CD40L-Activated DC Promotes Th17 Differentiation and Inhibits Th2 Differentiation in Sepsis-Induced Lung Injury via cGAS-STING Signaling.

Immune hemostasis due to an infection plays a vital role in sepsis-induced multiple organ dysfunction. Dendritic cells (DC) and T helper (Th) cells are the key members of the immune system maintaining immune homeostasis. This study aimed to explore the effect and mechanism of CD40L on the activation of DC and activated DC-induced Th2/Th17 differentiation. A CD40L knockout and cecal ligation and puncture (CLP) mouse model was established via cecal ligation. HE staining was used to evaluate the pathological changes. The gene expressions were studied using quantitative real-time polymerase chain reaction (qRT-PCR), while a transwell system was used to perform the co-culture of DC and T-cells. Flow cytometry was performed to detect the subtype of T and DC cells. ELISA was used to assess the amount of inflammatory factors. CD40L was highly expressed in the plasma of CLP mice. Knock out of CD40L inhibited the activation of DC cell and Th17 differentiation while promoting the Th2 differentiation. The mechanistic investigations revealed that CD40L promoted the activation of cGAS-STING pathway. Rescue experiments indicated that CD40L mediated DC activation via cGAS-STING signaling. Moreover, co-culturing of CD and CD+4 T-cells demonstrated that silencing of CD40L in DC suppressed the DC activation and inhibited Th17 differentiation while promoting Th2 differentiation. These findings revealed a relationship between CD40L, DC activation, and Th2/Th17 differentiation balance in sepsis-induced acute lung injury for the first time. These findings are envisaged to provide novel molecular targets for sepsis-induced lung injury treatment.

C-reactive protein to albumin ratio as a prognostic tool for predicting intravenous immunoglobulin resistance in children with kawasaki disease: a systematic review of cohort studies.

BACKGROUND: Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10-20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. METHODS: Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. RESULTS: Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58-0.72), specificity as 0.71 (95% CI 0.57-0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66-0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35-3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35-0.69), and the diagnostic odds ratio was 5 (95% CI 2-10). CONCLUSION: CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

Body mass index changes after transjugular intrahepatic portosystemic shunt in individuals with cirrhosis.

OBJECTIVES: Liver cirrhosis is often accompanied by portal hypertension and malnutrition, two common complications that seriously affect treatment efficacy and quality of life. This study aimed to investigate the effect of transjugular intrahepatic portosystemic shunt (TIPS) on body mass index (BMI) and metabolism in individuals with cirrhotic portal hypertension, and the risk factors that affect changes of BMI. METHODS: A retrospective study was performed to collect basic information before and after TIPS. This study included 77 participants. For each participant, we assayed body nutrition parameters: change of weight and BMI, routine liver and kidney function tests, and free fatty acids. In addition, we evaluated glucose and biochemical indexes. We used analysis of variance and regression analysis to investigate the effect of TIPS on BMI and metabolism in individuals with cirrhotic portal hypertension, and the risk factors that affect changes of BMI and metabolic components. RESULTS: After TIPS, there was significant improvement in weight, BMI, red blood cell count, blood platelet count, hemoglobin, and Child-Pugh score in individuals with cirrhotic portal hypertension. Average weight and BMI increased after TIPS by 3.2% and 3.4%, respectively (P < 0.05). After 36 months, there were no significant differences in weight and BMI between before and after TIPS. We also observed a dose-response association of pre-TIPS blood ammonia and increased post-TIPS BMI (P = 0.05) in men. CONCLUSIONS: This study suggests that individuals with cirrhosis treated with TIPS may see improvement in overall clinical and physical status, as measured by increased weight and BMI. Our data also indicate that pre-TIPS blood ammonia is positively associated with post-TIPS BMI.

Development and evaluation of a rapid CRISPR-based diagnostic for COVID-19.

The recent outbreak of human infections caused by SARS-CoV-2, the third zoonotic coronavirus has raised great public health concern globally. Rapid and accurate diagnosis of this novel pathogen posts great challenges not only clinically but also technologically. Metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR (RT-PCR) have been the most commonly used molecular methodologies. However, each has their own limitations. In this study, we developed an isothermal, CRISPR-based diagnostic for COVID-19 with near single-copy sensitivity. The diagnostic performances of all three technology platforms were also compared. Our study aimed to provide more insights into the molecular detection of SARS-CoV-2, and also to present a novel diagnostic option for this new emerging virus.

Heterostructured Bi2O2CO3/rGO/PDA photocatalysts with superior activity for organic pollutant degradation: Structural characterization, reaction mechanism and economic assessment.

Compared with conventional methods for organic pollutant degradation, photocatalysis is a promising treatment technology with broad application prospects. Bi2O2CO3 is often used for organic pollutants degradation but greatly restricted by having drawbacks of large band gap and high electron-hole recombination rate. Herein, heterostructured Bi2O2CO3 (BOC)/reduced graphene oxide (rGO)/polydopamine (PDA) (BGP) photocatalysts were first designed through a green chemical method. By incorporating rGO and PDA in BOC, the kinetic constant of BGP to catalytically degrade methyl orange (MO) was significantly increased; over fourfold elevated rather than that of BOC (kapp/BOC = 0.0019, kapp/BGP = 0.0089) due to the high electron transfer capability of rGO and superior adhesive force and semiconducting properties of PDA. DRS and photoelectrochemical results confirmed the improvement of the light absorption range and charge transfer capability because of the synergistic effect of rGO and PDA. Results of trapping experiment and ESR unraveled the catalytic mechanism that both holes (h+) and superoxide radicals (•O2-) were the main oxidative species for MO degradation. Economic assessment results demonstrated that Bi2O2CO3/rGO/PDA heterojunctions have great potentials in the field of organic wastewater purification. This study developed a low-cost and highly efficient BGP material and provided a deep understanding of the structure-performance relationships of materials for organic pollutant degradation.

CRISPR-based rapid and ultra-sensitive diagnostic test for Mycobacterium tuberculosis.

Rapid and simple-to-use diagnostic methods for tuberculosis are urgently needed. Recent development has unveiled the diagnostic power of the CRISPR system in the detection of viral infections. However, its potential use in detecting the Mycobacterium tuberculosis complex (MTB) remained unexplored. We developed a rapid CRISPR-based assay for TB detection and conducted a retrospective cohort study of 179 patients to evaluate the CRISPR-MTB test for identifying MTB in various forms of direct clinical samples. Its diagnostic performance was compared, in parallel with culture and the GeneXpert MTB/RIF assay (Xpert). The CRISPR-MTB test is highly sensitive with a near single-copy sensitivity, demands less sample input and offers shorter turnaround time than Xpert. When evaluated in the clinical cohort of both pulmonary and extra-pulmonary tuberculosis, the CRISPR-MTB test exhibited an overall improved sensitivity over both culture (79% vs 33%) and Xpert (79% vs 66%), without comprise in specificity (62/63, 98%). The CRISPR-MTB test exhibits an improved overall diagnostic performance over culture and Xpert across a variety of sample types, and offers great potential as a new diagnostic technique for both pulmonary and extra-pulmonary tuberculosis.

Impacts of Related Risk Factors on the Efficacy of Interventional Treatment Towards Intractable Postpartum Hemorrhage.

Objective: To investigate the risk factors that impact the efficacy of interventional treatment of intractable postpartum hemorrhage (IPH). Study Design: A total of 64 IPH patients were admitted and received interventional treatment at First Hospital of Shanxi Medical University from January 2012 to September 2014, among whom 57 cases were successfully treated (bleeding stopped), while 7 cases failed. The clinical data of the success group and the failure group were observed for the multivariate analysis of the possible reasons that might cause hemostatic failure. Results: The univariate analysis of each suspected factor of hemostatic failure showed that history of uterine scar, combined use of uterotonics, uterine inertia, and placenta exhibited statistically significant differences between the 2 groups (p<0.05); the multivariate logistic regression analysis showed that history of uterine scar and combined use of uterotonics were the risk factors for the interventional treatment failure of IPH, with OR values of 11.23 (95% CI 1.26~100.22) and 12.83 (95% CI 1.05-156.34), respectively. Conclusion: History of uterine scar and combined use of uterotonics were the risk factors for interventional treatment failure of IPH.

Clinical efficacy of percutaneous transluminal renal artery stenting for the treatment of renovascular hypertension associated with Takayasu arteritis.

BACKGROUND: This study aims to observe and analyze the clinical efficacy of interventional therapy for patients with Takayasu arteritis (TA) experiencing renovascular hypertension (RH). METHODS: Eight TA patients with RH underwent percutaneous transluminal renal artery stenting (PTRAS). Patients were followed up 1, 6, 12, and 24 months postoperatively for levels of blood pressure, number of antihypertensive drugs being taken, levels of serum creatinine, and the presence of renal artery restenosis. RESULTS: All 8 patients were successfully followed up 1, 6, and 12 months postoperatively, but 1 was lost to follow-up at 24 months. All patients had significantly lower average blood pressure levels compared with those at baseline (P < 0.05); treatment efficacy rates (recovery or improvement) at 1, 6, 12, and 24 months were 94%, 90%, 80%, and 80%, respectively. The average number of antihypertensive drugs being taken was 3.5 at baseline, 1.0 at 1 month, 0.5 at 6 months, 1.0 at 12 months, and 1.5 at 24 months. Serum creatinine levels during the follow-up period were not significantly different from those at the baseline. No patient developed renal artery restenosis during the follow-up period. CONCLUSIONS: PTRAS is a safe and effective treatment for TA-associated RH, with a high technical success rate and a low complication rate. This interventional therapy can effectively control TA-related hypertension and can also preserve and even improve kidney function.