Network pharmacology and transcriptomics to determine Danggui Yifei Decoction mechanism of action for the treatment of chronic lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Several children with pneumonia (especially severe cases) have symptoms of cough and expectoration during the recovery stage after standard symptomatic treatment, which eventually results in chronic lung injury. Danggui yifei Decoction (DGYFD), a traditional Chinese formula, has shown clinical promise for the treatment of chronic lung injury during the recovery stage of pneumonia, however, its mechanism of action is yet to be deciphered. AIM OF THIS STUDY: To investigate the therapeutic mechanism of DGYFD for the treatment of chronic lung injury by integrating network pharmacology and transcriptomics. MATERIALS AND METHODS: BALB/c mice were used to establish the chronic lung injury mouse model by intratracheal instillation of lipopolysaccharide (LPS). Pathological analysis of lung tissue, lung injury histological score, lung index, protein levels in bronchoalveolar lavage fluid (BALF), immunohistochemical staining, blood rheology, inflammatory cytokines, and oxidative stress levels were used to evaluate the pharmacological effects of DGYFD. Chemical components of DGYFD were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Integrated network pharmacology together with transcriptomics was used to predict potential biological targets. Western blot analysis was used to verify the results. RESULTS: In this study, we demonstrated that DGYFD could improve lung injury pathological changes, decreases lung index, down-regulate NO and IL-6 levels, and regulate blood rheology. In addition, DGYFD was able to reduce the protein levels in BALF, up-regulate the expression levels of occludin and ZO-1, improve the ultrastructure of lung tissues, and reverse the imbalance of AT I and AT II cells to repair the alveolar-capillary permeability barrier. Twenty-nine active ingredients of DGYFD and 389 potential targets were identified by UPLC-MS/MS and network pharmacology, and 64 differentially expressed genes (DEGs) were identified using transcriptomics. GO and KEGG analysis revealed that the MAPK pathway may be the molecular target. Further, we found that DGYFD inhibits phosphorylation levels of p38 MAPK and JNK in chronic lung injury mouse models. CONCLUSIONS: DGYFD could regulate the imbalance between the excessive release of inflammatory cytokines and oxidative stress, repair the alveolar-capillary permeability barrier and improve the pathological changes during chronic lung injury by regulating the MAPK signaling pathway.

New mechanisms and biomarkers of lymph node metastasis in cervical cancer: reflections from plasma proteomics.

OBJECTIVE: Lymph node metastasis (LNM) and lymphatic vasculature space infiltration (LVSI) in cervical cancer patients indicate a poor prognosis, but satisfactory methods for diagnosing these phenotypes are lacking. This study aimed to find new effective plasma biomarkers of LNM and LVSI as well as possible mechanisms underlying LNM and LVSI through data-independent acquisition (DIA) proteome sequencing. METHODS: A total of 20 cervical cancer plasma samples, including 7 LNM-/LVSI-(NC), 4 LNM-/LVSI + (LVSI) and 9 LNM + /LVSI + (LNM) samples from a cohort, were subjected to DIA to identify differentially expressed proteins (DEPs) for LVSI and LNM. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for DEP functional annotation. Protein-protein interaction (PPI) and weighted gene coexpression network analysis (WGCNA) were used to detect new effective plasma biomarkers and possible mechanisms. RESULTS: A total of 79 DEPs were identified in the cohort. GO and KEGG analyses showed that DEPs were mainly enriched in the complement and coagulation pathway, lipid and atherosclerosis pathway, HIF-1 signal transduction pathway and phagosome and autophagy. WGCNA showed that the enrichment of the green module differed greatly between groups. Six interesting core DEPs (SPARC, HPX, VCAM1, TFRC, ERN1 and APMAP) were confirmed to be potential plasma diagnostic markers for LVSI and LNM in cervical cancer patients. CONCLUSION: Proteomic signatures developed in this study reflected the potential plasma diagnostic markers and new possible pathogenesis mechanisms in the LVSI and LNM of cervical cancer.

Attention-guided Partial Domain Adaptation for Automated Pneumonia Diagnosis From Chest X-Ray Images.

Deep neural networks (DNN) supported by multicenter large-scale Chest X-Ray (CXR) datasets can efficiently perform tasks such as disease identification, lesion segmentation, and report generation. However, the non-ignorable inter-domain heterogeneity caused by different equipment, ethnic groups, and scanning protocols may lead to dramatic degradation in model performance. Unsupervised domain adaptation (UDA) methods help alleviate the cross-domain discrepancy for subsequent analysis. Nevertheless, they may be prone to 1) spatial negative transfer: misaligning non-transferable regions which have inadequate knowledge, and 2) semantic negative transfer: failing to extend to scenarios where the label spaces of the source and target domain are partially shared. In this work, we propose a classification-based framework named attention-guided partial domain adaptation (AGPDA) network for overcoming these two negative transfer challenges. AGPDA is composed of two key modules: (1) a region attention discrimination block (RADB) to generate fine-grained attention value via lightweight region-wise multi-adversarial networks. (2) a residual feature recalibration block (RFRB) trained with class-weighted maximum mean discrepancy (MMD) loss for down-weighing the irrelevant source samples. Extensive experiments on two publicly available CXR datasets containing a total of 8598 pneumonia (viral, bacterial, and COVID-19) cases, 7163 non-pneumonia or healthy cases, demonstrate the superior performance of our AGPDA. Especially on three partial transfer tasks, AGPDA significantly increases the accuracy, sensitivity, and F1 score by 4.35%, 4.05%, and 1.78% compared to recently strong baselines.

Identification and Characterization of the BBX Gene Family in Bambusa pervariabilis × Dendrocalamopsis grandis and Their Potential Role under Adverse Environmental Stresses.

Zinc finger protein (ZFP) transcription factors play a pivotal role in regulating plant growth, development, and response to biotic and abiotic stresses. Although extensively characterized in model organisms, these genes have yet to be reported in bamboo plants, and their expression information is lacking. Therefore, we identified 21 B-box (BBX) genes from a transcriptome analysis of Bambusa pervariabilis × Dendrocalamopsis grandis. Consequently, multiple sequence alignments and an analysis of conserved motifs showed that they all had highly similar structures. The BBX genes were divided into four subgroups according to their phylogenetic relationships and conserved domains. A GO analysis predicted multiple functions of the BBX genes in photomorphogenesis, metabolic processes, and biological regulation. We assessed the expression profiles of 21 BBX genes via qRT-PCR under different adversity conditions. Among them, eight genes were significantly up-regulated under water deficit stress (BBX4, BBX10, BBX11, BBX14, BBX15, BBX16, BBX17, and BBX21), nine under salt stress (BBX2, BBX3, BBX7, BBX9, BBX10, BBX12, BBX15, BBX16, and BBX21), twelve under cold stress (BBX1, BBX2, BBX4, BBX7, BBX10, BBX12, BBX14, BBX15, BBX17, BBX18, BBX19, and BBX21), and twelve under pathogen infestation stress (BBX1, BBX2, BBX4, BBX7, BBX10, BBX12, BBX14, BBX15, BBX17, BBX18, BBX19, and BBX21). Three genes (BBX10, BBX15, and BBX21) were significantly up-regulated under both biotic and abiotic stresses. These results suggest that the BBX gene family is integral to plant growth, development, and response to multivariate stresses. In conclusion, we have comprehensively analyzed the BDBBX genes under various adversity stress conditions, thus providing valuable information for further functional studies of this gene family.

From H12C4N2CdI4 to H11C4N2CdI3: a highly polarizable CdNI3 tetrahedron induced a sharp enhancement of second harmonic generation response and birefringence.

In this study, we identify a novel class of second-order nonlinear optical (NLO) crystals, non-π-conjugated piperazine (H10C4N2, PIP) metal halides, represented by two centimeter-sized, noncentrosymmetric organic-inorganic metal halides (OIMHs), namely H12C4N2CdI4 (P212121) and H11C4N2CdI3 (Cc). H12C4N2CdI4 is the first to be prepared, and its structure contains a CdI4 tetrahedron, which led to a poor NLO performance, including a weak and non-phase-matchable second harmonic generation (SHG) response of 0.5 × KH2PO4 (KDP), a small birefringence of 0.047 @1064 nm and a narrow bandgap of 3.86 eV. Moreover, H12C4N2CdI4 is regarded as the model compound, and we further obtain H11C4N2CdI3via the replacement of CdI4 with a highly polarizable CdNI3 tetrahedron, which results in a sharp enhancement of SHG response and birefringence. H11C4N2CdI3 exhibits a promising NLO performance including 6 × KDP, 4.10 eV, Δn = 0.074 @1064 nm and phase matchability, indicating that it is the first OIMH to simultaneously exhibit strong SHG response (>5 × KDP) and a wide bandgap (>4.0 eV). Our work presents a novel direction for designing high-performance NLO crystals based on organic-inorganic halides and provides important insights into the role of the hybridized tetrahedron in enhancing the SHG response and birefringence.

Cervical vertebral Hounsfield units are a better predictor of Zero-P subsidence than the T-score of DXA in patients following single-level anterior cervical discectomy and fusion with zero-profile anchored spacer.

OBJECTIVES: To determine the predictive effect of Hounsfield unit (HU) values in the cervical vertebral body measured by computed tomography (CT) and T-scores measured by dual-energy X-ray absorptiometry (DXA) on Zero-P subsidence after anterior cervical discectomy and fusion (ACDF)with Zero-P. In addition, we evaluated the most reliable measurement of cervical HU values. METHODS: We reviewed 76 patients who underwent single-level Zero-P fusion for cervical spondylosis. HU values were measured on CT images according to previous studies. Univariate analysis was used to screen the influencing factors of Zero-P subsidence, and then, logistic regression was used to determine the independent risk factors. The area under the receiver operating characteristic curve (AUC) was used to evaluate the ability to predict Zero-P subsidence. RESULTS: Twelve patients (15.8%) developed Zero-P subsidence. There were significant differences between subsidence group and non-subsidence group in terms of age, axial HU value, and HU value of midsagittal, midcoronal, and midaxial (MSCD), but there were no significant differences in lowest T-score and lowest BMD. The axial HU value (OR = 0.925) and HU value of MSCD (OR = 0.892) were independent risk factors for Zero-P subsidence, and the lowest T-score was not (OR = 1.186). The AUC of predicting Zero-P subsidence was 0.798 for axial HU value, 0.861 for HU value of MSCD, and 0.656 for T-score. CONCLUSIONS: Lower cervical HU value indicates a higher risk of subsidence in patients following Zero-P fusion for single-level cervical spondylosis. HU values were better predictors of Zero-P subsidence than DXA T-scores. In addition, the measurement of HU value in the midsagittal, midcoronal, and midaxial planes of the cervical vertebral body provides an effective method for predicting Zero-P subsidence.

Selectfluor-mediated tandem cyclization of enaminones with diselenides toward the synthesis of 3-selenylated chromones.

A practical and metal-free approach for the regioselective selenation of chromones employing Selectfluor reagent under mild conditions is described. The developed method is suitable for a wide substrate scope and affords 3-selenylated chromones in good to excellent yield with high selectivity. An ionic mechanism is proposed for this transformation. Furthermore, the application of potassium thiocyanate with enaminones for the synthesis of thiocyano chromones in this transformation is also successful.

A Cancer Cell Selective Replication Stress Nano Amplifier Promotes Replication Fork Catastrophe to Overcome Radioresistance.

Replication stress (RS) induced by DNA damage plays a significant role in conferring the anticancer effects of radiotherapy and is tightly associated with radioresistance of cancer cells. Amplification of RS represents an effective approach to improving the efficacy of radiotherapy, although the development of selective RS amplifiers remains an unexplored frontier. We herein present an RS nano amplifier (RSNA) consisting of a catalytic FePt nanoparticle loaded with the chemotherapeutic doxorubicin (DOX), which selectively exacerbates RS in cancer cells by promoting replication fork (RF) catastrophe. RSNA converts the excessive reactive oxygen species (ROS) in cancer cells into oxygen, enhancing the DNA-damaging effects of radiotherapy to create more template lesions that impede RF progression in coalition with DOX. After radiation, ROS scavenging by RSNA accelerates RF progression through damaged template strands, increasing the frequency of RF collapse into double-strand breaks. Moreover, pretreatment with RSNA accumulates cancer cells in the S phase, exposing more RFs to radiation-induced RS. These effects of RSNA convergently maximize RS in cancer cells, effectively overcoming the radioresistance of cancer cells without affecting normal cells. Our study demonstrates the feasibility of selectively amplifying RS to boost radiotherapy.

Enhancing infrared imaging systems with temperature-dependent nonuniformity correction via single-frame and inter-frame structural similarity.

Temperature-dependent nonuniformity in infrared images significantly impacts image quality, necessitating effective solutions for intensity nonuniformity. Existing variational models primarily rely on gradient prior constraints from single-frame images, resulting in limitations due to insufficient exploitation of intensity characteristics in both single-frame and inter-frame images. This paper introduces what we believe to be a novel variational model for nonuniformity correction (NUC) that leverages single-frame and inter-frame structural similarity (SISB). This approach capitalizes on the structural similarities between the corrected image, intensity bias map, and degraded image, facilitating efficient suppression of intensity nonuniformity in real-world scenarios. The proposed method diverges fundamentally from existing strategies and demonstrates superior performance in comparison with state-of-the-art correction models.

Strong non-uniformity correction algorithm based on spectral shaping statistics and LMS.

The existence of non-uniformity in infrared detector output images is a widespread problem that significantly degrades image quality. Existing scene-based non-uniformity correction algorithms typically struggle to balance strong non-uniformity correction with scene adaptability. To address this issue, we propose a novel scene-based algorithm that leverages the frequency characteristics of the non-uniformity, combine and improve single-frame stripe removal, multi-scale statistics, and least mean square (LMS) methods. Following the "coarse-to-fine" correction process, the coarse correction stage introduces an adaptive progressive correction strategy based on Laplacian pyramids. By improving 1-D guided filtering and high-pass filtering to shape high-frequency sub-bands, non-uniformity can be well separated from the scene, effectively suppressing ghosting. In the fine correction stage, we optimize the expected image estimation and spatio-temporal adaptive learning rates based on guided filtering LMS method. To validate the efficacy of our algorithm, we conduct extensive simulation and real experiments, demonstrating its adaptability to various scene conditions and its effectiveness in correcting strong non-uniformity.

Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by unexplained distressing pruritus in the mother and poses significant risk to the fetus of perinatal mortality. Occurring in the second and third trimester, the serum bile acid and aminotransferase are usually elevated in ICP patients. Ursodeoxycholic acid (UDCA) is the first line drug for ICP but the effectiveness for hepatoprotection is to a certain extent. In ICP patients with severe liver damage, combination use of hepatoprotective agents with UDCA is not uncommon. Herein, we reviewed the current clinical evidence on application of hepatoprotective agents in ICP patients. The underlying physiological mechanisms and their therapeutic effect in clinical practice are summarized. The basic pharmacologic functions of these hepatoprotective medications include detoxification, anti-inflammation, antioxidation and hepatocyte membrane protection. These hepatoprotective agents have versatile therapeutic effects including anti-inflammation, antioxidative stress, elimination of free radicals, anti-steatohepatitis, anti-fibrosis and anti-cirrhosis. They are widely used in hepatitis, non-alcoholic fatty liver disease, drug induced liver injury and cholestasis. Evidence from limited clinical data in ICP patients demonstrate reliable effectiveness and safety of these medications. Currently there is still no consensus on the application of hepatoprotective agents in ICP pregnancies. Dynamic monitoring of liver biochemical parameters and fetal condition is still the key recommendation in the management of ICP pregnancies.

Wastewater treatment plant effluents exert different impacts on antibiotic resistome in water and sediment of the receiving river: Metagenomic analysis and risk assessment.

Wastewater treatment plants (WWTPs) are considered as hotspots for the spread of antibiotic resistome into the environment. However, the differential contributions of WWTPs to the antibiotic resistome in the receiving river water and sediment are poorly understood. Here, based on metagenomic analysis, we found that the WWTP effluents significantly elevated the diversities and abundances of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in the receiving river water from the Qinghai-Tibet Plateau, but showed less interference with the antibiotic resistome in sediment. Estimated by SourceTracker, WWTPs contributed 60.691.8% of ARGs in downstream river water, much higher than those for sediment (7.7568.0%). A holistic comparison of ARG risks based on analysis of ARG combination, mobility risk, ARG hosts and ARG-carrying pathogens further revealed the great impacts of WWTP effluents on downstream river water rather than sediment. Among various MGEs, tnpA exhibited the greatest potential for the dissemination of ARGs, and displayed highest co-occurrence frequency with multiple ARGs. P. aeruginosa, E. cloacae, and E. coli were identified as the critical-priority pathogens of ARG hosts. This study demonstrated the much greater impacts of WWTP effluents on the downstream water compared with sediment, which is significant for developing effective strategies to mitigate ARG risks.

The effect of different timing of blood transfusion on oncological outcomes of patients undergoing radical cystectomy for bladder cancer: a systematic review and meta-analysis.

Highlights: This meta-analysis and systematic review aim to analyze the association between BT and oncological outcomes of patients undergoing RC for bladder cancer, and tries to find out whether the timing of blood transfusion could also have an effect on this relationship. A total of 20 retrospective studies from online databases and other sources are identified and enrolled in this study. The results show that BT administration during RC operation or perioperative period is significantly associated with worse oncological outcomes including ACM, CSM and DR. Background: Bladder cancer is one of the most common urological malignancies. Radical cystectomy (RC) remains the main treatment for localized muscle-invasive bladder cancer (MIBC) or high-grade non-muscle-invasive bladder cancer (NMIBC). In the process of RC, the administration of blood transfusion (BT) is sometimes needed, however, it may cause transfusion-related complications or lead to worse oncological outcomes. This meta-analysis and systematic review aims to give a comprehensive insight into the association between BT and oncological outcomes of patients undergoing RC, and tries to find out whether the timing of blood transfusion could also have an impact on this association. Methods: This systematic review and meta-analysis were carried out according to the PRISMA 2020 reporting guideline. We have searched four bibliographic databases including PubMed (Medline), EMBASE, Cochrane Library, and Web of Science with no language limitation. Studies investigating the association between BT and oncological outcomes of patients undergoing RC are identified and included in this research from inception through March 20, 2023. This research calculates the pooled hazard ratios (pHR) and 95% confidence intervals (95% CI) of all-cause mortality (ACM), cancer-specific mortality (CSM) and disease recurrence (DR) using Random Effects models or Fixed Effects models. Subgroup analyses stratified by parameters such as timing of transfusion are also conducted. This meta-analysis was registered with PROSPERO, CRD42022381656. Results: A total of 20 retrospective studies from online databases and other sources are identified and enrolled in this study. Results show that blood transfusion significantly increased the risks for ACM (HR = 1.33, 95% CI: 1.23-1.44), CSM (HR = 1.25, 95% CI: 1.15 - 1.35) and DR (HR = 1.26, 95% CI: 1.15 - 1.38). However, when stratified by the timing of BT, we find that only intraoperative and perioperative transfusion significantly increased in risks for worse prognosis, while postoperative transfusion raised none of the risks of ACM (HR = 1.26, 95% CI: 0.92-1.73), CSM (HR = 1.08, 95% CI: 0.93-1.26) nor DR (HR = 1.08, 95% CI: 0.90-1.29) significantly. Conclusion: BT administration during RC operation or perioperative period is significantly associated with worse oncological outcomes including ACM, CSM and DR. Clinicians should consider carefully when deciding to administrate BT to patients undergoing RC and carry out according to current guidelines.

Hepatic arterial infusion chemotherapy plus lenvatinib with or without programmed cell death protein-1 inhibitors for advanced cholangiocarcinoma.

Background: New treatment strategies are needed to improve outcomes for patients with advanced cholangiocarcinoma (CCA) due to the limited efficacy of current first-line chemotherapy regimens. Although the combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and programmed cell death protein-1 (PD-1) inhibitors has been extensively evaluated in the treatment of advanced hepatocellular carcinoma, their roles in advanced CCA remain poorly understood. The purpose of this study is to compare the efficacy and safety of HAIC plus lenvatinib with or without PD-1 inhibitors in patients with advanced CCA. Methods: Between March 2019 to June 2022, patients diagnosed with advanced CAA who received HAIC plus lenvatinib with or without PD-1 inhibitors treatment were reviewed for eligibility. Efficacy was evaluated according to survival and tumor response, and safety was evaluated according to the incidence of adverse events (AEs). Results: Fifty-five patients with advanced CCA were included in the study, and they were divided into the HAIC+lenvatinib (LEN)+PD-1 inhibitors (PD-1i) group (n = 35) and HAIC+LEN group (n = 20). The median follow-up time was 14.0 (5-42) months. Patients in the HAIC+LEN+PD-1i group had significantly better PFS (HR = 0.390; 95% CI 0.189-0.806; p = 0.001) and OS (HR = 0.461; 95% CI 0.229-0.927; p = 0.01) than those in the HAIC+LEN group. The HAIC+LEN+PD-1i group showed a higher objective response rate and disease control rate than the HAIC+LEN group but did not find a significant difference. The incidence of grade 1-2 and grade 3-4 AEs was not significantly higher in the HAIC+LEN+PD-1i group compared to the HAIC+LEN group, whereas two patients (5.7%) in the HAIC+LEN+PD-1i group experienced grade 5 immune-mediated pneumonia. Conclusion: HAIC plus lenvatinib with PD-1 inhibitors is safe and well-tolerated, and has the potential to prolong the survival of patients with advanced CCA. The addition of PD-1 inhibitors may enhance the efficacy of HAIC and lenvatinib. Therefore, the combined therapy has the potential to become a treatment option for advanced CCA.

Antibacterial Fusobacterium Nucleatum-Mimicking Nanomedicine to Selectively Eliminate Tumor-colonized Bacteria And Enhance Immunotherapy Against Colorectal Cancer.

Clinical evidence has indicated that tumor-colonizing bacteria would be closely related to the tumor development and therapeutic responses. Selectively eliminating bacteria within tumors may be an attractive approach to enhance cancer treatment without additional side effects. Herein, we found that owing to the high affinity between the membrane protein Fap-2 on Fusobacterium nucleatum (F. nucleatum) and D-galactose-ß (1-3)-N-acetyl-D-galactosamine (Gal-GalNAc) overexpressed on colorectal tumor cells, F. nucleatum would colonize in colorectal tumors, as evidenced by both clinical samples and animal tumor models. Notably, F. nucleatum colonized in colorectal tumors would lead to immunosuppressive tumor microenvironment, greatly reducing their responses to immune checkpoint blockade (ICB) therapy. Inspired by this finding, we designed a F. nucleatum-mimetic nanomedicine by fusing F. nucleatum cytoplasmic membrane (FM) with Colistin loaded liposomes to achieve selectively killing tumor-colonizing F. nucleatum without affecting gut microbes. As the results, the therapeutic responses of F. nucleatum-colonized tumors to ICB therapies could be successfully restored, as demonstrated in F. nucleatum-infected subcutaneous CT-26 tumor model, chemical-induced spontaneous colorectal cancer models and MC-38 tumor model. In summary, our work presented a F. nucleatum-Mimicking nanomedicine which could selectively eliminate tumor-colonized bacteria, promising for enhancing the responses of cancer immunotherapy against F. nucleatum-colonized colorectal cancer. This article is protected by copyright. All rights reserved.

Generation of a human iPSC line CIPi003-A from a patient with focal epilepsy harboring a heterozygous mutation in DEPDC5 gene.

The DEPDC5 gene (OMIM 614191) has been proven to be a frequent cause of familial and sporadic focal epilepsy. A human induced pluripotent stem cell (iPSC) line was generated from a child diagnosed with focal epilepsy, which was caused by DEDPC5 mutation. The iPSC line expresses high pluripotency markers, carries the DEDPC5 mutation, and can differentiate into three germ layers in vitro. The iPSC lines offer a promising technique for studying the pathogenesis and conducting drug screening of DEDPC5-related epilepsy.

Efficacy and safety of visually guided laser balloon versus cryoballoon ablation for paroxysmal atrial fibrillation: a systematic review and meta-analysis.

Background: Newly developed catheter ablation (CA) techniques, such as laser balloon ablation (LBA) and cryoballoon ablation (CBA), have been introduced in recent years and emerged as valuable alternatives to conventional radiofrequency CA strategies for paroxysmal atrial fibrillation (PAF) patients. However, evidence comparing LBA and CBA remain controversial. Thus, we conducted this meta-analysis to assess the efficacy and safety between these two techniques. Methods: Scientific databases (PubMed, Embase) and relevant websites (the Cochrane Library, ClinicalTrials.gov) were systematically searched from inception to March 2023. The primary outcomes of interest were the AF recurrence and the procedure-related complications. Secondary outcomes included procedural time, fluoroscopy time, and left atrial (LA) dwell time. Results: Seven clinical trials with a total of 637 patients were finally enrolled. No significant differences were found between LBA and CBA in terms of AF recurrence [16.3% vs. 22.7%, odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.42-1.05, p = 0.078] or total procedural-related complications (8.4% vs. 6.4%, OR = 1.33, 95% CI: 0.71-2.51, p = 0.371). LBA had a significantly longer procedural time [weighted mean difference (WMD) = 38.03 min, 95% CI: 13.48-62.58 min, p = 0.002] and LA dwell time (WMD = 46.67 min, 95% CI: 14.63-78.72 min, p = 0.004) than CBA, but tended to have shorter fluoroscopy time. Conclusions: LBA and CBA treatment have comparable efficacy and safety for PAF patients. LBA was associated with longer procedural and LA dwell times compared with CBA. Further large-scale studies are warranted to compare these two techniques with the newest generations.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=426513, identifier (CRD42023426513).

Exploring potential correlations between bacterial communities, organic acids, and volatile metabolites of traditional fermented sauerkraut collected from different regions of Heilongjiang Province in Northeast China.

In this study, the bacterial communities and flavor metabolites of 27 traditional naturally fermented sauerkraut samples collected from nine regions of Heilongjiang Province in Northeast China were investigated. The dominant genera were Lactobacillus, Pseudomonas, Alcaligenes, Arcobacter, Pseudarcobacter, Lactococcus, Comamonas, Pediococcus, Prevotella, and Insolitispirillum. A total of 148 volatile compounds were detected in seven categories; esters and acids were the most abundant volatiles. Additionally, the highest content (15.96 mg/g) of lactic acid was detected in YC1. Acetic acid, oleic acid, palmitic acid, elaidic acid, and dehydroacetic acid were the key differential volatile compounds, which may be related to the bacterial communities. Spearman's correlation analysis revealed that Lactococcus and Lactobacillus were significantly positively correlated with flavor metabolites, suggesting that they may play a more significant role in flavor formation. The results of this study can help in the development of better quality of fermented vegetables.

Pharmacokinetics, Tolerability, and Safety of Glecaprevir/Pibrentasvir Co-formulated Bilayer Tablet Following Repeated Administration in Healthy Chinese Adults.

Glecaprevir (GLE)/pibrentasvir (PIB) is an all-oral, interferon- and ribavirin-free, pan-genotypic fixed-dose combination regimen approved for the treatment of all major genotypes of hepatitis C virus (HCV) infection in many countries worldwide. To support clinical development in China, an open-label, single-center phase 1 study was conducted to evaluate the pharmacokinetics, safety, and tolerability of GLE/PIB in healthy Chinese adults in Mainland China. Eighteen participants received 3 tablets of coformulated GLE/PIB 100/40 mg once daily (QD) for 7 days. Following GLE/PIB 300 mg/120 mg administration, GLE and PIB reached maximum concentration in 4-5 hours with a terminal elimination half-life of 5.9 and 25 hours, respectively. Both GLE and PIB reached steady state by day 5, with no-to-minimal accumulation (≤17% higher). GLE/PIB exposures in healthy Chinese participants were similar to historical observations across phase 1 studies in healthy Western participants. GLE/PIB was safe and well-tolerated, with most adverse events being mild. These pharmacokinetics and safety data, together with existing global efficacy and safety data in healthy and HCV-infected Western participants, support the use of GLE/PIB 300 mg/120 mg QD in adult Chinese patients with chronic HCV infection.

Upregulation of SOX9 promotes the self-renewal and tumorigenicity of cervical cancer through activating the Wnt/ß-catenin signaling pathway.

Sry-box9 (SOX9) maintains stem cell properties and plays crucial roles in many cancers. However, whether SOX9 is correlated with cervical cancer cell stemness and its detailed mechanism remains obscure. We studied the relationship between SOX9 and prognosis of cervical cancer through public database, and SOX9 was related to poor prognosis of cervical cancer. Elevated SOX9 expression enhanced the self-renewal properties and promotes tumorigenicity in cervical cancer. Overexpression of SOX9 could promote the expression of stem cell-related factors in cervical cancer cells and xenografts. Meanwhile, overexpression of SOX9 could also enhance the expressions of FZD10, ß-catenin, and c-Myc in cervical cancer cells and xenografts, while inhibiting the expression of DDK1. The activation of Wnt pathway by chir-99 021 raised the tumor spheroid ability of SOX9 knockdown HeLa cells. In addition, SOX9 could transcriptional inhibit DKK1 and activate FZD10 and MYC by binding to their promoters to affect the Wnt/ß-catenin pathway. These results demonstrated SOX9 regulated the self-renewal and tumorigenicity of cervical cancer through Wnt/ß-catenin pathway by directly transcriptional activation of FZD10, MYC and transcriptional inhibition of DKK1.