Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVES: To assess the therapeutic effect of aucubin in mice with knee osteoarthritis (KOA) and investigate the underlying mechanism. METHODS: Sixty C57BL/6J mice were randomized equally into sham operation group, KOA model group, glucosamine (positive control) treatment group, and low-, medium-, and high-dose aucubin treatment groups (2, 4, and 8 mg/kg, respectively). KOA mouse models were established by transection of the anterior cruciate ligament (ACL), and the treatment was initiated on day 1 postoperatively and administered weekly for 8 weeks. Safranin O-fast green staining, immunohistochemistry, and microCT were used to evaluate the changes in cartilage pathology, inflammatory protein expression, and subchondral bone volume fraction (BV/TV). The expression levesl of COL2, SOX9, p-P65, IL-1β and MMP13 proteins in the cartilage tissues were detected using Western blotting. In a chondrocyte model with IL-1β treatment for mimicking KOA, the effect of aucubin on chondrogenic differentiation was observed with Alcian blue and Safranin O staining, and cellular COL2, SOX9 and TNF‑α mRNA expressions were detected with RT-qPCR. RESULTS: Compared with those in the model group, the mouse models receiving aucubin treatment showed significantly upregulated COL2 and SOX9 protein levels and downregulated p-P65, IL-1β and MMP13 expressions in the cartilage tissues. In the IL-1β-induced chondrocyte model, aucubin treatment significantly upregulated the mRNA expressions of SOX9 and COL2 but lowered the mRNA expression of TNF-α. Alcian blue and Safranin O staining confirmed that aucubin promoted the synthesis of cartilage extracellular matrix and enhanced chondrogenic differentiation of the cells. CONCLUSIONS Aucubin can effectively alleviate KOA in mice by inhibiting NF‑κB-mediated cartilage inflammation, promoting cartilage matrix synthesis, and improving subchondral bone microstructure.
Animals ; Mice, Inbred C57BL ; Mice ; Osteoarthritis, Knee/drug therapy* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Iridoid Glucosides/therapeutic use* ; SOX9 Transcription Factor/metabolism* ; Chondrocytes/drug effects* ; Male ; Interleukin-1beta/metabolism* ; Matrix Metalloproteinase 13/metabolism* ; Collagen Type II/metabolism* ; Disease Models, Animal

The human spine injury and various lumbar spine diseases caused by vibration have attracted extensive attention at home and abroad. To explore the biomechanical characteristics of different approaches for lumbar interbody fusion surgery combined with an interspinous internal fixator, device for intervertebral assisted motion (DIAM), finite element models of anterior lumbar interbody fusion (ALIF), transforaminal lumbar interbody fusion (TLIF) and lateral lumbar interbody fusion (LLIF) are created by simulating clinical operation based on a three-dimensional finite element model of normal human whole lumbar spine. The fusion level is at L4-L5, and the DIAM is implanted between spinous process of L4 and L5. Transient dynamic analysis is conducted on the ALIF, TLIF and LLIF models, respectively, to compute and compare their stress responses to an axial cyclic load. The results show that compared with those in ALIF and TILF models, contact forces between endplate and cage are higher in LLIF model, where the von-Mises stress in endplate and DIAM is lower. This implies that the LLIF have a better biomechanical performance under vibration. After bony fusion between vertebrae, the endplate and DIAM stresses for all the three surgical models are decreased. It is expected that this study can provide references for selection of surgical approaches in the fusion surgery and vibration protection for the postsurgical lumbar spine.
Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Lumbar Vertebrae/surgery* ; Pedicle Screws ; Range of Motion, Articular ; Spinal Fusion ; Vibration

Objective To investigate the value of automatic segmentation of carotid vessel wall in multicontrast MR images using U?Net neural network. Methods Patients were retrospectively collected from 2012 to 2015 in Carotid Atherosclerosis Risk Assessment (CARE II) study. All patients who recently suffered ischemic stroke and/or transient ischemic attack underwent identical, state?of?the?art multicontrast MRI technique. A total of 17 568 carotid vessel wall MR images from 658 subjects were included in this study after inclusion criteria and exclusion criteria. All MR images were analyzed using customized analysis platform (CASCADE). Randomly, 10 592 images were assigned into training dataset, 3 488 images were assigned into validating dataset and 3 488 images were assigned into test dataset according to a ratio of 6∶2∶2. Data augmentation was performed to avoid over fitting and improve the ability of model generalization. The fine?tuned U?Net model was utilized in the segmentation of carotid vessel wall in multicontrast MR images. The U?Net model was trained in the training dataset and validated in the validating dataset. To evaluate the accuracy of carotid vessel wall segmentation, the sensitivity, specificity and Dice coefficient were used in the testing dataset. In addition, the interclass correlation and the Bland?Altman analysis of max wall thickness and wall area were obtained to demonstrate the agreement of the U?Net segmentation and the manual segmentation. Results The sensitivity, specificity and Dice coefficient of the fine?tuned U?Net model achieved 0.878,0.986 and 0.858 in the test dataset, respectively. The interclass correlation (95% confidence interval) was 0.921 (0.915-0.925) for max wall thickness and 0.929 (0.924-0.933) for wall area. In the Bland?Altman analysis, the difference of max wall thickness was (0.037±0.316) mm and the difference of wall area was (1.182±4.953) mm2. The substantial agreement was observed between U?Net segmentation method and manual segmentation method. Conclusion Automatic segmentation of carotid vessel wall in multicontrast MR images can be achieved using fine?tuned U?Net neural network, which is trained and tested in the large scale dataset labeled by professional radiologists.

Objective: To investigate the value of automatic segmentation of carotid vessel wall in multicontrast MR images using U-Net neural network. Methods: Patients were retrospectively collected from 2012 to 2015 in Carotid Atherosclerosis Risk Assessment (CARE II) study. All patients who recently suffered ischemic stroke and/or transient ischemic attack underwent identical, state-of-the-art multicontrast MRI technique. A total of 17 568 carotid vessel wall MR images from 658 subjects were included in this study after inclusion criteria and exclusion criteria. All MR images were analyzed using customized analysis platform (CASCADE). Randomly, 10 592 images were assigned into training dataset, 3 488 images were assigned into validating dataset and 3 488 images were assigned into test dataset according to a ratio of 6∶2∶2. Data augmentation was performed to avoid over fitting and improve the ability of model generalization. The fine-tuned U-Net model was utilized in the segmentation of carotid vessel wall in multicontrast MR images. The U-Net model was trained in the training dataset and validated in the validating dataset. To evaluate the accuracy of carotid vessel wall segmentation, the sensitivity, specificity and Dice coefficient were used in the testing dataset. In addition, the interclass correlation and the Bland-Altman analysis of max wall thickness and wall area were obtained to demonstrate the agreement of the U-Net segmentation and the manual segmentation. Results: The sensitivity, specificity and Dice coefficient of the fine-tuned U-Net model achieved 0.878,0.986 and 0.858 in the test dataset, respectively. The interclass correlation (95% confidence interval) was 0.921 (0.915-0.925) for max wall thickness and 0.929 (0.924-0.933) for wall area. In the Bland-Altman analysis, the difference of max wall thickness was (0.037±0.316) mm and the difference of wall area was (1.182±4.953) mm². The substantial agreement was observed between U-Net segmentation method and manual segmentation method. Conclusion Automatic segmentation of carotid vessel wall in multicontrast MR images can be achieved using fine-tuned U-Net neural network, which is trained and tested in the large scale dataset labeled by professional radiologists.

Objective To investigate the CT performances and causes of misdiagnosis of parovarian cyst,to improve its diagnostic accuracy.Methods CT data of 75 patients with surgically and pathologically confirmed parovarian cyst were analyzed retrospectively. Results Among the 75 patients,there were 79 cysts,in which 48 patients (51 cysts)originated from the epoophoron and 27 patients (28 cysts) from the mesosalpinx.77 were simple serous cysts and 2 serous cystadenomas.38 were located in the right ovarian adnexa,36 in the left ovarian adnexa,3 in the anterosuperior uterus,1 in the rectouterine pouch and 1 in the right iliac fossa.The size of the cysts ranged from 10 mm × 13 mm to 174 mm × 227 mm.75 were single cysts and 4 double cysts,34 presented as ovoid cysts,25 as irregular cysts, 17 as round cysts and 3 as gourd-shaped cysts.All the 79 cysts showed clear boundaries,thin walls,non-mural nodules,cystic fluid with a homogeneous densitywith CT value of 0-31 HU.Enhanced scanning revealed curved “obvious enhancement of the fallopian tube”at the edge of 68 cysts.In addition,the ipsilateral ovary could be detected in 76 cysts.“Holding ball”was found in 1 9 cysts.Conclusion Indication in ipsilateral ovary,curved “obvious enhancement of the fallopian tube”at the edge of cysts and “holding ball”are distinctive CT performances of parovarian cysts.CT has an important diagnostic value in parovarian cyst.

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract (RPAE). A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx? software and mass defect filtering (MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.

Objective To explore the value of thinprep cytology in the diagnosis of thyroid nodules by thyroid fine needle aspiration.Methods Liquid-based thin-film cell production technology (TCT)and traditional producers technology (CS)were used in detection of 125 specimens by thyroid fine needle aspiration.Results TCT had the following characteristics :significant increased in cell number,cell morphology clear structure could be clearly observed especially pleomorphic nuclei,elon-gated or irregular nuclear membrane,nuclear grooves and nuclear inclusions,the cells showed a single layer arrangement,smear clean background,less blood cells and impurities.TCT and CS differences in the classification of cytologic diagnosis was obvious (χ2 =7.727,P =0.052 >0.05).TCT results in line with the pathological diagnosis was 98.9%,which was higher than CS and pathological diagno-sis compliance rate of 90.3% (χ2 =6.764,P =0.009 <0.05).Accuracy,sensitivity and specificity in TCT group were better than CS (P <0.01).Conclusion TCT producers can improve the quality of thyroid biopsy,sensitivity,specificity and accuracy of pathological diagnosis coincidence rate,so it is worthy of clinical application and popularization.

Objective To explore the value of thinprep cytology in the diagnosis of thyroid nodules by thyroid fine needle aspiration.Methods Liquid-based thin-film cell production technology (TCT)and traditional producers technology (CS)were used in detection of 125 specimens by thyroid fine needle aspiration.Results TCT had the following characteristics :significant increased in cell number,cell morphology clear structure could be clearly observed especially pleomorphic nuclei,elon-gated or irregular nuclear membrane,nuclear grooves and nuclear inclusions,the cells showed a single layer arrangement,smear clean background,less blood cells and impurities.TCT and CS differences in the classification of cytologic diagnosis was obvious (χ2 =7.727,P =0.052 >0.05).TCT results in line with the pathological diagnosis was 98.9%,which was higher than CS and pathological diagno-sis compliance rate of 90.3% (χ2 =6.764,P =0.009 <0.05).Accuracy,sensitivity and specificity in TCT group were better than CS (P <0.01).Conclusion TCT producers can improve the quality of thyroid biopsy,sensitivity,specificity and accuracy of pathological diagnosis coincidence rate,so it is worthy of clinical application and popularization.