OBJECTIVES: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality. METHODS: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay. RESULTS: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities. CONCLUSIONS The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Microspheres ; Hyaluronic Acid/chemistry* ; Humans

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Objective To analyze the achievement of target vancomycin concentration and the risk factors affecting the concentration to reach the target,providing a reference for the rational use of vancomycin and the implementation of therapeutic drug monitoring(TDM).Methods Patients who were hospitalized and received vancomycin TDM from January 2016 to June 2019 at Zhongshan Hospital,Fudan University were selected.Clinical data,vancomycin blood concentrations,and occurrences of acute kidney injury(AKI)during the hospitalization were collected.Factors affecting the attainment of target vancomycin concentrations were analyzed using logistic regression and grouped according to whether the target concentrations were attained.The correlation between drug concentration and the occurrence of AKI was analyzed.Results A total of 1 106 patients were included,with 70.7％being males and a median age of 60.0(IQR=20)years.Surgical departments accounted for 76.4％of the distribution.The median duration of vancomycin therapy was 10.8 d(IQR=9.0).A total of 21.6％of patients had their first concentration monitored before administration of doses 4 and 5.The drug concentration monitoring results of 46.8％(518/1 106)of patients were in the range between 10-20 μg·mL-1,reaching the target concentration range.The incidence of vancomycin-associated AKI was 25.9％.The incidence of AKI varied among patients with different vancomycin concentrations:when the concentrations are＜10,10-＜15,15-20,and＞20 μg·mL-1,the AKI rates are 15.8％,20.5％,25.8％,and 39.4％,respectively.Multivariate logistic regression analysis showed that target concentrations were more likely to be reached with a dosing course of＞7-14 d(OR=1.688,P=0.001)and＞14 d(OR=1.744,P=0.002)than with a dosing course of ≤7 d.Patients receiving conventional daily doses were more likely to achieve target concentrations than those receiving the non-conventional daily dose(OR=1.540,P=0.003).Conclusion The current status of vancomycin TDM in China still suffers from deficiencies,such as delayed timing of monitoring and low rate of target concentration attainment.Higher vancomycin concentrations are significantly associated with AKI,and the factors affecting the vancomycin concentration to reach the target mainly include treatment duration and the complexity of the dosing regimen.

The establishment of an economic operating mechanisms for hospitals is a key factor in advancing the growth of public hospitals in the modern age.At present,the due value of key factors such as medical resources and labor value of medical personnel in public hospitals in China has not been fully reflected,which not only restricts the overall operation efficiency of hospitals,but also makes it difficult to realize the marginal value of hospital operation and management.The economic operating mechanisms of public hospitals is in urgent need of reform.Large public hospitals in Henan Province has established an economic operating mechanisms of public hospitals based on intelli-gent finance,comprehensive budget management as the core,and cost control and performance management as the major tools to realize the interconnection of various systems and promote the high-quality development of hospi-tals with the three major supports of industry and finance integration,financial integration and financial integration.

Objective:To analyze the research hotspots and trends of the application of Kirkpatrick model in nursing education through bibliometrics analysis, so as to provides ideas for follow-up researchers to carry out research in related fields.Methods:Relevant literatures in CNKI, Wanfang, VIP and PubMed were retrieved from the establishment of databases until August 27, 2022. CiteSpace software was used to draw the literature topic clustering map, BICOMB was used to generate the co-occurrence matrix of bibliographic data, and gCLUTO software was used to make the visual hill map and analyze the literature hotspots.Results:A total of 230 literatures were included, including 145 in Chinese and 85 in English. Since 2016, the number of published papers had been on the rise. The papers were published in 134 journals at home and abroad, and the coauthor rate was 95.65% (220/230), and the funded papers accounted for 25.65% (59/230). The hot topic of Chinese literature research was the construction of training evaluation index system and training effectiveness evaluation. The research objects mainly included specialized nurses and in-service nurses.The research hotspot of English literature was nursing education and training. The research objects were specialized nurses and undergraduate students.Conclusions:The application of the Kirkpatrick model in the field of specialized nurse training is still in its infancy, and it needs to be extended to more specialist fields in the future. In addition, researchers should further explore the construction and application of a training evaluation index system based on the Kirkpatrick model in the future, and promote the horizontal development of training

Objective: To establish and evaluate a multiplex PCR method for rapid identification of Mycobacterium species in order to provide an approach for rapid diagnosis of pathogens causing tuberculosis. Methods: Four genes including 16S rRNA, Rv0577, RD9 and mtbk_20680 were selected to establish the multiplex PCR method. Specific primers were designed and the reaction system and conditions were optimized. The sensitivity and specificity of the multiplex PCR method were evaluated through identifying Mycobacterium africanum (M.africanum), Mycobacterium bovis (M.bovis), M. bovis BCG, seven common non-tuberculosis Mycobacterium (NTM), seven reference species of common respiratory bacteria and 93 clinical strains of Mycobacterium tuberculosis (MTB) isolated from patients with tuberculosis in Gansu Province of China. Results: The fragments of 16S rRNA, Rv0577, RD9 and mtbk_20680 genes were 543 bp, 786 bp, 369 bp and 231 bp in length, respectively. MTB strains of the Beijing genotype were positive for all of the four genes, while the non-Beijing genotype strains were negative for mtbk_20680. M. africanum, M. bovis and M. bovis BCG strains were negative for 16S rRNA and Rv0577. NTM strains only carried 16S rRNA and none of four genes were detected in the seven species of respiratory bacteria. Among the 93 clinical MTB strains, 80 (86.02%) belonged to the Beijing genotype and the other 13 (13.98%) were non-Beijing genotype strains. The specificity of the multiplex PCR method was 100%. Conclusions The established multiplex PCR method could accurately distinguish Mycobacterium, Mycobacterium tuberculosis complex (MTBC), NTM, MTB, and Beijing and non-Beijing genotype MTB with high sensitivity and specificity.

Objective: Autoregressive integrated moving average (ARIMA) model was used to predict the incidence of tuberculosis in China from 2018 to 2019, providing references for the prevention and control of pulmonary tuberculosis. Methods: The monthly incidence data of tuberculosis in China were collected from January 2005 to December 2017. R 3.4.4 software was used to establish the ARIMA model, based on the monthly incidence data of tuberculosis from January 2005 to June 2017. Both predicted and actual data from July to December 2017 were compared to verify the effectiveness of this model, and the number of tuberculosis cases in 2018-2019 also predicted. Results: From 2005 to 2017, a total of 13 022 675 cases of tuberculosis were reported, the number of pulmonary tuberculosis patients in 2017 was 33.68% lower than that in 2005, and the seasonal character was obvious, with the incidence in winter and spring was higher than that in other seasons. According to the incidence data from 2005 to 2017, we established the model of ARIMA (0,1,2)(0,1,0)₁₂. The relative error between the predicted and actual values of July to December 2017 fitted by the model ranged from 1.67% to 6.80%, and the predicted number of patients in 2018 and 2019 were 789 509 and 760 165 respectively. Conclusion The ARIMA (0, 1, 2)(0, 1, 0)₁₂ model well predicted the incidence of tuberculosis, thus can be used for short-term prediction and dynamic analysis of tuberculosis in China, with good application value.

Ovarian cancer is the fifth leading cause of cancer-related death in women. 75% of ovarian cancer patients were detected at an advanced stage. At present,the disease lacks effective early screening method and the clinical therapy effect is poor,which has become a serious threat to women's health. The use of animal models of ovarian cancer is an important mean to elucidate the pathogenesis of the disease,and to screen effective diagnosis and treatment. The disease models are mainly divided into four types: spontaneous, induced, transplanted and gene intervention type. Mice, rats, hens,Mirotus Fortis and Mongolian gerbil are mainly selected to prepare animal models of ovarian cancer. Based on recent literature reports,we reviewed the preparation method of animal models of ovarian cancer and introduced the evaluation standards and main characteristics of these animal models.

Objective To investigate the clinical effect of the V-Y advancement flap based on double perfo-rators of the posterior tibial artery for reconstruction of small-area tissue defect in the achilles tendon. Methods From June, 2014 to June, 2017, a total of 8 patients with small-area tissue defect in the achilles tendon were repaired by the V-Y advancement flap based on double perforators of the posterior tibial artery. The size of defects ranged from 1.5 cm ×3.5 cm to 3.5 cm ×5.0 cm, and the size of flaps ranged from 2.0 cm ×8.0 cm to 4.0 cm ×12.0 cm. The donor area was directly sutured. Eight cases were followed-up, and the appearance, quality, color and elasticity was raorded. Results All V-Y advancement flaps based on double perforators of the posterior tibial artery survived, and all donor sites were directly sutured. Followed-up for 3 to 12 months. All V-Y advancement flaps were flat with the sur-rounding tissue. The appearance, quality, color and elasticity of flaps were good. According to the related evaluation criteria made by the American Orthopedic Foot and Ankle Surgery Society (AOFAS), the results of 8 patients were ex-cellent in 6 cases, and good in 2 cases. The patients had a high degree of satisfaction. Conclusion Application of the V-Y advancement flap based on the double perforators of the posterior tibial artery is an ideal method to repair the small-area tissue defect in the achilles tendon. This kind of surgery is simple, safe and has minimal donor site mor-bidity.

Objective: To build risk prediction models for acute kidney injury (AKI) in severely burned patients, and to compare the prediction performance of machine learning method and logistic regression model. Methods: The clinical data of 157 severely burned patients in August 2nd Kunshan factory aluminum dust explosion accident conforming to the inclusion criteria were collected. Patients suffering AKI within 90 days after admission were enrolled in group AKI, while the others were enrolled in non-AKI group. Single factor analysis was used to choose independent factors associated with AKI, including sex, age, admission time, features of basic injuries, initial score on admission, treatment condition, and mortality on post injury days 30, 60, and 90. Data were processed with Mann-Whitney U test, chi-square test, and Fisher′s exact test. Variables with P<0.1 in single factor analysis and those with possible clinical significance were brought into the establishment of prediction model. Logistic regression and XGBoost machine learning algorithm were used to build the prediction model of AKI. The area under receiver operating characteristic curve (AUC) was calculated, and the sensitivity and specificity for optimal threshold value were also calculated for each model. Nonparametric resampling test was used to compare the significance of difference of AUC of the two models. Results: (1) Eighty-nine (56.7%) patients developed AKI within 90 days from admission. Compared with 68 patients in non-AKI group, 89 patients in group AKI were older (Z=-2.203, P<0.05), with larger total burn area and full-thickness burn area (Z=-5.200, -6.297, P<0.01), worse acute physical and chronic health evaluation (APACHE) Ⅱ score, abbreviated burn severity index score, and sequential organ failure assessment (SOFA) score on admission (Z=-7.485, -4.739, -4.590, P<0.01), higher occurrence rate of sepsis (χ²=33.087, P<0.01), higher rates of accepting tracheotomy, mechanical ventilation, and continuous renal replacement therapy (χ²=12.373, 17.201, 43.763, P<0.01), larger first excision area (Z=-2.191, P<0.05), and higher mortality on post injury days 30, 60, and 90 (χ²=7.483, 37.259, 45.533, P<0.01). There were no statistically significant differences in sex, open decompression, admission time, 24-hour fluid volume after admission, 48-hour fluid volume after admission, the first 24-hour urine volume, the second 24 hour urine volume, the first excision time, and inhalation injury (χ²=0.529, 3.318, Z=-1.746, -0.016, -1.199, -1.824, -0.625, -1.747, P>0.05). The rates of deep vein catheterization of patients in the two groups were both 100%. (2) There were twenty possible prediction variables for preliminary establishment of model according to the difference results of single factor analysis and clinical significance of variables. (3) The logistic regression prediction model had three variables: APACHE Ⅱ score [odds ratio (OR)=1.36, 95% confidence interval (CI)=1.20-1.53, P<0.001], sepsis (OR=2.63, 95% CI=0.90-7.66, P>0.05), and the first 24-hour urine volume (OR=0.71, 95% CI=0.50-1.01, P>0.05). The AUC of the logistic regression prediction model was 0.875 (95% CI=0.821-0.930), with the specificity and sensitivity of optimal threshold value 84.4% and 77.7%, respectively. (4) XGBoost machine learning model had seven main predictive variables: APACHE Ⅱ score, full-thickness burn area, 24-hour fluid volume after admission, sepsis, the first 24-hour urine volume, SOFA score, and 48-hour fluid volume after admission. The AUC of machine learning model was 0.920 (95% CI=0.879-0.962), higher than that of logistic regression model (P<0.001), with the specificity and sensitivity of optimal threshold value 89.7% and 82.0%, respectively. Conclusions Sepsis and fluid resuscitation are two important predictive variables that can be intervened for AKI in severely burned patients. Machine learning method has a better performance and can provide more accurate prediction for individuals than logistic regression prediction model, and therefore has good clinical application prospect.