Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective:To investigate the intention of medical students to be vaccinated against COVID-19 and to analyze the influencing factors.Methods:A self-filled electronic questionnaire survey was conducted among medical students from a medical school in Shanghai randomly selected from June 21 to 29, 2021. The questionnaire contained items of basic information, intention for COVID-19 vaccination, awareness of COVID-19 prevention measures and awareness of COVID-19 vaccine. Logistic regression was used to analyze the influencing factors.Results:The average age of the 966 respondents was (20.4±2.9) years, and 63.6% (614/966) of them were female;23.7% (229/966) of them had family members or relatives who had participated in anti-pandemic work or volunteer service;90.6% (875/966) of the respondents expressed they were very willing or willing to be vaccinated against COVID-19. The majority of the respondents thought that “COVID-19 infection is very serious” (94.3%, 911/966), “good protection can effectively prevent COVID-19 infection” (92.4%, 893/966), and “they can fully implement all kinds of protection measures” (73.5%, 710/966). About half of the respondents (51.8%, 501/966) knew about the adverse reactions and contraindications of COVID-19 vaccine. The low protected capability (47.4%, 458/966), short duration of protection (50.6%, 489/966), and many side effects (48.7%, 470/966) were the major concerns about COVID-19 vaccine. Logistic regression analysis showed that people thought that “COVID-19 infection is very serious” ( OR=5.30, 95 %CI:2.60-10.81, P<0.001), thought that “good protection can effectively prevent COVID-19 infection” ( OR=2.46, 95 %CI:1.26-4.81, P=0.009), thought that “they can fully implement all kinds of protection measures” ( OR=2.55, 95 %CI:1.53-4.25, P<0.001) were more willing to receive COVID-19 vaccination. While those concerned about vaccine quality did the opposite ( OR=0.29, 95 %CI:0.13-0.65, P=0.003). Conclusions:Medical students have a high intention of vaccination against COVID-19. The vaccine-related knowledge quality should be emphasized in future publicity to further enhance the intention of COVID-19 vaccination.

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.
Animals ; Brain Ischemia ; Carotid Stenosis/drug therapy* ; Cognitive Dysfunction/etiology* ; Digoxin ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; White Matter

Objective:To explore the application value of single source dual energy CT (DECT) scanning technique in improving the image quality of the pancreas.Methods:Imaging data of 21 patients with normal pancreas and 36 patients with pancreas related diseases in the First Affiliated Hospital of Naval Medical University from July 2021 to August 2021 were collected. All the patients first underwent multi-slice CT (MDCT) scan with no-contrast, and then dynamic enhanced MDCT scan. And the DECT scan was used in the delay period. Virtual single energy images (VMI, 40~100keV) of normal pancreas and mixed energy images of pancreatic lesions (PI, 80 and 140kVp) were obtained. The regions of interest (ROI) of fat on abdominal wall, normal pancreas and abdominal aorta were delineated, the CT values and standard deviation (SD) of each ROI were measured and recorded, and the pancreatic signal-to-noise ratio (SNR) and contrast-to-noise ratio (SNR) of each energy image were calculated. The objective index and subjective score of VMI(40-100keV) and PI (80kVp and 140kVp) with iodine (water) base map and VMI best CNR were compared between groups. The correlation between VMI(40-100keV) and PI(80, 140kVp) with iodine (water) base map and VMIbest CNR was analyzed by univariate regression.Results:In VMI(40-100keV) of normal pancreas, the highest SNR value was VMI best CNR and iodine (water) base map, and the highest CNR values were VMI 60keV and iodine (water) base map. There were significant differences on SNR and CNR values between different energy VMI and iodine (water) base map ( P<0.05). Among the four images of PI 80kVp, PI 140kVp, VMI best CNR and iodine (water) base map for pancreatic lesions, the SNR and CNR values of iodine (water) base map were the highest. The SNR and CNR values of VMI best CNR were higher than those of PI 80kVp, and the differences were statistically significant ( P<0.05). The lesion significance and edge sharpness score of iodine (water) base map was the highest, which was better than other groups; the lesion significance and edge sharpness score of VMI best CNR was better than PI 140kVp, and the differences were statistically significant ( P<0.05). The results of univariate regression analysis showed that the SNR values of PI 80kVp, PI 140kVp and VMI best CNR for pancreatic lesions were positively correlated with those of the iodine (water) base map ( P<0.05), the CNR values of PI 140kVp and VMI best CNR images were positively correlated with the iodine (water) base map ( P<0.05), and the SNR and CNR values of PI 140kVp were positively correlated with VMI best CNR ( P<0.05). Conclusions:VMI with different energy and iodine (water) base maps can be obtained by single source DECT enhanced scanning of pancreas related diseases. The VMI best CNR was the best among all VMIs, while the SNR and CNR values of iodine (water) base maps were the highest in all images. The VMI best CNR and iodine (water) base maps can improve the image quality of pancreas related diseases.

Wuhan is the city with the most serious outbreak of corona virus disease 2019 (COVID-19) in China. The outbreak of community has exhausted the current medical resources. With integrating local and support medical resources from other province, Wuhan City has rapidly rebuilt a new emergency medical system of classified treatment, and effectively responded to the overload medical demand after the outbreak in the community.

Objective:To explore the association of serum liver enzymes with thyroid hormones and Chinese visceral adipose index (CVAI) in patients with type 2 diabetes mellitus (T2DM), and to evaluate the influencing factors of liver enzymes.Methods:A total of 700 patients with T2DM were divided into elevated liver enzyme group and normal liver enzyme group, or three groups according to tertiles in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamyltransferase (GGT). The differences of thyroid hormones and CVAI among groups were compared, and the correlations of liver enzyme levels with thyroid hormones and CVAI were determined.Results:Compared with the normal liver enzyme group, thyroxine(T 4)and CVAI were increased in the elevated liver enzyme group ( P<0.05). Free triiodothyroid (FT 3), triiodothyroid (T 3), and T 4 levels were elevated with the increase of ALT and AST ( P<0.05). CVAI was elevated with the increase of ALT and GGT ( P<0.05). Correlation analysis showed that FT 3, T 3, and T 4were positively correlated with ALT and AST. ALT and GGT were positively correlated with CVAI. CVAI was positively correlated with FT 3 and T 3. HbA 1Cwas negatively correlated with FT 3, T 4, and T 3. Regression analysis showed that FT 3, CVAI, and HbA 1C were the influencing factors for ALT, T 4 was the influencing factor for AST, T 3 and HbA 1Cwere the influencing factors for GGT. Conclusions:In patients with T2DM, thyroid hormones and CVAI are correlated with liver enzymes.

Objective:Based on the policy goals of family doctors′ contracted services, to build an indicator system as policy tools for policy outcomes assessment and policy delivery optimization.Methods:Through literature and policy review, an evaluation conceptual framework was built based on policy goals of family doctors′ contracted services, and an indicator system was established using Delphi method.Results:Upon consultation of 21 experts, an indicator system for policy effect assessment of the family doctors′ contracted services was established, covering both policy implementations and goal effects. This system consisted of 7 level-2 indicators and 23 level-3 indicators.Conclusions:The indicator system oriented to policy goals, ensures the pertinence of policy effect assessment to play a strong guidance on practical implementation of the family doctors′ contracted services.

Objective:To analyze the policy implementation of family doctors′ contracted services in different regions based on practices in typical regions.Methods:From April to October 2019, we conducted field investigations in 14 regions, collected data on policy formulation and implementation, organizational form and service content of contracting service, incentive mechanism and capacity development. By means of key persons′ interview, we tried to understand the background of district/county policy implementation, as well as policy delivery and existing difficulties. The measurement data were expressed by means, and the qualitative data were used to extract the key content through semantic analysis.Results:The policy of family doctors′ contracted services had been promoted from pilot exploration to normative development. 71.0% of responsible entities of the contracted services in research regions were family doctor teams. Contraction fee has begun to reflect the value of family doctors′ work, while the average contracted service fees in the eastern, central and western regions were 125, 31.25 and 42.5 yuan/person/year respectively. Comprehensive incentives and health insurance policies in some regions played a role in promoting contracted services.Conclusions:It is necessary to establish the family doctors′ " three roles" management concept, namely health gatekeeper, rights exchanger and resource coordinator; strengthen the professional training and capacity promoting of family doctors, implement the connotation of contracted service fees and economic incentives, in order to play the policy′s basic role in constructing a health-centered system.

Objective To explore the safety and feasibility of laparoscopic hepatectomy combined with radiofrequency ablation for primary liver cancer difficult to manage.Methods A retrospective study was conducted to analyze the clinical data of 16 patients who underwent laparoscopic hepatectomy combined with radiofrequency ablation in the Zhejiang Provincial People's Hospital from Apr 2015 to Dec 2017.Results 2 more tumors were found by intraoperative laparoscopic ultrasound.All patients underwent laparoscopic hepatectomy combined with radiofrequency ablation successfully.There were 2 laparoscopic left hepatectomy combined with radiofrequency ablation,2 laparoscopic right hepatectomy combined with radiofrequency ablation,6 laparoscopic left lateral lobectomy combined with radiofrequency ablation,4 laparoscopic right postrior lobectomy combined with radiofrequency ablation and 2 irregular laparoscopic hepatectomy combined with radiofrequency ablation.The intraoperative blood loss ranged from 100-800 ml.The average operative time was (283 ± 112) min.The length of postoperative hospital stay ranged from 5 to 12 days.The tumor-free survival rate after operation is 100％ (16/16) on 6 to 38 months follow up.Conclusion It is safe and feasible to carry out laparoscopic hepatectomy combined with radiofrequency ablation in difficult to manage primary liver cancer.

Objective To investigate the value of the apparent diffusion coefficient (ADC)measurement in assessment of tumor grade and myometrial invasion of endometrial carcinoma (EC).Methods 80 EC patients and 28 cervical cancer patients with normal endometrium were studied retrospectively.1.5T conventional MRI and DWI (b=0,1 000 s/mm2)were performed,and ADC values were calculated by two radiologists.Statistical analyses were performed by using SPSS 19.0 and Medcalc software.Results The mean ADC values (×10-3mm2/s)were 0.851±0.131,0.752±0.099,0.681±0.089 for G1,G2 and G3 EC,respectively.Significant statistical differences were achieved for the three groups (G1 vs G2:P=0.005;G2 vs G3:P=0.03;G1 vs G3:P< 0.000 1).For the prediction of G3,the area under the curve (AUC)of 0.851 and the cut-off value of ≤0.742×10-3mm2/s were identified,with the sensitivity, specificity and accuracy of 88.24%,76.19% and 85%,respectively.Conclusion There are significant statistical differences between histologic grades of EC.ADC measurement may have the potential to select G3 EC patients.