Objective To explore the effect and mechanism of penehyclidine hydrochloride (PHCD) on vascular endothelial injury in septic rats. Methods Fifty male SD rats were randomly divided into control group, lipopolysaccharide (LPS) induced sepsis group (model group), low dose PHCD (0.3 mg/kg) group, medium dose PHCD (1.0 mg/kg) group and high dose PHCD (3.0 mg/kg) groups, ten mice for each group. Normal saline was injected into the tail vein of the control group, and 10 mg/kg lipopolysaccharide (LPS) was injected into the tail vein of the rats in other groups to prepare the sepsis rat models. After the models were successfully established, low, medium and high doses (0.3, 1.0, 3.0 mg/kg) of PHCD solution were injected into the tail vein of the rats of corresponding groups. Wet/dry mass ratio (W/D) of lung tissue of rats in each group was measured, and ELISA was used to assay interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 content and rat plasma angiopoietin 2 (Ang2) content in bronchoalveolar lavage fluid (BALF). HE staining was used to observe the pathological changes of lung tissues. Immunohistochemical staining was used to observe the expression of Ang2 in the right lung tissues. Western blot analysis was performed to detect Ang2 and vascular endothelial cadherin (VE-cadherin) protein in lung tissues. Results Compared with the control group, the W/D ratio of the lung tissues of rats in the model group and the contents of IL-1β, IL-6 and TNF-α in BALF were significantly increased; the lung tissues showed obvious pathological damage, with up-regulation of Ang2 expression and down-regulation of VE-Cadherin expression. Compared with the model group, the W/D ratio of the lung tissues of rats in three PHCD treatment groups and the contents of IL-1β, IL-6 and TNF-α in BALF were significantly reduced; the pathological damage of lung tissue was significantly reduced, with down-regulation of Ang2 expression and up-regulation of VE-cadherin expression. Conclusion PHCD can reduce LPS-induced lung inflammation in rats with sepsis by regulating the Ang2/VE-Cadherin pathway, thereby improving vascular endothelial injury.
Rats ; Mice ; Animals ; Male ; Lipopolysaccharides/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Angiopoietin-2/pharmacology* ; Interleukin-6/metabolism* ; Rats, Sprague-Dawley ; Lung ; Acute Lung Injury/metabolism* ; Sepsis/metabolism*

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Background: and Purpose To evaluate whether the thrombus enhancement sign (TES) can be used to differentiate embolic large vessel occlusion (LVO) from in situ intracranial atherosclerotic stenosis (ICAS)-related LVO in the anterior circulation of patients with acute ischemic stroke (AIS). Methods: Patients with LVO in the anterior circulation who underwent both non-contrast computed tomography (CT) and CT angiography and mechanical thrombectomy were retrospectively enrolled. Both embolic LVO (embo-LVO) and in situ ICAS-related LVO (ICAS-LVO) were confirmed by two neurointerventional radiologists after reviewing the medical and imaging data. TES was assessed to predict embo-LVO or ICAS-LVO. The associations between occlusion type and TES, along with clinical and interventional parameters, were investigated using logistic regression analysis and a receiver operating characteristic curve. Results: A total of 288 patients with AIS were included and divided into an embo-LVO group (n=235) and an ICAS-LVO group (n=53). TES was identified in 205 (71.2%) patients and was more frequently observed in those with embo-LVO, with a sensitivity of 83.8%, specificity of 84.9%, and area under the curve (AUC) of 0.844. Multivariate analysis showed that TES (odds ratio [OR], 22.2; 95% confidence interval [CI], 9.4–53.8; P<0.001) and atrial fibrillation (OR, 6.6; 95% CI, 2.8–15.8; P<0.001) were independent predictors of embolic occlusion. A predictive model that included both TES and atrial fibrillation yielded a higher diagnostic ability for embo-LVO, with an AUC of 0.899. Conclusion TES is an imaging marker with high predictive value for identifying embo- and ICAS-LVO in AIS and provides guidance for endovascular reperfusion therapy.

Imaging is an essential tool in the management of spinal disorders. Most spine surgeons focus on bony structures and the spinal cord when reading imaging examinations, while the interpretation of the morphology and characteristics of soft tissues such as paraspinal muscles and fat has been a "relative blind spot". As the imaging features of the non-bony structures of the spine have been studied and reinterpreted, it has become clear that these non-bony structural changes are also associated with spinal diseases. Soft tissue parameters such as "paraspinal muscle cross-sectional area," "subcutaneous fat thickness," and "paraspinal muscle fat infiltration rate" on CT, MRI, and other imaging studies have been shown to play a role in spine diseases, and have been shown to be reproducible in the diagnosis, treatment and prognosis of spinal disorders and have potential for clinical application. In addition, the association of sarcopenia and spinal epidural lipomatosis with spinal disorders is gaining attention. In recent years, with a better understanding of the pathogenesis of spinal disorders, techniques such as 3D gait analysis and photographic postural measurement have also shown promise in the diagnosis and assessment of the outcome of degenerative spinal disorders and adolescent idiopathic scoliosis. In view of this, this article summarizes the latest research progress in the basic and clinical aspects of non-bony structures of the spine and analyzes the significance of the imaging features of these non-bony structures in the basic research and diagnosis of spinal diseases.

Psoraleae Fructus (PF) is an important traditional herbal medicine with a long history of clinical application. It is widely used to treat various diseases, such as osteoporosis, leucoderma and diarrhea. As a traditional nontoxic herb, it has aroused worldwide concern about the potential risks due to increasing adverse reaction events. This article reviews the botany, ancient records of medical uses, adverse reactions, toxicological research advance and detoxification methods of PF. According to clinical studies, liver injury is the most predominant in PF-related adverse reactions. The underlying mechanisms include bile acid metabolism and transport disorders, oxidative stress, mitochondrial damage, inhibition of liver cell regeneration and inflammatory reactions. Furthermore, the potential toxins of PF are summarized. Traditional methods of processing and compatibility will provide reference for reducing the toxicity of PF, which requires further research. In sum, this work systematically summarizes the reserach progress on the safety of PF, which will provide comprehensive insights into the toxicity of PF and facilitate its safe use and future development.
Drugs, Chinese Herbal/toxicity* ; Fruit/toxicity* ; Liver

ObjectiveTo explore the activating effects of ten important effective components in seven medicinal and edible substances on human pregnane X receptor （PXR）， including Glycyrrhizae Radix et Rhizoma （liquiritin and glycyrrhizic acid）， Houttuyniae Herba （quercetin and houttuyfonate）， Prunellae Spica （rosmarinic acid）， Cassiae Semen （aurantio-obtusin）， Poria （pachymic acid）， Lilii Bulbus （Lilium brownii saponin and colchicine）， and Lycii Fructus （Lycium barbarum polysaccharide） and screen potentially toxic components. MethodCell counting kit-8 （CCK-8） assay was used to investigate the cytotoxic effect of liquiritin， glycyrrhizic acid， quercetin， houttuyfonate， rosmarinic acid， pachymic acid， aurantio-obtusin， and colchicine （10， 20， and 50 μmol·L^-1）， and L. brownii saponin and L. barbarum polysaccharide （10， 20， and 50 mg·L^-1） on normal human hepatocyte cell line （L02）. The release of lactate dehydrogenase （LDH） in L02 cells after drug treatments was detected by the biochemical analyzer. The apoptosis induced by ten effective components was explored by Hoechst 33342 staining. The secreted luciferase reporter system was used to co-transfect the PXR expression vector and reporter gene vector containing cytochrome P450 3A4 （CYP3A4） transcriptional regulatory region into L02 cells， with 10 μmol·L^-1 rifampicin （RIF） as a positive control. After treated with liquiritin， glycyrrhizic acid， quercetin， houttuyfonate， rosmarinic acid， aurantio-obtusin， pachymic acid， and colchicine （5， 10， and 20 μmol·L^-1） and L. brownii saponin and L. barbarum polysaccharide （5， 10， and 20 mg·L^-1） for 24 h， the cells were tested for secreted luciferase activity. ResultCompared with the control group， colchicine， L. brownii saponin， and quercetin decreased the cell viability （P<0.05， P<0.01）. Compared with the control group， quercetin， rosmarinic acid， glycyrrhizic acid， colchicine， aurantio-obtusin， and pachymic acid increased the release rate of LDH in L02 cells （P<0.05， P<0.01）. The proportion of hyperchromatic nuclei increased gradually after rosmarinic acid， liquiritin， and L. barbarum polysaccharide treatments as compared with the control group （P<0.05， P<0.01）. In terms of co-transfection of pcDNA3.1-PXR and pGLuc-CYP3A4 into L02 cells， compared with the control group， aurantio-obtusin and pachymic acid showed activating effects on PXR （P<0.05）， whereas liquiritin and glycyrrhizic acid showed inhibitory effects （P<0.05）. ConclusionThe findings suggest that when medicinal and edible substances are taken for a long time， attention should be paid to their influence on drug-metabolizing enzymes and possible interactions， so as to improve their safety.

Objective: To study the learning curve of laparoscopic pacreaticoduodenectomy (LPD) with a view to find an appropriate way to develop LPD step by step. Methods: 112 consecutive patients who completely underwent LPD in a single surgery center at the First People’s Hospital of Changzhou from December 2015 to February 2018 were retrospectively reviewed. By using both the cumulative sum (CUSUM) and the risk-adjusted CUSUM (RA-CUSUM) methods to analyze the perioperative data of these patients, the learning curve of LPD was studied in a more scientific way. Results: The learning curve could be divided into three phases: Phase 1, the initial period (the initial 45 patients); Phase 2, the enhancement period (the subsequent 31 patients); Phase 3, the maturation period (the remaining patients). For these 3 phases, the corresponding operative times were (448.4±75.0), (381.3±74.3), and (336.2±52.1) min, respectively (P<0.05). The intraoperative blood losses were (373.3±250.1), (332.3±211.6), and (265.3±253.2) ml, respectively (P<0.05). The times to oral intake were 6.0(5.0, 8.0), 5.0(3.0, 6.0), and 3.0(3.0, 5.0) days, respectively (P<0.05). The number of lymph nodes harvested were (10.0±7.0), (8.8±4.3), and (13.3±6.2), respectively (P<0.05). All these showed significant improvement through the 3 phases. On the other hand, the postoperative stays, the postoperative pancreatic fistula rates were also decreased. But these failed to reach statistical significance. Vascular reconstruction was carried out in the 48th patient in phase 2 of the study. Conclusions The initial phase of LPD passed after LPD for 46 patients, but the maturation phase occurred after LPD on 76 patients. Vascular reconstruction should be considered as passing through the learning phase rather than reaching the maturity phase. Adjustments made in the enhancement phase helped to get through the maturation phase earlier.

Liver can be regenerated after chemical injury or localized resection of the surgery by dynamic interactions between hepatocytes and non-parenchymal cells. Liver sinusoidal endothelial cells (LSECs) are the most abundant cells in liver non-parenchymal cells and participate in liver development, injury and regeneration. Currently more and more studies have shown that LSECs are essential for hepatocyte regeneration. In this paper, we summarized the research progress of LSECs and liver regeneration in recent years, aiming to provide new ideas for promoting liver regeneration by targeting LSECs.

Objective To assess the safety and efficiency of systematic transperineal ultrasound guided template positioning biopsy for the high-risk population of prostate cancer.Methods From January 2010 to January 2012 a total of 42 high-risk men of prostate cancer underwent systematic ultrasound guided biopsy using the transperineal template positioning technique.All patients got at least one previous biopsy,and all the patients showed negative results,including prostatic intraepithelial neoplasia,and/or atypical small cell acinar proliferation.During the follow-up,all the patients still had high prostate specific antigen (PSA) velocity (＞ 0.75 μg/L) or high PSA level (＞ 10 μg/L).Results A mean of 18.7 biopsy cores had been obtained.Cancer was identified in 19 of the 42 men (44％).The mean Gleason score was 6 (from 4 to 9).Mean prostate volume in the positive and negative biopsy groups was 44 and 71 ml.The only significant independent influence factor for positive biopsy was prostate volume (P ＜ 0.05).The positive rate showed no statistic difference in term of presence of PIN,AHH,the number of biopsy sites,or PSA value (P ＞0.05).Adenocarcinoma was found in transition zone in 14 of 19 cases (74％),and 5 (36％) was positive only in the transition zone.Complications were rare and self-limiting,including hematuria (29％)and urinary retention (0.9％).Conclusions Systematic transperineal template positioning biopsy of the prostate is a safe and precise biopsy technique in patients who remain at high-risk for prostate adenocarcinoma.

Objective To investigate the inhibition effects of an hTERT-promoter-dependent oncolytic adenovirus Ad-VT that expresses apoptin on human prostatic carcinoma cell PC-3. Methods MTT assay was used to measure viability of PC-3 cell which was infected by recombinant adenovirus.The viability was measured at time points of 12,24,36,48,60,72,84 and 96 h after infection.AO/EB staining,DAPI staining,Annexin V assay were used to investigate the lethal effect and style of Ad-VT on PC-3 cell in vitro.The Caspases were measured by whole cell extraction of PC-3 cells 48hrs after infection. Results Ad-VT,Ad-VP3 and Ad-GT inhibited the proliferation of PC-3 cell in vitro.Ad-VT and Ad-GT were more effective than Ad-VP3 on cell growth,P ＜ 0.05.At 48,72,96 h time points,the inhibition effect of Ad-VT on PC-3 cell exhibited a dose related manner.When infection at MOI 100,the inhibition effect of Ad-VT on PC-3 cells exhibited time related manner.The AO/EB staining,DAPI staining,Annexin V assay,Annexin V assays and Caspase assays showed that Ad-VT inhibited the proliferation of PC-3 cells by inducing apoptosis of prostate cancer cells,Loss of cytoplasmic membrane integrity. Conclusions The hTERT-promoterdependent oncolytic adenovirus Ad-VT could effectively suppress prostate cancer cells PC-3 growth.