BACKGROUND:Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems.Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway,but are limited to their easy agglomeration and colloidal morphology,which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE:To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS:The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold.The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized.The microstructure,porosity,permeability,rheology,in vitro hemostasis,and antibacterial properties of the composite hydrogel were characterized.The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining,and the optimization effects of low-intensity pulsed ultrasound on the permeability,porosity,and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION:(1)Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers.The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability.(2)Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility.(3)Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure,and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation.The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials.The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold.Under the irradiation of low-intensity pulsed ultrasound,the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties.(4)Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles,and more uniform dispersion could be obtained under ultrasonic excitation.(5)The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets,which showed stronger mechanical properties.The elongation at break was 122%,and the ductility was better than that without gold nanoparticles-nanodroplets(P<0.05).(6)These findings indicate that the composite hydrogel scaffold has good biocompatibility,antibacterial property,oxidation resistance,and hemostatic effect.

Objective:To explore the impact of transcatheter edge-to-edge repair (TEER) devices on mitral valve regurgitant flow convergence post-procedure using computational fluid dynamics(CFD), and to seek solutions for accurately measuring effective regurgitant orifice area(EROA) after TEER.Methods:Multimodal fusion was conducted based on preoperative cardiac CT images and intraoperative three-dimensional transesophageal echocardiography(3DTEE) of 33 patients with mitral valve regurgitation undergoing TEER at Renmin Hospital of Wuhan University from January 2020 to August 2023. Using this data, CFD models of mitral valve regurgitation post-TEER, including with and without the TEER device, were constructed. The distance (D) from the midpoint of the mitral regurgitation orifice to the TEER device was measured. The proximal isovelocity surfice area(PISA) radius with and without the TEER device was measured, and the corresponding EROA1 and EROA2 based on this was calculated. The EROA correction factor CC=EROA2/EROA1 was calculated.Results:A total of 42 sets of CFD models with mild or greater residual mitral regurgitation, both with and without the TEER device, and 50 sets of PISA were obtained. Based on the relative position of PISA to the TEER device, four types of PISA were observed: Type 1: PISA away from the TEER device (D>R, 14 cases), with a CC of 0.93±0.07; Type 2: PISA adjacent to the TEER device (D

Objective:To explore the prognostic predictive value of deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis of ST-elevated myocardial infarction (STEMI) patients after successful percutaneous coronary intervention(PCI).Methods:A retrospective analysis was performed in 97 STEMI patients with thrombolysis in myocardial infarction-3 flow in infarct vessel after primary PCI in Renmin Hospital of Wuhan University from June to November 2021. MCE was performed within 48 h after PCI. Patients were followed up to 120 days. The adverse events were defined as cardiac death, hospitalization for congestive heart failure, reinfarction, stroke and recurrent angina. The framework consisted of the U-net and hierarchical convolutional LSTMs. The plateau myocardial contrast intensity (A), micro-bubble rate constant (β), and microvascular blood flow (MBF) for all myocardial segments were obtained by the framework, and then underwent variability analysis. Patients were divided into low MBF group and high MBF group based on MBF values, the baseline characteristics and adverse events were compared between the two groups. Other variables included biomarkers, ventricular wall motion analysis, MCE qualitative analysis, and left ventricular ejection fraction. The relationship between various variables and prognosis was investigated using Cox regression analysis. The ROC curve was plotted to evaluate the diagnostic efficacy of the models, and the diagnostic efficacy of the models was compared using the integrated discrimination improvement index (IDI).Results:The time-cost for processing all 3 810 frames from 97 patients was 377 s. 92.89% and 7.11% of the frames were evaluated by an experienced echocardiographer as "good segmentation" and "correction needed". The correlation coefficients of A, β, and MBF ranged from 0.97 to 0.99 for intra-observer and inter-observer variability. During follow-up, 20 patients met the adverse events. Multivariate Cox regression analysis showed that for each increase of 1 IU/s in MBF of the infarct-related artery territory, the risk of adverse events decreased by 6% ( HR 0.94, 95% CI =0.91-0.98). There was a 4.5-fold increased risk of adverse events in the low MBF group ( HR 5.50, 95% CI=1.55-19.49). After incorporating DNN-assisted MCE quantitative analysis into qualitative analysis, the IDI for prognostic prediction was 15% (AUC 0.86, sensitivity 0.78, specificity 0.73). Conclusions:MBF of the area supplied by infarct-related artery after STEMI-PCI is an independent protective factor for short-term prognosis. The DNN-assisted MCE quantitative analysis is an objective, efficient, and reproducible method to evaluate microvascular perfusion. Assessment of culprit-MBF after PCI in STEMI patients adds independent short-term prognostic information over qualitative analysis.It has the potential to be a valuable tool for risk stratification and clinical follow-up.

In order to further strengthen the training and management of clinical teachers, broaden the career development channels of clinical teachers, and truly stimulate their teaching enthusiasm and initiative, this study further classifies clinical teachers according to the principle of the Snell model, focuses on the training of educational clinicians, and explores the training mechanism of teaching talents in line with the actual development needs of hospitals affiliated to universities from the aspects of selection, training, incentive, and assessment. The results of practice show that related practices have a good effect, and the mean number of teaching achievements was 1.98 for the 56 educational physicians, which was 3.9 times that for non-educational physicians. The per capita teaching achievements of educational physicians tended to increase every year compared with those of non-educational physicians. The training path for educational physicians provides useful experience for the construction of clinical teaching team and the high-quality development of education and teaching, and at the same time, it is necessary to further strengthen the dynamic adjustment of talent echelon, the improvement of operating mechanism, and the introduction of new technology.

Objective:To investigate the diagnostic value of postsystolic shortening (PSS) and early systolic lengthening (ESL) on myocardial microvascular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).Methods:A total of 83 patients with STEMI who received emergency PCI in Renmin Hospital of Wuhan University from June to October 2021 were retrospectively collected. All patiets underwent two-dimensional echocardiography and myocardial contrast echocardiography (MCE) within 7 days after PCI. The patients were divided into global normal perfusion group and poor perfusion group according to global myocardial perfusion score index (MPSI). Left ventricular myocardium was divided into left anterior descending branch (LAD), left circumflex branch (LCx) and right coronary artery (RCA) regions, which were divided into regional normal perfusion group and poor perfusion group based on whether there were segments with microvascular dysfunction. Left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were measured by modified biplane Simpson method. Tomtec software was used to obtain conventional echocardiographic parameters, global longitudinal strain (GLS), as well as PSS and ESL parameters including postsystolic index (PSI), duration of postsystolic shortening (PSSduration), early systolic index (ESI) and duration of early systolic lengthening (ESLduration). Differences of parameters of global normal and poor perfusion groups, as well as regional normal and poor perfusion groups were compared. ROC curve was used to analyze the diagnostic value of PSS and ESL parameters and GLS in myocardial regions with microvascular dysfunction.Results:Significant differences were observed in LVEF, LVESV, GLS, PSI, ESI and PSSduration between global poor perfusion group and global normal perfusion group (all P<0.05). Compared with regional normal perfusion group, PSI, ESI and ESLduration of LAD and LCx regions, as well as PSI of RCA region in regional poor perfusion group were increased (all P<0.05). For GLS in different myocardial regions, LAD-GLS was the only parameter that decreased in regional poor perfusion group compared to regional normal perfusion group ( P<0.05). ROC curve analysis showed LAD-PSI, LAD-GLS, LCx-PSI, LCx-ESLduration and RCA-PSI were valuable parameters for diagnosis of myocardial microvascular dysfunction in different regions, among which LAD-PSI had the highest area under curve (AUC=0.809). Conclusions:PSS and ESL parameters are helpful for early diagnosis of myocardial microvascular dysfunction in STEMI patients after PCI, and can provide regional myocardial perfusion information according to the blood supply of different coronary arteries.

Objective: To deepen the knowledge of HIV-negative plasmablastic lymphoma (PBL) . Methods: Medical records from 8 HIV-negative PBL patients diagnosed in Peking Union Medical College Hospital from January 1997 to May 2015 were collected, and the clinical features and prognosis of these patients were analyzed. Results: All of these 8 patients were diagnosed as HIV-negative PBL, 3 of 8 patients were males, and others were female. The median age was 60 (43-80) year. Among these patients, 4 cases had underlying immunosuppressive state. These patients all had extra-nodular involvement, and 6 cases of them were at stage Ⅳ according to Ann Arbor Staging, 5 patients had bone marrow involvement. CD38 and CD138 were diffusely positive for all patients, while the positive rate of B cell marker including PAX-5 and Bcl-6 were relative low. 5 of 8 patients had been detected for EBV-DNA, and all of them were negative. The median follow-up for the 7 patients receiving chemotherapy and regular follow-ups was 36 (11-57) months, the median progression-free survival (PFS) was 15 (6-52) months, and the median overall survival was 36 (2-52) months. Among these patients, 4 cases had received chemotherapy combined with Bortezomib, showing 3 cases of effective, but it seems to be difficult to keep the long term efficacy, and disease progression occurred in 2, 9, and 21 months after treatment. 2 patients at stageⅠ-Ⅱ were treated effectively, without disease progression and survival, 5 patients at stage Ⅳacquired the efficacy unsustainably, with a median PFS of 10 (2-21) months and a median overall survival of 12 (6-52) months. Conclusion HIV-negative PBL is relatively prevalent in elderly patients, and presenting with high invasiveness in clinical, extremely prone to extra-nodular involvement, especially the bone marrow. The immunophenotype of PBL is more resemble to that of plasmacytoma. Patients who were in late stage at diagnosis show poor prognosis.

Objective: To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm. Method: Clinical records of 6 patients diagnosed with blastic plasmacytoid dendritic cell neoplasm in our hospital from January 2008 to May 2016 were collected and retrospectively analyzed. Results: Six patients manifested with initial symptoms of skin lesions, other common symptoms included bone marrow involvement (5/6) , lymphadenectasis (4/6) , splenomegaly (4/6) , and hepatomegaly (3/6) . In addition, extra-nodal involvement except skin was also observed, including breast (1/6) , maxillary sinus (1/6) , vertebrae (1/6) , and central nervous system (1/6) . Characteristic immunophenotype, CD4, CD56, and CD123 were all positive. All these patients were treated with acute lymphoblastic leukemia type (ALL-type) chemotherapy and complete remission (CR) were reached in 4 patients. The median follow-up was 9.5 (7-37) months, median progression free survival was 7 months; while median overall survival was 9 months. A total of 3 patients died during the follow-up, which were all happened in the first year after diagnosis, and all resulted from the relapse or disease progression. Conclusion Blastic plasmacytoid dendritic cell neoplasm is highly aggressive, in which the skin lesions are always manifested as initial symptoms, and bone marrow involvement, lymphadenectasis, splenomegaly, and hepatomegaly is also common. Characteristic immunophenotype include the positivity of CD4, CD56, and CD123. Effective and standard therapy is limited in this disease, which indicates the poor prognosis.

Objective To establish and apply the procedure of survey on quality indicator in clinical laboratory and to analyze the status in quo of the 15 quality indicators in Zhejiang province .Methods A network platform for the survey on quality indicator in clinical laboratory was designed and developed by our center.The online questionnaires that should be reported back within one month were assigned to 473 laboratories.The developed software and SPSS 13.0 were used for statistical analysis .13 indicators expressed in rate were further evaluated with sigma scales .The 25th percentile, 50th percentile, and 75th percentile of the distribution of each quality indicator were regarded as the minimum , appropriate and optimum quality specifications, respectively.Results Totally 444 laboratories submitted the survey results.The overall sigma levels of 10/13 indicators were all >3, of which the inappropriate CV of internal quality control and unacceptable performances in EQA were still less than 3σin 15.8%and 9.2%of the laboratories.The rates of quality indicators in different scales of laboratories and diverse disciplines were significantly different .Pre-analytical TAT in routine examination for clinical chemistry and immunology was 50 min, on average.And the time for routine examination of blood , urine and stool was 30 min.Pre-analytical TAT in emergency examination for all four disciplines were all between 10 and 15 min. Intra-analytical TAT for clinical immunology was the longest , which was 154 min for routine examination and 40 min for emergency examination, respectively.The optimum quality specifications for 8 indicators were 6σ, while the minimum quality specifications were less than 1σfor 4 indicators.Conclusions According to the results of our survey, the pre-analytical quality indicator perform better than that of Intra-analytical and post-analytical phase.The laboratory should strengthen the laboratory information system technology construction to ensure the reliable data collection and long-time monitoring.

Objective To study the expression of metastasic suppressor gene( KAI1 / CD82)and cell adhesion molecules(CD44v6)in human laryngeal squamous cell carcinoma(LSCC),precancerous lesion,polyps,and normal mucosa. Methods Immunohistochemical technique( Envision)was used to detect the expression of KAI1 / CD82 protein and CD44v6 protein in 64 cases of LSCC,21 cases of laryngeal precancerous lesion(LPL),15 cases of polyp of larynx(LP)and 15 cases of normal laryngeal mucosa(NLM). Results The result turned out to be as follows:①KAI1 / CD82 protein was highly expressed in NLM and LP,and lowly expressed in LPL and LSCC,the positive rates of KAI1 / CD82 protein expression were 86. 67%(13 / 15),80. 00%(12 / 15),38. 10%(8 / 21)and 37. 50%(24 /64),respectively. There was statistically significant difference in NLM and LSCC. ② CD44v6 protein was lowly ex-pressed in NLM and LP and highly expressed in LPL and LSCC,the positive rates of CD44v6 protein expression were 26. 67%(4 / 15),33. 33%(5 / 15),80. 95%(17 / 21)and 75. 00%(48 / 64),respectively. There was statisti-cally significant difference in NLM and LSCC. Conclusion ① The down-regulation or deletion of KAI1 / CD82 and the up-regulation of CD44v6 are related to carcinogenesis,development of LSCC. ② The combined detection of KAI1 / CD82 and CD44v6 may provide clinical basis for the early diagnosis of LSCC.

Objective To observe the lung protective effect of Tongfu Xiefei method (TFXF) in rats with sepsis, and to discuss its possible mechanism.Methods Forty-two Sprague-Dawley (SD) rats were randomly divided into blank control group (n = 6), model group (n = 18) and TFXF group (n = 18). Sepsis model was reproduced by cecal ligation and puncture (CLP) in rats of model group and TFXF group. After the reproduction of sepsis model, rats in TFXF group received Tongfu Xiefei granules 0.01 mL/g by gavge, while those in model group were given equal dose of normal saline by the same way. The rats in blank control group received no treatment. At 3, 6, 12 hours after CLP, abdominal aorta blood was collected for blood gas analysis and inferior vena cava blood was collected for determination of the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Bronchoalveolar lavage fluid (BALF) was collected for measurement of concentrations of total protein (TP), total phospholipid (TPL), and desaturated phosphatidyl choline (DSPC). The ratio of wet/dry lung weight ratio (W/D) was measured, and malondialdehyde (MDA) and myeloperoxidase (MPO) in lung tissues were determined. The pathologic changes in their lungs were observed with light microscopy.Results Compared with those in blank control group, the levels of pH value, arterial oxygen partial pressure (PaO2), HCO3-, base excess (BE) were lowered, and partial pressure of carbon dioxide of arterial blood (PaCO2) was increased in model group. The serum concentrations of TNF-α and IL-6 were gradually increased after the reproduction of sepsis model. Compared with those in blank control group, the levels of TP, TPL, and DSPC/TPL in model group were decreased, while the levels of W/D, MDA and MPO were increased. Compared with those in model group, pH value was elevated in TFXF group at 3 hours (7.27±0.04 vs. 7.18±0.07,P < 0.05). PaO2 (mmHg, 1 mmHg = 0.133 kPa) was improved at 3, 6, 12 hours (3 hours: 128.00±16.05 vs. 106.78±10.73, 6 hours: 98.46±15.97 vs. 72.80±16.33, 12 hours: 90.70±9.31 vs. 74.28±12.19, allP < 0.05). The serum concentrations of TNF-α (ng/L) in TFXF group were significantly lower than those in model group at 12 hours (508.20±94.08 vs. 756.60±138.77,P < 0.05), and the serum concentrations of IL-6 (ng/L) in TFXF group were significantly lower than those in model group at 6 hours and 12 hours (6 hours: 687.80±35.00 vs. 849.40±148.28, 12 hours: 728.80±214.41 vs. 917.00±245.96, bothP < 0.05). Compared with those of model group, the levels of TP (g/L) in BALF in TFXF group were significantly decreased at 12 hours (1.01±0.23 vs. 1.60±0.47,P < 0.05), and the levels of TPL (mg/L) in TFXF group were significantly increased at 12 hours (86.40±11.33 vs. 62.40±16.33,P < 0.05). The levels of DSPC/TPL in TFXF group were significantly higher than those in model group at 6 hours and 12 hours (6 hours: 0.58±0.13 vs. 0.38±0.10, 12 hours: 0.45±0.13 vs. 0.24±0.07, bothP < 0.05). The levels of W/D in TFXF group were significantly higher than those in model group at 3 hours (3.84±0.25 vs. 2.99±0.50,P < 0.01), but lower than those in model group at 12 hours (3.21±0.53 vs. 4.89±1.14,P < 0.05). The levels of MDA (nmol/mg) in TFXF group were significantly lower than those in model group at 6 hours and 12 hours (6 hours: 4.04±2.58 vs. 8.89±2.61, 12 hours: 11.31±3.60 vs. 20.60±8.10, bothP < 0.05), while the levels of MPO (U/g) in TFXF group were lower than those in model group at 12 hours (4.79±0.66 vs. 7.22±1.76,P < 0.05). Compared with model group, the lungs in TFXF group showed less morphological changes under light microscopy, such as pulmonary edema, congestion, effusion and fibrosis.Conclusions The method of Tongfu Xiefei may improve hypoxemia and metabolic acidosis, alleviate lung edema and ameliorate pulmonary pathological changes in rat sepsis model. Tongfu Xiefei method shows a protective effect in sepsis by the way of reducing peroxidative damage, inhibiting the release of proinflammatory factors and abating degradation of lung surfactant.