Metformin alleviates lung ischemia-reperfusion injury in a rat lung transplantation model.

Background: Lung ischemia-reperfusion injury (LIRI) is among the complications observed after lung transplantation and is associated with morbidity and mortality. Preconditioning of the donor lung before organ retrieval may improve organ quality after transplantation. We investigated whether preconditioning with metformin (Met) ameliorates LIRI after lung transplantation. Methods: Twenty Lewis rats were randomly divided into the sham, LIRI, and Met groups. The rats in the LIRI and Met groups received saline and Met, respectively, via oral gavage. Subsequently, a donor lung was harvested and kept in cold storage for 8 h. The LIRI and Met groups then underwent left lung transplantation. After 2 h of reperfusion, serum and transplanted lung tissues were examined. Results: The partial pressure of oxygen (PaO2) was greater in the Met group than in the LIRI group. In the Met group, wet-to-dry (W/D) weight ratios, inflammatory factor levels, oxidative stress levels and apoptosis levels were notably decreased. Conclusions: Met protects against ischemia-reperfusion injury after lung transplantation in rats, and its therapeutic effect is associated with its anti-inflammatory, antioxidative, and antiapoptotic properties.

Esophageal tuberculosis mimicking submucosal tumor: A rare case.

INTRODUCTION: Esophageal tuberculosis (ET) is a rare form of infectious esophagitis. Here, we present a case of primary ET in an immunocompetent patient with dysphagia. CASE PRESENTATION: Esophagogastroduodenoscopy (EGD) revealed a submucosal tumor (SMT)-like lesion in the distal esophagus. Subsequent endoscopic ultrasonography (EUS) showed ulceration, esophageal wall discontinuities, thickening, and hypoechoic masses. Histopathological analysis confirmed a tuberculoid granuloma within the lesion. Imaging studies ruled out pulmonary tuberculosis and lymph node involvement. The patient received six months of antituberculosis treatment, resulting in significant improvement on follow-up EGD. DISCUSSION: ET is often misdiagnosed due to its rarity and nonspecific symptoms. In this case, the clinical presentation of dysphagia, combined with the characteristic findings on EGD and EUS, led to the diagnosis of primary esophageal tuberculosis. CONCLUSION: Prompt consideration of ET in dysphagia patients with SMT-like lesions and timely initiation of appropriate antituberculosis treatment can improve clinical outcomes and help avoid unnecessary surgeries.

Donor and recipient age matching in lung transplantation: A retrospective study.

Purpose: This study aimed to clarify the effect of donor and recipient age combinations on the short-term survival rates of patients undergoing lung transplantation. Patients and methods: We retrospectively reviewed the 2017-2020 data of the Affiliated Wuxi People's Hospital of Nanjing Medical University database for all adults (≥18 years), lung transplant recipients, and their associated donors. The impact of donor and recipient ages on survival was analyzed using a multivariable Cox proportional hazards regression model. Subgroup analysis was also performed based on recipient and donor ages. Results: Different donor and recipient age combinations affected the short-term postoperative survival rates. When recipients were ≤55 years, the survival rates of the younger donor age group were significantly higher than the older donor age group at 30 days after surgery (P = 0.040); when the donors were ≤40 years, the postoperative survival rates of the younger recipient age group were significantly higher than the older recipient age group (P = 0.031, P = 0.026, P = 0.034, and P = 0.018 for 30 days, 90 days, 180 days, and 1 year after surgery, respectively). Conclusion: Younger recipients had a higher survival rate after transplantation than older recipients, and this benefit could be compromised by older donors. Furthermore, the influence of donor age on patient survival rate was limited and more pronounced in younger recipients and shortly after surgery.

CD4 levels and NSCLC metastasis: the benefits of maintaining moderate levels.

OBJECTIVES: Prior researches indicate that peripheral blood CD4 levels have an inverse correlation with distant tumor metastasis in non-small cell lung cancer (NSCLC). However, the linear relationship between CD4 and distant metastasis lacks clarity. Hence, the objective of this study was to ascertain the linear relationship between CD4 and distant metastasis in NSCLC patients. METHODS: This retrospective study analyzed clinical and laboratory data of NSCLC patients between March 2016 and July 2022 at the Cancer Hospital of Anhui University of Technology. The study first applied a generalized summation model and smoothing curve fitting to determine if there was a linear relationship between CD4 and NSCLC metastasis. Secondarily, univariate logistic analysis and multiple linear regression were used to analyze the odds ratio (OR) of CD4 as a continuous variable, dichotomous variable, and trichotomous variable when predicting NSCLC metastasis. In addition, stratified and subgroup analyses were conducted to assess the reliability of CD4 in different NSCLC patient populations. RESULTS: The study included a total of 213 NSCLC patients, among which 122 had distant metastasis and 91 had no metastasis. The smoothing curve fitting analysis revealed a U-shaped relationship between CD4 and NSCLC metastasis with a threshold effect. The univariate logistic analysis indicated that continuous CD4 expression was not significantly associated with NSCLC metastasis (P = 0.051); however, high levels of CD4 expression (≥ 35.06%) were found to be a protective factor against NSCLC metastasis when CD4+ T was a dichotomous variable (OR = 0.49, P = 0.010). Furthermore, multivariate linear regression models showed that low (< 32%) or high levels (> 44%) of CD4 significantly increased the risk of NSCLC metastasis compared to medium levels (32-44%) when CD4+ T was trichotomized. The significance was maintained in stratified analysis in relation to age, sex, type of pathology, smoke, PS, and T stage. CD4 levels were U-shaped in relation to different sites of distant metastases (bone, brain, liver), but not with lung metastases. CONCLUSIONS: A threshold effect is shown to exist between the peripheral blood CD4 and distant metastasis in NSCLC patients. It was revealed that the risk of distant metastasis is lower when CD4 is maintained between 32 and 44%, whereas low (< 32%) or high (> 44) levels of CD4 are associated with an increased risk of distant metastasis in NSCLC patients.

Ligustilide, a novel SIRT1 agonist, alleviates lipopolysaccharide-induced acute lung injury through deacetylation of NICD.

Development and progression of sepsis-induced acute lung injury (ALI) involve apoptosis and oxidative stress in lung epithelial cells. Ligustilide (LIG) is one of the main bioactive constituents derived from the Angelica sinensis. As a novel SIRT1 agonist, LIG owns powerful anti-inflammatory and antioxidative properties, exerting remarkable therapeutic effects on cancers, neurological disorders, and diabetes mellitus. However, whether LIG could protect against lipopolysaccharide (LPS)-induced ALI by activating SIRT1 remains unclear. Mice underwent intratracheal LPS injection to mimic sepsis-induced ALI while MLE-12 cells were treated with LPS for 6 h to establish an in vitro ALI model. At the same time, mice or MLE-12 cells were treated with different doses of LIG to access its pharmacological effect. The results demonstrated that LIG pretreatment could improve LPS-induced pulmonary dysfunction and pathological injury, apart from increasing 7-day survival rate. In addition, LIG pretreatment also decreased inflammation, oxidative stress and apoptosis during LPS-induced ALI. Mechanically, LPS stimulation decreased the expression and activity of SIRT1 but increased the expression of Notch1 and NICD. And LIG could also enhance the interaction between SIRT1 and NICD, thus deacetylating NICD. In vitro experiments also unveiled that EX-527, a selective SIRT1 inhibitor, could abolish LIG-elicited protection in LPS-treated MLE-12 cells. And in SIRT1 knockout mice with ALI, LIG pretreatment also lost its effects on inflammation, apoptosis, and oxidative stress during ALI.

Liproxstatin-1 Alleviates Lung Transplantation-induced Cold Ischemia-Reperfusion Injury by Inhibiting Ferroptosis.

BACKGROUND: Primary graft dysfunction, which is directly related to cold ischemia-reperfusion (CI/R) injury, is a major obstacle in lung transplantation (LTx). Ferroptosis, a novel mode of cell death elicited by iron-dependent lipid peroxidation, has been implicated in ischemic events. This study aimed to investigate the role of ferroptosis in LTx-CI/R injury and the effectiveness of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, in alleviating LTx-CI/R injury. METHODS: LTx-CI/R-induced signal pathway alterations, tissue injury, cell death, inflammatory responses, and ferroptotic features were examined in human lung biopsies, the human bronchial epithelial (BEAS-2B) cells, and the mouse LTx-CI/R model (24-h CI/4-h R). The therapeutic efficacy of Lip-1 was explored and validated both in vitro and in vivo. RESULTS: In human lung tissues, LTx-CI/R activated ferroptosis-related signaling pathway, increased the tissue iron content and lipid peroxidation accumulation, and altered key protein (GPX4, COX2, Nrf2, and SLC7A11) expression and mitochondrial morphology. In BEAS-2B cells, the hallmarks of ferroptosis were significantly evidenced at the setting of both CI and CI/R compared with the control, and the effect of adding Lip-1 only during CI was much better than that of only during reperfusion by Cell Counting Kit-8. Furthermore, Lip-1 administration during CI markedly relieved LTx-CI/R injury in mice, as indicated by significant improvement in lung pathological changes, pulmonary function, inflammation, and ferroptosis. CONCLUSIONS: This study revealed the existence of ferroptosis in the pathophysiology of LTx-CI/R injury. Using Lip-1 to inhibit ferroptosis during CI could ameliorate LTx-CI/R injury, suggesting that Lip-1 administration might be proposed as a new strategy for organ preservation.

Development and validation of a nomogram model to predict primary graft dysfunction in patients after lung transplantation based on the clinical factors.

BACKGROUND: Primary graft dysfunction (PGD), a significant complication that can affect patients' prognosis and quality of life, develops within 72 h post lung transplantation (LTx). Early detection and prevention of PGD should be given special consideration. The purpose of this study was to create a clinical prediction model to forecast the occurrence of PGD. METHODS: We collected information on 622 LTx patients from Wuxi People's Hospital from 2016 to 2020 and used the data to construct the prediction model. Information on 224 patients from 2021 to June 2022 was used for external validation. We used LASSO regression for variable screening. A nomogram was developed for model presentation. Distinctness, fit, and calibration were used to evaluate the performance of the model. RESULTS: Subjects with respiratory failure, who received fresh frozen plasma, donor age, donor gender, donor mechanism of death, donor smoking, donor ventilator use time, and donor PaO 2/FiO 2 ratio were independent predictor variables for the occurrence of PGD. The area under the curve of the nomogram was .779. The Hosmer-Lemeshow test showed a good model fit (P = .158). The calibration curve of the nomogram is fairly close to the ideal diagonal. Moreover, the decision curve analysis revealed a positive net benefit of the model. External validation also confirmed the reliability of the model. CONCLUSIONS: The nomogram of PGD based on clinical risk factors in postoperative LTx patients was established with high reliability. It provides clinicians and nurses with a new and effective tool for early prediction of PGD and early intervention.

[Risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis complicated with pulmonary arterial hypertension].

OBJECTIVE: To investigate the risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension (PAH). METHODS: A retrospective cohort study was conducted. The clinical data of 134 patients with IPF and PAH who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020 were collected. The donor's gender, age, duration of mechanical ventilation, and cold ischemia time, the recipient's gender, age, body mass index (BMI), smoking, history of hypertension and diabetes, preoperative usage of hormones, mean pulmonary arterial pressure (mPAP), cardiac echocardiography and cardiac function, serum creatinine (SCr), N-terminal pro-brain natriuretic peptide (NT-proBNP) as well as surgical type, extracorporeal membrane oxygenation (ECMO) treatment, duration of operation, and plasma and red blood cell infusion ratio were collected. The cumulative survival rates of patients at 30, 60, and 180 days after lung transplantation were calculated by Kaplan-Meier method. The univariate and multivariate Cox proportional hazards regression models were used to analyze the effects of donor, recipient, and surgical factors on early survival in donors after lung transplantation. RESULTS: The majority of donors were male (80.6%). There was 63.4% of the donors older than 35 years old, 80.6% of the donors had mechanical ventilation duration less than 10 days, and the median cold ischemia time was 465.00 (369.25, 556.25) minutes. The recipients were mainly males (83.6%). Most of the patients were younger than 65 years old (70.9%). Most of them had no hypertension (75.4%) or diabetes (67.9%). The median mPAP of recipients was 36 (30, 43) mmHg (1 mmHg ≈ 0.133 kPa). There were 73 patients with single lung transplantation (54.5%), and 61 with double lung transplantation (45.5%). The survival rates of 134 IPF patients with PAH at 30, 60, 180 days after lung transplantation were 81.3%, 76.9%, and 67.4%, respectively. Univariate Cox proportional risk regression analysis showed that recipient preoperative use of hormone [hazard ratio (HR) = 2.079, 95% confidence interval (95%CI) was 1.048-4.128], mPAP ≥ 35 mmHg (HR = 2.136, 95%CI was 1.129-4.044), NT-proBNP ≥ 300 ng/L (HR = 2.411, 95%CI was 1.323-4.392), New York Heart Association (NYHA) cardiac function classification III-IV (HR = 3.021, 95%CI was 1.652-5.523) were the risk factors of early postoperative death in patients with IPF complicated with PAH (all P < 0.05). In the multivariable Cox proportional risk regression analysis, recipient preoperative hormone usage (model 1: HR = 2.072, 95%CI was 1.044-4.114, P = 0.037; model 2: HR = 2.098, 95%CI was 1.057-4.165, P = 0.034), NT-proBNP ≥ 300 ng/L (HR = 2.246, 95%CI was 1.225-4.116, P = 0.009) and NYHA cardiac function classification III-IV (HR = 2.771, 95%CI was 1.495-5.134, P = 0.001) were independent risk factors of early postoperative death in patients with IPF. CONCLUSIONS: Preoperative hormone usage, NT-proBNP ≥ 300 ng/L, NYHA cardiac function classification III-IV are independent risk factors for early death in patients with IPF and PAH after lung transplantation. For these patients, attention should be paid to optimize their functional status before operation. Preoperative reduction of receptor hormone usage and improvement of cardiac function can improve the early survival rate of such patients after lung transplantation.

An immune indicator based on BTK and DPEP2 identifies hot and cold tumors and clinical treatment outcomes in lung adenocarcinoma.

In lung adenocarcinoma (LUAD), immune heterogeneity of hot and cold tumors has been recognized as one of the major factors affecting immunotherapy and other common treatments. However, there is still a lack of biomarkers that can effectively identify the immunophenotype of cold and hot tumors. First, the immune signatures were obtained based on literature mining, including macrophage/monocyte, IFN-γ response, TGF-ß response, IL12 response, lymphocyte activation, and ECM/Dve/immune response. Subsequently, LUAD patients were further clustered into different immune phenotypes based on these immune signatures. Next, the key genes related to the immune phenotypes were screened by WGCNA analysis, univariate analysis, and lasso-cox analysis, and the risk signature was established via the key genes. In additional, we compared the clinicopathological characteristics, drug sensitivity, the abundance of immune infiltration, and the efficacy of immunotherapy and commonly used therapies between patients in the high- and low-risk groups in LUAD. LUAD patients were divided into immune hot phenotype and immune cold phenotype groups. The clinical presentation showed that patients with the immune hot phenotype had higher immunoactivity (including higher MHC, CYT, immune, stromal, ESTIMATE scores, higher abundance of immune cell infiltration, higher abundance of TIL, and enrichment of immune-enriched subtypes) and better survival outcomes than those with the immune cold phenotype. Subsequently, WGCNA analysis, univariate analysis, and lasso-cox analysis identified the genes highly associated with the immune phenotype: BTK and DPEP2. The risk signature, consisting of BTK and DPEP2, is highly correlated with the immune phenotype. High-risk scores were enriched in patients with immune cold phenotype and low-risk scores were enriched in patients with immune hot phenotype. Compared to the high-risk group, the low-risk group had better clinical performance, higher drug sensitivity, and a higher degree of immunoactivity, as well as better efficacy in receiving immunotherapy and common adjuvant therapy. This study developed an immune indicator consisting of BTK and DPEP2 based on the heterogeneity of hot and cold Immunophenotypes of the tumor microenvironment. This indicator has good efficacy in predicting prognosis and assessing the efficacy of immunotherapy, chemotherapy, and radiotherapy. It has the potential to facilitate personalized and precise treatment of LUAD in the future.

[Bioinformatic analysis of prognostic metabolism-related genes in lung adenocarcinoma].

Objective To construct and validate a prognostic model for lung adenocarcinoma based on bioinformatics of metabolic genes. Methods Lung adenocarcinoma-related data from The Cancer Genome Atlas (TCGA) database and gene expression omnibus (GEO) were acquired, and LASSO regression was used to construct multi-gene prognostic models and calculate risk-score (RS). Univariate and multivariate Cox independent prognostic analysis was performed. The area under receiver operating characteristic (ROC) curve (AUC) of the model was evaluated by ROC curve and survival analysis was performed. Nomogram were constructed to evaluate the feasibility of the model, and metabolic gene functional enrichment analysis was performed by GSEA. Tumor immune estimation resource (TIMER) database was used to analyze the correlation of patients RS with immune cell infiltration and with the expression of immune checkpoint molecules. Results The TCGA database was used to construct a prognostic model for lung adenocarcinoma based on 18 metabolism-related genes, and RS was used as an independent prognostic factor. The area under the ROC curve was 0.713. Survival analysis showed that overall survival was higher in the low-risk group compared to the high-risk group, and the prognostic model was associated with infiltration of immune cells and with the expression of immune checkpoint molecules. Conclusion RS is an independent prognostic factor in the prognostic model of lung adenocarcinoma with metabolic genes, suggesting a high prognostic value of this model.

Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients aged over 65 years.

The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged ≽ 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65-70 years (111 recipients, group 65-70) and ≽ 70 years (55 recipients, group ≽ 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group ≽ 70 (30.9% vs. 14.4% in group 65-70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65-70) and 7.3% (group ≽ 70) of patients. Kaplan-Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.

Point-of-Care Platform for Diagnosis of Venous Thrombosis by Simultaneous Detection of Thrombin Generation and D-Dimer in Human Plasma.

Venous thromboembolism (VTE) refers to a blood clot that starts in a vein. The risk of developing VTE is highest after major surgery or a major injury, or when someone has heart failure, cancer, or infectious disease (e.g., COVID-19). Without prompt treatment to break up clots and prevent more from forming, VTE can restrict or block blood flow and oxygen, which can damage the body tissue or organs. VTE can occur without any obvious signs, and imaging technologies are used. Alternatively rapid measurement of thrombin generation (TG) and D-dimer could be used to make a fast, portable, and easy-to-use diagnostic platform for VTE. Here, we have demonstrated a diagnostic sensing platform with the ability of simultaneous detection of TG and D-dimer in human plasma. Modifications were made to both the assay protocols to eliminate the need for sample dilution and incubation steps. Using a substantially reduced sample volume, the measurement results show comparable performance to the gold standard method. Our platform is able to deliver accurate and cost-effective results for both TG and D-dimer assays when using undiluted plasma in under 15 min. The assays presented are therefore a good candidate technology for use in a point-of-care platform to diagnose VTE.

Long-Term Exposure to Dust and Noise Can Increase the Risk of Hypertension-A Population Based, Cross-sectional Study.

OBJECTIVE: The aim of the study is to assess whether occupational groups exposed to dust and noise increase their risk of developing hypertension and to identify associated risk factors. METHODS: Logistic regression analysis was used to analyze the influence of exposure factors on the occurrence of hypertension, and confounding factors were adjusted to identify independent effects. Stratified analysis and smoothed curve fitting were used to explore the effects in different populations. RESULTS: Combined dust + noise exposure significantly increased the risk of hypertension in workers (model 1: odds ratio [OR], 2.75; model 2: OR, 2.66; model 3: OR, 2.85). Further analysis showed that when exposed to dust and noise for more than 17 years, the risk of hypertension increased by 15%. CONCLUSIONS: The combined exposure of dust and noise significantly increases the risk of hypertension among occupational groups, especially among workers who have worked for more than 17 years.

[Effects of urogenital mycoplasma and chlamydial infections on male fertility].

Objective： This study aimed to assess the impact of urogenital ureaplasma urealyticum (Uu), Mycoplasma hominis (Mh), and Chlamydia trachomatis (Ct) infections on semen quality in men.Methods： In this study, 1022 males were enrolled at the Department of Reproductive Medicine, Rizhao People's Hospital, Shandong Province from October 2014 to January 2023. The participants included 393 in the infertility group, 139 in the recurrent miscarriage group, and 490 in the control group. Based on age, 852 cases were < 36 years old, and 170 cases were ≥ 36 years old. All patients underwent routine semen analysis and tests for Uu, Mh, and Ct, with results statistically analyzed for their impact on semen quality and compared among different age groups. Results: Among the 1022 patients, 344 (33.6%) were Uu-positive, 49 (4.7%) were Mh-positive, and 31 (3.0%) were Ct positive. The sperm concentration, total sperm count, forward sperm motility rate (PR), sperm motility rate (PR+NP) and normal sperm morphology rate of Uu Mh and/or Ct-positive patients were significantly lower than those of the negative group, and the overall difference between the two groups was statistically significant (P<0.05). The positive rate of Uu infection was 41.7% in the infertility group, 30.2% in the recurrent miscarriage group and 28.2% in the control group, and the overall positive rate of the three groups was statistically significant(P<0.05). The positive rate of Mh infection was 6.9% in the infertility group, 8.6% in the recurrent miscarriage group and 2.0% in the control group, and the overall positive rate of the three groups was statistically significant (P<0.001). The positive rate of Ct infection was 6.1% in the infertility group, 2.9% in the recurrent miscarriage group and 0.6% in the control group, and the overall positive rate of the three groups was statistically significant (P<0.001). The positivity rate of Uu infection was 35.8% at the age of <36 years and 22.9% at the age ≥ 36 years, and there was a statistically significant difference in the positivity rate between the two groups (P<0.05). Conclusion: The prevalence of Uu infection in the male urogenital tract is significantly higher than that of Mh and Ct, which is the main pathogen of urogenital tract infection in men. Uu, Mh and Ct infections have adverse effects on sperm concentration, total sperm count, sperm forward motility rate (PR), sperm motility rate (PR+NP) and normal sperm morphology rate, which will lead to a decrease in semen quality and affect male fertility. Genital tract infections are closely related to age, and the prevalence of Uu infection is higher in the younger age group.

Integrating Microfluidics and Electronics in Point-of-Care Diagnostics: Current and Future Challenges.

Point-of-Care (POC) diagnostics have gained increasing attention in recent years due to its numerous advantages over conventional diagnostic approaches. As proven during the recent COVID-19 pandemic, the rapidity and portability of POC testing improves the efficiency of healthcare services and reduces the burden on healthcare providers. There are hundreds of thousands of different applications for POC diagnostics, however, the ultimate requirement for the test is the same: sample-in and result-out. Many technologies have been implemented, such as microfluidics, semiconductors, and nanostructure, to achieve this end. The development of even more powerful POC systems was also enabled by merging multiple technologies into the same system. One successful example is the integration of microfluidics and electronics in POC diagnostics, which has simplified the sample handling process, reduced sample usage, and reduced the cost of the test. This review will analyze the current development of the POC diagnostic systems with the integration of microfluidics and electronics and discuss the future challenges and perspectives that researchers might have.

Factor VIII companion diagnostic for haemophilia.

Haemophilia is predominantly an inherited disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. The condition of this disease is complex to manage, but many patients do so through home therapy and often only see their core multidisciplinary healthcare team annually. There is an increasing need for patients to be able to monitor their condition efficiently at home while staying connected with their healthcare team. As a consequence, a low-cost handheld self-monitoring solution for clotting factor is required. Here we have demonstrated a suitable one-step Factor VIII companion diagnostic sensing approach based on a chromogenic assay for haemophilia A. The results show comparable performance to the gold standard method. Our approach is able to deliver accurate cost-effective results in under 5 min from undiluted human plasma. It has the potential to be able to reduce the human and monetary costs of over- or under-medication for haemophiliacs.

Cervical sympathetic trunk transection alleviates acute lung injury caused by intestinal obstruction via inhibition of phospholipase A2 in rats.

BACKGROUND: Intestinal obstruction can result in inflammatory injury to distant organs, especially the lungs. Stellate ganglion block (SGB) provides sympathetic nervous homeostasis and inhibits the systemic inflammatory response. This study aimed to investigate whether SGB can alleviate acute lung injury by inhibiting phospholipase A2 expression in rats. METHODS: Thirty healthy male Sprague-Dawley rats were divided into three groups: C group (sham-operated); CLP group (cecal ligation and puncture with intestinal obstruction), and cervical sympathetic trunk transection (CSTT) group (transection of the cervical sympathetic trunk following CLP).Arterial blood samples were obtained to determine the ratio of partial arterial pressure of oxygen (PaO2) to fraction of oxygen in inspired air (FiO2). Venous blood samples were used to evaluate the serum concentrations of chemokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 using enzyme-linked immunosorbent assays. Following euthanasia, the lungs were isolated to estimate the wet/dry lung weight (W/D) ratio, evaluate the pathological damage to lung tissues on microscopy, and determine secretory-type phospholipase A2 (sPLA2) expression using western blotting. RESULTS: Rats in the CLP group showed increased fatigue, decreased activity levels, and coarse, gray hair. The levels of chemokines, TNF-α, and IL-6 in the CLP and CSTT groups were higher than those in the C group. However, the levels were lower in the CSTT group than those in the CLP group. IL-10 levels in the CLP group were higher and lower than those in the C and CSTT groups, respectively. W/D ratios and PaO2/FiO2 in the CLP and CSTT groups were higher than those in the C group, whereas these ratios in the CSTT group were lower than those in the CLP group. No lung injury was noted in group C, and the lung injury scores were lower in the CSTT group than those in the CLP group. sPLA2 expression levels in the CLP group were higher than those in the C group, whereas these levels in the CSTT group were lower than those in the CLP group. CONCLUSIONS: sPLA2 overexpression in the lungs may be a pathogenic factor in acute lung injury. CSTT alleviated acute lung injury by inhibiting sPLA2 expression.

BMI1 promotes cholangiocarcinoma progression and correlates with antitumor immunity in an exosome-dependent manner.

BACKGROUND: Cholangiocarcinoma (CCA) is a class of malignant tumors originating from bile duct epithelial cells. Due to difficult early diagnosis and limited treatment, the prognosis of CCA is extremely poor. BMI1 is dysregulated in many human malignancies. However, the prognostic significance and oncogenic role of BMI1 in cholangiocarcinoma (CCA) are not well elucidated. METHODS: In the present study, we investigated its clinical importance and the potential mechanisms in the progression of CCA. We detected BMI1 expression in a large CCA cohort. We demonstrated that BMI1 was substantially upregulated in CCA tissues and was identified as an independent prognostic biomarker of CCA. Moreover, overexpression of BMI1 promoted CCA proliferation, migration, and invasion. And BMI1 knockdown could inhibit proliferation and metastases of CCA in vitro and in vitro/vivo validation. Interestingly, we found that CCA-derived exosomes contain BMI1 proteins, which can transfer BMI1 between CCA cells. The unique BMI1-containing exosomes promote CCA proliferation and metastasis through autocrine/paracrine mechanisms. In addition, we demonstrated that BMI1 inhibits CD8+T cell-recruiting chemokines by promoting repressive H2A ubiquitination in CCA cells. CONCLUSIONS: BMI1 is an unfavorable prognostic biomarker of CCA. Our data depict a novel function of BMI1 in CCA tumorigenesis and metastasis mediated by exosomes. Besides, BMI1 inhibition may augment immune checkpoint blockade to inhibit tumor progression by activating cell-intrinsic immunity of CCA.

A narrative review of the protective effects of curcumin in treating ischemia-reperfusion injury.

Background and Objective: Ischemia-reperfusion (IR) injury is the cause of morbidity and mortality in a variety of diseases and surgical procedures including organ transplantation surgeries, acute coronary syndrome, strokes, and limb injuries. IR injury causes dysfunction of tissues and organs, and oxidative stress plays an important role in driving this process. Curcumin (CUR), a polyphenolic compound derived from turmeric, protects against IR injury by alleviating oxidative stress, reactive oxygen species (ROS) inflammation, apoptosis, and fibrosis. We review the protective effects of CUR against IR. Methods: We searched PubMed, ScienceDirect, and Web of Science databases using the keywords: ischemic reperfusion, CUR and summarized the results. Key Content and Findings: The effects of CUR during IR have been reported for animal models in vitro and in vivo and the compound has been shown in various organs by suppression of oxidative stress, prevention of inflammation, inhibition of apoptosis and autophagy. CUR with nanocarriers showed many advantages than free CUR in the treatment of IR injury, such as improved bioavailability, sustained-release, better water solubility, better target organ accumulation, improved permeability across the blood-brain-barrier and more effective. Conclusions: Nanotechnology offers significant improvements and promising strategies to improve drug delivery to IR-injured tissues and achieve the desired protective effects. Thus, it is necessary to promote further clinical trials to promote the clinical application of CUR with nanocarriers.

Relationship between lymphocyte to monocyte ratio and brain metastasis in non-smalll cell lung cancer patients.

OBJECTIVE: To observe whether there is an association between the lymphocyte/monocyte ratio (LMR) and the occurrence of brain metastases in non-small cell lung cancer (BM-NSCLC) patients. METHOD: Retrospective collection of patients' information meeting the standards of nano-excretion, was done from January 2016 to September 2021. We calculated the odds ratio (OR) and 95% confidence interval (CI) of LMR versus BM-NSCLC using multivariate logistic regression, and stratified analysis was performed. The linear or nonlinear relationships that exist between the two were explored by generalized additive model and smoothed curve fitting. RESULTS: In all three models, LMR was negatively associated with BM-NSCLC (Model 1: OR, 0.72; 95% CI, 0.57-0.9; P=0.0037. Model 2: OR, 0.64; 95% CI, 0.50-0.82; P=0.0005. Model 3: OR, 0.62; 95% CI, 0.47-0.81; P=0.0005). This negative association was shown to be significant in patients with adenocarcinoma (ADC), who were, female, and in T2-T4 stages, and N1-N3 stages (ADC: OR, 0.59; 95% CI, 0.44-0.80; P=0.0006. female: OR, 0.37; 95% CI, 0.20-0.68; P=0.0013. T2-T4: OR, 0.59; 95% CI, 0.43-0.82; P=0.0014; N1-N3: OR, 0.62; 95% CI, 0.45-0.86; P=0.0042), according to subgroup analysis. CONCLUSION: After controlling for relevant confounders, this study demonstrated that increased LMR levels in NSCLC patients were substantially and inversely connected to their likelihood of BM, particularly in patients with ADC, who were female, or had T2-T4, and N1-N3 stages.