ObjectiveTo investigate the regulatory effect of icariin （ICA） on transforming growth factor-β₁ （TGF-β₁）/Smad pathway in bone microvascular endothelial cells （BMECs） and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured， and the cell types were identified by immunofluorescence. Cells were divided into the control group， model group （0.1 g·L^-1 methyl prednisolone）， ICA group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA）， and TGF-β inhibitor group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA +1×10^-5 mol·L^-1 LY2157299）. Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β₁/ Smad pathway. ResultsAfter cell separation culture， platelet endothelial cell adhesion molecule （CD31） and von willebrand factor （vWF） immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged， and the nucleus was pyknotic and broken in the model group. Compared with the model group， the ICA group had complete cell membranes， clear structures， with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes， and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group， in the model group and the LY2157299 group， autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group， the mRNA and protein expressions of autophagy effector protein 1 （Beclin1） and microtubule-associated protein 1 light chain 3B （LC3B） in the model group were significantly decreased （P<0.01）， and those of ubiquitin-binding protein （p62） were significantly increased （P<0.01）. The mRNA expression of TGF-β₁， Smad homolog 2 （Smad2）， and Smad homolog 3 （Smad3） decreased （P<0.05， P<0.01）. The protein expressions of TGF-β₁， p-Smad2， and p-Smad3 were significantly decreased （P<0.01）. Compared with those of the model group， the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased （P<0.01）， and those of p62 significantly reduced （P<0.01）. The mRNA expression of TGF-β₁， Smad2， and Smad3 increased significantly （P<0.01）. The protein expression of TGF-β₁， p-Smad2， and p-Smad3 increased significantly （P<0.01）. Compared with those in the model group， the mRNA and protein expressions of Beclin1， LC3B， and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β₁ pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs， and its mechanism may be related to activating the TGF-β₁/Smad signaling pathway.

Objective:To construct a medical education metaverse based on cloudytization virtual reality (VR) technique,so as to resolve various issues encountered with conventional VR devices in use process,and enhance the user's experience and teaching effect of virtual space education. Methods:The technical architecture of the medical education metaverse was conducted from the perspectives included the underlying technique layer,learning interface layer,teaching activity space and knowledge layer. The medical education mateverse,which based on cloudytization VR technique,was constructed,and the system performance and user's experience were optimized from a supporting environment included the content layer,platform layer,cloud computing layer,network layer and terminal layer. Results:The medical students could conduct practical operation in virtual environment at any time and any place by the deployment approach on cloudy terminal and lightweight devices. The efficient and convenient cross-disciplinary collaborative learning was convenient for students to acquire knowledge from multiple perspectives,to better response complex medical environments. The real-time interactive remote medical approach expanded the boundaries of medical education,and ensured equity and inclusivity in medical education. Conclusion:The application of medical education metaverse based on cloudytization VR technique in medical teaching can effectively reduce the application threshold of medical education metaverse,and expand the coverage of educational resources of high quality,and enhance the use experience of teaching of the virtual space of medical education based on VR,and meet the demands of medical teaching for diverse application scenarios.

Objective:To construct a medical education metaverse based on cloudytization virtual reality (VR) technique,so as to resolve various issues encountered with conventional VR devices in use process,and enhance the user's experience and teaching effect of virtual space education. Methods:The technical architecture of the medical education metaverse was conducted from the perspectives included the underlying technique layer,learning interface layer,teaching activity space and knowledge layer. The medical education mateverse,which based on cloudytization VR technique,was constructed,and the system performance and user's experience were optimized from a supporting environment included the content layer,platform layer,cloud computing layer,network layer and terminal layer. Results:The medical students could conduct practical operation in virtual environment at any time and any place by the deployment approach on cloudy terminal and lightweight devices. The efficient and convenient cross-disciplinary collaborative learning was convenient for students to acquire knowledge from multiple perspectives,to better response complex medical environments. The real-time interactive remote medical approach expanded the boundaries of medical education,and ensured equity and inclusivity in medical education. Conclusion:The application of medical education metaverse based on cloudytization VR technique in medical teaching can effectively reduce the application threshold of medical education metaverse,and expand the coverage of educational resources of high quality,and enhance the use experience of teaching of the virtual space of medical education based on VR,and meet the demands of medical teaching for diverse application scenarios.

【Objective】 To construct an easy-to-use individual survival prognostic tool based on competing risk analyses to predict the risk of 1-, 2- and 3- year recurrence for patients with non-muscle invasive bladder cancer (NMIBC). 【Methods】 The follow-up data of 419 NMIBC patients were obtained. The patients were randomly divided into training cohort (n=293) and validation cohort (n=126). The variables included age at diagnosis, sex, history of smoking, tumor number, tumor size, histolo-gic grade, pathological stage, and bladder perfusion drug. The cumulative incidence function (CIF) of recurrence was estimated using all variables in the training cohort and potential prognostic variables were determined with Gray’s test. The Fine-Gray subdistribution proportional hazard approach was used as a multivariate competitive risk analysis to identify independent pro-gnostic variables. A competing risk nomogram was developed to predict the recurrence. The performance of the competing risk model was evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and Brier score. 【Results】 Five independent prognostic factors including age, number of tumors, tumor size, histologic grade and pathological stage were used to construct the competing risk model. In the validation cohort, the AUC of 1-, 2- and 3- year recurrence were 0.895 (95%CI: 0.831-0.959), 0.861(95%CI: 0.774-0.948) and 0.827(95%CI: 0.721-0.934), respectively, indicating that the model had a high predictive performance. 【Conclusion】 We successfully constructed a competing risk model to predict the risk of 1-, 2- and 3-year recurrence for NMIBC patients. It may help clinicians to improve the postoperative management of patients.

Objective: The primary aim was to evaluate the influence of depressive and anxiety symptoms on the 1-year recurrence rate of non-muscle invasive bladder cancer (NMIBC) patients. The secondary aim was to examine the risk factors leading to psychological distress. Methods: A total of 104 NMIBC patients were enrolled for interviews, and the Hospital Anxiety and Depression Scale (HADS) questionnaire survey was administered 1 month after their operation. Their cystoscopy results were followed up. The risk factors affecting their 1-year recurrence rate were evaluated through univariate analysis, Cox regression and Kaplan-Meier analysis. The risk factors causing depressive and anxiety symptoms were evaluated through univariate analysis and logistic regression. Results: In addition to American Urological Association risk stratification, depressive symptoms were another independent risk factor for recurrence in NMIBC patients (HR: 2.493, 95% CI: 1.048–5.930, p=0.039), and the increase in the recurrence rate was highly significant in intermediate-risk patients (HR: 8.496, 95% CI: 2.178–33.138, p=0.019). Anxiety symptoms were not an independent risk factor for recurrence (HR: 1.655, 95% CI: 0.714–3.837, p=0.240). We also observed that the burden of medical expenses of NMIBC on the family was an independent risk factor for depressive symptoms (p=0.029) and anxiety symptoms (p=0.048); chronic pain was an independent risk factor for anxiety symptoms (OR: 3.447, 95% CI: 1.182–10.052, p=0.023). Conclusion Depression symptoms are an independent risk factor for recurrence in NMIBC patients. Moreover, the burden of medical expenses on the family is an independent risk factor for depressive and anxiety symptoms in NMIBC patients. Additionally, chronic pain is a risk factor for anxiety symptoms in NMIBC patients. This study provided a theoretical foundation for clinical oncologists to pay more attention to the mental health of NMIBC patients.

Objective: The primary aim was to evaluate the influence of depressive and anxiety symptoms on the 1-year recurrence rate of non-muscle invasive bladder cancer (NMIBC) patients. The secondary aim was to examine the risk factors leading to psychological distress. Methods: A total of 104 NMIBC patients were enrolled for interviews, and the Hospital Anxiety and Depression Scale (HADS) questionnaire survey was administered 1 month after their operation. Their cystoscopy results were followed up. The risk factors affecting their 1-year recurrence rate were evaluated through univariate analysis, Cox regression and Kaplan-Meier analysis. The risk factors causing depressive and anxiety symptoms were evaluated through univariate analysis and logistic regression. Results: In addition to American Urological Association risk stratification, depressive symptoms were another independent risk factor for recurrence in NMIBC patients (HR: 2.493, 95% CI: 1.048–5.930, p=0.039), and the increase in the recurrence rate was highly significant in intermediate-risk patients (HR: 8.496, 95% CI: 2.178–33.138, p=0.019). Anxiety symptoms were not an independent risk factor for recurrence (HR: 1.655, 95% CI: 0.714–3.837, p=0.240). We also observed that the burden of medical expenses of NMIBC on the family was an independent risk factor for depressive symptoms (p=0.029) and anxiety symptoms (p=0.048); chronic pain was an independent risk factor for anxiety symptoms (OR: 3.447, 95% CI: 1.182–10.052, p=0.023). Conclusion Depression symptoms are an independent risk factor for recurrence in NMIBC patients. Moreover, the burden of medical expenses on the family is an independent risk factor for depressive and anxiety symptoms in NMIBC patients. Additionally, chronic pain is a risk factor for anxiety symptoms in NMIBC patients. This study provided a theoretical foundation for clinical oncologists to pay more attention to the mental health of NMIBC patients.

OBJECTIVE: To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19). METHODS: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare,the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.
Betacoronavirus ; isolation & purification ; China ; Coronavirus Infections ; diagnostic imaging ; pathology ; Disease Progression ; Humans ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; pathology ; Tomography, X-Ray Computed

OBJECTIVE: To analyze the dynamic changes of chest CT images of patients with corona virus disease-19 (COVID-19). METHODS: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare, the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.

Objective The application of nano-carbon tracer technique in radical antegrade modular pancreatosplenectomy (RAMPS) to treat malignant tumors of pancreatic body and tail.To investigate whether radical anterograde modulization of pancreatic body and tail combined with nano-carbon tracer technique is more beneficial to the prognosis of patients.Methods From January 2014 to September 2018,a retrospective analysis was performed in 48 patients in Linyi Central Hospital,all patients underwent RAMPS,all of whom were pathologically proved to be pancreatic carcinoma of the body and tail.Based on whether the nano-carbon lymph node tracer was performed during the operation,the patients were divided into two groups:nano-carbon group (nano-carbon lymph node tracing) and conventional operation group (no nano-carbon lymph node tracer).The differences between the two groups were analyzed,including operative time,intraoperative blood loss,postoperative complications (pancreatic fistula),postoperative hospitalization time,postoperative pathological lymph node status (number of dissection,number of positive lymph nodes,the positive rate of lymph node black staining in nano-carbon group) and survival time after operation.The measurement data were expressed as mean ± standard deviation (Mean ± SD),t-test were used for comparison among groups;Chi-square test was used for comparison of counting data,and Kaplan-Meier test was used for comparison of survival rate.Results There was no significant difference in the time of operation [(4.45 ± 0.59) h vs (4.41 ±0.65) h],the amount of blood lost during operation [(447.39 ± 109.51) ml vs (434.8 ± 76.38) ml] and the time of hospitalization after operation [(16.52 ± 4.12) d vs (16.56 ±2.92) d] between the two groups (P＞0.05).There were 1 case of pancreatic fistula in the nano-carbon group and 2 cases of pancreatic fistula in the convertional operation group,but the difference was not statistically significant (P =0.55).The number of lymph nodes dissected and positive lymph nodes in nano-carbon group were significantly higher than those in conventional operation group [(18.26 ± 2.49) vs (12.16 ± 2.19);(5.52 ± 1.50) vs (3.32 ± 0.85).The difference was statistically significant (P ＜ 0.05).The positive rate of lymph nodes in black stained lymph nodes (38.10％,96/252) was significantly higher than that in non-stained lymph nodes (18.45％,31/168),and the difference was statistically significant (P ＜ 0.05).The average survival time in the nano-carbon group [(25.48 ± 11.74) months] was significantly longer than that in the conventional operation group [(15.80 ± 11.64) months],and the difference was statistically significant (P ＜ 0.05).Conclusions It is safe,effective and feasible to treat malignant tumors of pancreatic body and tail by RAMPS combined with nano-carbon tracer technique.The positive rate of lymph node dissection and the detection rate of total lymph nodes are increased,and the prognosis of patients is improved,to improve the survival time of patients after operation is improved.

A series of oxazole[5,4-d] pyrimidine derivatives were designed and synthesized to discover novel compounds with antitumor activity.Compounds 8a-8m were synthesized using acetamidine hydrochloride as the start material.The structures of synthesized compounds were confirmed by IR,1H NMR,EI-MS and elemental analysis.The antiangiogenesis activities of the synthesized compounds were determined by MTT in human umbilical vein endothelial cell (HUVEC).The in vitro antitumor activities of the synthesized compounds were determined by MTT assay in A549,HepG2 and U251.Compounds 8c,8d,8g,8i and 8l were found to inhibit the proliferation of all the tested cell lines.Compound 8l exhibited noteworthy activities in A549,HepG2 and U251 cell lines with IC50value lower than the positive reference sunitinib,suggesting that compound 8l might be the promising antitumor agent for further investigation.