Objective To prepare recombinant human epidermal growth factor (rhEGF) sustained-release microspheres and evaluate their morphology, rhEGF releasing activities and cell proliferation activity in vitro and compare difference of rhEGF sustained-release microspheres and rhEGF in facilitaring ulcer healing in diabetic rats. Methods (1) rhEGF sustained-release microspheres were prepared by the modified double emulsion method. Morphology of the microspheres was detected by transmission electron microscope and size distribution measured by laser granularity meter/Zeta electric potential meter. ELISA assays were applied to determine rhEGF releasing. (2)Proliferation of mouse fibroblasts was analyzed by MTr method. (3) Diabetic rat models were prepared and divided into four groups, ie, rhEGF sustained-release mierospheres group (Group A), rhEGF stock solution group (Group B), blank sustainedrelease mierospheres group (Group C) and PBS meustruum control group (Group D), which were given drug once a day. The wound healing rate was calculated by taking photographs at days 3,7,14 and 21. Skin specimens from the wound edge were harvested partially for observation of hydroxyproline (HYP) contents. Immunohistochemistry was employed to detect integrin 131 and keratin-19 and measure their positive staining area ratio. Results (1) The particle diameter of rhEGF sustained-release microspheres was 193.5 nm, with relative uniform particle diameter distribution. There showed no conglutination among rhEGF susrained-release microspheres, with good dispersibility. Releasing drug lasted for 24 hours and accorded with Higuchi release kinetic model. (2) Different concentrations of rhEGF sustained-release microspheres could promote the proliferation of mouse fibroblast, especially the concentration of 10 μg/L (P <0.05, compared with the control). (3) From the 7th day after treatment, Group A had the fastest wound healing rate, with statistical difference compared with other three groups (P < 0.05). Group A had higher HYP contents and positive area ratio of integrin β1 and keratin-19 than Group B. Conclusions rhEGF sustained-release microspheres prepared by the modified double emulsion method have uniform particle size and can last release for 24 hours. Compared with rhEGF stock solution, rhEGF sustained-release microspheres have faster and better ulcer healing and higher healing quality in diabetic rats.

Objective:To analyze the characteristics of adverse events of active medical devices in Shandong province, as well as the impact of device use duration on the risk rate of adverse events, for reference in improving the monitoring system of active medical device adverse events in China and the level of hospital medical quality management.Methods:The data came from the adverse event reporting data of active medical devices collected by Shandong Adverse Drug Reaction Monitoring Center from January 2019 to October 2021. The R software was used to analyze the distribution, cause and severity of adverse events, and a linear regression model of adverse event risk rate(Y) and adverse event time point(X) was established.Results:A total of 35 254 adverse events of active devices were included, of which 3 059 were serious injuries. The province/municipality with the largest number of reported adverse events was Shanghai(8 006 cases), and the least was Hainan province(4 cases); The majority of adverse events were reported by hospitals, with 34 056(96.60%). The medical devices reporting a higher number of adverse events were ventilators(688 cases), monitors(4 623 cases), infusion pumps(1 079 cases), syringe infusion pumps(1 995 cases), medical electron accelerators(529 cases)and infant incubators(513 cases). In the linear regression model, the risk rate of adverse events increased with the useduration of the device when 0.00%≤ X<14.14%; the risk rate of adverse events decreased with the increase of service time when 14.14%≤ X<100.00%. Conclusions:The number of adverse events reported in each province is different, and hospitals are the main reporting units.The causes of adverse events of different medical devices indicate different correlation strengths with the product itself. The use duration of medical devices poses a great impact on the risk rate of adverse events.

Objective:To investigate the effect of reverse saphenous nerve neurocutaneous flaps for skin defects of forefoot with the help of the three dimensional computerized tomography angiography(3D-CTA).Methods:From November 2013 to February 2018, 19 patients with anterior foot defects were treated in the Yidu Central Hospital of Weifang. There were 12 males and 7 females. The patients ranged from 16 to 45 years old, with an average age of 29.6 years. Preoperative 3D-CTA examination of the ipsilateral foot was performed to find out the blood vessels in the donor site, to determine the location, course, length of the superficial branch of the medial plantar toe artery and its relationship with the surrounding tissues, and to design the medial saphenous nerve nutrient vessel skin flap for retrograde repair of the skin and soft tissue defect at the front of the foot. Sensitive recovery were evaluated according to Swanson evaluation of clinical effect of peripheral nervous impairment.Results:Preoperative three-dimensional CT angiography showed that the superficial branches of the medial plantar toe artery were detected, and the perforating vessels during the operation were basically consistent according to the result of the examination. The 19 cases of forefeet skin detects were successfully reconstructed with the reverse saphenous nerve neurocutaneous flaps. All patients were followed up with the mean of 8 months. All flaps survived totally without diabrosis and swelling. The walking and weight-bearing were normal and the blood supply of foot were good. The functional recovery of foot and ankle was excellent in 8 cases, good in 10 cases and middle in 1 case. The sensory recovery of the forefoot: S4 5 feet, S3 10 feet, S2 4 feet; R4 3 feet, R3 9 feet, R2 7 feet.Conclusions:Preoperative 3D-CTA examination can confirm the anatomy of the superficial branch of the medial toe base artery in the donor site and guide the design of the medial saphenous nerve nutrient vessel flap for retrograde repair of skin and soft tissue defects of the distal foot. The blood supply is reliable, the wound is small and the effect is satisfactory.

Objective:To investigate the effect of reverse saphenous nerve neurocutaneous flaps for skin defects of forefoot with the help of the three dimensional computerized tomography angiography(3D-CTA).Methods:From November 2013 to February 2018, 19 patients with anterior foot defects were treated in the Yidu Central Hospital of Weifang. There were 12 males and 7 females. The patients ranged from 16 to 45 years old, with an average age of 29.6 years. Preoperative 3D-CTA examination of the ipsilateral foot was performed to find out the blood vessels in the donor site, to determine the location, course, length of the superficial branch of the medial plantar toe artery and its relationship with the surrounding tissues, and to design the medial saphenous nerve nutrient vessel skin flap for retrograde repair of the skin and soft tissue defect at the front of the foot. Sensitive recovery were evaluated according to Swanson evaluation of clinical effect of peripheral nervous impairment.Results:Preoperative three-dimensional CT angiography showed that the superficial branches of the medial plantar toe artery were detected, and the perforating vessels during the operation were basically consistent according to the result of the examination. The 19 cases of forefeet skin detects were successfully reconstructed with the reverse saphenous nerve neurocutaneous flaps. All patients were followed up with the mean of 8 months. All flaps survived totally without diabrosis and swelling. The walking and weight-bearing were normal and the blood supply of foot were good. The functional recovery of foot and ankle was excellent in 8 cases, good in 10 cases and middle in 1 case. The sensory recovery of the forefoot: S4 5 feet, S3 10 feet, S2 4 feet; R4 3 feet, R3 9 feet, R2 7 feet.Conclusions:Preoperative 3D-CTA examination can confirm the anatomy of the superficial branch of the medial toe base artery in the donor site and guide the design of the medial saphenous nerve nutrient vessel flap for retrograde repair of skin and soft tissue defects of the distal foot. The blood supply is reliable, the wound is small and the effect is satisfactory.

Objective:To analyze the patterns of antibacterial agents in Chinese children surveyed by the China multi-center monitoring network for the application of antibacterial agents in children and neonates in 2019 by using World Health Organization (WHO) Access, Watch, Reserve and Not-recommended (AWaRe) and typical anatomical/therapeutic/chemical (ATC) in this study.Methods:The cross-sectional method was adopted.A multi-center cross-sectional survey was conducted on one day from September to December 2019.The information of all inpatients taking antibiotics was uploaded to the network-based data collection system (https: //garpec-31.mobilemd.cn/login.aspx? relogin=true). This study covered 13 hospitals from 10 provinces and cities in China.All hospitalized children in the Respiratory Department, Infectious Disease Department, General Surgery Department, Pediatric Intensive Care Units, Neonatal Intensive Care Units and Neonatology joined in this survey.The clinically used antibacterial agents were classified by AWaRe and ATC, and the AWaRe and ATC distributions of antibacterial agents prescribed for Chinese children and neonates were described.Results:Of the 2 644 antibiotic prescriptions included from 13 hospitals, 2 134 (80.71%) were for children and 510 (19.29%) were for neonates.Of all antibiotic prescriptions, there were 368 (13.92%) Access antibiotics prescriptions, 1 973 (74.62%) Watch prescriptions, 60 (2.27%) Reserve prescriptions and 243 (9.19%) Not-recommended prescriptions.The top-five antibiotics prescribed for children and neonates were third-generation cephalosporins (1 056, 39.94%), macrolides (492, 18.61%), carbapenems (275, 10.40%), beta lactam-beta lactamase inhibitors (246, 9.30%), and second-generation cephalosporins (136, 5.14%). The use ratios of Access, Watch, Reserve and Not-recommended antibiotics in each center ranged from 0 to 30.00%, 36.67% to 97.20%, 0 to 17.02% and 0 to 33.33%, respectively.In 1 360 antibiotic prescriptions for children and neonates with pneumonia, there were 152 (11.18%) Access antibiotics, 1 051 (77.28%) Watch antibiotics, 37 (2.72%) Reserve antibiotics, and 120 (8.82%) Not-recommended antibiotics.The top-five antibiotics prescribed for children with pneumonia were third-generation cephalosporins (522, 38.38%), macrolides (388, 28.53%), beta lactam-beta lactamase inhibitors (141, 10.37%), carbapenems (117, 8.6%) and penicillins (49, 3.60%).Conclusions:Watch antibiotics and broad spectrum antibiotics such as third-generation cephalosporins and macrolides prone to induce resistance are the main antibacterial agents used in Chinese children and neonates with pneumonia.Broad-spectrum antibiotics may be overused in Chinese children and neonates.

OBJECTIVE： To explore the method for the development and implementation of drug abuse monitoring in medical institutions， and to provide reference for drug abuse monitoring in medical institutions. METHODS： Our hospital （the affiliated hospital of Binzhou medical college） had established the corresponding drug abuse monitoring mode from the two aspects of real-time monitoring and retrospective analysis， supplemented by relevant management measures， defined the content of drug abuse monitoring in medical institutions， and finally evaluated the implementation effect through the effective reporting quantity of drug abuse information， etc. RESULTS & CONCLUSIONS： The main contents of drug abuse monitoring in our hospital included the establishment of drug abuse monitoring management group， the improvement of drug abuse monitoring system and the sorting out of drug monitoring catalogue； the real-time drug abuse monitoring mode was established through timely reporting drug abuse information by medical， nursing and pharmaceutical personnel in daily diagnosis and treatment activities； at the same time， the retrospective analysis model of drug abuse was established by analyzing the relevant drug use data regularly through the hospital information system， paying attention to the key groups of key departments， and mining drug abuse information； a series of auxiliary management measures were taken， such as strengthening training and publicity， and establishing reward and punishment mechanism. Since the monitoring work was started in 2016， the effective number of drug abuse information reported in 2016-2018 was 38， 126 and 237 respectively， and through the monitoring， it was found that the elderly women over 60 years old （69.83％） were abusing in iatrogenic sedative hypnotic drugs. The development of drug abuse monitoring in hospital can collect drug abuse status， behavior characteristics and relevant information timely and effectively， analyze local drug abuse trends， find drug abuse risks， and provide basis for drug control of narcotics and psychotropic substances supervision.

Objective:To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection.Methods:This multicenter cross-sectional parallel control study was conducted in 11 children′s hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman′s rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection.Results:A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum ( r=0.97 , P<0.01). The linear regression equation was PCT?venous serum=0.135+0.929×PCT peripheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods ( r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. Conclusions:There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.