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Abstract Background Quinic acid (QA) and its derivatives have good lipid-lowering and hepatoprotective functions, but their role in atherosclerosis remains unknown. This study attempted to investigate the mechanism of QA on atherogenesis in Apoe−/− mice induced by HFD. Methods HE staining and oil red O staining were used to observe the pathology. The PCSK9, Mac-3 and SM22a expressions were detected by IHC. Cholesterol, HMGB1, TIMP-1 and CXCL13 levels were measured by biochemical and ELISA. Lipid metabolism and the HMGB1-SREBP2-SR-BI pathway were detected by PCR and WB. 16 S and metabolomics were used to detect gut microbiota and serum metabolites. Results QA or low-frequency ABX inhibited weight gain and aortic tissue atherogenesis in HFD-induced Apoe−/− mice. QA inhibited the increase of cholesterol, TMA, TMAO, CXCL13, TIMP-1 and HMGB1 levels in peripheral blood of Apoe−/− mice induced by HFD. Meanwhile, QA or low-frequency ABX treatment inhibited the expression of CAV-1, ABCA1, Mac-3 and SM22α, and promoted the expression of SREBP-1 and LXR in the vascular tissues of HFD-induced Apoe−/− mice. QA reduced Streptococcus_danieliae abundance, and promoted Lactobacillus_intestinalis and Ileibacterium_valens abundance in HFD-induced Apoe−/− mice. QA altered serum galactose metabolism, promoted SREBP-2 and LDLR, inhibited IDOL, FMO3 and PCSK9 expression in liver of HFD-induced Apoe−/− mice. The combined treatment of QA and low-frequency ABX regulated microbe-related Glycoursodeoxycholic acid and GLYCOCHENODEOXYCHOLATE metabolism in HFD-induced Apoe−/− mice. QA inhibited TMAO or LDL-induced HCAECs damage and HMGB1/SREBP2 axis dysfunction, which was reversed by HMGB1 overexpression. Conclusions QA regulated the gut-liver lipid metabolism and chronic vascular inflammation of TMA/TMAO through gut microbiota to inhibit the atherogenesis in Apoe−/− mice, and the mechanism may be related to the HMGB1/SREBP2 pathway.

Endometriosis is classically defined as a chronic inflammatory heterogeneous disorder occurring in any part of the body, characterized by estrogen-driven periodic bleeding, proliferation, and fibrosis of ectopic endometrial glands and stroma outside the uterus. Endometriosis can take overwhelmingly serious damage to the structure and function of multi-organ, even impair whole-body systems, resulting in severe dysmenorrhea, chronic pelvic pain, infertility, fatigue and depression in 5–10% women of reproductive age. Precisely because of a huge deficiency of cognition about underlying etiology and complex pathogenesis of the debilitating disease, early diagnosis and treatment modalities with relatively minor side effects become bottlenecks in endometriosis. Thus, endometriosis warrants deeper exploration and expanded investigation in pathogenesis. The gut microbiota plays a significant role in chronic diseases in humans by acting as an important participant and regulator in the metabolism and immunity of the body. Increasingly, studies have shown that the gut microbiota is closely related to inflammation, estrogen metabolism, and immunity resulting in the development and progression of endometriosis. In this review, we discuss the diverse mechanisms of endometriosis closely related to the gut microbiota in order to provide new approaches for deeper exploration and expanded investigation for endometriosis on prevention, early diagnosis and treatment.

Gastrointestinal bleeding (GIB) after heart transplantation (HT) remains a significant clinical issue. This study aimed to explore the incidence, trends, outcomes, and clinical predictors of GIB in HT patients. Adult patients who underwent HT between 2015 and 2021 at Union Hospital were recruited and divided into two groups based on the presence or absence of postoperative GIB. The primary outcomes were evaluated at follow-up. Independent predictors of GIB after HT were identified using a logistic regression analysis. A nomogram prediction model was constructed according to these independent variables, and the accuracy of the model was assessed using the receiver operating characteristic (ROC) curve and the calibration curve. Among the 461 patients, 40 (8.7%) developed GIB post-HT. HT patients with postoperative GIB exhibited higher in-hospital, 30-day, 90-day, and 1-year mortality (all p < 0.05). A multivariate analysis was used to identify age, preoperative warfarin, postoperative continuous renal replacement therapy, and postoperative nasogastric tubes as independent risk factors for GIB following HT. A nomogram prediction model was applied using the four variables. The area under the curve (AUC) of this model was 0.852 (95% CI: 0.787–0.917, p < 0.001), and the calibration curve was close to the ideal diagonal line. GIB following HT is associated with a poor clinical prognosis. The constructed nomogram demonstrated a favorable predictive value for GIB.

Epidural spinal cord stimulation (ESCS) is a potential treatment for the recovery of the motor function in spinal cord injury (SCI) patients. Since the mechanism of ESCS remains unclear, it is necessary to study the neurophysiological principles in animal experiments and standardize the clinical treatment. In this paper, an ESCS system is proposed for animal experimental study. The proposed system provides a fully implantable and programmable stimulating system for complete SCI rat model, along with a wireless charging power solution. The system is composed of an implantable pulse generator (IPG), a stimulating electrode, an external charging module and an Android application (APP) via a smartphone. The IPG has an area of ${25} \times {25}$ mm2 and can output 8 channels of stimulating currents. Stimulating parameters, including amplitude, frequency, pulse width and sequence, can be programmed through the APP. The IPG was encapsulated with a zirconia ceramic shell and two-month implantable experiments were carried out in 5 rats with SCI. The main focus of the animal experiment was to show that the ESCS system could work stably in SCI rats. The IPG implanted in vivo can be charged through the external charging module in vitro without anesthetizing the rats. The stimulating electrode was implanted according to the distribution of ESCS motor function regions of rats and fixed on the vertebrae. The lower limb muscles of SCI rats can be activated effectively. The two-month SCI rats needed greater stimulating current intensity than the one-month SCI rats The results indicated that the stimulating system provides an effective and simplified tool for studying the ESCS application in motor function recovery for untethered animals.

Abstract Isodon amethystoides (Lamiaceae) is a popular plant in folk medicine in the southern provinces of China. Our phytochemical investigation of the twigs and leaves of this plant led to the discovery of five new diterpenoids with isopimarane and 3,4-seco isopimarane scaffolds [isoamethinols A–E (1–5)], along with the known compound 3,4-seco isopimara-4(18),7,15-triene-3-oic acid methylester (6). The chemical structures of these compounds, including the absolute configurations of the new diterpenoids, were determined by comprehensive spectroscopic analyses and single crystal X-ray diffraction measurements. These compounds were evaluated for their biological activities against a panel of human cancer cell lines, gram-positive bacterial strains and HIV. Notably, the 3,4-seco-isopimarane isoamethinol D (4) showed toxicity to the cervical Hela cancer (Hela) cells with an IC50 value of 27.21 μM and the lung (A549) cancer cells with an IC50 value of 21.47 μM. Compound 4 also exhibited mild antimicrobial activity against the oral bacterial strain Streptococcus mutans. These findings suggested that the diterpenoids with a 3,4-seco-isopimarane diterpenoids isolated from I. amethystoides could provide a novel structure scaffold for the discovery of anticancer and antimicrobial compounds. Graphical Abstract

Abstract MicroRNAs (miRNAs) packaged into exosomes mediate cell communication and contribute to the pathogenesis of acute type A aortic dissection (ATAAD) with acute lung injury (ALI). The expression profile of plasma exosomal miRNAs in ATAAD patients with ALI hasn’t been identified. We performed a miRNA-sequencing to analyze the differentially expressed miRNAs (DE-miRNAs) of circulating exosomes in ATAAD patients with ALI compared to patients without ALI, founding 283 specific miRNAs in two groups. We respectively selected the top 10 downregulated and upregulated DE-miRNAs for further studies. The predicted transcription factors (TFs) of these DE-miRNAs were SMAD2, SRSF1, USF1, etc. The Gene Ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) analysis predicted their target genes mainly involved acute inflammatory response, cell junction, cytoskeleton, NF-κB signaling pathway, etc. Construction and analysis of the PPI network revealed that RHOA and INSR were considered hub genes with the highest connectivity degrees. Moreover, we confirmed two exosomal miRNAs (hsa-miR-485-5p and hsa-miR-206) by real-time quantitative polymerase chain reaction (RT-qPCR) in a validation cohort. Our study identified a plasma exosomal miRNAs signature related to ATAAD with ALI. Certain DE-miRNAs may contribute to the progression of this disease, which help us better understand the pathogenesis of ATAAD with ALI.

Abstract Background Inflammation underlies both the pathogenesis and prognosis in patients with acute aortic dissection (AAD). This study aimed to assess the association of ICU admission of white blood cell count (WBCc) with post-discharge mortality in these patients. Methods Clinical data were extracted from the MIMIC-III V1.4 database. After adjusted to covariables, Cox regression analysis and Kaplan–Meier survival curve were performed to determine the relationship between WBCc on admission and post-discharge mortality (30-day, 90-day, 1-year and 5-year) in AAD patients. Subgroup analysis and receiver operating characteristic (ROC) curve analysis were used to test the performance of WBCc in predicting mortality in AAD patients. Results A total of 325 eligible patients were divided into 2 groups: normal-WBCc group (≤ 11 k/uL) and high-WBCc group (> 11 K/uL). In univariate Cox regression analysis, high WBCc was significant risk predictor of 30-day, 90-day, 1-year and 5-year mortality [hazard ratio (HR), 95% CI, P 2.58 1.36–4.91 0.004; 3.16 1.76–5.70 0.000; 2.74 1.57–4.79 0.000; 2.10 1.23–3.54 0.006]. After adjusting for age and other risks, high WBCc remained a significant predictor of 30-day, 90-day and 1-year mortality in AAD patients (HR, 95% CI, P 1.994 1.058–3.76 0.033; 2.118 1.175–3.819 0.013; 2.37 1.343–4.181 0.003). The area under ROC curve of WBCc for predicting 30-day, 90-day, 1-year and 5-year mortality were 0.69, 0.70, 0.66 and 0.61, respectively. The results from subgroups analysis showed that there was no interaction in most strata and patients who were younger than 69 years of age or had history of respiratory disease with an elevated WBCc had an excess risk of 30-day mortality (HR, 95% CI, P 3.18 1.41–7.14 0.005; 3.84 1.05–14.13 0.043). Conclusions Higher than normal WBCc on admission may predict post-discharge mortality in patients with AAD.

ObjectiveThe study aimed to determine the relationship between body mass index (BMI) and the risk of acute aortic syndrome (AAS) with preoperative oxygenation impairment.MethodsA meta-analysis of published observational studies involving BMI and AAS with preoperative oxygenation impairment was conducted. A total of 230 patients with AAS were enrolled for retrospective analysis. All patients were divided into 2 groups (Non-oxygenation impairment group and Oxygenation impairment group). Logistic regression analysis was performed to assess the relation between BMI and the risk of preoperative oxygenation impairment after the onset of AAS. Dose-response relationship curve and subgroup analysis were conducted to test the reliability of BMI as an independent factor of it.ResultsFor the meta-analysis, the quantitative synthesis indicated that excessive BMI increased the risk of preoperative oxygenation impairment (OR: 1.30, 95% CI: 1.05-1.60, Pheterogeneity = 0.001). For the retrospective analysis, a significant association was observed after adjusting for a series of variables. BMI was significantly related to preoperative oxygenation impairment after the onset of AAS (OR: 1.34, 95% CI: 1.15-1.56, p

Objective: Oxygenation impairment is a common complication of acute aortic syndrome (AAS) patients after surgical repair. The aim of this study is to identify the relationship between body mass index (BMI) and the risk of postoperative oxygenation impairment in AAS patients.Methods: A total of 227 consecutive patients who were diagnosed as AAS and underwent surgical repair were recruited. They were divided into two groups based on the postoperative oxygenation impairment (non-oxygenation impairment group and oxygenation impairment group). Logistic regression was conducted to evaluate the association between BMI and the risk of oxygenation impairment after surgery. Dose-response curve and subgroup analysis were used to test the reliability of the results of regression analysis. A meta-analysis was then performed to further confirm these results using Pubmed, Embase, and Web of Science databases.Results: For the retrospective study, a significant association was observed after adjusting for a series of variables. BMI was significantly correlated with postoperative oxygenation impairment in patients with AAS (OR, 95% CI, P: 1.27, 1.17–1.46, 0.001). Compared with the normal weight group (18.5 kg/m2 ≤ BMI

Adhesion is a significant biological characteristic of endometriosis, and accurate evaluation of the pelvic adhesion is necessary for surgical treatment. Serum CA125 is yet the most common used biomarker in the diagnosis and follow-up of patients with endometriosis despite of its high false-positive rate and low specificity. Herein, we aimed to examine the diagnostic value of the combination of the platelet-to-lymphocyte ratio (PLR) and CA125 for patients with different stages of endometriosis and their correlations with pelvic adhesion. We retrospectively analyzed the clinical data and blood count parameters of patients with both endometriosis and other benign ovarian tumors. The mean level of CA125, the PLR and the combined marker (the CA125 level multiplied by the PLR) in the EMs group were significantly higher than those in the Cyst group (P < 0.05). ROC curve analysis was used to compare the diagnostic values of serum PLR, CA125, and the combined marker in ovarian endometriosis. The cut-off value of the PLR was 176.835, with 28.3% sensitivity and 96.9% specificity. The cut-off value of CA125 was 31.67 U/mL, with 84.1% sensitivity and 87.4% specificity. The cut-off value of the combined marker was 3894.97, with 83.4% sensitivity and 95.8% specificity. It was found that the severity of adhesion in endometriosis was positively correlated with the PLR (r = 0.286, P < 0.01), CA125 (r = 0.276, P < 0.01), and combined marker (r = 0.369, P < 0.01). The combined marker showed the highest AUC value (0.751, 95% CI: 0.666–0.837), with a sensitivity of 56.0% and a specificity of 89.6%, and the cut-off value was 9056.94. Besides, the levels of CA125, PLR, and their combination were significantly elevated in patients with endometriosis. The combined marker was not only positively correlated with pelvic adhesion but also showed a greater diagnostic value and specificity than CA125 alone. These findings indicate that the combined marker may be a potential inflammatory biomarker playing an important role in the diagnosis and assessment of adhesion in endometriosis.

Abstract Here, a common‐mode rejection ratio (CMRR) enhancement circuit is proposed by employing an auxiliary buffer (AB) to the pseudo resistors of the capacitively coupled instrumentation amplifier (CCIA). After applying AB to CCIA, the differential‐mode gain remains the same with an extended bandwidth, and the common‐mode gain is reduced, and therefore, the CMRR is enhanced.

Claudin-6 (CLDN6) is one of the 27 family members of claudins and majorly involved in the tight junction and cell-to-cell adhesion of epithelial cell sheets, playing a significant role in cancer initiation and progression. To provide a more systematic and comprehensive dimension of identifying the diverse significance of CLDN6 in a variety of malignant tumors, we explored CLDN6 through multiple omics data integrative analysis, including gene expression level in pan-cancer and comparison of CLDN6 expression in different molecular subtypes and immune subtypes of pan-cancer, targeted protein, biological functions, molecular signatures, diagnostic value, and prognostic value in pan-cancer. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and further investigated CLDN6 from the perspective of the correlations with clinical characteristics, prognosis in different clinical subgroups, co-expression genes, and differentially expressed genes (DEGs), basing on discussing the validation of its established monoclonal antibody by immunohistochemical staining and semi-quantification reported in the previous study. As a result, CLDN6 expression differs significantly not only in most cancers but also in different molecular and immune subtypes of cancers. Besides, high accuracy in predicting cancers and notable correlations with prognosis of certain cancers suggest that CLDN6 might be a potential diagnostic and prognostic biomarker of cancers. Additionally, CLDN6 is identified to be significantly correlated with age, stage, weight, histological type, histologic grade, and menopause status in UCEC. Moreover, CLDN6 high expression can lead to a worse overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in UCEC, especially in different clinical subgroups of UCEC. Taken together, CLDN6 may be a remarkable molecular biomarker for diagnosis and prognosis in pan-cancer and an independent prognostic risk factor of UCEC, presenting to be a promising molecular target for cancer therapy.

Background: The efficacy of poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPi) as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer remains unclear. We conducted a meta-analysis to assess the benefits and safety of PARPi maintenance therapy in patients with newly diagnosed advanced ovarian cancer.Methods: We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), which assessed the efficacy of PARPi as a maintenance therapy for newly diagnosed advanced ovarian cancer. Progression-free survival (PFS) was the primary endpoint, which was assessed using hazard ratios (HRs) with 95% confidence intervals (95% CI). Progression-free survival was extracted independently, and the pooled results were used to compare the prognoses of patients who received PARPi maintenance therapy and those who received a placebo.Results: Three RCTs, SOLO1, VELIA/GOG-3005, and PRIMA, which included 1,881 patients with newly diagnosed advanced ovarian cancer, were included in the meta-analysis. The overall analysis showed that PARPi maintenance therapy significantly increased PFS (HR, 0.51; 95% CI, 0.33–0.80; P = 0.004) compared to placebo. Subgroup analyses confirmed this result. We also observed an improved PFS in patients with homologous recombination deficiency (HR, 0.50; 95% CI, 0.38–0.66; P < 0.001) and in patients with BRCA mutations (HR, 0.42; 95% CI, 0.31–0.57; P < 0.001). Moreover, there were no significant differences in health-related quality of life between the PARPi and placebo groups.Conclusions: Patients with newly diagnosed advanced ovarian cancer who received PARPi maintenance therapy had a better prognosis than did those who received a placebo. Moreover, no significant changes in health-related quality of life were seen in PARPi-treated individuals.

Background: The effect of systematic lymphadenectomy (SL) on survival in patients with optimally debulked advanced ovarian cancer remains unclear. We evaluated the therapeutic value of SL in advanced ovarian cancer patients who underwent primary optimal debulking surgery.Methods: A meta-analysis was carried out using articles retrieved from the PubMed, Embase, and Cochrane databases. Overall survival (OS) and progression-free survival (PFS) were compared between patients who underwent SL and those who underwent unsystematic lymphadenectomy (USL).Results: Seven studies that included 2,425 patients with advanced ovarian cancer were included in the meta-analysis. The overall analyses indicated significantly improved OS [hazard ratio (HR) = 0.64, 95% confidence interval (CI): 0.49–0.84, P < 0.01] but not PFS (HR = 0.89, 95% CI: 0.69–1.15, P = 0.38) in patients who underwent SL compared to those who underwent USL. Subgroup analyses based on study type, study quality, total numbers of patients, and International Federation of Gynecology and Obstetrics (FIGO) stage provided similar results. However, subgroup analysis of patients with no residual tumor revealed that SL was not associated with improved OS (HR = 0.81, 95% CI: 0.66–1.00, P = 0.05) or PFS (HR = 1.09, 95% CI: 0.91–1.30, P = 0.33).Conclusions: In patients with optimally debulked advanced ovarian cancer, SL may improve OS but not PFS. However, SL does not provide a survival advantage when macroscopically complete resection of all visible tumors is achieved.

In order to estimate traffic densities in a large-scale urban freeway network in an accurate and timely fashion when traffic sensors do not cover the freeway network completely and thus only local measurement data can be utilized, this paper proposes a decentralized state observer approach based on a macroscopic traffic flow model. Firstly, by using the well-known cell transmission model (CTM), the urban freeway network is modeled in the way of distributed systems. Secondly, based on the model, a decentralized observer is designed. With the help of the Lyapunov function and S-procedure theory, the observer gains are computed by using linear matrix inequality (LMI) technique. So, the traffic densities of the whole road network can be estimated by the designed observer. Finally, this method is applied to the outer ring of the Beijing’s second ring road and experimental results demonstrate the effectiveness and applicability of the proposed approach.