same time, some skills of EUS-RV are provided for endoscopists.

Thromboembolic Presentations among Patients Hospitalized to the Intensive Care Unit for Coronavirus Disease 2019 (COVID-19) - A Northern Taiwan Single Center Experience.

Coronavirus Disease 2019 (COVID-19) has been associated with a high thromboembolic risk among patients in intensive care units. Asian populations may share a similar thromboembolic risk, but with a higher prevalence of arterial thromboembolism than venous thromboembolism. To clarify this risk in Taiwan, this single-center retrospective study collected 27 consecutive intensive care unit patients with COVID-19 confirmed by polymerase chain reaction, with a median age of 67.6 years (male 81.5%). Twenty-three patients received prophylactic anticoagulation (85.2%), and there were four bleeding events (14.8%). Nine patients had thromboembolism (33.3%), including three with deep vein thrombosis, two with peripheral artery thromboembolism, and four with ischemic stroke. There were no significant clinical differences between the patients with or without thromboembolism. Initial serum ferritin [adjusted odds ratio (OR): 13.19, 95% confidence interval (CI): 1.01-172.07] and peak serum procalcitonin (adjusted OR: 18.93, 95% CI: 1.08-330.91) were associated with a higher risk of thromboembolism. Furthermore, prophylactic anticoagulation (adjusted OR: 0.01, 95% CI: < 0.001-0.55) was associated with a lower risk of thromboembolism. All cases of deep vein thrombosis and one peripheral artery thromboembolism occurred at intravascular catheter locations. No association between thromboembolism and survival was found (age-adjusted hazard ratio: 0.55, 95% CI: 0.10-2.95). In conclusion, the prevalence of COVID-19 thromboembolism among Taiwanese patients in intensive care units was high, even with prophylactic anticoagulation. Serum ferritin and procalcitonin may identify high-risk populations. Prophylactic anticoagulation may reduce the risk of thromboembolism with a manageable bleeding risk. Larger prospective studies are needed to clarify the risk of COVID-19 thromboembolism and its risk factors in the post-Omicron era.

Graphene Hollow Micropatterns via Capillarity-Driven Assembly for Drug Storage and Neural Cell Alignment.

Electrical conductivity, cell-guided surface topology, and drug storage capacity of biomaterials are attractive properties for the repair and regeneration of anisotropic tissues with electrical sensitivity, such as nerves. However, designing and fabricating implantable biomaterials with all these functions remain challenging. Herein, we developed a freestanding graphene substrate with micropatterned surfaces by a simple templating method. Importantly, the raised surface micropatterns had an internal hollow structure. The morphology results showed that the template microgroove width and the graphene nanosheet size were important indicators of the formation of the hollow structures. Through real-time monitoring and theoretical analysis of the formation process, it was found that the main formation mechanism was the delamination and interlayer movement of the graphene nanosheets triggered by the evaporation-induced capillary force. Finally, we achieved the controlled release of loaded microparticles and promoted the orientation of rat dorsal root ganglion neurons by applying an electric field to the hollow micropatterns. This capillarity-induced self-assembly strategy paves the way for the development of high-performance graphene micropatterned films with a hollow structure that have potential for clinical application in the repair of nerve injury.

Elevated expression of interleukin 16 in chronic lymphocytic leukemia is associated with disease burden and abnormal immune microenvironment.

Interleukin-16 (IL-16) is a novel biomarker that has been implicated in many cancers as well as inflammatory diseases. In this study, we examined plasma levels of 30 cytokines and chemokines in chronic lymphocytic leukemia (CLL) and monoclonal B cell lymphocytosis (MBL) patients, and examined their association with disease stage, CLL biomarkers and T cell subsets. Interleukin 16 (IL-16) was identified as a relatively uncharacterized cytokine significantly elevated in CLL patients compared to healthy controls and MBL patients. Plasma levels of IL-16 were significantly elevated by Rai stage 0, increased by Rai stage 3-4, correlated strongly with lymphocyte count and were decreased after Ibrutinib treatment. CLL cells expressed IL-16 mRNA and spontaneously secreted IL-16 in vitro. CLL cells express IL-16 mRNA at significantly higher levels in lymphoid tissues than blood, and we observed that IL-16 release was increased in co-cultures of CLL and autologous CD4 + T cells. Elevated plasma IL-16 levels were associated with abnormalities in the immune microenvironment including multiple inflammatory cytokines and chemokines and expansion of type 1 follicular helper T cells. Taken together, our results identify IL-16 as a novel biomarker in CLL with potential functional roles in cellular interactions between CLL cells and T cells.