AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.

Objective:To construct a knowledge graph,to design an intelligent risk assessment model for adverse events and a risk factor analysis control system for the disinfection supply of stomatological medical devices,and improve the quality of disinfection supply of stomatology instruments through system application.Methods:The automatic collection,conversion and loading of stomatological medical devices disinfection supply data were realized by constructing data access services,the knowledge graph of adverse events of stomatology disinfection supply was constructed by using failure mode and effect analysis(FMEA)and dynamic risk assessment theory,and the risk prediction model and root cause analysis method of adverse events of disinfection supply were constructed by using recurrent neural network(RNN),and the risk assessment and root cause analysis of adverse events of stomatology medical devices disinfection supply were carried out.Results:The top four risk factors of the adverse events of"cleaning"in disinfection supply were incorrect cleaning parameter settings,stains on the instrument after cleaning,substandard lumen cleaning after cleaning,failure to meet the standard of luminal cleaning after cleaning,and scale presence in the instrument after cleaning,respectively,and the systematic prediction probabilities were 4.67%,2.33%,1.50%,and 1.39%,respectively,which were consistent with the actual probability of occurrence of 2.14%,1.85%,0.75%,and 0.50%.The top four risk factors for the adverse event of"water stains on the surface of disinfection equipment"were too high temperature setting of disinfection equipment,too long disinfection time of disinfection equipment,residual dirt on the surface of disinfection equipment and scale residue of heating pipe,which were consistent with the composition order of the first four risk factors in the actual statistical results.Conclusion:The application of the risk assessment model of adverse events and the risk factor analysis and control system of intelligent stomatological medical device disinfection supply can timely discover the quality hidden dangers in the operation of stomatology device disinfection supply and implement risk control,and provide reference for the construction of related business systems.

Objective:To prepare an affinity-based radionuclide therapeutic drug targeting human epidermal growth factor receptor 2 (HER2), named 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-HER2-BCH, and preliminarily evaluate its biodistribution, therapeutic efficacy, and safety in HER2-positive tumor models, in order to explore its feasibility as a radiopharmaceutical for treatment of HER2-positive tumor. Methods:177Lu labeling was accomplished by using a hydrochloric acid-sodium acetate buffer system. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio high performance liquid chromatography. Biodistribution, 177Lu-DOTA-HER2-BCH radionuclide targeting therapy, and trastuzumab therapy were performed in the HER2-positive NCI-N87 tumor-bearing mice. Repeated measures analysis of variance and Bonferroni method were utilized to analyze data. Results:177Lu-DOTA-HER2-BCH was obtained, with the radiolabeling yield >80%, radiochemical purity >98%, and good in vitro stability. Biodistribution data showed that 177Lu-DOTA-HER2-BCH was well targeted, with high tumor uptake and high retention. The tumor uptake values at 4, 24, 72 and 96 h post-injection were (11.93±0.46), (8.65±0.40), (5.89±0.69) and (3.26±0.36) percentage activity of injection dose per gram of tissue (%ID/g), respectively. In the treatment experiment, 177Lu-DOTA-HER2-BCH significantly inhibited tumor growth. On the 3rd day, the tumor volume of mice treated with 177Lu-DOTA-HER2-BCH was significantly smaller than that of the control group (mean difference 146.97 mm 3;F=4.02, P=0.016 (Bonferroni correction method), and then differences of tumor volume between the 2 groups increased with time. The differences of tumor volume between 177Lu-DOTA-HER2-BCH and trastuzumab treatment groups were not statistically significant throughout the treatment process ( F values: 0.05-61.21, all P>0.017(Bonferroni correction method)). At the end of treatment, no histological abnormality was seen in all organs of the mice. Conclusion:177Lu-DOTA-HER2-BCH radionuclide therapy demonstrates good tumor growth inhibition in HER2-positive tumor-bearing mice, which is expected to be an alternative treatment for HER2-positive tumors.

Objective To establish a palmitic acid(PA)-induced model of lipotoxic bone formation inhibition in zebrafish.Methods AB strain zebrafish embryos were divided randomly into a blank control group,PA group,and simvastatin(SIM)group.Embryos in the PA and SIM groups received PA from 3 days post-fertilization(dpf),and embryos in the SIM group received SIM continuously for 4 days from 5 dpf.Establishment of the model was confirmed at 9 dpf by calcein staining,Nile red staining,triglyceride and total cholesterol content determination,and q-PCR.Results PA significantly decreased the number of vertebrae,promoted lipid accumulation,increased triglyceride and total cholesterol contents,promoted the expression of lipid-related genes PPARγ、c/EBPα,and inhibited the expression of osteogenic genes ALP and RUNX2.SIM improved the inhibitory effect of PA on bone formation in zebrafish.Conclusions PA can successfully create a lipotoxic model of bone-formation inhibition,similar to the pathological process of osteoporosis,using a simple,sensitive,and controllable method.This model can then be used for drug screening for osteoporosis and related diseases.

Objective To establish a fast,stable,and sensitive zebrafish model of osteoporosis(OP)using different method.Methods OP models were induced by iron overload or prednisolone(Pred),and bone formation and mortality were observed.The groups were divided into:Control group,model group(include FAC group and Pred group),and positive control group(AC group).Ammonium ferric citrate was used as the model drug in the iron-overload induction method.For the Pred induction models,the modeling time for the Pred-3 days post-fertilization(dpf)method was 3～9 dpf,the modeling time for the Pred-5 dpf method was 5～10 dpf,and Pred was administered from 3 dpf and removed from 7～9 dpf for the Pred withdrawal method.To compare the anti-osteoporosis(OP)effects of commonly used drugs such as Alfacalcidol(AC),Calcitriol(CA),and Alendronate(AL),it's important to select a stable and sensitive positive control drug and to further optimize different staining methods and conditions.Results There was no significant effect of ammonium ferric citrate 500 μg/mL on bone formation.Bone formation and the length of the first vertebra were significantly decreased in the Pred group induced by Pred-3 dpf compared with those in the control group(P＜0.01,P＜0.05),but zebrafish mortality was higher.There was no significant difference between the Pred-5 dpf method,but bone formation was significantly reduced in the Pred withdrawal group(P＜0.01),with no mortality.Alfacalcidol,calcitriol,and alendronate all had anti-OP effects,with CA having the most sensitive and stable anti-OP effect.Alizarin red staining showed that the optimal dye parameters were 0.02%concentration for dyeing 2 h,with washing in 0.5%KOH and glycerol under the conditions of a 3∶1 ratio for 3 h followed by a 1∶1 ratio for 14 h.The result of staining showed that calcein was more sensitive for staining bone nodes and ARS staining was more sensitive for staining the first vertebra.Conclusions The Pred withdrawal method can be used to establish a rapid,stable,and sensitive OP model in zebrafish as a reliable model for studying OP.

Objective:To observe the differences in clinical efficacy of Jieyu Anshen Decoction combined with auricular points and oral tibolone in the treatment of patients with perimenopausal sleep disorders, and provide effective treatment for patients with contraindications to hormone supplement therapy in clinicalMethods:Using a randomized trial design, from July 2018 to August 2020,102 perimenopausal insomnia patients in International Peace Maternity and Child Health Hospital of China Welfare Institutewith kidney deficiency and liver depression who met the inclusion criteria were randomly divided into a treatment group and a control group with 51 cases each. The treatment group took Jieyu Anshen Recipe. At the same time, unilateral auricular point pressing treatment was given, and the opposite ear was changed in 5 d. The control group was treated with tiburon for a period of 3 months. The changes in the scores of each scale were observed in the two groups after 1 month and 3 months treatment. The scale included Pittsburgh sleep quality index (PSQI), modified Kupperman score (KMI), Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire Depression Screening Scale (PHQ-9). Its effectiveness and differences were evaluated and analyzed comprehensively through the above scale.Results:PSQI, KMI, GAD-7, PHQ-9 scores decreased significantly in the control and treatment groups after 1 month and 3 months of treatment, and the difference were statistically significant: PSQI: (8.58 ± 1.94) and (5.81 ± 1.93) scores vs. (13.10 ± 2.53), (9.15 ± 2.59) and (6.33 ± 1.98) scores vs.(13.52 ± 2.27) scores; KMI: (19.92 ± 2.16) and (14.67 ± 4.11) scores vs. (28.54 ± 7.65) scores, (19.02 ± 5.92) and(14.10 ± 4.37) scores vs. (27.42 ± 7.34) scores; GAD-7: (4.54 ± 2.03) and (3.81 ± 1.63) scores vs. (5.69 ± 2.95) scores, (3.71 ± 2.48) and (3.32 ± 1.73) scores vs. (4.90 ± 3.17) scores; PHQ-9:(6.90 ± 2.52) and (4.98 ± 1.96) scores vs. (9.83 ± 3.71) scores, (6.15 ± 2.62) and (4.44 ± 1.81) scores vs. (9.02 ± 3.73) scores ( P<0.01). PSQI, KMI, PHQ-9, and GAD-7 scores declined between the two groups, but there were no significant differences between the two groups ( P>0.05). After 1 month and 3 months of treatment, using PSQI scale and KMI score, the total efficiency of patients in the control group was slightly higher than that of the treatment group, but the difference was not statistically significant ( P>0.05); after 1 month and 3 months of treatment, using PHQ-9 score and GAD-7 score, the total efficiency of patients in the treatment group was slightly higher than that of the control group, but the difference was not statistically significant ( P>0.05). Conclusions:Traditional Chinese medicine combined with ear acupoint pressing has similar effects to tibolone in treating perimenopausal insomnia with kidney deficiency and liver depression. It can significantly improve the quality of sleep and quality of life of patients, and has good safety. For patients who are not suitable for hormone, Chinese medicine can be used as an alternative. The therapies are worthy of clinical application.

Objective:To produce the solid target nuclide 89Zr , and prepare the probe 89Zr-desferrioxamine (DFO)-Trastuzumab. Methods:The 89Y(p, n) 89Zr nuclear reaction was used for 89Zr production. 89Y target was irradiated by 20 μA proton in a medical cyclotron ( E=12.5 MeV) for about 1-2 h. 89Zr was purified from hydroxamate resin using 1 mol/L oxalic acid solution. The characteristic peak, radionuclide purity and radiochemical purity of 89Zr were determined by γ-ray spectroscopy. 89Zr-DFO-Trastuzumab probe was synthesized by the reaction of 89Zr-oxalate and DFO-Trastuzumab at room temperature, and the radiochemical purity was measured. Results:89Zr was prepared successfully for 11 times, and the production of 89Zr was 555-1 506 MBq, with production rate of (34.8±5.2) MBq·μA -1·h -1. After the purification (purification rate: 42%-87%), 227.2-991.6 MBq 89Zr was obtained, with the concentration of 1.0×10 6 MBq/L. The γ spectrum showed that the characteristic peak of 89Zr were 511 and 909 keV, and no impurities were found. The radionuclide purity and radiochemical purity were both close to 100%. 89Zr-DFO-Trastuzumab was successfully labeled with radiochemical purity more than 95%, and it was above 90% within 72 h in human serum albumin (HSA) solution. Conclusion:Through the self-designed target assembling, the solid target PET nuclide 89Zr with high quality and labeling are successfully achieved, which provides guarantee for the clinical application of the 89Zr drug.

Objective To summarize clinicopathologic features of papillary thyroid carcinoma (PTC) coexistent with chronic lymphocytic thyroiditis (CLT) and investigate risk factors for lymph node metastasis.Methods The medical records of 4 264 consecutive papillary thyroid carcinoma patients who received surgical treatment from Oct 2013 to Oct 2015 in Peking Union Medical College Hospital were reviewed.The diagnoses was confirmed by histopathological tests.Univariate analysis was performed to identify specific clinicopathologic features of PTC with CLT.Univariate and multivariate analysis were performed to determine whether each clinicopathologic feature was an independent risk factor for lymph node metastasis.Results In all 4 265 cases,there were 3 059 papillary thyroid microcarcinoma (PTMC) (71.7％),1 010 PTC patients (23.7％) with CLT.909 female patients (90％),624 cases with multifocal lesions (61.8％),422 cases with extra-thyroid extension (41.8％),429 cases with lymph node metastasis (42.5％),and 133 cases with metastatic lymph nodes(LNs) ≥6 (13.2％).The median age was 43 years old and median tumor size was 0.8 cm.Patients with CLT were more females (90.0％ vs.70.2％;P ＜ 0.001),younger median age (43 vs.44 years;P =0.001),and lower incidence of lymph node metastasis (42.5％ vs.50.9％;P ＜0.001).CLT was not associated with tumor size,multifocal lesions,extra-thyroid extension and metastatic LNs≥6 (0.8 cm vs.0.7 cm,61.8％ vs.62.9％,41.8％ vs.42.1％ and 13.2％ vs.14.8％,respectively,all P ＞ 0.05).In multivariate analysis,CLT was an independent protective factor for lymph node metastasis (OR =0.713,95％ CI 0.609-0.835,P ＜0.001).In PTC patients with lymph node metastasis,CLT was not associated with lymph node metastasis number (3 vs.3,P =0.300).Conclusions Chronic lymphocytic thyroiditis was an independent protective factor for papillary thyroid carcinoma patients with lymph node metastasis.But in patients with lymph node metastasis,the metastatic number didn't decrease.

Objective To prepare a novel somatostatin receptor (SSTR) antagonist 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-JR11 (Cpa-c(D-Cys-Aph(Hor)-D-Aph(Cbm)-Lys-Thr-Cys)-D-Tyr-NH2 ) tracer and observe its biodistribution and microPET imaging in mice. Methods One ml HCl (0.05 mol/L) containing 68GaCl3(148 MBq) was added into 65μl NaAc (1 mol/L) and 4μg NOTA-JR11. The mixture reacted at 95 ℃ for 15 min, and then was purified with Sep-Pak? C18 Light column to obtain 68 Ga-NOTA-JR11. 68 Ga-NOTA-JR11 was subjected to quality control analysis including radiochemical purity and in vitro stability by radio-high performance liquid chromatography. Biodistribution of 68Ga-NOTA-JR11 (0.37 MBq) in BALB/c mice (n=9) at 5, 30, 60 min postinjection were observed (n=3 for each time point), and the percentage activity of injection dose per gram of tissue (％ID/g) was calculated. 68Ga-NOTA-JR11 (14.8 MBq) microPET imaging of BALB/c mice (n=1) at 60 min postinjection was observed. Results 68 Ga-NOTA-JR11 was obtained successfully within 15 min, with yielding rate of 90％, radiochemical purity of more than 99％, and specific activity of 6. 10 GBq/μmol. The tracer showed excellent stability ( radio-chemical purity:95％) in different buffers within 150 min. The biodistribution was basically consistent with microPET imaging results. 68 Ga-NOTA-JR11 was metabolized through the kidneys and had low uptake in the liver ((0.75±0.26) ％ID/g) at 60 min postinjection. Conclusions 68 Ga-NOTA-JR11 can be prepared rapidly, with high yielding rate and radiochemical purity. Biodistribution and imaging results provide basic information for the further study of somatostatin receptor imaging in neuroendocrine tumors.

Taking the application of logistics robots in intravenous drug distribution at our hospital as an example, this paper discussed the application effect of hospital logistics robots in actual operation, and discussed how to use data analysis to carry out a comprehensive scientific evaluation of the work effect of hospital logistics robots. The results showed that the hospital logistics robots can take charge of the daily heavy workload by using of unmanned technology. And at the same time, the transportation of medical materials by such means ensures the safety of transportation. It can also realize the whole process monitoring and closed-looping of transportation information. Analysis of operational data proves that the use of hospital logistics robots conforms to the expectation of higher quality requirements in hospital logistics, thus strengthening and improving the level of modern management of hospital logistics.