In this study, we conducted this network meta-analysis (based on the ANOVA model) to evaluate the predictive efficacy of each early predictor. Persistent organ failure (POF) is one of the determining factors in patients with acute pancreatitis (AP); however, the diagnosis of POF has a long-time lag (>48h). It is of great clinical significance for the early noninvasive prediction of POF. We conducted a comprehensive and systematic search in PubMed, Cochrane library, Embase, and Web of Science to identify relevant clinical trials, case-control studies, or cohort studies, extracted the early indicators of POF in studies, and summarized the predictive efficacy of each indicator through network meta-analysis. The diagnostic odds ratio (DOR) was used to rank the prediction efficiency of each indicator. We identified 23 studies in this network meta-analysis, including 10,393 patients with AP, of which 2014 patients had POF. A total of 10 early prediction indicators were extracted. The mean and 95% CI lower limit of each predictive indicator were greater than 1.0. Albumin had the largest diagnostic odds ratio, followed by high-density lipoprotein-cholesterol (HDL-C), Ranson Score, beside index for severity in acute pancreatitis Score, acute physiology and chronic health evaluation II, C-reactive protein (CRP), Interleukin 6 (IL-6), Interleukin 8 (IL-8), Systemic Inflammatory Response Syndrome (SIRS) and blood urea nitrogen. Albumin, high-density lipoprotein-cholesterol, Ranson Score, and beside index for severity in acute pancreatitis Score are effective in the early prediction of POF in patients with AP, which can provide evidence for developing effective prediction systems. However, due to the limitations of the extraction method of predictive indicators in this study, some effective indicators may not be included in this meta-analysis.

This cross-sectional study aimed to analyze the relationship between live birth and the prevalence of obesity in Chinese women over 40 years of age. From April to November 2011, the Endocrinology Branch of the Chinese Medical Association conducted the REACTION project, a national, multicenter, cross-sectional study of Chinese adults aged 40 years and older. Demographic and medical data were collected through validated questionnaires and equipment. Anthropometric indicators, blood pressure, and biochemical data were measured by professional medical personnel. Data were analyzed using descriptive statistics and logistic analysis. Multivariate regression models were used to analyze obesity-related risk factors. The prevalence of obesity among women increased gradually from 3.8% to 6.0% with an increasing number of live births. Women with two live births had the highest prevalence of overweight at 34.3%. Overall, the obesity and overweight rates were slightly higher in premenopausal women than in postmenopausal women. Univariate regression analysis showed that the risk of obesity in women increased with an increasing number of live births. In addition, multivariate regression analysis showed that the risk of obesity increased with an increasing number of live births in women with systolic blood pressure (SBP) < 121 mmHg or current smoking (P < 0.05). The risk of obesity increases with the number of live births in Chinese women over 40 years of age with SBP < 121 mmHg or current smoking. Our findings may facilitate the development of interventions to prevent obesity in this population.

A novel nucleic acid aptamer nanoprobes-mediated hairpin allosteric and aptamer-assisted CRISPR system for detection of Streptococcus pneumoniae and Staphylococcus aureus is presented.In this fluorescence assay system, utilizing the hairpin allosteric effect caused by the aptamer binding to the target bacteria, the detection of S. pneumoniae is first achieved through changes in fluorescence due to FRET. Subsequently, aCas12a protein mixture is added to detect S. aureus. The amplified output signal is triggered by two methods to ensure the sensitivity of the method: the synergistic FRET effect is achieved by the assembly of multi-aptamer through the conjugation of streptavidin-biotin, and the trans-cleavage function of CRISPR/Cas 12a. Under the optimized conditions, the proposed hairpin allosteric aptasensor could achieve high sensitivity (a detection limit of 135cfu/mL) and broad-concentration quantification (dynamic range of 103-107cfu/mL) of S. pneumoniae. The aptamer-assisted CRISPR system for S. aureus detection showed good linearity (R2 = 0.996) in the concentration range 102-108cfu/mL, with a detection limit of 39cfu/mL. No cross-reactivity with other foodborne pathogenic bacteria was observed in both systems. Taking only 55min, this method of multiple pathogen detection proved to be promising.

A ketogenic diet (KD) and β-hydroxybutyrate (βOHB) have been widely reported as effective therapies for metabolic diseases. β-Hydroxybutyrate dehydrogenase 1 (BDH1) is the rate-limiting enzyme in ketone metabolism. In this study, we examined the BDH1-mediated βOHB metabolic pathway in the pathogenesis of diabetic kidney disease (DKD). We found that BDH1 is downregulated in the kidneys in DKD mouse models, patients with diabetes, and high glucose- or palmitic acid-induced human renal tubular epithelial (HK-2) cells. BDH1 overexpression or βOHB treatment protects HK-2 cells from glucotoxicity and lipotoxicity by inhibiting reactive oxygen species overproduction. Mechanistically, BDH1-mediated βOHB metabolism activates NRF2 by enhancing the metabolic flux of βOHB-acetoacetate-succinate-fumarate. Moreover, in vivo studies showed that adeno-associated virus 9-mediated BDH1 renal expression successfully reverses fibrosis, inflammation, and apoptosis in the kidneys of C57 BKS db/db mice. Either βOHB supplementation or KD feeding could elevate the renal expression of BDH1 and reverse the progression of DKD. Our results revealed a BDH1-mediated molecular mechanism in the pathogenesis of DKD and identified BDH1 as a potential therapeutic target for DKD.

ObjectiveTo characterize potential mechanisms of fisetin on hepatic insulin resistance (IR) using network pharmacology and in vitro validation.MethodsPutative targets of fisetin were retrieved from the Traditional Chinese Medicine Systems Pharmacology database, whereas the potential genes of hepatic IR were obtained from GeneCards database. A protein–protein interaction (PPI) network was constructed according to the intersection targets of fisetin and hepatic IR using the Venn diagram. The biological functions and potential pathways related to genes were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Cell experiments were also conducted to further verify the mechanism of fisetin on hepatic IR.ResultsA total of 118 potential targets from fisetin were associated with hepatic IR. The areas of nodes and corresponding degree values of TP53, AKT1, TNF, IL6, CASP3, CTNNB1, JUN, SRC, epidermal growth factor receptor (EGFR), and HSP90AA1 were larger and could be easily found in the PPI network. Furthermore, GO analysis revealed that these key targets were significantly involved in multiple biological processes that participated in oxidative stress and serine/threonine kinase activity. KEGG enrichment analysis showed that the PI3K/AKT signaling pathway was a significant pathway involved in hepatic IR. Our in vitro results demonstrated that fisetin treatment increased the expressions of EGFR and IRS in HepG2 and L02 cells under normal or IR conditions. Western blot results revealed that p-AKT/AKT levels were significantly up-regulated, suggesting that fisetin was involved in the PI3K/AKT signaling pathway to regulate insulin signaling.ConclusionWe explored the pharmacological actions and the potential molecular mechanism of fisetin in treating hepatic IR from a holistic perspective. Our study lays a theoretical foundation for the development of fisetin for type 2 diabetes.

Mesenchymal stem cells (MSCs) are getting attention in the field of cancer immunotherapy. The main effects of MSCs on tumors are homing and regulation of inflammatory and immune responses. Indeed, cancer immunotherapy has become a promising treatment and MSCs play a potential role in regulating the efficacy of immunotherapy. In addition, MSCs are an ideal carrier for immunomodulatory protein transmission. As such MSCs combined with immunotherapy drugs could act synergistically against tumors, throwing a great impact on cancer therapy. And MSCs may have potential in the treatment of cytokine storm or cytokine release syndrome (CRS). It is assumed that MSCs can form chimeric antigen receptor MSCs (CAR-MSCs). Whether CAR-MSCs can provide a new idea of cancer immunotherapy is unknown. It is a prime time to review the latest progress of MSCs in cancer immunotherapy, in order to clarify to fully understand the role of MSCs in cancer therapy in clinical practice.

This translational study aimed to determine the maximum tolerated dose (MTD), safety, dosimetry, and therapeutic efficacy of 177Lu-PSMA-EB-01 (denoted as [177Lu]Lu-LNC1003) in patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 13 patients with mCRPC were recruited in this study. A standard 3 + 3 dose escalation protocol was performed. The following dose levels were ultimately evaluated: 1.11, 1.85, and 2.59GBq/cycle. Patients received [177Lu]Lu-LNC1003 therapy for up to two cycles at a 6-week interval. Patients received fractionated doses of [177Lu]Lu-LNC1003 ranging from 1.11 to 2.59GBq per cycle. Myelosuppression was dose-limiting at 2.59GBq, and 1.85GBq was determined to be the MTD. The total-body effective dose for 177Lu-LNC1003 was 0.35 ± 0.05mSv/MBq. The salivary glands were found to receive the highest estimated radiation dose, which was calculated to be 3.61 ± 2.83mSv/MBq. The effective doses of kidneys and red bone marrow were 1.88 ± 0.35 and 0.22 ± 0.04mSv/MBq, respectively. The tumor mean absorbed doses for bone and lymph node metastases were 8.52 and 9.51mSv/MBq. Following the first treatment cycle, PSA decline was observed in 1 (33.3%), 4 (66.7%), and 2 (50.0%) patients at dose levels 1 (1.11GBq), 2 (1.85GBq), and 3 (2.59GBq), respectively. Compared with the baseline serum PSA value, 1 (33.3%) at dose level 1 and 4 (66.6%) patients at dose level 2, presented a PSA decline after the second treatment cycle. This phase 1 trial revealed that the MTD of [177Lu]Lu-LNC1003 is 1.85GBq. The treatment with multiple cycles at the dose of 1.11GBq /cycle and 1.85GBq /cycle was well tolerated. [177Lu]Lu-LNC1003 has higher tumor effective doses in bone and lymph nodes metastases while the absorbed dose in the red bone marrow should be closely monitored in future treatment studies with higher doses and multiple cycles. The frequency of administration also needs to be further explored to assess the efficacy and side effects of [177Lu]Lu-LNC1003 treatment. 177Lu-PSMA-EB-01 in patients with metastatic castration-resistant prostate cancer (NCT05613738, Registered 14 November 2022). URL of registry https://classic. gov/ct2/show/NCT05613738.