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Objectives. The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9-mAbs in the treatment of familial hypercholesterolemia (FH). Methods. A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: "AMG 145", "evolocumab", "SAR236553/REGN727", "alirocumab", "RG7652", "LY3015014", "RN316/bococizumab", "PCSK9", and "familial hypercholesterolemia" up to November 2020. Study quality was assessed with the Cochrane Collaboration's tool, and publication bias was evaluated by a contour-enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta-analysis was performed using R software, version 4.0.3. Results. A meta-analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9-mAbs reduced the LDL-C level by the greatest margin, WMD −49.14%, 95% CI: −55.81 to −42.47%, on FH versus control groups. PCSK9-mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein-B (Apo-B), and non-high-density lipoprotein cholesterol (non-HDL-C) levels and increased HDL-C and apolipoprotein-A1 (Apo-A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9-mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. Conclusion. PCSK9-mAbs significantly decreased LDL-C and other lipid levels with satisfactory safety and tolerability in FH treatment. [ABSTRACT FROM AUTHOR]

Background: To use ddPCR to quantify plasma exosomal class III β‐tubulin (βIII‐tubulin, TUBB3, encoded by the TUBB3 gene) mRNA expression in metastatic castration‐resistant prostate cancer (mCRPC) patients, and study the association of this expression with abiraterone efficacy. Methods: Blood samples were prospectively collected from 52 mCRPC patients using abiraterone as first‐line therapy to measure plasma exosomal TUBB3 mRNA expression value before the initiation of abiraterone. Study endpoints were PSA response rate, PSA‐progression‐free survival (PSA‐PFS), and overall survival (OS, from CRPC to death). Results: Patients with positive exosomal TUBB3 expression showed shorter PSA‐PFS (negative TUBB3 vs. positive TUBB3: 11.0 vs. 7.9 months; p = 0.014). Further analysis demonstrated that patients with strongly positive exosomal TUBB3 (>20 copies/20 µl) was associated with even shorter PSA‐PFS (negative TUBB3 vs. positive TUBB3 [<20 copies/20 µl] vs. strongly positive TUBB3 [>20 copies/20 µl]: 11.0 vs. 8.3 vs. 3.6 months, p = 0.005). In multivariate analyzes, TUBB3 (+) (HR: 2.114, p = 0.033) and ECOG score >2 (HR: 3.039, p = 0.006) were independent prognosticators of poor PSA‐PFS. PSA response and OS did not present significant differences. Conclusion: The exosomal TUBB3 mRNA expression level is associated with poor PSA‐PFS of abiraterone in mCRPC patients. The detection of exosomal TUBB3 can be valuable in their management. [ABSTRACT FROM AUTHOR]

Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC- δ -(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC- δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3 β signaling via nuclear-export signal blockage independent of PKC- δ activation. By demonstrating independent modulation of PKC- δ and PKB/GSK-3 β /Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo , further supporting the potential applicability of this rationale. Dihydrotanshinone-I activates PKC- δ -regulated NRF2 nuclear import signaling and meanwhile blocks nuclear export via PKB/GSK-3 β /Fyn cascades, convergently potentiating nuclear accumulation and activation of NRF2 signaling and ameliorates myocardial ischemia/reperfusion injury. Image 1 [ABSTRACT FROM AUTHOR]

Background and Aim: Currently, endoscopic drainage (ED) and percutaneous drainage (PD) are both widely used effective interventions in the management of patients with symptomatic pancreatic fluid collections (PFCs). This study aimed to compare the clinical effectiveness and safety of ED to those of PD in the treatment of PFCs. Methods: A prospective cohort study of PFC patients who underwent ED or PD was conducted between January 2009 and December 2017. In this study, the initial success rate, adverse events, intervention, requirement of surgical treatment, hospital mortality within 30 days, length of hospital stay, and expenses during hospitalization were monitored, and a follow‐up investigation of treatment outcome was conducted. Long‐term recovery, recurrence, and mortality were determined according to telephone follow up. Results: In total, 129 patients were included in the study; 62 patients underwent ED, and 67 patients underwent PD during the 8‐year study period. Initial treatment success was considerably higher in patients whose PFCs were managed by ED than in patients whose PFCs were managed by PD (94.9% vs 65.0%, P = 0.003). The rate of procedural adverse events, reintervention, length of hospitalization, and expense were all higher in the PD group than in the ED group, but the long‐term recovery rate and requirement of surgical intervention were not clearly different between patients who underwent the two treatment measures. Conclusion: ED of symptomatic PFCs was associated with higher rates of initial treatment success, lower rates of reintervention and adverse events, and a shorter hospital stay than PD of symptomatic PFCs. [ABSTRACT FROM AUTHOR]

Background: Skewed T helper (Th)2 response plays a crucial role in the pathogenesis of allergic diseases. The therapeutic efficacy for allergic diseases is unsatisfactory currently. This study aims to regulate the skewed Th2 response with CARsomes. Methods: The CARsome consisted of an epitope of Dermatophagoides farina‐1 (Derf1), a segment of the anti‐DEC205 antibody, the scFv, and an open reading frame of perforin. This fusion protein binds to DEC205 molecule on the surface of exosomes derived from dendritic cells (DC). The effects of CARsome on inducing antigen (Ag)‐specific Th2 cell apoptosis were assessed both in vivo and in vitro. Results: Exposure to CARsomes in the culture induced Ag‐specific Th2 cell apoptosis. Injection of CARsomes through the vein puncture also induced Ag‐specific Th2 cell apoptosis in the lungs of sensitized mice. CARsomes could induce Ag‐specific regulatory T cells. Administration of CARsomes efficiently inhibited experimental allergic airway inflammation. Conclusions: The CARsomes can inhibit allergic airway inflammation by inducing Ag‐specific Th2 cell apoptosis and induce Ag‐specific regulatory T cells. The data suggest that CARsomes have the translational potential to be used to treat allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Design: This a retrospective study in single centre.Objective: The objective of this retrospective clinical study is to compare the long-term clinical efficacy of posterior long-segment and short-segment fixation with single-stage transpedicular debridement and fusion for the treatment of thoracolumbar spinal tuberculosis in adults.Methods: Sixty-six cases of thoracolumbar tuberculosis were treated by single-stage transpedicular debridement, bone graft fusion, and pedicle screw fixation. Thirty-five cases were under long-segment fixation (group A) and 31 cases were under short-segment fixation (group B). These patients were followed up for a minimum of five years. The clinical and radiographic results for these patients were analyzed and compared.Results: All 66 patients were completely cured during the follow-up. All patients had significant improvement of neurological condition and visual analogue scale pain scores at the final follow-up. The average operation duration and blood loss in group A were more than that in group B. Kyphosis Cobb angle of both groups was significantly corrected after surgical management. The correction rate of Cobb angle in group A was significantly higher than that in group B at the time of immediate post-operative period or the last follow-up (P < 0.05). The correction loss of group A was significantly less than that in group B (P < 0.05).Conclusion: Both posterior long-segment and short-segment pedicle screw fixations for the treatment of thoracolumbar spinal tuberculosis have significant effects in the correction of kyphosis and the improvement of neurological function. Although the blood loss and operation time of long-segment fixation were more than that of short-segment fixation, long-segment fixation was superior to the short-segment fixation in the correction of kyphosis and the maintenance of spinal stability, especially in the prevention of long-term correction loss. [ABSTRACT FROM AUTHOR]

Background: Infected pancreatic necrosis (IPN) is a serious local complication of acute pancreatitis, with high mortality. Minimally invasive therapy including percutaneous catheter drainage (PCD) has become the preferred method for IPN instead of traditional open necrosectomy. However, the efficacy of double-catheter lavage in combination with percutaneous flexible endoscopic debridement after PCD failure is unknown compared with surgical necrosectomy.Methods: A total of 27 cases of IPN patients with failure PCD between Jan 2014 and Dec 2015 were enrolled in this retrospective cohort study. Fifteen patients received double-catheter lavage in combination with percutaneous flexible endoscopic debridement, and 12 patients underwent open necrosectomy. The primary endpoint was the composite end point of major complications or death. The secondary endpoint included mortality, major complication rate, ICU admission length of stay, and overall length of stay.Results: The primary endpoint occurrence rate in double-catheter lavage in combination with percutaneous flexible endoscopic debridement group (8/15, 53%) was significantly lower than that in open necrosectomy group (11/12, 92%) (RR = 1.71, 95% CI = 1.04 - 2.84, P < 0.05). Though the mortality between two groups showed no statistical significance (0% vs. 17%, P = 0.19), the rate of new-onset multiple organ failure and ICU admission length of stay in the experimental group was significantly lower than that in open necrosectomy group (13% vs. 58%, P = 0.04; 0 vs. 17, P = 0.02, respectively). Only 40% of patients required ICU admission after percutaneous debridement, which was markedly lower than the patients who underwent surgery (83%; P < 0.05).Conclusions: Double-catheter lavage in combination with percutaneous flexible endoscopic debridement showed superior effectiveness, safety, and convenience in patients with IPN after PCD failure as compared to open necrosectomy. [ABSTRACT FROM AUTHOR]

Background and Study Aim: The commonly used minimally invasive methods for patients with infected pancreatic necrosis (IPN) are initial endoscopic transluminal drainage (ETD) and percutaneous catheter drainage (PCD), which are followed, if necessary, by endoscopic or surgical necrosectomy. This study intends to explore which of the two minimally invasive treatments leads to a better prognosis.Patients and Methods: Patients with IPN and an indication for intervention were prospectively enrolled and underwent either initial ETD or PCD followed, if necessary, by endoscopic or surgical necrosectomy.Results: Initial treatment success occurred in 8 of 11 patients after ETD (72.7%) and in 3 of 13 patients after PCD (30.8%) (risk ratio [RR] with ETD, 2.36; 95% CI 0.97-5.77; P = 0.04). After 1 year of follow-up, 72.7% of patients survived with ETD, and 69.2% survived with PCD (RR 1.05; 95% CI 0.63-1.75; P = 0.85). Intestinal fistula seems to have occurred less in the patients who received initial ETD rather than PCD therapy (9.1 vs. 38.5%; RR 0.24; 95% CI 0.03-1.73; P = 0.098). Fewer patients who underwent an initial ETD were transferred to surgery (9.1 vs. 46.2%; RR 0.20; 95% CI 0.03-1.40; P = 0.047). A higher rate of new-onset diabetes (3 cases) or impaired glucose tolerance (1 case) occurred in initial PCD compared to ETD (40 vs. 0%, P = 0.042).Conclusion: The outcomes of initial endoscopic transluminal drainage are superior to percutaneous drainage for patients with infected pancreatic necrosis (ChiCTR-ONRC-13003653). [ABSTRACT FROM AUTHOR]

Background: There is limited evidence to guide treatment for pediatric cervical spinal tuberculosis with kyphosis (PCSTK). This study retrospectively evaluates the safety, feasibility and efficacy of 360-degree arthrodesis combined with anterior debridement and decompression for treating PCSTK, while simultaneously emphasizing the role of posterior fixation for the correction and maintenance of the kyphosis angle. Methods: From May 2006 to December 2012, a total of 12 children with PCSTK underwent 360-degree cervical spinal arthrodesis followed by debridement of focus and decompression of the spinal cord. Data on the angle of kyphosis correction, visual analogue scale scores of pain, the American Spinal Injury Association scoring system of nerve function scores, erythrocyte sedimentation rate (ESR) and body weight were collected at certain periods. Clinical efficacy was evaluated by statistical analysis based on collected data. Results: Average follow-up period was 34.3 ± 8.6 months. No postoperative complications related to the instrumentation occurred, and neurologic function improved in various degrees. Preoperative kyphosis angle was 41.4 ± 5.2°, and significantly decreased to -4.9 ± 4.9° after surgery. The correction of kyphosis and loss of correction were 47.1 ± 4.9° and 0.6 ± 1.4°, respectively. Average pretreatment ESR was 49.8 ± 13.2 mm/h, which normalized (8.5 ± 0.6 mm/h) within three months in all patients. Average preoperative visual analogue scale was 6.6 ± 1.6, which decreased to 2.3 ± 1.4 postoperatively and 0.3 ± 0.5 during the final follow-up. Mean preoperative body weight was 25.9 ± 5.1 kg, and body weight was 33.5 ± 4.8 kg at the third month of post-operation. Bone healing was achieved in all patients after a mean period of 5.4 months. Conclusions: 360-degree arthrodesis combined with anterior debridement and decompression is a safe and effective method for the treatment of PCSTK. For the correction and maintenance of the kyphosis angle, additional posterior fixation is recommended. [ABSTRACT FROM AUTHOR]

Choledochocele, or type III choledochal cyst, is a rare congenital disease and is even less common among adults compared with children. In this case, a 75-year-old female was admitted to our hospital presented with epigastric pain and vomiting for one day. Abdominal computed tomography revealed dilated common bile duct, pancreatitis and peripancreatic effusion. The patient was treated with fasting, fluid resuscitation, anti-acid agents, somatostatin and antibiotics. Endoscopic retrograde cholangiopancreatography was employed for the further diagnosis of choledochocele, choledocholithiasis and biliary stenosis. Endoscopic sphincterotomy, stone extraction and plastic stent placement were performed for treatment. The patient recovered quickly after the treatment and no signs of recurrence and complications were observed during the first follow-up. Endoscopic management may be a promising and alternative therapy for choledochocele although long-term follow-up is necessary to confirm the efficacy and safety of this procedure in the future. [ABSTRACT FROM AUTHOR]

Yishen Gushu Formula (YSGSF) is composed of Epimedium, prepared Rehmannia, Drynaria, Eucommia, Dodder, ginseng, Astragalus, Ligusticum wallichii, Aucklandia and Panax notoginseng. It can improve bone mineral density by regulating bone metabolism. However, the mechanism of YSGSF in the treatment of Postmenopausal osteoporosis (PMOP) remains unclear. The compounds, targets, and molecular mechanisms of YSGSF in the treatment of PMOP were investigated using broad-spectrum target metabolomics from plants, combined with network pharmacology and animal studies, leading to a discussion on a novel approach to understanding YSGSF's action in PMOP treatment. Using ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) within a comprehensive targeted metabolomics framework, the active constituents of YSGSF were identified. This, alongside network pharmacology and molecular docking, facilitated the identification of critical signaling pathways and targets pertinent to YSGSF's therapeutic effect on PMOP. Subsequently, an animal model for PMOP was developed. Following intervention grouping, rats' weight changes were recorded; serum bone metabolic factors were assessed via ELISA; bone microstructure was examined using HE staining and Micro-CT; and key signaling pathway proteins and genes were analyzed through immunohistochemistry to validate YSGSF's potential mechanism in PMOP treatment. A total of 84 main active components of YSGSF were identified. The key signaling pathways affected by YSGSF in the treatment of PMOP were the TNF and IL-7 signaling pathways, closely related to TNF-α, IL-1β, c-jun and other protein targets. The results of animal experiments showed that YSGSF could downregulate the expression of TNF-a, IL-1β and c-Jun proinflammatory factors by regulating the TNF and IL-7 signaling pathways and regulate the inflammatory response, osteocyte differentiation and apoptosis to control the development of PMOP. YSGSF activates the TNF-α and IL-7 signaling pathways in PMOP rats, reducing TNF-α and IL-1β levels, the c-Jun inflammatory response, and osteocyte differentiation and apoptosis, thus playing a significant role in treating PMOP. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Despite frequent use of prophylactic antibiotics for patients undergoing transrectal prostate biopsy (TRPB), the incidences of urinary tract infection (UTI) and bacteria resistance are increasing. The aim of this study is to evaluate the current regimen of antimicrobial prophylaxis in TRPB.Methods: A systematic search of PubMed(®), Embase(®), and the Cochrane Library was performed to identify all randomized controlled trials (RCT) related to the effects of antibiotic prophylaxis for TRPB. The outcomes included bacteriuria, bacteremia, drug-resistant bacteria on urine/blood culture, fever, UTI, sepsis, and hospitalization.Results: A total of 22 RCTs with 3846 patients were identified and included. Nine trials analyzed antibiotics versus placebo/no treatment, with all outcomes substantially favoring antibiotic use (p<0.05), including bacteriuria (risk ratio [RR] 0.25, 95% confidence interval [CI] 0.15-0.42), bacteremia (RR 0.67, 95% CI 0.49-0.92), fever (RR 0.39, 95% CI 0.23-0.64), UTI (RR 0.37, 95% CI 0.22-0.62), and hospitalization (RR 0.13, 95% CI 0.03-0.55). There were no substantial differences between long-course versus short-course treatment and single versus multiple dose respectively, except for a greater risk of bacteriuria for short-course treatment (RR 2.09, 95% CI 1.17-3.73, p=0.01) and single-dose treatment (RR 1.98, 95% CI 1.18-3.33, p=0.01). There were no substantial differences among the groups for bacteriuria, fever, UTI, and hospitalization, when comparing oral versus systemic administration of antibiotics. The efficacy of several classes of antibiotics was compared without any difference among them. Despite the lack of significance, the synthesized data of three RCTs indicated a trend towards the use of combined antibiotics.Conclusions: Prophylactic antibiotics could be beneficial for the reduction of infective complications after TRPB. Single-dose or short-course oral administration with any type of antibiotic appears to be optimal. One additional type of antibiotic added to the basic antibiotic agent may contribute to the minimization of severe infection and drug resistance. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of interleukin-8 (IL-8) as a possible biomarker for diagnosis and treatment of benign prostatic hyperplasia (BPH) with chronic prostatitis. Histologic inflammation can be demonstrated in most BPH pathologic specimens. To provide objective parameters of inflammation, this prospective study quantified the IL-8 in expressed prostatic secretion (EPS) from BPH patients with or without histologic inflammation. Methods: White blood cell (WBC) count and enzyme-linked immunosorbent assays of the EPS for IL-8 were done in 44 patients who underwent transurethral prostatic resection because of benign prostatic enlargement before the operations. The correlation between IL-8 and WBC count in EPS; prostatic specific antigen; and International Prostate Symptom Score, irritative, and obstructive subscores was determined by Pearson correlation analysis. Results: IL-8 was detectable in all patients (the threshold of detection for IL-8 is 5 pg/mL). Twenty-one (47.7%) BPH patients had chronic prostatitis. The mean level of IL-8 in EPS was higher in BPH with chronic prostatitis than in simple BPH (median ± SE, 8175 ± 3789 pg/mL vs 2806 ± 1009 pg/mL). The catheter and age seemed to have no impact on the level of IL-8 in EPS. Statistically significant correlation was only found between IL-8 and WBC count. The sensitivity and specificity of IL-8 in EPS identifying the BPH with chronic prostatitis from the simple BPH were 85.7% and 91.3% respectively, at a cut-point of 3992 pg/mL. Conclusions: IL-8 is significantly elevated in BPH patients with chronic prostatitis. IL-8 in EPS can serve as a reliable biomarker applicable to identifying BPH with chronic prostatitis from simple BPH. [Copyright &y& Elsevier]