Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome.

BACKGROUND: Chronic heart failure is a complex clinical syndrome. The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure; however, the underlying molecular mechanism is still not clear. AIM: To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure. METHODS: The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target genes of chronic heart failure were searched in the Genecards database. The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drug-disease targets, which were then used to construct a key chemical component-target network using Cytoscape 3.7.2 software. The protein-protein interaction network was constructed using the String database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database. Finally, our previously published relevant articles were searched to verify the results obtained via network pharmacology. RESULTS: A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified, of which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, HSP90AA1, p65, MAPK8, MAPK14, IL6, EGFR, EDN1, FOS, and other proteins. The pathways identified by KEGG enrichment analysis include pathways in cancer, IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, cAMP signaling pathway, NF-kappaB signaling pathway, AMPK signaling pathway, etc. Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α, IL-6, MAPK, cAMP, and AMPK pathways to affect the mitochondrial structure of myocardial cells, oxidative stress, and energy metabolism, thus achieving the therapeutic effects on chronic heart failure. CONCLUSION: The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes, oxidative stress, energy metabolism, and other processes. Future studies are warranted to investigate the role of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Based on 3D-PDU and clinical characteristics nomogram for prediction of lymph node metastasis and lymph-vascular space invasion of early cervical cancer preoperatively.

PURPOSE: To develop and validate a nomogram based on 3D-PDU parameters and clinical characteristics to predict LNM and LVSI in early-stage cervical cancer preoperatively. MATERIALS AND METHODS: A total of first diagnosis 138 patients with cervical cancer who had undergone 3D-PDU examination before radical hysterectomy plus lymph dissection between 2014 and 2019 were enrolled for this study. Multivariate logistic regression analyses were performed to analyze the 3D-PDU parameters and selected clinicopathologic features and develop a nomogram to predict the probability of LNM and LVSI in the early stage. ROC curve was used to evaluate model differentiation, calibration curve and Hosmer-Lemeshow test were used to evaluate calibration, and DCA was used to evaluate clinical practicability. RESULTS: Menopause status, FIGO stage and VI were independent predictors of LNM. BMI and maximum tumor diameter were independent predictors of LVSI. The predicted AUC of the LNM and LSVI models were 0.845 (95%CI,0.765-0.926) and 0.714 (95%CI,0.615-0.813). Calibration curve and H-L test (LNM groups P = 0.478; LVSI P = 0.783) all showed that the predicted value of the model had a good fit with the actual observed value, and DCA indicated that the model had a good clinical net benefit. CONCLUSION: The proposed nomogram based on 3D-PDU parameters and clinical characteristics has been proposed to predict LNM and LVSI with high accuracy, demonstrating for the first time the potential of non-invasive prediction. The probability derived from this nomogram may have the potential to provide valuable guidance for physicians to develop clinical individualized treatment plans of FIGO patients with early cervical cancer.

Association between pre- and post-diagnosis healthy eating index 2020 and ovarian cancer survival: evidence from a prospective cohort study.

Background: Previous studies on the association between diet quality and ovarian cancer (OC) survival are limited and inconsistent. We evaluated the relationship between pre- and post-diagnosis diet quality based on the Healthy Eating Index-2020 (HEI-2020), as well as their changes and OC survival. Methods: This prospective cohort study involved 1082 patients with OC aged 18-79 years, enrolled between 2015 and 2022. Detailed dietary intake before and after diagnosis was recorded using a validated food frequency questionnaire. Deaths were ascertained until February 16th, 2023 via medical records and active follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: We included 549 OC cases with a median follow-up of 44.9 months, representing 206 total deaths. Higher HEI scores were associated with better OS (pre-diagnosis: HRT3 vs. T1 0.66, 95%CI: 0.46-0.93, HR1-SD 0.84, 95%CI: 0.73-0.96; post-diagnosis: HRT3 vs. T1 0.68, 95%CI: 0.49-0.96, HR1-SD 0.80, 95%CI: 0.69-0.92). Compared to the stable group, the group with decreased HEI scores (>3%) from pre- to post-diagnosis had worse OS (HR 1.93, 95%CI: 1.26-2.97). Conclusion: High pre- and post-diagnosis diet quality was associated with improved OC survival, whereas deterioration in diet quality after diagnosis was associated with decreased OC survival.

Transition-Metal-Free Hydrodefluoroamination of Trifluoromethyl Enones for the Synthesis of α-Fluoroenamides.

A three-component strategy was developed to enable hydrodefluoroamination of ß-trifluoromethyl enones by selectively activating two C(sp3)-F bonds in the trifluoromethyl group. The method involved a sequence of carbonyl reduction, hydrodefluorination, and defluoroamination under transition-metal-free conditions. Synthetically useful (E)-stereospecific α-fluoroenamides were obtained in good yields with diverse functional group tolerance, which could be easily transformed into valuable organofluorides and heterocycles. The carbonyl auxiliary exerts both electronic and steric impacts on the CF3-alkenes, allowing for controllable and selective defluorination.

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Associations between dietary macronutrient quality and asthenozoospermia risk: a hospital-based case-control study.

Background & aims: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). Methods: A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. Results: No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers (Ptrend < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; Ptrend < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk (P < 0.05). Conclusions: Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Long-Term Results From the PKUFH Randomized Phase 3 Trial.

PURPOSE: In the randomized, single-center, PKUFH phase 3 trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the 2 cohorts at 4 years. In the current analysis, we provide 7-year outcomes. METHODS AND MATERIALS: Patients with stage pT3-4, positive surgical margins, or a prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image guided intensity modulated radiation therapy. The primary endpoint was bPFS. Secondary endpoints were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) as estimated using the Kaplan-Meier method. RESULTS: Between September 2011 and November 2016, 144 patients were enrolled with 73 and 71 in the 72- and 66-Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72- and 66-Gy cohorts (70.3% vs 61.2%; hazard ratio [HR], 0.73; 95% CI, 0.41-1.29; P = .274). However, in patients with a higher Gleason score (8-10), the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66-Gy cohort (66.5% vs 30.2%; HR, 0.37; 95% CI, 0.17-0.82; P = .012). In addition, in patients with multiple positive surgical margins, the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR, 0.36; 95% CI, 0.13-0.99; P = .037). The 7-year DMFS (88.4% vs 84.9%; HR, 0.93; 95% CI, 0.39-2.23; P = .867), CSS (94.1% vs 95.5%; HR, 1.19; 95% CI, 0.42-3.39; P = .745), and OS (92.8% vs 94.1%; HR, 1.29; 95% CI, 0.51-3.24; P = .594) had no statistical differences between the 72- and 66-Gy cohorts. CONCLUSIONS: The current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared with the 66-Gy regimen. However, patients with a higher Gleason score (8-10) or multiple positive surgical margins might benefit from the 72-Gy regimen, but this requires further prospective research.

Targeted chemical profiling for p-HAP glycosides by using molecular networking and comparative analysis of their contents between Artemisia japonica and Artemisia capillaris.

A total of 65 phenolic acid compounds were annotated or identified by UHPLC-MS/MS method, among them, 17 p-HAP (p-hydroxyacetophenone) glycosides were firstly targeted profiled based on molecular networking. Their characteristic product ions of MS/MS spectra were found and examined on the guideline of targeted isolation. As a result, a new p-HAP glycoside was thus obtained and determined as 2'-O-caffeoyl-p-HAP-4-O-ß-D-glucopyranoside (33) based on 1D and 2D NMR data. Besides, multicomponents quantitative analysis indicated the distinct regional variability in chemicals distribution of A. japonica, and meanwhile, the contents of p-HAP glycosides from A. japonica were higher than those in A. capillaris as a whole, which further suggested the potential medicinal value of A. japonica.

Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes.

Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

Glutamate-pantothenate pathway promotes antibiotic resistance of Edwardsiella tarda.

Although cellular metabolic states have been shown to modulate bacterial susceptibility to antibiotics, the interaction between glutamate (Glu) and chloramphenicol (CAP) resistance remains unclear because of the specificity of antibiotics and bacteria. We found that the level of Glu was upregulated in the CAP-resistant strain of Edwardsiella tarda according to a comparative metabolomics approach based on LC-MS/MS. Furthermore, we verified that exogenous metabolites related to Glu, the tricarboxylic acid (TCA) cycle, and glutathione (GSH) metabolism could promote CAP resistance in survival assays. If GSH metabolism or the TCA cycle is inhibited by L-buthionine sulfoximine or propanedioic acid, the promotion of CAP resistance by Glu in the corresponding pathway disappears. According to metabolomic analysis, exogenous Glu could change pantothenate metabolism, affecting GSH biosynthesis and the TCA cycle. These results showed that the glutamate-pantothenate pathway could promote CAP resistance by being involved in the synthesis of GSH, entering the TCA cycle by direct deamination, or indirectly affecting the metabolism of the two pathways by pantothenate. These results extend our knowledge of the effect of Glu on antibiotic resistance and suggest that the potential effect, which may aggravate antibiotic resistance, should be considered before Glu and GSH administration in the clinic.

3D-Printed MOFs/Polymer Composite as a Separatable Adsorbent for the Removal of Phenylarsenic Acid in the Aqueous Solution.

Metal-organic frameworks (MOFs) are emerging as advanced nanoporous materials to remove phenylarsenic acid, p-arsanilic acid (p-ASA), and roxarsone (ROX) in the aqueous solution, while MOFs are often present as powder state and encounter difficulties in recovery after adsorption, which greatly limit their practical application in the aqueous environments. Herein, MIL-101 (Fe), a typical MOF, was mixed with sodium alginate and gelatin to prepare MIL-101@CAGE by three-dimensional (3D) printing technology, which was then used as a separatable adsorbent to remove phenylarsenic acid in the aqueous solution. The structure of 3D-printed MIL-101@CAGE was first characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and thermogravimetry and differential thermogravimetry (TG-DTG). The octahedral morphology of MIL-101 (Fe) was found unchanged during the 3D printing process. Then, the adsorption process of MIL-101@CAGE on phenylarsenic acids was systematically investigated by adsorption kinetics, adsorption isotherms, adsorption thermodynamics, condition experiments, and cyclic regeneration experiments. Finally, the adsorption mechanism between MIL-101@CAGE and phenylarsenic acid was further investigated. The results showed that the Langmuir, Freundlich, and Temkin isotherms were well fit, and according to the Langmuir fitting results, the maximum adsorption amounts of MIL-101@CAGE on p-ASA and ROX at 25 °C were 106.98 and 120.28 mg/g, respectively. The removal of p-ASA and ROX by MIL-101@CAGE remained stable over a wide pH range and in the presence of various coexisting ions. The regeneration experiments showed that the 3D-printed MIL-101@CAGE could still maintain a more than 90% removal rate after five cycles. The adsorption mechanism of this system might include π-π stacking interactions between the benzene ring on the phenylarsenic acids and the organic ligands in MIL-101@CAGE, hydrogen-bonding, and ligand-bonding interactions (Fe-O-As). This study provides a new idea for the scale preparation of a separatable and recyclable adsorbent based on MOF material for the efficient removal of phenylarsenic acid in the aqueous solution.

Current advances in the detection and removal of organic arsenic by metal-organic frameworks.

Arsenic (As) is a highly toxic heavy metal and has been widely concerned for its hazardous environmental impact. Aromatic organic arsenic (AOCs) has been frequently used as an animal supplement to enhance feed utilization and prevent dysentery. The majority of organic arsenic could be discharged from the body and evolve as highly toxic inorganic arsenic that is hazardous to the environment and human health via biological conversion, photodegradation, and photo-oxidation. Current environmental issues necessitate the development and application of multifunctional porous materials in environmental remediation. Compared to the conventional adsorbent, such as activated carbon and zeolite, metal-organic frameworks (MOFs) exhibit a number of advantages, including simple synthesis, wide variety, simple modulation of pore size, large specific surface area, excellent chemical stability, and easy modification. In recent years, numerous scientists have investigated MOFs related materials involved with organic arsenic. These studies can be divided into three categories: detection of organic arsenic by MOFs, adsorption to remove organic arsenic by MOFs, and catalytic removal of organic arsenic by MOFs. Here, we conduct a critical analysis of current research findings and knowledge pertaining to the structural characteristics, application methods, removal properties, interaction mechanisms, and spectral analysis of MOFs. We summarized the application of MOFs in organic arsenic detection, adsorption, and catalytic degradation. Other arsenic removal technologies and conventional substances are also being investigated. This review will provide relevant scientific researchers with references.

Outcomes of catheter-directed thrombolysis versus systemic thrombolysis in the treatment of pulmonary embolism: a meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) versus systemic thrombolysis (ST) in the treatment of pulmonary embolism (PE). METHODS: The Cochrane Library, PubMed, and Embase databases were searched to collect the literature on the comparison of the results of CDT and ST in the treatment of PE from the beginning of their records to May 2020, and meta-analysis was performed by STATA software (version 15.1). Using standardized data-collection forms, the authors screened the studies and independently extracted data, and assessed the quality of the studies using the Newcastle-Ottawa Scale for cohort studies. Cohort studies that examined the following results were included in the current study: in-hospital mortality, all-cause bleeding rate, gastrointestinal bleeding rate, intracranial hemorrhage rate, the incidence of shock, and hospital length of stay. RESULTS: A total of eight articles, with 13,242 participants, involving 3962 participants in the CDT group and 9280 participants in the ST group were included. CDT compared with ST in the treatment of PE can significantly affect in-hospital mortality rate [odds ratio (OR) = 0.41, 95% CI: 0.30-0.56, P < 0.05], all-cause bleeding rate (OR = 1.20, 95% CI: 1.04-1.39, P = 0.012), gastrointestinal bleeding rate (OR = 1.43, 95% CI: 1.13-1.81, P = 0.003), the incidence of shock (OR = 0.46, 95% CI: 0.37-0.57, P < 0.05), and hospital length of stay [standard mean difference (SMD) = 0.16, 95% CI: 0.07-0.25, P < 0.05]. However, there was no significant effect on intracranial hemorrhage rate in patients with PE (OR = 0.70, 95% CI: 0.47-1.03, P = 0.070). CONCLUSIONS: CDT is a viable alternative to ST in the treatment of PE, as it can significantly reduce in-hospital mortality rate, all-cause bleeding rate, gastrointestinal bleeding rate, and incidence of shock. However, CDT may prolong hospital length of stay to a certain extent. Further research is needed to evaluate the safety and efficacy of CDT and ST in the treatment of acute PE and other clinical outcomes.

Overexpression of Taetr1-1 promotes enhanced seed dormancy and ethylene insensitivity in wheat.

MAIN CONCLUSION: Taetr1-1 can promote enhanced seed dormancy and ethylene insensitivity in wheat, indicating a conserved function of ETR1 in regulating seed dormancy. Lots of wheat cultivars have weak dormant seed. Weak seed dormancy can cause pre-harvest sprouting (PHS) in grain which significantly reduces grain yield and quality. The mining of causal genes of PHS resistance will serve to enhance breeding selection and cultivar development. In a previous study in Arabidopsis, we identified reduced dormancy 3 as a loss-of-function mutant of the ethylene receptor 1 (ETR1), which can control seed dormancy through the ERF12-TPL-DOG1 pathway. However, it is unknown whether ETR1 also functions in the regulation of wheat seed dormancy. To identify the regulatory role of ETR1 in wheat, we cloned TaETR1 and overexpressed the gain-of-function mutant Taetr1-1. The result indicated that overexpression of Taetr1-1 can promote enhanced seed dormancy and ethylene insensitivity in wheat. This study contributed to our understanding of the molecular basis for the regulation of wheat PHS resistance.

Efficacy and safety of vena cava filters in preventing pulmonary embolism: A systematic review and meta-analysis.

OBJECTIVES: To assess the treatment effectiveness of inferior vena cava filters (IVCF) versus non-IVCF for patients undergoing varies conditions. METHODS: We systematically searched the databases to identify eligible RCTs from their inception up to 9/20/2020. The primary endpoint was pulmonary embolism (PE), while the secondary endpoints included deep-vein thrombosis (DVT), major bleeding, and all-cause mortality. The RRs with 95% CIs were applied as effect estimates for the treatment effectiveness of IVCF versus non-IVCF and calculated by using the random-effects model. RESULTS: 1,137 patients of 5 RCTs were enrolled. There were no significant differences between IVCF and non-IVCF for the risk of PE, major bleeding, and all-cause mortality, while the risk of DVT was significantly increased for patients treated with IVCF. CONCLUSIONS: The use of IVCF did not yield any benefits on PE, major bleeding, and all-cause mortality risk for patients undergoing various conditions, while the risk of DVT was significantly increased for patients treated with IVCF.

Steatotic hepatocyte-derived extracellular vesicles promote ß-cell apoptosis and diabetes via microRNA-126a-3p.

Extracellular vesicles (EVs) have emerged as a unique mediator of interorgan communications, playing important roles in the pathophysiologic process of various diseases, including diabetes and other metabolic diseases. Here, we reported that the EVs released by steatotic hepatocytes exerted a detrimental effect on pancreatic ß cells, leading to ß-cell apoptosis and dysfunction. The effect was profoundly attributable to an up-regulation of miR-126a-3p in the steatotic hepatocyte-derived EVs. Accordingly, overexpression of miR-126a-3p promoted, whereas inhibition of miR-126a-3p prevented ß-cell apoptosis, through a mechanism related to its target gene, insulin receptor substrate-2. Moreover, inhibition of miR-126a-3p by its specific antagomir was able to partially reverse the loss of ß-cell mass and ameliorate hyperglycaemia in diabetic mice. Thus, the findings reveal a novel pathogenic role of steatotic hepatocyte-derived EVs, which mechanistically links nonalcoholic fatty liver disease to the development of diabetes.

Strong Cumulative Evidence of Associations of 6 Single Nucleotide Polymorphisms with Ovarian Cancer Risk: An Umbrella Review.

Background: An increasing number of studies have reported associations between single nucleotide polymorphisms (SNPs) and ovarian cancer (OC) risk. However, some of the findings were inconsistent. The objective of this umbrella review was to evaluate the associations comprehensively and quantitatively. Methods: The protocol of this review was registered in PROSPERO (No. CRD42022332222). We searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses from inception to 15 October 2021. In addition to estimating the summary effect size by using fixed and random effects models and calculating the 95% prediction interval, we evaluated the cumulative evidence for associations with nominally statistical significance based on the Venice criteria and false positive report probability (FPRP). Results: Forty articles were included in this umbrella review, which referred to a total of 54 SNPs. The median number of original studies per meta-analysis was four, while the median number of total subjects was 3455. All included articles had greater than moderate methodological quality. A total of 18 SNPs were nominally statistically associated with OC risk; 6 SNPs (8 genetic models), 5 SNPs (7 genetic models), and 16 SNPs (25 genetic models) were identified as strong, moderate, and weak cumulative evidence, respectively. Conclusion: This umbrella review revealed associations between SNPs and OC risk and suggested strong cumulative evidence of associations of six SNPs (eight genetic models) with OC risk.