The aim of this study was to prepare a high drug-carrying capacity micellar drug delivery system(CTD@Sol)of the polymer zebra tetracycline and to preliminarily investigate the feasibility of this drug delivery system for the treatment of breast cancer.Firstly,CTD@Sol was prepared using sol as the carrier material and CTD as the model drug,and its pharmacological properties such as appearance and morphology,particle size,potential and in vitro release were evaluated.The growth inhibitory and apoptotic effects of CTD@Sol on breast cancer(4T1)cells were investigated by MTT assay and Annexin V-FITC/PI double staining assay;the uptake efficiency of 4T1 to this delivery system was investigated by flow cytometry;and the in vivo tissue distribution of the delivery system and the targeting of tumour tissues were investigated by small animal in vivo imaging technique.The results showed that CTD@Sol appeared as a light pale blue creamy white colour,with an average particle size of(159.73±1.96)nm,a PDI of 0.198±0.006,Zeta potential of-(47.60±1.77)mV,an encapsulation rate of(90.29±1.69)%and a drug loading capacity of(45.00±0.84)%;the in vitro release and haemolysis experiments showed that the drug release rate of CTD@Sol in acidic environment(pH 5.5)was significantly faster than that in neutral environment(pH 7.4),suggesting that the system is acid-sensitive and has good biosafety under endocytosed pH conditions.Cellular uptake,cytotoxicity and apoptosis experiments showed that CTD@Sol was more lethal to 4T1 cells,and the sol-gel polymer micelles as a drug delivery vehicle could significantly improve the cellular uptake efficiency of the drug;in vivo experiments showed that the delivery system had a significant targeting effect on tumour tissues.In conclusion,this study has successfully produced a CTD@Sol drug delivery system with high drug loading capacity(>45%),good pharmacological performance,strong targeting and biosafety,which has the potential to be used in the treatment of breast cancer.

Objective To analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease (KBD) in China,and provide the basis for formulating prevention and control measures. Methods Fixed-point monitoring,moving-point monitoring,and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7-12 years old) underwent clinical and right-hand X-ray examinations every year. According to the KBD diagnosis criteria,clinical and X-ray assessments were used to confirm the diagnosis. Results In 1990,the national KBD detectable rate was 21.01％. X-ray detection decreased to below 10％ in 2003 and below 5％ in 2007. Between 2010 and 2018,the prevalence of KBD in children was less than 0.4％,which fluctuated at a low level,and has decreased to 0％ since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas. Conclusion The evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care.

Objective:To investigate the dynamic prevalence of Kashin-Beck disease (KBD) in 2020, and to provide the basis for assessment of KBD control and elimination.Methods:According to the "Kashin-Beck Disease Monitoring Plan (2019 Edition)", collection of basic information of endemic areas and children KBD examination were executed in all endemic areas from every endemic county (city, district, banner) of 13 endemic provinces. All children aged 7 - 12 years in endemic areas underwent clinical examination, X-ray examination was performed for clinically positive children. According to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), KBD cases were diagnosed by both clinical examination and X-ray check.Results:In monitoring of 827 986 children of 7 - 12 years old, a total of 703 children with similar clinical signs of KBD were suspected positive cases. X-ray results showed that 703 children were normal, with no X-ray positive change, they were not children KBD cases.Conclusions:In 2020, no cases of Kashin-Beck disease are detected in children nationwide, and the condition of Kashin-Beck disease in children nationwide continues to be at a level of elimination.

Objective:To investigate the effects of hypertensive disorders during pregnancy (HDP) on preterm newborns in terms of umbilical cord blood serum ferritin (SF), hemoglobin (Hb) at birth and outcome.Methods:Among inpatients of the First Maternity and Infant Health Hospital Affiliated to Tongji University from October 1, 2015 to December 31, 2016, totally 1 419 cases of preterm newborns were prospectively collected.Preterm infants whose mothers with diagnosis of HDP were recruited as the HDP group.Meanwhile, premature newborns whose mothers without HDP were recruited as the control group.Umbilical cord blood SF levels, Hb levels at birth, outcome of preterm newborns and the basic information for maternity were compared between the two groups.The data of normal distribution between the two groups were compared by independent sample t test.The count data was tested by χ2, and the count data with frequency <5 was tested by Fisher′ s exact test. Results:SF levels of HDP group were significantly lower than the control group [(85.6±67.2) μg/L vs. (103.9±95.5) μg/L]. But Hb levels of HDP group were much higher than the control group [(206.2±33.8) g/L vs. (193.2±31.9) g/L]. The difference between two groups was statistically significant ( t=2.791, 4.825 all P<0.05). Umbilical cord blood SF levels were negatively correlated with Hb levels at birth ( r=-0.120, P<0.001). Moreover, compared to the control group, statistically significant lower incidence of neonatal respiratory distress syndrome (NRDS), pneumonia and bronchopulmonary dysplasia (BPD) in HDP group was observed (all P<0.05). Conclusions:HDP was correlated with umbilical cord blood SF levels and Hb levels at birth in premature newborns.Higher Hb levels and relatively lower incidences of NRDS, pneumonia and BPD were observed in these newborns delivered by mothers with diagnosis of HDP.

Objective:To investigate the effects of glucosamine sulfate, chondroitin sulfate and diacerein on liver function in patients with Kashin-Beck disease.Methods:According to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), 333 cases of Kashin-Beck disease were selected from the disease severely affected areas, and randomly divided into 3 groups according to the matching principle of age, gender and disease grading: glucosamine sulfate group (group A, 118 cases), chondroitin sulfate group (group B, 99 cases) and diacerein group (group C, 116 cases), and the patients in each group were treated for 180 days. Fasting venous blood samples were collected from the patients in the three groups at 0, 90 and 180 days after treatment. Serum was separated. The biochemical analyzer was used to determine the serum levels of albumin (ALB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), glutamyl transpeptidase (GGT), total bilirubin (TBIL), and total protein (TP) of the three groups of patients.Results:There was no difference in the expression levels of 8 liver function indexes between the groups on day 0 of treatment ( P > 0.05). After 90 days of treatment, the expression level of GGT in group B was higher than that in group A ( P < 0.05); compared with 0 day of treatment, ALB levels of groups A, B and C were all decreased, ALP and TBIL levels increased ( P < 0.05), the abnormal expression rate of ALB index decreased in all the three groups ( P < 0.001), the abnormal expression rate of TBIL index in group A was decreased ( P = 0.006). After 180 days of treatment, ALB level of group B was higher than that of group A, ALP level of group B was higher than that of groups A and C, and AST level of group B was higher than that of group C ( P < 0.05); compared with 90 days of treatment, ALB levels of groups A, B and C were all increased, ALP, ALT and AST levels of groups A and C were decreased, GGT levels of groups B and C were decreased ( P < 0.05); compared with 0 day of treatment, the abnormal expression rate of ALB index increased in all the three groups at 180 days of treatment ( P < 0.001), and the abnormal expression rate of ALP index decreased in group C ( P = 0.031). Conclusion:The liver function indicators ALB, ALP and TBIL should be monitored when taking the three oral drugs for a short time, especially the GGT, ALP and AST indicators when taking chondroitin sulfate for a long time.

OBJECTIVE：To establish quantitative e valuation system of the prophylactic use of antibiotics in orthopedic type Ⅰ incision surgery ，and to provide reference for evaluating the rational prevention use of antibiotics in this type surgery scientifically. METHODS：Based on the Guidelines of Clinical Use of Antimicrobial Agents （2015 edition），drug instructions ，related guidelines and references ，experts from relevant departments jointly discussed and formulated the evaluation criteria for the rationality of the use of antibiotics in type Ⅰ incision in orthopedic surgery. AHP method was used to assign the weights for various indexes of evaluation criteria ；TOPSIS method was used to retrospectively analyze and evaluate the rationality of 120 cases of type Ⅰ incision surgery from 3 orthopedic departments in Peking University People ’s Hospital during Sept. 1st-30th，2019. RESULTS ：Established evaluation system included 4 primary indicators （medication indication ，usage and dosage ，medication timing ，other factors ）and 12 secondary indicators. Among the secondary indicators ，indications，drug selection and timing of preoperative administration were the most important （weights were 0.209，0.140，0.117）. Among 120 cases，30.83％ of drug use were reasonable ，47.50％ were basically reasonable and 21.67％ were unreasonable. Evaluation results obtained by AHP-TOPSIS were consistent with the actual situation. CONCLUSIONS ：The rationality evaluation method of prophylactic use of antibiotics in type Ⅰ incision surgery based on AHP-TOPSIS method can quantitatively evaluate the rationality of drug use by combining multiple indicators. The method is feasible ，operable，and the evaluation results can be quantified ，which has a wide range of application.

Objective:To master the status of Kashin-Beck disease (KBD) in 2019, to provide the basis for assessment of KBD control and elimination.Methods:Data of endemic areas basic information collection and children KBD examination were executed in all endemic villages from every endemic county (city, district, banner) of 13 endemic provinces. All children aged 7 - 12 years in endemic villages underwent clinical examination, and X-ray examination was performed for clinically positive children. When both the clinical examination and X-ray reexamination were positive, the diagnosis was KBD.Results:In monitoring of 823 365 7 - 12 years old children, a total of 3 057 children with similar clinical signs of KBD were suspected positive cases. The results of X-ray reexamination showed that the X-ray manifestations of 3 057 children were normal, and no X-ray positive changes were found, that is, there was no case of KBD in children. A total of 16 559 endemic villages in 13 endemic provinces were monitored, and all reached the criteria for KBD elimination. Surveillance of all endemic villages was completed except Tibet Autonomous Region, the KBD elimination rates of endemic villages were 100.00% in 12 endemic provinces and 99.01% (16 559/16 725) in all 13 endemic provinces.Conclusions:No children KBD case is detected in 2019, children KBD stays at its eliminating level throughout the country. And 100.00% endemic villages meet the criteria for KBD elimination in the remaining 12 endemic provinces except Tibet Autonomous Region.

Objective:To investigate the oral medication treatment of adult patients with Kashin-Beck disease(KBD) in China, so as to provide theoretical basis for medication screening of KBD and to provide scientific guidance for clinical treatment of KBD.Methods:Based on the "Endemic Disease Prevention and Control Project of Special Funds for Local Public Health Subsidized by the Central Government" and "Major Public Health Service Endemic Disease Prevention and Control Project", the treatment information of adult patients with KBD in 11 provinces (autonomous regions, referred to as provinces) in China from 2006 to 2017 was collected, and the treatment coverage of adult patients with KBD in different years and regions was analyzed, and the curative effect of patients with different severity was evaluated.Results:From 2006 to 2017, the number of provinces participating in the treatment project was from 2 to 11. The actual total number of people treated in China was 68 061, with a completion rate of 78.10% (68 061/87 149); the annual number of people treated increased linearly; the overall clinical symptom remission rates of adult patients with KBD in all regions reached more than 50%, and the overall treatment effect showed an upward trend year by year; compared with patients with grade Ⅲ, after oral medication, the remission rates of clinical symptoms in patients with gradeⅠandⅡ were higher (the average remission rate of clinical symptoms was 84.13% for gradeⅠ, 80.71% for grade Ⅱ and 72.11% for grade Ⅲ, P < 0.05). Conclusions:Oral medication treatment can effectively alleviate the clinical symptoms of most adult patients with KBD of grade Ⅰ and Ⅱ. Patients of grade Ⅲ should be considered treating with oral medication combined with other treatment methods. A considerable number of patients are still ineffective in taking drugs at this stage, and it is urgent to carry out the screening, research and development of specific medications for KBD.

Objective:To observe and compare the therapeutic effects of glucosamine sulfate (GS) and diacerein (DCN) on adult Kashin-Beck disease (KBD).Methods:A clinical randomized controlled trial was conducted in the historical severe KBD areas Fanrong Township, Fulu Town, Long'anqiao Town, Lianghe Town, Shaowen Township of Heilongjiang Province, and 240 patients were selected according to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), then divided into GS and DCN groups (gender, age, and KBD condition balanced) via the random number table method, with 120 patients in each group. Followed up once a month to investigate the patient's medication and clinical symptoms, and distributed drugs for the next stage. Fasting blood samples and urine samples were collected before, during, and at the end of treatment (0, 90, and 180 days). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-1β level and urine pyridinol (PYD) level. Visual analog scale (VAS) scores, evaluation of affected joints, self-evaluated efficacy, and evaluation of adverse reactions were carried out through questionnaires. Joint dysfunction scores and medications efficacy determination were performed according to the "Judgment of Kaschin-Beck Disease Treatment Effect" (WS/T 79-2011).Results:Expression of cytokines related to cartilage metabolism: after 180 days of treatment, serum IL-1β levels, urine PYD levels in GS group and urine PYD levels in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.332, - 5.420, - 5.204, P < 0.05). VAS scores: after 90 days of treatment, the pain, stiffness scores of patients in GS group and the pain, stiffness, and function scores in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.612, - 2.359, - 3.637, - 2.881, - 2.238, P < 0.05); after 180 days of treatment, the pain, stiffness and function scores of patients in GS and DCN groups were significantly lower than those of the same group at 0 day of treatment ( Z = - 6.738, - 9.530, - 7.781, - 5.428, - 3.761, - 3.587, P < 0.01). Evaluation of affected joints: after 90 and 180 days of treatment, except for pain of weather changes in DCN group, the scores of symptomatic joints in the two groups were lower than those at 0 day of treatment ( P < 0.05). Efficacy self-evaluation: after 180 days of treatment, the self-evaluated efficacy ratio of DCN group was higher than that of GS group and the same group after 90 days of treatment (χ 2 = 4.165, 4.022, P < 0.05). Evaluation of adverse reactions: after 90 and 180 days of treatment, the main adverse reactions of patients in GS and DCN groups were gastrointestinal symptoms. Joint dysfunction scores: after 90 days of treatment, the sum of the effective rate and the markedly effective rate of GS group was higher than that of DCN group (χ 2 = 4.993 , P < 0.05); while after the 180 days of treatment, there was no significant difference between the two groups (χ 2 = 0.417 , P > 0.05). Conclusions:Both GS and DCN have a certain therapeutic effect on adult KBD and can improve clinical symptoms. The GS takes effect quickly, and long-term use can protect cartilage from inflammatory factors to a certain extent.

Objective:To investigate the effects of glucosamine sulfate, chondroitin sulfate and diacetarine on urinary renal function indexes UREA, creatinine (CREA), urinary microprotein(mALB) and N-acetyl-β-D-glucosidase (NAG) in adult patients with Kashin-Beck disease.Methods:According to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), adult patients with degrees Ⅰ and Ⅱ Kashin-Beck disease in Heilongjiang Province were selected in 2019. They were randomly divided into three treatment groups according to age, gender, disease classification and other condition by clinical randomized controlled trial, group A (glucosamine sulfate group), group B (chondroitin sulfate group) and group C (diacetarine group). Fasting mid-morning urine was collected at 0, 90 and 180 days of treatment. The levels of UREA, CREA, mALB and NAG were measured using an automatic biochemical analyzer. And the abnormal rates of the above indexes were analyzed.Results:At 0 day of treatment, there were 118, 99 and 116 people in the 3 groups, respectively; after 90 days of treatment, 115, 93 and 106 people remained in the 3 groups; after 180 days of treatment, 95, 80 and 93 people remained in the 3 groups. The results showed that there was no significant difference in the levels of UREA, CREA, NAG and mALB among the 3 groups at 0 and 180 days of treatment ( H = 0.055, 0.923, 0.276, 1.125, 1.635, 3.873, 1.045, 4.135, P > 0.05). After 90 days of treatment, there was no significant difference in CREA level among the 3 groups ( H = 1.719, P > 0.05), the levels of UREA and NAG in group C were higher than those in group B ( P < 0.05), and the level of mALB in group B was higher than that in group C ( P < 0.05). The comparison results of all indexes before and after treatment showed that after 90 days of treatment, the levels of mALB in the 3 groups were lower than those of 0 day ( Z = - 2.858, - 3.217, - 2.124, P < 0.05), the levels of NAG were higher than those of 0 day ( Z = - 3.700, - 2.222, - 4.672, P < 0.05); and the level of UREA in group C was higher than that of 0 day ( Z = - 2.393, P < 0.05). After 180 days of treatment, the levels of CREA in the 3 groups were higher than those of 0 day ( Z = - 5.853, - 6.984, - 6.255, P < 0.05), and the levels of mALB in the 3 groups were lower than those of 0 day ( Z = - 3.785, - 2.624, - 3.427, P < 0.05). The abnormal rates of CREA in the 3 groups after 180 days of treatment were higher than those of 0 and 90 days (χ 2 = 39.499, 37.707, 71.534, 57.959, 58.160, 55.129, P < 0.05). There was no significant difference in the abnormal rate of CREA between 0 day and 90 days of treatment (χ 2 = 0.004, 2.068, 0.053, P > 0.05). The abnormal rates of NAG in groups A and C after 90 days of treatment were higher than those of 0 day (χ 2 = 8.999, 11.227, P < 0.05). The abnormal rates of NAG in group C after 180 days of treatment was higher than that of 0 day (χ 2 = 5.006, P < 0.05). There was no significant difference in the abnormal rate of NAG between group A and group C after 90 days and 180 days of treatment (χ 2 = 1.976, 1.413, P > 0.05). The abnormal rates of mALB in groups A and B after 90 days and 180 days of treatment were lower than those of 0 day (χ 2 = 6.461, 8.881, 7.563, 4.999, P < 0.05), and there was no significant difference between 90 days of treatment and 180 days of treatment (χ 2 = 0.638, 0.013, P > 0.05). Conclusions:The effects of glucosamine sulfate, compound chondroitin sulfate and diacetarine on renal function of the patients are not significantly different after 180 days of medication, but the three drugs all have certain effects on CREA and NAG. Follow-up work should be done during drug treatment to closely monitor the changes of the two indicators.