Regulation of NCOA4-mediated iron recycling ameliorates paraquat-induced lung injury by inhibiting ferroptosis.

Paraquat (PQ) is an irreplaceable insecticide in many countries for the advantage of fast-acting and broad-spectrum. However, PQ was classified as the most prevailing poisoning substance for suicide with no specific antidote. Therefore, it is imperative to develop more effective therapeutic agents for the treatment of PQ poisoning. In the present study, both the RNA-Seq and the application of various cell death inhibitors reflected that ferroptosis exerts a crucial regulatory role in PQ poisoning. Moreover, we found PQ strengthens lipid peroxidation as evidenced by different experimental approaches. Of note, pretreatment of iron chelation agent DFO could ameliorate the ferroptotic cell death and alleviate the ferroptosis-related events. Mechanistically, PQ treatment intensively impaired mitochondrial homeostasis, enhanced phosphorylation of AMPK, accelerated the autophagy flux and triggered the activation of Nuclear receptor coactivator 4-ferritin heavy chain (NCOA4-FTH) axis. Importantly, the activation of autophagy was observed prior to the degradation of ferritin, and inhibition of autophagy could inhibit the accumulation of iron caused by the ferritinophagy process. Genetic and pharmacological inhibition of ferritinophagy could alleviate the lethal oxidative events, and rescue the ferroptotic cell death. Excitingly, in the mouse models of PQ poisoning, both the administration of DFO and adeno-associated virus-mediated FTH overexpression significantly reduced PQ-induced ferroptosis and improved the pathological characteristics of pulmonary fibrosis. In summary, the current work provides an in-depth study on the mechanism of PQ intoxication, describes a framework for the further understanding of ferroptosis in PQ-associated biological processes, and demonstrates modulation of iron metabolism may act as a promising therapeutic agent for the management of PQ toxicity.

Protective effect of Inonotus obliquus polysaccharide on mice infected with Neospora caninum.

The study aimed to explore the protective effects of Inonotus obliquus polysaccharide (IOP) on Neospora caninum (N. caninum) infection. Our data showed that the survival rate of the mice was the highest and the survival time was the longest when the IOP was 2 mg/10 g. In agreement with these observations, IOP alleviated the pathological damage in the various organs and tissues of the mice. Compared with that in the Neosporidium infection model group, the content of N. caninum in the heart, liver, spleen, lung, kidney and brain, determined through HE staining, was significantly lower. In addition, IOP inhibited the levels of immunoglobulin G1 (IgG1) and immunoglobulin G2 (IgG2a) from the 21st to 42nd day of the administration group, whereas the levels of interleukin-12 (IL-12) and serum tumor necrosis factor alpha (TNF-α) were down-regulated at 7 d - 42 d. The production of CD4+ T lymphocytes was promoted, the number of CD8+ T lymphocytes were significantly lower and the CD4+/CD8+ ratio was significantly elevated. Furthermore, IOP effectively balanced the levels of hormones including gonadotropin-releasing hormone (GnRH), luteotropic hormone (LH) and testosterone (T) in male mice, and progesterone (PROG), estradiol (E2) and prolactin (PRL) in female mice. These findings demonstrate that IOP exerts protective effects against pathological damage caused by N. caninum infection in mice, and improve the immune function of the organism and regulate the secretion balance of sex hormones.

Immunotherapies of acute myeloid leukemia: Rationale, clinical evidence and perspective.

Acute myeloid leukemia (AML) is a prevalent hematological malignancy that exhibits a wide array of molecular abnormalities. Although traditional treatment modalities such as chemotherapy and allogeneic stem cell transplantation (HSCT) have become standard therapeutic approaches, a considerable number of patients continue to face relapse and encounter a bleak prognosis. The emergence of immune escape, immunosuppression, minimal residual disease (MRD), and other contributing factors collectively contribute to this challenge. Recent research has increasingly highlighted the notable distinctions between AML tumor microenvironments and those of healthy individuals. In order to investigate the potential therapeutic mechanisms, this study examines the intricate transformations occurring between leukemic cells and their surrounding cells within the tumor microenvironment (TME) of AML. This review classifies immunotherapies into four distinct categories: cancer vaccines, immune checkpoint inhibitors (ICIs), antibody-based immunotherapies, and adoptive T-cell therapies. The results of numerous clinical trials strongly indicate that the identification of optimal combinations of novel agents, either in conjunction with each other or with chemotherapy, represents a crucial advancement in this field. In this review, we aim to explore the current and emerging immunotherapeutic methodologies applicable to AML patients, identify promising targets, and emphasize the crucial requirement to augment patient outcomes. The application of these strategies presents substantial therapeutic prospects within the realm of precision medicine for AML, encompassing the potential to ameliorate patient outcomes.

Prediction models of surgical site infection after gastrointestinal surgery: a nationwide prospective cohort study.

OBJECTIVE: This study aimed to construct and validate a clinical prediction model for surgical site infection (SSI) risk 30 days after gastrointestinal surgery. MATERIALS AND METHODS: This multicentre study involving 57 units conducted a 30-day postoperative follow-up of 17 353 patients who underwent gastrointestinal surgery at the unit from 1 March 2021 to 28 February 2022. The authors collected a series of hospitalisation data, including demographic data, preoperative preparation, intraoperative procedures and postoperative care. The main outcome variable was SSI, defined according to the Centres for Disease Control and Prevention guidelines. This study used the least absolute shrinkage and selection operator (LASSO) algorithm to screen predictive variables and construct a prediction model. The receiver operating characteristic curve, calibration and clinical decision curves were used to evaluate the prediction performance of the prediction model. RESULTS: Overall, 17 353 patients were included in this study, and the incidence of SSI was 1.6%. The univariate analysis combined with LASSO analysis showed that 20 variables, namely, chronic liver disease, chronic kidney disease, steroid use, smoking history, C-reactive protein, blood urea nitrogen, creatinine, albumin, blood glucose, bowel preparation, surgical antibiotic prophylaxis, appendix surgery, colon surgery, approach, incision type, colostomy/ileostomy at the start of the surgery, colostomy/ileostomy at the end of the surgery, length of incision, surgical duration and blood loss were identified as predictors of SSI occurrence ( P <0.05). The area under the curve values of the model in the train and test groups were 0.7778 and 0.7868, respectively. The calibration curve and Hosmer-Lemeshow test results demonstrated that the model-predicted and actual risks were in good agreement, and the model forecast accuracy was high. CONCLUSIONS: The risk assessment system constructed in this study has good differentiation, calibration and clinical benefits and can be used as a reference tool for predicting SSI risk in patients.

A Novel Optical Fiber Terahertz Biosensor Based on Anti-Resonance for The Rapid and Nondestructive Detection of Tumor Cells.

The sensitive and accurate detection of tumor cells is essential for successful cancer therapy and improving cancer survival rates. However, current tumor cell detection technologies have some limitations for clinical applications due to their complexity, low specificity, and high cost. Herein, we describe the design of a terahertz anti-resonance hollow core fiber (THz AR-HCF) biosensor that can be used for tumor cell detection. Through simulation and experimental comparisons, the low-loss property of the THz AR-HCF was verified, and the most suitable fiber out of multiple THz AR-HCFs was selected for biosensing applications. By measuring different cell numbers and different types of tumor cells, a good linear relationship between THz transmittance and the numbers of cells between 10 and 106 was found. Meanwhile, different types of tumor cells can be distinguished by comparing THz transmission spectra, indicating that the biosensor has high sensitivity and specificity for tumor cell detection. The biosensor only required a small amount of sample (as low as 100 µL), and it enables label-free and nondestructive quantitative detection. Our flow cytometry results showed that the cell viability was as high as 98.5 ± 0.26% after the whole assay process, and there was no statistically significant difference compared with the negative control. This study demonstrates that the proposed THz AR-HCF biosensor has great potential for the highly sensitive, label-free, and nondestructive detection of circulating tumor cells in clinical samples.

The potential role of ferroptosis in COVID-19-related cardiovascular injury.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global health threat in 2019. An important feature of the disease is that multiorgan symptoms of SARS-CoV-2 infection persist after recovery. Evidence indicates that people who recovered from COVID-19, even those under the age of 65 years without cardiovascular risk factors such as smoking, obesity, hypertension, and diabetes, had a significantly increased risk of cardiovascular disease for up to one year after diagnosis. Therefore, it is important to closely monitor individuals who have recovered from COVID-19 for potential cardiovascular damage that may manifest at a later stage. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the production of reactive oxygen species (ROS) and increased lipid peroxide levels. Several studies have demonstrated that ferroptosis plays an important role in cancer, ischemia/reperfusion injury (I/RI), and other cardiovascular diseases. Altered iron metabolism, upregulation of reactive oxygen species, and glutathione peroxidase 4 inactivation are striking features of COVID-19-related cardiovascular injury. SARS-CoV-2 can cause cardiovascular ferroptosis, leading to cardiovascular damage. Understanding the mechanism of ferroptosis in COVID-19-related cardiovascular injuries will contribute to the development of treatment regimens for preventing or reducing COVID-19-related cardiovascular complications. In this article, we go over the pathophysiological underpinnings of SARS-CoV-2-induced acute and chronic cardiovascular injury, the function of ferroptosis, and prospective treatment approaches.

Carbohydrate antigen 125 in atrial fibrillation.

Atrial fibrillation is the most common arrhythmia in clinical settings. It is associated with an increased risk of death, stroke, and peripheral vascular embolism. Catheter ablation (CA) is an effective treatment for patients with AF. However, many studies have reported suboptimal outcomes, as AF recurrence rates often remain high after CA. Therefore, there is a need for early identification of patients who are prone to recurrence and require anti-inflammatory and/or antiarrhythmic treatment after CA. In recent years, Prediction of AF and AF recurrence after CA has become a hot topic in clinical practice. A lot of biomarkers (Such as B-type natriuretic peptide, N-terminal pro-BNP, high sensitivity C reactive protein etc.) have been identified as markers for predicting the risk of AF and AF recurrence after CA. Although these markers have been shown to predict AF and AF recurrence after CA, there are currently no relevant guidelines to indicate which of these markers have absolute predictive value. Therefore, Finding the appropriate indicators that can efficiently and accurately predict AF recurrence after AF ablation is important to provide the best treatment for each patient. These indicators still need exploration. Carbohydrate antigen 125 (CA-125) is a tumor marker suitable for the screening, diagnosis, and monitoring of ovarian malignant tumors. It has been widely studied in patients with heart failure. In recent years, the role of CA-125 in AF has been widely studied, and we provide a review in this article. It is wide availability and low cost provide additional advantages for its rapid implementation. This article reviews the role of CA-125 in patients with atrial fibrillation.

FAM3 family genes are associated with prognostic value of human cancer: a pan-cancer analysis.

Family with sequence similarity three member (FAM3) plays a crucial role in the malignant development of various cancers of human. However, there remains doubtful what specific role of FAM3 family genes in pan-cancer. Our study aimed to investigate the role of FAM3 family genes in prognosis, immune subtype, tumor immune microenvironment, stemness score, and anticancer drug sensitivity of pan-cancer. We obtained data from UCSC Xena GDC and CellMiner databases, and used them to study the correlation of the expression, survival, immune subtype, tumor microenvironment, stemness score, and anticancer drug sensitivity between FAM3 family genes with pan-cancer. Furthermore, we investigated the tumor cellular functions and clinical prognostic value FAMC3 in pancreatic cancer (PAAD) using cellular experiments and tissue microarray. Cell Counting Kit-8 (CCK-8), transwell invasion, wound-healing and apoptosis assays were performed to study the effect of FAM3C on SW1990 cells' proliferation, migration, invasion and apoptosis. Immunohistochemical staining was used to study the relationship between FAM3C expression and clinical characteristics of pancreatic cancer patients. The results revealed that FAM3 family genes are significantly differential expression in tumor and adjacent normal tissues in 7 cancers (CHOL, HNSC, KICH, LUAD, LUSC, READ, and STAD). The expression of FAM3 family genes were negatively related with the RNAss, and robust correlated with immune type, tumor immune microenvironment and drug sensitivity. The expression of FAM3 family genes in pan-cancers were significantly different in immune type C1 (wound healing), C2 (IFN-gamma dominant), C3 (inflammatory), C4 (lymphocyte depleted), C5 (immunologically quiet), and C6 (TGF-beta dominant). Meanwhile, overexpression FAM3C promoted SW1990 cells proliferation, migration, invasion and suppressed SW1990 cells apoptosis. While knockdown of FAM3C triggered opposite results. High FAM3C expression was associated with duodenal invasion, differentiation and liver metastasis. In summary, this study provided a new perspective on the potential therapeutic role of FAM3 family genes in pan-cancer. In particular, FAM3C may play an important role in the occurrence and progression of PAAD.

Clinicopathological Characteristics, Prognosis, and Correlated Tumor Cell Function of Tropomodulin-3 in Pancreatic Adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a frequent malignant tumor with a high mortality rate. Searching for novel biomarkers that can influence its prognosis may help patients. It has been shown that tropomodulin-3 (TMOD3) may influence tumor progression, but its role in pancreatic cancer is not clear. We aimed to explore the expression and prognostic value of TMOD3 in PAAD. METHODS: We used bioinformatics analysis to analyze the relationship between TMOD3 expression and clinicopathological features and prognosis and verified it with clinical data from tissue microarray. We also conducted in vitro cell experiments to explore the effects of TMOD3 on the function of PAAD cells. RESULTS: TMOD3 expression was found to be significantly higher in PAAD tissues than in matched paracancerous tissues (P < 0.05). Meanwhile, high TMOD3 expression was associated with significantly poorer overall survival (P < 0.05). Analysis of relevant clinicopathological characteristics data obtained from TCGA showed that high TMOD3 expression correlated with age, TNM stage, N stage, and M stage (P < 0.05). Analysis of correlation data obtained from tissue microarrays showed that high TMOD3 expression was associated with lymph node invasion, nerve invasion, macrovascular invasion, and TNM stage (P < 0.05). In addition, siRNA knockdown of TMOD3 significantly reduced the migration and invasion of PAAD cells. CONCLUSION: Our study shows that TMOD3 may be associated with the progression of PAAD cells, and that it is an independent risk factor for poor pathological features and prognosis of PAAD. It may be helpful as a prognostic indicator of clinical outcomes in PAAD patients.

Comprehensive analysis identifies CLEC1B as a potential prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: C-type lectin domain family 1 member B (CLEC1B, encoding the CLEC-2 protein), a member of the C-type lectin superfamily, is a type II transmembrane receptor involved in platelet activation, angiogenesis, and immune and inflammatory responses. However, data regarding its function and clinical prognostic value in hepatocellular carcinoma (HCC) remain scarce. METHODS: The expression of CLEC1B was explored using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RT-qPCR, western blot, and immunohistochemistry assays were employed to validate the downregulation of CLEC1B. Univariate Cox regression and survival analyses were used to evaluate the prognostic value of CLEC1B. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential association between cancer hallmarks and CLEC1B expression. The TISIDB database was applied to search for the correlation between immune cell infiltration levels and CLEC1B expression. The association between CLEC1B and immunomodulators was conducted by Spearman correlation analysis based on the Sangerbox platform. Annexin V-FITC/PI apoptosis kit was used for the detection of cell apoptosis. RESULTS: The expression of CLEC1B was low in various tumors and exhibited a promising clinical prognostic value for HCC patients. The expression level of CLEC1B was tightly associated with the infiltration of various immune cells in the HCC tumor microenvironment (TME) and positively correlated with a bulk of immunomodulators. In addition, CLEC1B and its related genes or interacting proteins are implicated in multiple immune-related processes and signaling pathways. Moreover, overexpression of CLEC1B significantly influenced the treatment effects of sorafenib on HCC cells. CONCLUSIONS: Our results reveal that CLEC1B could serve as a potential prognostic biomarker and may be a novel immunoregulator for HCC. However, its function in immune regulation should be further explored.

Identification of Risk Factors and Phenotypes of Surgical Site Infection in Patients After Abdominal Surgery.

OBJECTIVES: We aimed to determine the current incidence rate and risk factors for surgical site infection (SSI) after abdominal surgery in China and to further demonstrate the clinical features of patients with SSI. BACKGROUND: Contemporary epidemiology and clinical features of SSI after abdominal surgery remain poorly characterized. METHODS: A prospective multicenter cohort study was conducted from March 2021 to February 2022; the study included patients who underwent abdominal surgery at 42 hospitals in China. Multivariable logistic regression analysis was performed to identify risk factors for SSI. Latent class analysis (LCA) was used to explore the population characteristics of SSI. RESULTS: In total, 23,982 patients were included in the study, of whom 1.8% developed SSI. There was a higher SSI incidence in open surgery (5.0%) than in laparoscopic or robotic surgeries (0.9%). Multivariable logistic regression indicated that the independent risk factors for SSI after abdominal surgery were older age, chronic liver disease, mechanical bowel preparation, oral antibiotic bowel preparation, colon or pancreas surgery, contaminated or dirty wounds, open surgery, and colostomy/ileostomy. LCA revealed 4 subphenotypes in patients undergoing abdominal surgery. Types α and ß were mild subclasses with a lower SSI incidence; whereas types γ and δ were the critical subgroups with a higher SSI incidence, but their clinical features were different. CONCLUSIONS: LCA identified 4 subphenotypes in patients who underwent abdominal surgery. Types γ and δ were critical subgroups with a higher SSI incidence. This phenotype classification can be used to predict SSI after abdominal surgery.

Biallelic variants in CRIPT cause a Rothmund-Thomson-like syndrome with increased cellular senescence.

PURPOSE: Rothmund-Thomson syndrome (RTS) is characterized by poikiloderma, sparse hair, small stature, skeletal defects, cancer, and cataracts, resembling features of premature aging. RECQL4 and ANAPC1 are the 2 known disease genes associated with RTS in >70% of cases. We describe RTS-like features in 5 individuals with biallelic variants in CRIPT (OMIM 615789). METHODS: Two newly identified and 4 published individuals with CRIPT variants were systematically compared with those with RTS using clinical data, computational analysis of photographs, histologic analysis of skin, and cellular studies on fibroblasts. RESULTS: All CRIPT individuals fulfilled the diagnostic criteria for RTS and additionally had neurodevelopmental delay and seizures. Using computational gestalt analysis, CRIPT individuals showed greatest facial similarity with individuals with RTS. Skin biopsies revealed a high expression of senescence markers (p53/p16/p21) and the senescence-associated ß-galactosidase activity was elevated in CRIPT-deficient fibroblasts. RECQL4- and CRIPT-deficient fibroblasts showed an unremarkable mitotic progression and unremarkable number of mitotic errors and no or only mild sensitivity to genotoxic stress by ionizing radiation, mitomycin C, hydroxyurea, etoposide, and potassium bromate. CONCLUSION: CRIPT causes an RTS-like syndrome associated with neurodevelopmental delay and epilepsy. At the cellular level, RECQL4- and CRIPT-deficient cells display increased senescence, suggesting shared molecular mechanisms leading to the clinical phenotypes.

A plasma 3-marker microRNA biosignature distinguishes spinal tuberculosis from other spinal destructive diseases and pulmonary tuberculosis.

Accurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB) from pulmonary tuberculosis (PTB) and other spinal diseases of different origins (SDD). For a case-controlled investigation, a total of 423 subjects were voluntarily recruited, with 157 cases of STB, 83 cases of SDD, 30 cases of active PTB, and 153 cases of healthy controls (CONT) in 4 clinical centers. To discover the STB-specific miRNA biosignature, a high-throughput miRNA profiling study was performed in the pilot study with 12 cases of STB and 8 cases of CONT using the Exiqon miRNA PCR array platform. A bioinformatics study identified that the 3-plasma miRNA combination (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) might serve as a candidate biomarker for STB. The subsequent training study developed the diagnostic model using multivariate logistic regression in training data sets, including CONT(n=100) and STB (n=100). Youden's J index determined the optimal classification threshold. Receiver Operating Characteristic (ROC) curve analysis showed that 3-plasma miRNA biomarker signatures have an area under the curve (AUC) = 0.87, sensitivity = 80.5%, and specificity = 80.0%. To explore the possible potential to distinguish spinal TB from PDB and other SDD, the diagnostic model with the same classification threshold was applied to the analysis of the independent validation data set, including CONT(n=45), STB(n=45), brucellosis spondylitis (BS, n=30), PTB (n=30), spinal tumor (ST, n=30) and pyogenic spondylitis (PS, n=23). The results showed diagnostic model based on three miRNA signatures could discriminate the STB from other SDD groups with sensitivity=80%, specificity=96%, Positive Predictive Value (PPV)=84%, Negative Predictive Value (NPV)=94%, the total accuracy rate of 92%. These results indicate that this 3-plasma miRNA biomarker signature could effectively discriminate the STB from other spinal destructive diseases and pulmonary tuberculosis. The present study shows that the diagnostic model based on 3-plasma miRNA biomarker signature (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) may be used for medical guidance to discriminate the STB from other spinal destructive disease and pulmonary tuberculosis.

CS-iCCA, A New Clinically Based Staging System for Intrahepatic Cholangiocarcinoma: Establishment and External Validation.

INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with poor prognosis. Current prognostic methods are most accurate for patients with surgically resectable disease. However, a significant proportion of patients with iCCA are not surgical candidates. We aimed to develop a generalizable staging system based on clinical variables to determine prognosis of all patients with iCCA. METHODS: The derivation cohort included 436 patients with iCCA seen between 2000 and 2011. For external validation, 249 patients with iCCA seen from 2000 to 2014 were enrolled. Survival analysis was performed to identify prognostic predictors. All-cause mortality was the primary end point. RESULTS: Eastern Cooperative Oncology Group status, tumor number, tumor size, metastasis, albumin, and carbohydrate antigen 19-9 were incorporated into a 4-stage algorithm. Kaplan-Meier estimates for 1-year survival were 87.1% (95% confidence interval [CI] 76.1-99.7), 72.7% (95% CI 63.4-83.4), 48.0% (95% CI 41.2-56.0), and 16% (95% CI 11-23.5), respectively, for stages I, II, III, and IV. Univariate analysis yielded significant differences in risk of death for stages II (hazard ratio [HR] 1.71; 95% CI 1.0-2.8), III (HR 3.32; 95% CI 2.07-5.31), and IV (HR 7.44; 95% CI 4.61-12.01) compared with stage I (reference). Concordance indices showed the new staging system was superior to the TNM staging for predicting mortality in the derivation cohort, P < 0.0001. In the validation cohort, however, the difference between the 2 staging systems was not significant. DISCUSSION: The proposed independently validated staging system uses nonhistopathologic data to successfully stratify patients into 4 stages. This staging system has better prognostic accuracy compared with the TNM staging and can assist physicians and patients in treatment of iCCA.

Retraction of "SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis".

[This retracts the article DOI: 10.1515/med-2022-0418.].

Spontaneous perforation of a primary duodenal diverticulum stepped treatment model: A 10-patient case report.

After colonic diverticula, a duodenal diverticulum (DD) is the second most common type of gastrointestinal diverticulum. DD is mainly caused by poor congenital development, resulting in a limited outward protrusion of the duodenal wall in a sac (primary diverticula). Perforation is one of the infrequent but most severe complications of DD, most commonly in the second segment of the duodenum (D2, 58%), followed by the third segment (D3, 30%). In the current case reports on the treatment of DD perforation, preoperative diagnosis is rare, with most patients being diagnosed and treated by laparotomy; the surgical approach is complex and varied, with artificial choices; and there is a high rate of complications and mortality (6%-34%) after surgical treatment. This study aimed to review our experience treating spontaneous perforation of the primary duodenal diverticulum, focusing on the surgical treatment model. A retrospective review of all spontaneous perforations of primary DD was conducted at one center between January 2010 and January 2022. We identified 10 patients with spontaneous perforation of primary DD (6 women and 4 men; median age: 51.5 years; range: 24-87 years). The patients had a median American Society of Anesthesiologists (ASA) score of 2. All patients underwent surgical treatment, of which six had percutaneous retroperitoneal drainage, two had diverticulectomy, one had distal gastrectomy + gastrojejunostomy + diverticuloplasty, and one had diverticulum repair. No patients died. The median length of stay was 12 days (range: 3-21 days). There were no long-term complications during the follow-up period (median follow-up of 12 months). A stepwise treatment model for spontaneous perforation of primary DD appears to have more advantages, and transabdominal exploratory surgery should probably not be the preferred treatment modality.

A preoperative prediction model based on Lymphocyte-C-reactive protein ratio predicts postoperative anastomotic leakage in patients with colorectal carcinoma: a retrospective study.

BACKGROUND & AIMS: Lymphocyte-C-reactive Protein Ratio (LCR) has been demonstrated as a promising new marker for predicting surgical and oncological outcomes in colorectal carcinoma (CRC). However, anastomotic leakage (AL) is also likely related to this inflammatory marker. Herein, we aimed to identify preoperative predictors of AL and build and develop a novel model able to identify patients at risk of developing AL. METHODS: We collected 858 patients with CRC undergoing elective radical operation between 2007 and 2018 at a single center were retrospectively reviewed. We performed univariable and multivariable analyses and built a multivariable model that predicts AL based on preoperative factors. Propensity adjustment was used to correct the bias introduced by non-random matching of the LCR. The model's performance was evaluated by using the area under the receiver operator characteristic curves (AUROCs), decision curve analysis (DCA), Brier scores, D statistics, and R2 values. RESULTS: Age, nutrition risk screening 2002 (NRS2002) score, tumor location and LCR, together with hemoglobin < 90 g/l, were independent predictors of AL. The models built on these variables showed good performance (internal validation: c-statistic = 0.851 (95%CI 0.803-0.965), Brier score = 0.049; temporal validation: c-statistic = 0.777 (95%CI 0.823-0.979), Brier score = 0.096). A regression equation to predict the AL was also established by multiple linear regression analysis: [Age(≥ 60 year) × 1.281] + [NRS2002(≥ 3) × 1.341] + [Tumor location(pt.) × 1.348]-[LCR(≤ 6000) × 1.593]-[Hemoglobin(< 90 g/L) × 1.589]-6.12. CONCLUSION: Preoperative LCR is an independent predictive factor for AL. A novel model combining LCR values, age, tumor location, and NRS2002 provided an excellent preoperative prediction of AL in patients with CRC. The nomogram can help clinical decision-making and support future research.

Agreement of Potassium, Sodium, Glucose, and Hemoglobin Measured by Blood Gas Analyzer With Dry Chemistry Analyzer and Complete Blood Count Analyzer: A Two-Center Retrospective Analysis.

Background: Blood gas analyzers (BGAs) and dry biochemistry analyzers for potassium and sodium are based on direct electrode methods, and both involve glucose oxidase for glucose detection. However, data are lacking regarding whether the results of the two assay systems can be used interchangeably. In addition, there remains controversy over the consistency between BGA-measured hemoglobin and complete blood count analyzer data. Here, we compared the consistency of sodium, potassium, glucose, and hemoglobin levels measured by BGA and dry chemistry and complete blood count analyzers. Methods: Data from two teaching hospitals, the Zhejiang Provincial People's Hospital (ZRY) and the Qianfoshan Hospital (QY), were retrospectively analyzed based on dry biochemistry and complete blood count analyzer results as the reference system (X) and BGA as the experimental system (Y). Plasma was used for biochemical analysis at the ZRY Hospital, and serum at the QY Hospital. Paired data from the respective hospitals were evaluated for consistency, and biases between methods were assessed by simple correlation, Passing-Bablok regression, and Bland-Altman analyses. Results: The correlations of potassium, sodium, glucose, and hemoglobin measured by BGA and dry biochemistry and complete blood count analyzers were high, at 0.9573, 0.8898, 0.9849, and 0.9883 for the ZRY Hospital and 0.9198, 0.8591, 0.9764, and 0.8666, respectively, for the QY Hospital. The results of Passing to Bablok regression analysis showed that the predicted biases at each medical decision level were within clinically acceptable levels for potassium, sodium, glucose, and hemoglobin at the ZRY Hospital. Only the predicted bias of glucose was below the clinically acceptable medical decision levels at the QY Hospital, while potassium, sodium, and hemoglobin were not. Compared with the reference system, the mean bias for BGA measurements at the ZRY Hospital was -0.08 mmol/L (95% confidence interval [CI] -0.091 to -0.069) for potassium, 1.2 mmol/L (95% CI 1.06 to 1.42) for sodium, 0.20 mmol/L (95% CI 0.167 to 0.228) for glucose, and -2.8 g/L for hemoglobin (95% CI -3.14 to -2.49). The mean bias for potassium, sodium, glucose, and hemoglobin at the QY Hospital were -0.46 mmol/L (95% CI -0.475 to -0.452), 3.7 mmol/L (95% CI 3.57 to 3.85), -0.36 mmol/L (95% CI -0.433 to -0.291), and -8.7 g/L (95% CI -9.40 to -8.05), respectively. Conclusion: BGA can be used interchangeably with plasma electrolyte results from dry biochemistry analyzers but does not show sufficient consistency with serum electrolyte results from dry biochemistry analyzers to allow data interchangeability. Good consistency was observed between BGA and plasma or serum glucose results from dry biochemistry analyzers. However, BGA-measured hemoglobin and hematocrit assay results should be treated with caution.

Mycobacterium tuberculosis Induced Osteoblast Dysregulation Involved in Bone Destruction in Spinal Tuberculosis.

Disturbance of bone homeostasis caused by Mycobacterium tuberculosis (Mtb) is a key clinical manifestation in spinal tuberculosis (TB). However, the complete mechanism of this process has not been established, and an effective treatment target does not exist. Increasing evidence shows that abnormal osteoclastogenesis triggered by an imbalance of the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) axis may play a key role in the disturbance of bone homeostasis. Previous studies reported that RANKL is strongly activated in patients with spinal TB; however, the OPG levels in these patients were not investigated in previous studies. In this study, we investigated the OPG levels in patients with spinal TB and the dysregulation of osteoblasts caused by Mtb infection. Inhibition of the Mce4a gene of Mtb by an antisense locked nucleic acid (LNA) gapmer (Mce4a-ASO) was also investigated. Analysis of the serum OPG levels in clinical samples showed that the OPG levels were significantly decreased in patients with spinal TB compared to those in the group of non-TB patients. The internalization of Mtb in osteoblasts, the known major source of OPG, was investigated using the green fluorescent protein (GFP)-labeled Mycobacterium strain H37Ra (H37RaGFP). The cell-associated fluorescence measurements showed that Mtb can efficiently enter osteoblast cells. In addition, Mtb infection caused a dose-dependent increase of the CD40 mRNA expression and cytokine (interleukin 6, IL-6) secretion in osteoblast cells. Ligation of CD40 by soluble CD154 reversed the increased secretion of IL-6. This means that the induced CD40 is functional. Considering that the interaction between CD154-expressing T lymphocytes and bone-forming osteoblast cells plays a pivotal role in bone homeostasis, the CD40 molecule might be a strong candidate for mediating the target for treatment of bone destruction in spinal TB. Additionally, we also found that Mce4a-ASO could dose-dependently inhibit the Mce4a gene of Mtb and reverse the decreased secretion of IL-6 and the impaired secretion of OPG caused by Mtb infection of osteoblast cells. Taken together, the current finding provides breakthrough ideas for the development of therapeutic agents for spinal TB.

SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis.

In this study, we intended to figure out the biological significance of long non-coding RNAs (lncRNAs) solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1-AS1) in pancreatic cancer (PC). Cell counting kit-8, colony formation, wound healing, transwell, and flow cytometry experiments were performed to reveal how SLCO4A1-AS1 influences PC cell proliferation, migration, invasion, and apoptosis. Thereafter, bioinformatics analysis, RNA immunoprecipitation assay, luciferase reporter assay, and RNA pull-down assay were applied for determining the binding sites and binding capacities between SLCO4A1-AS1 and miR-4673 or kinesin family member 21B (KIF21B) and miR-4673. The results depicted that SLCO4A1-AS1 was upregulated in PC, and SLCO4A1-AS1 knockdown suppressed PC cell growth, migration, invasion, and induced cell apoptosis. Furthermore, SLCO4A1-AS1 was verified to modulate the expression of KIF21B by binding with miR-4673. SLCO4A1-AS1 exerted an oncogenic function in PC. The overexpression of SLCO4A1-AS1 aggravated the malignant behaviors of PC via the upregulation of KIF21B by sponging miR-4673. Our findings revealed a novel molecular mechanism mediated by SLCO4A1-AS1, which might play a significant role in modulating the biological processes of PC.