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

Marine microorganisms, especially marine fungi, have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites (Deshmukh et al., 2018; Carroll et al., 2022). The corals constitute a dominant part of reefs with the highest biodiversity, and harbor highly diverse and abundant microbial symbionts in their tissue, skeleton, and mucus layer, with species-specific core members that are spatially partitioned across coral microhabitats (Wang WQ et al., 2022). The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds, terpenes, alkaloids, peptides, aromatics, lactones, and steroids. They demonstrate a wide range of bioactivity such as anticancer, antimicrobial, and antifouling activity (Chen et al., 2022). The genetically powerful genus Emericella (Ascomycota), which has marine and terrestrial sources, includes over 30 species and is distributed worldwide. It is considered a rich source of diverse secondary metabolites with antimicrobial activity or cytotoxicity (Alburae et al., 2020). Notably, Emericella nidulans, the sexual state of a classic biosynthetic strain Aspergillus nidulans, was recently reported as an important source of highly methylated polyketides (Li et al., 2019) and isoindolone-containing meroterpenoids (Zhou et al., 2016) with unusual skeletons.
Animals ; Aspergillus nidulans ; Polyketides/chemistry* ; Anthozoa/microbiology* ; Anti-Infective Agents/pharmacology* ; Alkaloids

Diffusion-weighted imaging (DWI) is currently the most sensitive technique to diagnose early ischemic stroke. DWI signal hyperintensity is usually considered to suggest irreversible infarct core, but recent studies demonstrated that DWI hyperintensity signal could be reversible on small embolic lesions. Herein we present a case in a 63-year-old male patient, who was admitted to the emergency department with altered mental status and complaint of weakness in the left arm and leg 6.8 h prior to the admission. Emergency cranial magnetic resonance imaging (MRI) and angiography (MRA) revealed occlusion of his right middle cerebral artery (MCA) and large lesions on DWI. The patient underwent intra-artery thrombectomy after evaluation in spite of the large volume of the DWI lesions up to 91.5 mL at the baseline. His right MCA was recanalized at 8.5 h from symptom onset. One week after the procedure, the patient showed reduced DWI lesion volume to 11.58 mL. In this case we observed the reversibility of a large lesion of the anterior artery circulation presenting with hyperintensity on DWI, suggesting that the clinical implication of DWI hyperintensity should be interpreted with caution, and a large volume of baseline DWI hyperintensity may not be a contraindication to thrombectomy. This conclusion, however, awaits further validation by future large-scale randomized controlled trials.
Diffusion Magnetic Resonance Imaging ; Humans ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Stroke ; Thrombectomy

Objective To retrospectively analyze the outcomes of wake-up stroke (WUS) patients with occlusion of large vessel occlusion (LVO), who were selected for mechanical thrombectomy according to the mismatch of Alberta Stroke Program Early CT Score (ASPECTS) based on arterial spin labeling (ASL) and diffusion-weighted image (DWI) on admission magnetic resonance (MR) scans. Methods Twelve consecutive WUS patients with acute LVO of the anterior circulation undergoing MR scans with ASL and DWI prior to thrombectomy were retrospectively evaluated. The mismatch of ASPECTS was defined as the difference between ASL-ASPECTS and DWI-ASPECTS, and a higher score indicates a greater mismatch. Results The procedures led to successful reperfusion in all the cases (Thrombolysis in Cerebral Infarction Grade 2b-3). Eleven patients (91.7％) had significantly decreased National Institute of Health Stroke scale (NIHSS) score at discharge. A mRS score of≤2 at 90 days was achieved in 8 of the 12 patients (66.7％). Conclusion The mismatch between ASPECTS assessed based on ASL and DWI can detect a true mismatch in patients with acute LVO of the anterior circulation, and can be used for rapid screening of patients eligible for thrombectomy.

Objective To retrospectively analyze the outcomes of wake-up stroke (WUS) patients with occlusion of large vessel occlusion (LVO), who were selected for mechanical thrombectomy according to the mismatch of Alberta Stroke Program Early CT Score (ASPECTS) based on arterial spin labeling (ASL) and diffusion-weighted image (DWI) on admission magnetic resonance (MR) scans. Methods Twelve consecutive WUS patients with acute LVO of the anterior circulation undergoing MR scans with ASL and DWI prior to thrombectomy were retrospectively evaluated. The mismatch of ASPECTS was defined as the difference between ASL-ASPECTS and DWI-ASPECTS, and a higher score indicates a greater mismatch. Results The procedures led to successful reperfusion in all the cases (Thrombolysis in Cerebral Infarction Grade 2b-3). Eleven patients (91.7％) had significantly decreased National Institute of Health Stroke scale (NIHSS) score at discharge. A mRS score of≤2 at 90 days was achieved in 8 of the 12 patients (66.7％). Conclusion The mismatch between ASPECTS assessed based on ASL and DWI can detect a true mismatch in patients with acute LVO of the anterior circulation, and can be used for rapid screening of patients eligible for thrombectomy.

This study aims to develop multifunctional drug delivery system based on hollow mesoporous copper sulfide (HMCuS) nanoparticles. This type of nanoparticles is expected to achieve the synergistic treatment of tumor by targeted phototherapy and chemotherapy. The carrier was synthesized by a substitution method, and the anti-cancer drug doxorubicin (DOX) was loaded and then modified by hyaluronic acid (HA) to prepare the anti-cancer drug system DOX/HMCuS-HA. The results suggested that DOX/HMCuS-HA presented uniform spherical structure, with the drug loading efficiency of 33.6%, the particle size and zeta potential being 113.8 ± 6.9 nm and 18.4 ± 2.8 mV, respectively. When 100 μg·mL^-1 HMCuS was irradiated under 808 nm laser (2 W·cm^-2) for 8 min, the temperature can heat up 51 ℃, demonstrating high photothermal conversion efficacy. Electron spin resonance (ESR) tests and methylene blue degradation experiments showed that HMCuS nanoparticles could simultaneously produce hydroxyl radical (•OH) mediated photodynamic therapy. In addition, HA was responsible for minimizing premature drug release and increasing tumor targeting efficiency by acting as a smart gatekeeper with tumor specific targeting moiety. In vitro drug release experiments showed that the coated HA could be degraded by intracellular lysosomal enzyme hyaluronidase, which facilitated DOX release. The acidic micro-environment of tumor cell and external near infrared (NIR) stimulus could trigger further release of DOX from the nanoparticles. These results point to a new strategy for timely and effective anti-tumor treatment.

Objective To investigate the ultrasonic features of fetal isolated coronary artery fistula ( CAF) . Methods A total of 13 cases of fetal isolated CAF from December 2011 to M arch 2018 were retrospectively analyzed . Data of echocardiography and follow‐up were collected .All cases were divided into retrograde group and no retrograde group based on the presence of diastolic retrograde flow in aortic arch . T he inner diameters of affected coronary arteries ( CA ) and aortic annulus ( AO ) were measured ,and the CA to AO ratios ( CA/AO ) were then calculated .Correlations between CA ,CA/AO and the presence of retrograde flow were analyzed . Adverse birth outcomes including abortion , enlarged cardiac cavity , pulmonary hypertension were recorded at follow‐up . Correlation between diastolic retrograde flow in aortic arch and the rate of adverse birth outcomes was analyzed . Results ① T hirteen cases of fetal CAF were characterized by the varying degrees of dilation of affected coronary arteries . T hirteen cases were presented with abnormal blood flow in the large arteries or cardiac cavities :biphasic continuous flow pattern in atrio‐ coronary fistula and biphasic bidirectional continuous flow pattern with a diastolic dominant flow in coronary artery to ventricle fistula . Seven cases were presented with retrograde holodiastolic flow in aortic arch . ②T he CA/AO ratios of retrograde group was higher than in no retrograde group [ ( 0 .63 ± 0 .24 ) mm vs ( 0 .39 ± 0 .09) mm , P ＝0 .047] ,there was no significant difference of CA between the two groups [ ( 3 .00 ± 1 .25) mm vs ( 2 .03 ± 0 .62) mm , P ＝0 .115] . ③T he rate of adverse birth outcomes in retrograde group was higher than in no retrograde group ( 80% vs 20% ,χ2 ＝4 .80 , P ＝0 .028) . Conclusions Fetal isolated CAF has distinct ultrasonic features . Abnormal CA/AO ratio and diastolic retrograde flow in aortic arch are significant ultrasonic features and has prognostic values .

Objective: To investigate the ultrasonic features of fetal isolated coronary artery fistula (CAF). Methods: A total of 13 cases of fetal isolated CAF from December 2011 to March 2018 were retrospectively analyzed. Data of echocardiography and follow-up were collected.All cases were divided into retrograde group and no retrograde group based on the presence of diastolic retrograde flow in aortic arch. The inner diameters of affected coronary arteries (CA) and aortic annulus (AO) were measured, and the CA to AO ratios (CA/AO) were then calculated.Correlations between CA, CA/AO and the presence of retrograde flow were analyzed. Adverse birth outcomes including abortion, enlarged cardiac cavity, pulmonary hypertension were recorded at follow-up. Correlation between diastolic retrograde flow in aortic arch and the rate of adverse birth outcomes was analyzed. Results: ①Thirteen cases of fetal CAF were characterized by the varying degrees of dilation of affected coronary arteries. Thirteen cases were presented with abnormal blood flow in the large arteries or cardiac cavities: biphasic continuous flow pattern in atrio-coronary fistula and biphasic bidirectional continuous flow pattern with a diastolic dominant flow in coronary artery to ventricle fistula. Seven cases were presented with retrograde holodiastolic flow in aortic arch. ②The CA/AO ratios of retrograde group was higher than in no retrograde group [(0.63±0.24)mm vs (0.39±0.09)mm, P=0.047], there was no significant difference of CA between the two groups [(3.00±1.25)mm vs (2.03±0.62)mm, P=0.115]. ③The rate of adverse birth outcomes in retrograde group was higher than in no retrograde group (80% vs 20%, χ²=4.80, P=0.028). Conclusions Fetal isolated CAF has distinct ultrasonic features. Abnormal CA/AO ratio and diastolic retrograde flow in aortic arch are significant ultrasonic features and has prognostic values.

Objective To evaluate and compare the analytical performances and application values of three nucleic acid extraction methods for quantification of plasma Epstein-Barr Virus ( EBV ) DNA. Methods It used silica membrane spin column , boiling and automated magnetic bead method to extract viral nucleic acid in parallel , and combined real-time fluorescence quantitative PCR assays for quantitative EBV-DNA quantification.The performances of three methods were determined and compared by using the third-party reference materials , and the clinical values were analyzed by pairing detecting 100 NPC patients and 100 healthy subjects in pair .Results The accuracy and imprecision of three methods were all in line with requirements , and the results of clinical samples were linearly correlated . But actually the reproducibility and intermediate imprecision of the magnetic bead method were smaller and stable than those of the spin column method and the boiling method ( all <3％);the limit of detection for the magnetic bead method was 3.334 ×101 IU/ml, better than that of spin column method (4.159 ×101 IU/ml) and boiling method (8.511 ×101 IU/ml);the linear range of the magnetic bead method was 5.4 ×101 -5.4 ×105 IU/ml, slightly wider than that of the boiling method (5.4 ×102 -5.4 ×105 IU/ml); the ability of anti -Hb interference ability of magnetic bead method is better than that of boiling method ;and the positive rate and the mean viral load of the NPC samples measured with the magnetic bead method were significantly higher (95％, 8.342 ×103 IU/ml) than those measured with the spin column method (84％, 4.707 ×103 IU/ml) and the boiling method (78％, 2.571 ×103 IU/ml) ( P all<0.05).Conclusion The automated magnetic bead nucleic acid extraction method offered better analytical performance and higher clinical value for EBV DNA quantification in plasma .

Objective To investigate the predictive value of C-reactive protein/albumin ratio (CAR) for 30 d survival status in patients with acute ischemic stroke.Methods Patients with acute ischemic stroke admitted to the Neurological Intensive Care Unit (NICU),Nanfang Hospital,Southern Medical University were selected from 2013 to 2016.They were divided into a survival group and a death group according to the 30 d survival status.The clinical data of both groups were compared and analyzed.Multivariate logistic regression analysis was used to determine the independent risk factors for 30 d survival status.The predictive value of the variables was analyzed using the receiver operating characteristic (ROC) curve.Results A total of 236 patients were enrolled in the study,including 64 (27.12％) in the death group and 172 (72.88％) in the survival group.The baseline National Institutes of Health Stroke Scale score,procalcitonin,C-reactive protein,CAR,and onset to NICU time in patients of the survival group were significantly lower or shorter than those of the death group,and the serum albumin level of the survival group was higher than that of the death group (all P ＜0.05).Pearson's correlation analysis showed that C-reactive protein (r =0.647,P ＜ 0.001),CAR (r =0.632,P ＜ 0.001),and onset to NICU time (r =0.596,P ＜ 0.001) were closely associated with the 30 d survival status in patients with acute ischemic stroke.Multivariate logistic regression analysis showed that CAR was an independent risk factor for 30 d mortality in patients with acute ischemic stroke (odds ratio 1.895,95％ confidence interval 1.573-2.282;P ＜ 0.001).ROC curve analysis showed that the area under the curve of CAR was 0.873 (95％ confidence interval 0.815-0.931),the optimal cut-off value was 2.197,the sensitivity of predicting 30 d death risk was 82.8％,and the specificity was 87.8％.Conclusion CAR is an independent risk factor for 30 d death in patients with acute ischemic stroke and can be used for 30 d survival assessment in patients with acute ischemic stroke.