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.

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

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.

A 60-year-old male patient was hospitalized due to acute attack of bronchial asthma and pneumonia and antitussive, antiasthmatic, and anti-inflammatory treatments was given. Then his symptoms were improved. Discharge medication included budesonide and formoterol fumarate powder for inhalation and montelukast sodium. On the 4th day of medication after discharge, the patient developed bilateral metatarsophalangeal joint pain with redness and swelling, abdominal distension, fatigue, and dark urine. Laboratory tests showed serum creatinine (Scr) 112 μmol/L, serum uric acid 228 μmoL/L, urine protein (+), and urine occult blood (++). Gout, rheumatoid arthritis, and other autoimmune diseases were excluded and the possibility of acute kidney injury and metatarsophalangeal joint pain related to montelukast sodium was considered. Montelukast sodium was discontinued, budesonide and formoterol fumarate powder for inhalation was continued, and symptomatic treatment was given at the same time. Seven days later, the pain of metatarsophalangeal joint was improved and the urine color returned to normal. Two weeks later, his Scr level returned to normal (75 μmol/L).

A 60-year-old male patient was hospitalized due to acute attack of bronchial asthma and pneumonia and antitussive, antiasthmatic, and anti-inflammatory treatments was given. Then his symptoms were improved. Discharge medication included budesonide and formoterol fumarate powder for inhalation and montelukast sodium. On the 4th day of medication after discharge, the patient developed bilateral metatarsophalangeal joint pain with redness and swelling, abdominal distension, fatigue, and dark urine. Laboratory tests showed serum creatinine (Scr) 112 μmol/L, serum uric acid 228 μmoL/L, urine protein (+), and urine occult blood (++). Gout, rheumatoid arthritis, and other autoimmune diseases were excluded and the possibility of acute kidney injury and metatarsophalangeal joint pain related to montelukast sodium was considered. Montelukast sodium was discontinued, budesonide and formoterol fumarate powder for inhalation was continued, and symptomatic treatment was given at the same time. Seven days later, the pain of metatarsophalangeal joint was improved and the urine color returned to normal. Two weeks later, his Scr level returned to normal (75 μmol/L).

A 32-year-old male patient received oral desloratadine citrate disodium tablets 8.8 mg once daily for allergic rhinitis. On the 6th day of medication, he developed sporadic red rashes on his abdomen, but he didn′t pay attention to it. On the 7th day of medication, the rashes increased and were with itching; urine color became dark brown; and he developed yellowish discoloration of hand skin and sclera. Laboratory tests showed alanine aminotransferase (ALT) 323 U/L, aspartate aminotransferase (AST) 186 U/L, gamma glutamyl transferase (γ-GT) 309 U/L, total bilirubin (TBil) 63.9 μmol/L, and direct bilirubin (DBil) 33.6 μmol/L. He was diagnosed as having drug-induced liver injury and allergic dermatitis, which were considered to be caused by desloratadine citrate disodium. Then the drug was stopped and the patient was given liver-protective treatments and external application of mometasone furoate cream. On day 2 of desloratadine citrate disodium withdrawal, the color of his urine became lighter. On day 4 of drug withdrawal, the color of the rashes became lighter, the color of urine returned to normal, and there were no new rashes. On day 9 of drug withdrawal, the rashes disappeared basically. Liver function examination showed ALT 84 U/L, AST 29 U/L, γ-GT 187 U/L, TBil 19.5 μmol/L, and DBil 8.0 μmol/L. Two weeks later, his ALT was 54 U/L, and other examination results were within the reference fange.

A 32-year-old male patient received oral desloratadine citrate disodium tablets 8.8 mg once daily for allergic rhinitis. On the 6th day of medication, he developed sporadic red rashes on his abdomen, but he didn′t pay attention to it. On the 7th day of medication, the rashes increased and were with itching; urine color became dark brown; and he developed yellowish discoloration of hand skin and sclera. Laboratory tests showed alanine aminotransferase (ALT) 323 U/L, aspartate aminotransferase (AST) 186 U/L, gamma glutamyl transferase (γ-GT) 309 U/L, total bilirubin (TBil) 63.9 μmol/L, and direct bilirubin (DBil) 33.6 μmol/L. He was diagnosed as having drug-induced liver injury and allergic dermatitis, which were considered to be caused by desloratadine citrate disodium. Then the drug was stopped and the patient was given liver-protective treatments and external application of mometasone furoate cream. On day 2 of desloratadine citrate disodium withdrawal, the color of his urine became lighter. On day 4 of drug withdrawal, the color of the rashes became lighter, the color of urine returned to normal, and there were no new rashes. On day 9 of drug withdrawal, the rashes disappeared basically. Liver function examination showed ALT 84 U/L, AST 29 U/L, γ-GT 187 U/L, TBil 19.5 μmol/L, and DBil 8.0 μmol/L. Two weeks later, his ALT was 54 U/L, and other examination results were within the reference fange.