Discovery of a botanical compound as a broad-spectrum inhibitor against gut microbial ß-glucuronidases from the Tibetan medicine Rhodiola crenulata.

Gut microbial ß-glucuronidases (gmß-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmß-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmß-GUS enzymes. Subsequently, the anti-gmß-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmß-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmß-GUS in a non-competitive manner, with the Ki values ranging from 0.12 µM to 1.29 µM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmß-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmß-GUS activity in mice feces, with the IC50 value of 1.24 µM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmß-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmß-GUS associated enterotoxicity.

Xanthohumol ameliorates drug-induced hepatic ferroptosis via activating Nrf2/xCT/GPX4 signaling pathway.

BACKGROUND: As a canonical iron-dependent form of regulated cell death (RCD), ferroptosis plays a crucial role in chemical-induced liver injuries. Previous studies have demonstrated that xanthohumol (Xh), a natural prenylflavonoid isolated from hops, exhibits anti-inflammatory, anti-antioxidative and hepatoprotective properties. However, the regulatory effects of Xh on hepatic ferroptosis and the underlying mechanism have not yet been fully elucidated. PURPOSE: To investigate the hepatoprotective effects of Xh against drug-induced liver injury (DILI) and the regulatory effects of Xh on hepatic ferroptosis, as well as to reveal the underlying molecular mechanisms. METHODS/STUDY DESIGN: The hepatoprotective benefits of Xh were investigated in APAP-induced liver injury (AILI) mice and HepaRG cells. Xh was administered intraperitoneally to assess its in vivo effects. Histological and biochemical studies were carried out to evaluate liver damage. A series of ferroptosis-related markers, including intracellular Fe2+ levels, ROS and GSH levels, the levels of MDA, LPO and 4-HNE, as well as the expression levels of ferroptosis-related proteins and modulators were quantified both in vivo and in vitro. The modified peptides of Keap1 by Xh were characterized utilizing nano LC-MS/MS. RESULTS: Xh remarkably suppresses hepatic ferroptosis and ameliorates AILI both in vitro and in vivo, via suppressing Fe2+ accumulation, ROS formation, MDA generation and GSH depletion, these observations could be considerably mitigated by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Mechanistically, Xh could significantly activate the Nrf2/xCT/GPX4 signaling pathway to counteract AILI-induced hepatocyte ferroptosis. Further investigations showed that Xh could covalently modify three functional cysteine residues (cys151, 273, 288) of Keap1, which in turn, reduced the ubiquitination rates of Nrf2 and prolonged its degradation half-life. CONCLUSIONS: Xh evidently suppresses hepatic ferroptosis and ameliorates AILI via covalent modifying three key cysteines of Keap1 and activating Nrf2/xCT/GPX4 signaling pathway.

Transcatheter arterial chemoembolisation combined with lenvatinib and cabozantinib in the treatment of advanced hepatocellular carcinoma.

OBJECTIVE: The objective of this study was to evaluate the effect and prognosis of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and cabozantinib in the treatment of advanced unresectable hepatocellular carcinoma (uHCC) and identify the predictors of prognosis related to cellular inflammation and body mass index (BMI). To the best of our knowledge, this is the first study to report the efficacy and prognosis of TACE combined with lenvatinib and cabozantinib in patients with uHCC and propose the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as predictors of response and survival outcomes in this context. METHODS: The clinicopathologic data of 217 patients with advanced uHCC who underwent TACE combined with systemic therapy (lenvatinib mesylate + cabozantinib) in the Department of Hepatobiliary Surgery, Dazhou Central Hospital between October 2017 and February 2020 were collected retrospectively, and the relevant parameters were analysed and compared. RESULTS: Univariate and multivariate logistic regression analyses showed that BMI, NLR, PLR and prothrombin time were independent factors for the objective response rate (ORR) of transformed therapy for uHCC (OR = 0.812 vs 1,290.68 vs 1.067 vs 0.626, 95 % CI: 0.719-0.897 vs 108.081-11,541.137 vs 1.037-1.099 vs 0.414-0.946, respectively, p < 0.05). The results showed that BMI, NLR and PLR had certain predictive values for the ORR in patients with liver cancer undergoing translational therapy (p < 0.05); the combined predictive effect of the three was the best, and the area under the curve (AUC) of BMI + NLR + PLR for predicting the ORR in patients with liver cancer undergoing translational therapy was 0.951 (95 % CI: 0.921, 0.964). A total of 181 patients experienced adverse reactions at different grades, including 104 cases at grade 1, 50 cases at grade 2, 22 cases at grade 3 and 5 cases at grade 4. There was a significant difference in overall survival (OS) between low- and high-NLR groups, low- and high-PLR groups and low- and high-BMI groups (χ2 = 9.644, 8.313 and 10.314, respectively, p < 0.05). There was a significant difference in progression-free survival (PFS) between the low- and high-NLR groups, the low- and high-PLR groups and the low- and high-BMI groups (χ2 = 8.965, 9.783 and 6.343, respectively, p < 0.05). CONCLUSION: Transcatheter arterial chemoembolisation combined with lenvatinib and cabozantinib is safe and effective in the treatment of advanced uHCC, with controllable adverse reactions. High NLR and PLR and low BMI values before treatment were independent risk factors for the ORR. Body mass index, NLR and PLR predicted responses to triple switch therapy and survival outcomes in uHCC. Patients with pretreatment NLR ≥ 2.96 and PLR ≥ 184.41 had worse OS and PFS rates. Patients with pretreatment BMI ≥ 23 kg/m2 had improved OS and a reduced risk of death.

Different Degrees of Sulfated Laminaria Polysaccharides Recovered Damaged HK-2 Cells and Inhibited Adhesion of Nano-COM and Nano-COD Crystals.

Purpose: The crystal adhesion caused by the damage of renal tubular epithelial cells (HK-2) is the key to the formation of kidney stones. However, no effective preventive drug has been found. This study aims to explore the recovery effects of four Laminaria polysaccharides (SLPs) with different sulfate (-OSO3-) contents on damaged HK-2 cells and the difference in the adhesion of damaged cells to nanometer calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) before and after recovery. Methods: Sodium oxalate (2.6 mmol/L) was used to damage HK-2 cells to establish a damaged model. SLPs (LP0, SLP1, SLP2, and SLP3) with -OSO3- contents of 0.73%, 15.1%, 22.8%, and 31.3%, respectively, were used to restore the damaged cells, and the effects of SLPs on the adhesion of COM and COD, with a size of about 100 nm before and after recovery, were measured. Results: The following results were observed after SLPs recovered the damaged HK-2 cells: increased cell viability, restored cell morphology, decreased reactive oxygen levels, increased mitochondrial membrane potential, decreased phosphatidylserine eversion ratio, increased cell migration ability, reduced expression of annexin A1, transmembrane protein, and heat shock protein 90 on the cell surface, and reduced adhesion amount of cells to COM and COD. Under the same conditions, the adhesion ability of cells to COD crystals was weaker than that to COM crystals. Conclusions: As the sulfate content in SLPs increases, the ability of SLPs to recover damaged HK-2 cells and inhibit crystal adhesion increases. SLP3 with high -OSO3- content may be a potential drug to prevent kidney stones.

Synergistic Cation Solvation Reorganization and Fluorinated Interphase for High Reversibility and Utilization of Zinc Metal Anode.

Batteries based on zinc (Zn) chemistry offer a great opportunity for large-scale applications owing to their safety, cost-effectiveness, and environmental friendliness. However, the poor Zn reversibility and inhomogeneous electrodeposition have greatly impeded their practical implementation, stemming from water-related passivation/corrosion. Here, we present a multifunctional electrolyte comprising gamma-butyrolactone (GBL) and Zn(BF4)2·xH2O to resolve these intrinsic challenges. The systematic results confirm that water reactivity toward a Zn anode is minimized by forcing GBL solvents into the Zn2+ solvation shell and constructing a fluorinated interphase on the Zn anode surface via anion decomposition. Furthermore, NMR was selected as an auxiliary testing protocol to elevate and understand the role of electrolyte composition in building the interphase. The combined factors in synergy guarantee high Zn reversibility (average Coulombic efficiency is 99.74%), high areal capacity (55 mAh/cm2), and high Zn utilization (∼91%). Ultimately, these merits enable the Zn battery utilizing a VO2 cathode to operate smoothly over 5000 cycles with a low-capacity decay rate of ∼0.0083% per cycle and a 0.23 Ah VO2/Zn pouch cell to operate over 400 cycles with a capacity retention of 77.3%.

In vitro study of miRNA-369-3p targeting TCF4 regulating the malignant biological behavior of colon cancer cells.

Background: Colorectal carcinoma (CRC) is a common malignant tumor of the digestive tract. It is characterized by a high degree of malignancy, early metastasis and poor prognosis. Studies have shown the effect of miR-369-3p on the biological function of a variety of tumors. However, the mechanism by which miR-369-3p and its potential target genes participate in the pathogenesis of CRC has not been elucidated. This study aims to study the relationship between miR-369-3p and transcription factor 4 (TCF4), to reveal the mechanism of the occurrence and development of CRC, and to provide a promising target for the treatment of CRC. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the miR-369-3p levels in CRC tissues and cells. miR-369-3p mimics and/or TCF4 overexpression vectors were transfected into SW480 cells. The expression of miR-369-3p and TCF4 mRNA was detected using RT-qPCR. Bioinformatics analysis predicted the binding site of miR-369-3p to the TCF4 3'UTR, and the targeting relationship was verified by a dual luciferase reporter gene assay. Cell proliferation and invasion were investigated by labeled immunofluorescence assay using BrdU antibody and Transwell assay. The oxidative stress ability of cells was determined by commercial kits. The levels of proteins related to cell proliferation and invasion were measured by western blotting. Results: The level of miR-369-3p was significantly down-regulated in CRC tissues and cell lines, especially in SW480 cells (P<0.05). The expression of TCF4 was negatively correlated with that of miR-369-3p. High levels of miR-369-3p targeting TCF4 suppressed cell proliferation and downregulated the protein expression of Ki67 and PCNA (P<0.05). Overexpressed miR-369-3p binding TCF4 inhibited cell invasion and decreased the protein levels of vascular endothelial growth factor (VEGF) and E-cadherin (P<0.05). Furthermore, upregulation of miR-369-3p increased the activity of superoxide dismutase (SOD) while decreasing the content of malondialdehyde (MDA) and activity of lactate dehydrogenase (LDH) by blocking the expression of TCF4 (P<0.05). Conclusions: MiR-369-3p inhibits the proliferation, invasion and oxidative stress of CRC cells by targeting TCF4, thus defining miR-369-3p as a potential target for the diagnosis and treatment of CRC.

Effect of orange solid waste diet on flesh quality and metabolic profile of common carp (Cyprinus carpio).

In this study, we aimed to evaluate the effects of solid waste of Citrus sinensis (SWC) supplementation in diet on common carp (Cyprinus carpio) flesh quality and the potential mechanisms underlying these effects. Four diets, each with different levels of SWC (0%, 5%, 10%, and 15%), were formulated and administered to C. carpio (48.83 ± 5.59 g) for 60 days. The results showed that SWC diet significantly enhanced specific growth rate, muscle sweetness (via sweet amino acids and sweet molecules), and the nutritional value of fish meat (increased protein, α-vitamin E, and allopurinol). Chromatography-mass spectrometry analyses indicated that SWC supplementation increased the essential amino acid content in the diet. In addition, SWC diet promoted biosynthesis of non-essential amino acids in muscle by enhancing glycolysis and the tricarboxylic acid cycle. In conclusion, SWC could be a cost-effective solution for providing nutritious and flavourful aquatic products.

Strategies involving low-molecular-weight heparin for the treatment and prevention of venous thromboembolism in patients with obesity: A systematic review and meta-analysis.

Introduction: Recent studies have indicated that the dosage of LMWH in patients with specific weights may be controversial. Therefore, we conducted a meta-analysis to explore an appropriate dosage of LMWH for the prevention and treatment of venous thromboembolism (VTE) in patients with obesity. Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases up to July 23, 2022. Study selection, bias analysis, and information extraction were performed by three independent reviewers. The occurrence or recurrence of VTE and bleeding events were the primary outcomes we assessed. Results: Eleven studies (a total of 6266 patients) were included in the prevention group, and 6 studies (a total of 3225 patients) were included in the treatment group. For VTE prophylaxis, compared with the standard-dosage group, the high-dosage group had a lower incidence of VTE (OR: 0.47, 95% CI: 0.27-0.82, P=0.007) and a similar incidence of bleeding events (OR: 0.86, 95% CI: 0.69-1.08, P=0.020). For VTE therapy, compared to the standard-dosage group, the reduced-dosage group had a similar incidence of VTE recurrence (OR: 0.86, 95% CI: 0.11-6.84, P=0.89) but a lower incidence of bleeding events (OR: 0.30, 95% CI: 0.10-0.89, P=0.03). Conclusion: In patients with obesity, increasing the dosage of LMWH is a more appropriate option for the prevention of VTE. Due to the limited evidence, reducing the therapeutic dosage of LMWH requires careful consideration. Larger-scale, well-designed randomized controlled trials are necessary. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier ID=CRD42022298128.

Endovascular Retrieval of a Dislocated Stent in the Right Ventricle of a Patient with Nutcracker Syndrome.

Left renal vein stenting is a preferable therapeutic option for patients with nutcracker syndrome (NS). As a potential complication of stent implantation, stent migration from the original placement to the right ventricle is relatively rare but can seriously threaten the patient's life. Endovascular stent retrieval is the most beneficial procedure for coping with this fatal complication. In this report, we aimed to describe an effective but relatively feasible endovascular approach using the combination of a goose neck snare and a large bore sheath for the retrieval of a stent dislodged in the right ventricle.

Percutaneous Mechanical Thrombectomy for Acute Symptomatic Iliofemoral Deep Venous Thrombosis Patients With Recent Aneurysmal Subarachnoid Hemorrhage.

PURPOSE: To investigate the efficacy, safety, and mid-term outcomes of percutaneous mechanical thrombectomy (PMT) for acute symptomatic iliofemoral deep venous thrombosis (DVT) patients with recent (within 4 weeks) aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: From January 2016 to February 2020, 11 acute symptomatic iliofemoral DVT patients with a recent history of aSAH were enrolled in this study. All patients had a history of aneurysm ligation or clipping previously, computed tomography (CT) scans revealed ventricular hemorrhage had been absorbed obviously and no residual aneurysm. The mean time of DVT onset after aSAH ictus was 19.2±4.5 days, and the mean Glasgow score was 6.8 ± 0.7 (range, 6-8). These patients underwent PMT with an 8 French Aspirex®S device (Straub Medical AG, Wangs, Switzerland), subsequent stenting was performed to relieve the underlying stenosis, followed by anticoagulation alone. The procedure-related complications were assessed after intervention. The follow-ups were conducted up to 1 year, the patency was evaluated via duplex ultrasonography, and the incidence of post-thrombotic syndrome (PTS) was evaluated using the Villalta scale. RESULTS: Grade III (>90%) clearance was achieved in all 11 patients. Stenting was performed in 7 patients (63.6%). There were no cerebral rebleeding events or other severe complications except 1 puncture site bleeding during treatment. A total of 90.9% (10 of 11) of patients were alive at the 12 month follow-up, and 7 patients achieved a good functional outcome. At the 1 year follow-up, there was 1 patient (10%) with mild PTS. The ultrasound showed that the patency of the iliofemoral veins was 100%, and femoral valvular incompetence was observed in 1 patient. CONCLUSION: Percutaneous mechanical thrombectomy seems to be a feasible and safe treatment for acute iliofemoral DVT in selected patients with recent aSAH, and it shows promising results in restoring patency and reducing the risk of PTS.

MicroRNA-494-3p facilitates the progression of bladder cancer by mediating the KLF9/RGS2 axis.

Bladder cancer (BC) is a familiar malignancy with high morbidity and mortality. The effect of treatment is unsatisfactory after the metastasis and invasion of BC. Hence, more studies should be carried out to explore the metastasis of BC. RT-qPCR or/and western blot was conducted to evaluate miR-494-3p, KLF9, and RGS2 expression. Cell proliferation and invasion were estimated by MTT assay and transwell assay, respectively. Cell migration was tested by wound healing assay and transwell assay. Dual-luciferase reporter gene assay was employed to validate the interplay between miR-494-3p and KLF9 mRNA. The interaction between KLF9 and RGS2 promoter was verified using dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. miR-494-3p expression was upregulated, whereas KLF9 and RGS2 were downregulated in BC cells. miR-494-3p inhibition was competent to limit the growth of BC cells. KLF9 knockdown abolished the miR-494-3p depletion-mediated inhibitory growth of BC cells. Mechanistically, we found that KLF9 was a downstream gene of miR-494-3p and could bind to the promoter region of RGS2 to promote the expression of RGS2. Moreover, RGS2 knockdown abrogated the suppressive effects of miR-494-3p knockdown on the proliferation, migration, and invasion of BC cells. Notably, miR-494-3p inhibition obstructed the tumor growth in nude mice. miR-494-3p silencing inhibited the progression of BC by regulating the KLF9/RGS2 axis in vitro and in vivo, which laid the foundation for experiments of miR-494-3p in BC and provided therapeutic targets for BC.

The Origin of High-Voltage Stability in Single-Crystal Layered Ni-Rich Cathode Materials.

Compared with the polycrystal (PC) Ni-rich cathode materials, the single-crystal (SC) counterpart displayed excellent structural stability, high reversible capacity and limited voltage decay during cycling, which received great attention from academics and industry. However, the origin of fascinating high-voltage stability within SC is poorly understood yet. Herein, we tracked the evolution of phase transitions, in which the destructive volume change and H3 phase formation presented in PC, are effectively suppressed in SC when cycling at a high cut-off voltage of 4.6 V, further clarifying the origin of high-voltage stability in SC cathode. Moreover, SC electrode displayed crack-free morphology, and excellent electrochemical stability during long-term cycling, whereas PC suffered severe capacity and voltage fade because of the spinel-like phase, decoding the failure mechanisms of PC and SC during cycling at high cut-off voltages. This finding provides universal insights into high-voltage stability and failure mechanisms of layered Ni-rich cathode materials.

Value of TCT combined with serum CA153 and CA50 in early diagnosis of cervical cancer and precancerous lesions.

Objectives: To determine the application value of thinprep cytologic test (TCT) combined with serum carbohydrate antigen 153 (CA153) and carbohydrate antigen 50 (CA50) detection in the early diagnosis and screening of cervical cancer and precancerous lesions. Methods: A total of 187 females with cervical lesions admitted to Shanghai 7th People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2017 to December 2018 were selected and divided into two groups: the cervical cancer group and the cervical precancerous lesion group, with 16 cases in the cervical cancer group and 171 cases in the cervical precancerous lesion group (cervical precancerous lesions were divided into 63 cases of the CNI group, 59 cases of the CNII group and 49 cases of the CNIII group). During the same period, 106 healthy females were selected as the healthy group. The serum tumor markers CA153 and CA50 of all subjects were detected by chemiluminescence method; The diagnostic value of TCT combined with serum CA153 and CA50 in cervical cancer and precancerous lesions was analyzed with colposcopy pathological diagnosis results as gold standard; ROC curve was drawn to evaluate the diagnostic value of serum TCT, CA153 and CA50 in cervical cancer and precancerous lesions. Results: The levels of serum CA153 and CA50 in the cervical cancer group were significantly higher than those in the cervical precancerous lesion group and the healthy group (p< 0.05), and the levels of serum CA153 and CA50 in the cervical precancerous lesion group were significantly higher than those in the healthy group (p< 0.05). The sensitivity of TCT, serum CA153 and serum CA50 in the single detection of cervical cancer and precancerous lesions was 95.93%, 97.54% and 96.00%, the specificity was 59.41%, 60.23%, 60.12%, the accuracy was 74.74%, 75.77%, 75.43%, the positive predictive value was 62.03%, 63.64%, 63.10%, and the negative predictive value was 96.22%, 97.17% and 95.28%, respectively. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of TCT combined with serum CA153 and CA50 were 96.77%, 73.19%, 85.67%, 80.21% and 95.28%, respectively. ROC curve showed that the area under the curve (AUC) of TCT and serum CA153 and CA50 in the single detection of cervical cancer and precancerous lesions was 0.791, 0.864 and 0.787, respectively, the AUC of combined detection of TCT and serum CA153 and CA50 in patients with cervical cancer and precancerous lesions was 0.877, which was significantly higher than that of single detection (p< 0.05). Conclusions: TCT combined with serum CA153 and CA50 has been reported as a treatment regimen with high accuracy, which has a high diagnostic efficiency for early diagnosis of cervical cancer and precancerous lesions, and can significantly improve the sensitivity.

Ilio-femoral calcium score may assist Glasgow Aneurysm Score prediction of long-term survival of low-risk patients after infrarenal EVAR.

BACKGROUND: The aim of this study is to evaluate if ilio-femoral calcium score (CS) combined with Glasgow Aneurysm Score (GAS) can improve the prediction of long-term survival after EVAR. METHODS: All the patients who underwent infrarenal endovascular aortic repair (EVAR) for non-ruptured AAA between January 2004 and December 2012 at a tertiary referral center were retrospectively included if the preoperative imaging was of sufficient quality and they had survived for more than 30 days. Preoperative non-contrast enhanced CT were used to measure ilio-femoral calcium score using dedicated postprocessing software. GAS was calculated and patients were divided into low or high GAS by a cutoff of 80. RESULTS: Two hundred and eighty-eight out of 500 patients were included in the study with no difference in survival compared to excluded patients (P=0.529). Patients were followed-up for a median of 7 (range 4-9) years. GAS correlated positively with ilio-femoral calcium score (r=0.123; P=0.037). One hundred and thirty-five patients (46.9%) had low GAS, and 153 (53.1%) had high GAS. Patients with high GAS had lower survival compared to the ones with low GAS (P≤0.0001). GAS was associated with long-term mortality in a uni- and multivariate regression (P≤0.0001 and P≤0.0001). Ilio-femoral calcium score was significantly associated with mortality in the group with low GAS (P=0.028), but not in the group with high GAS (P=0.297). Significance retained in multivariate regression analysis (P=0.029). Moreover, in the low GAS group, ilio-femoral calcium score was further divided in high and low according to the median. Patients with high calcium score had lower survival compared to the ones with low calcium score (P=0.047). CONCLUSIONS: Long-term survival in patients who have had infrarenal EVAR can be predicted by the clinically based Glasgow Aneurysm Score. Measuring the ilio-femoral calcium score preoperatively may refine GAS assessment in low-risk patients.

Endothelial progenitor cells overexpressing platelet derived growth factor-D facilitate deep vein thrombosis resolution.

To assess the therapeutic efficacy of PDGF-D-overexpressing endothelial progenitor cells (EPCs) in deep vein thrombosis. Inferior vena cava thrombosis was induced in female Sprague Dawley (SD) rats. Animals were injected via the distal vena cava with EPCs overexpressing PDGF-D after transfection with a lentiviral vector containing the PDGF-D gene. The effect on thrombosis in animals who received EPCs was evaluated using MSB staining, immunohistochemistry, immunofluorescence, and venography; the steady-state mRNA and protein levels of PDGF-D and its receptor (PDGF-Rß) were determined by RT-PCR and Western blotting, respectively; and the PDGF-D-induced mobilization of circulating EPCs was estimated by flow cytology. Compared with controls, injection of EPCs overexpressing PDGF-D was associated with increased thrombosis resolution; recanalization; PDGF-D and PDGF-Rß expression; induction of monocyte homing; and mobilization of EPCs to the venous circulation. In a rat model, transplantation of PDGF-D-overexpressing EPCs facilitated the resolution of deep vein thrombosis.

Safety and Efficacy of Rivaroxaban for Inferior Vena Cava Thrombosis after Successful Catheter-Directed Thrombolysis.

Rivaroxaban use for inferior vena cava (IVC) thrombosis after successful catheter-directed thrombolysis (CDT) is rarely reported. This study aimed at investigating the safety and efficacy of rivaroxaban for IVC thrombosis after CDT. The clinical data on 38 consecutive patients with IVC thrombosis (68% male; mean age, 51.5 ± 16.5), who received rivaroxaban after CDT between July 2017 and January 2020, were retrospectively analyzed in this study. Safety and efficacy of rivaroxaban (bleedings and recurrent venous thromboembolism), cumulative prevalence of post-thrombotic syndrome (PTS), primary patency, clinically driven target lesion revascularization rate, and other adverse events including all-cause mortality and vascular events (systemic embolism, acute coronary syndrome, ischemic stroke, and transient ischemic attack) were retrospectively analyzed. Of the 38 patients who received rivaroxaban for IVC thrombosis after CDT, 27 (71%) had an anticoagulant duration of 6 months and 11 patients (29%) of more than 6 months. Four patients (10%) suffered recurrent thrombosis. No patient suffered major bleeding, while clinically relevant nonmajor bleeding occurred in two (5%) patients. The cumulative prevalence of PTS was 18% (7/38) during the 12 months follow-up period. Primary patency at 1, 3, 6, and 12 months was 97, 92, 90, and 90%, respectively. According to follow-up data, the clinically driven target lesion revascularization of this study was 10%. Cardiovascular events and mortality did not occur in any patient during the study period. Rivaroxaban for IVC thrombosis after successful CDT can be safe and effective.

MiR-145-5p Inhibits the Invasion of Prostate Cancer and Induces Apoptosis by Inhibiting WIP1.

Prostate cancer (PCa) is a common malignant tumor of the male genitourinary system that seriously affects the quality of life of patients. Studying the pathogenesis and therapeutic targets of PCa is important. In this study, we investigated the role of miR-145-5p in PCa and its potential molecular mechanisms. The expression levels of miR-145-5p in PCa tissues and adjacent control tissues were detected by real-time quantitative polymerase chain reaction. The effects of miR-145-5p overexpression on PCa were studied using cell proliferation, migration, and invasion experiments. Furthermore, WIP1 was the target gene of miR-145-5p through the bioinformatics website and dual-luciferase reporter gene experiment. Further studies found that WIP1 downregulation could inhibit the proliferation, invasion, and cloning of PCa cells. Overexpression of WIP1 reversed the anticancer effects of miR-145. The anticancer effect of miR-145 was achieved by inhibiting the PI3K/AKT signaling pathway and upregulating ChK2 and p-p38MAPK. Taken together, these results confirmed that miR-145-5p inhibited the growth and metastasis of PCa cells by inhibiting the expression of proto-oncogene WIP1, thereby playing a role in tumor suppression in PCa and may become a potential therapeutic target for the treatment of PCa.

Sheng Jing Decoction Can Promote Spermatogenesis and Increase Sperm Motility of the Oligozoospermia Mouse Model.

Sheng Jing Decoction (SJD), as a traditional Chinese medicine prescription, is mainly be used to treat male infertility. However, the pharmacological functions and molecular mechanisms of SJD are poorly understood. In this study, we investigated the functions of SJD on spermatogenesis and sperm motility and explored the potential mechanisms involved. Here, we demonstrated that high, medium, and low doses of SJD are effective in restoring the impairments of the whole body and testicular tissue by cyclophosphamide inducing and to rescue the damage of testicular tissue cells including Sertoli cells and germ cells. SJD can partly restore the decrease in sperm concentration, sperm vitality, sperm motility, and normal sperm morphology rate in oligozoospermic mouse models. Ki67 staining analyses confirm SJD can promote testicular tissue cell proliferation. Real-time RT-PCR analyses also reveal that SJD can upregulate the expression of proliferation-associated gene Lin28a and differentiation-associated genes Kit, Sohlh2, and Stra8. SJD can also reduce the impairment of mitochondrial membrane potential (MMP) and sperm plasma membrane integrity by cyclophosphamide inducing. Our results reveal that SJD is effective in improving both sperm quantity and quality by increasing the sperm concentration, sperm vitality, sperm motility, and normal sperm morphology rate. SJD can promote spermatogenesis by upregulating the expression of the proliferation-associated gene Lin28a and the differentiation-associated genes (Kit, Sohlh2, and Stra8). SJD can sustain MMP and sperm plasma membrane integrity to increase sperm motility.

Visualization of the renal vein filled with contrast agent may indicate the renal vein injury during percutaneous nephrolithotomy: two case reports.

BACKGROUND: Intravenous misplacement of a nephrostomy tube is a rare complication of percutaneous nephrolithotomy (PCNL) or percutaneous nephrostomy. The mechanism of misplacement of a nephrostomy tube into the vascular system is seldom investigated. One type of the possible mechanism is that the puncture needle penetrates a major intrarenal tributary of the renal vein and enters the collecting system. However, the guidewire is located outside the collecting system near the large branches of renal vein or perforates into the renal vein. The dilation is performed and causes a large torn injury. Subsequently, the nephrostomy tube is placed inside the vessel when radiological monitoring is not used. However, there is no imaging evidence and the scene of procedure is not demonstrated. This paper reports two cases of visualization of the renal vein filled with contrast agent during PCNL. The findings may be good evidence to support the step of renal vein injury in patients with intravenous nephrostomy tube misplacement. CASE PRESENTATION: We presented two cases with visualization of the renal vein filled with contrast agent during PCNL. In the process of injecting the contrast agent through the puncture needle, we could see the renal vein. Moreover, it was identified that the puncture needle tip was not on the optimal position. The position of puncture needle tip lay outside the collecting system, which was close to the calyceal infundibulum and branches of renal vein. CONCLUSIONS: Visualization of the renal vein filled with contrast agent may be good evidence to verify the renal vein injury in patients with intravenous nephrostomy tube misplacement during PCNL or percutaneous nephrostomy. The suboptimal location of the puncture needle tip and visualization of the renal vein filled with contrast agent indicate the renal vein injury. One type of mechanism of intravenous nephrostomy tube misplacement is as following. Firstly, the guidewire stays outside the collecting system. Subsequently, dilatation directed by the guidewire results in the injury of the vein. Then, the nephrostomy tube migrates into the venous system due to prompt tube inserting and the direction of the sheath and/or the guidewire to the injured vein.