Objective:To investigate the drug resistance of Yersinia pestis to 11 kinds of antibiotics in the natural foci of plague in Inner Mongolia Autonomous Region, and to provide a theoretical basis for scientifically and effectively selecting antibiotics for treatment of the plague. Methods:A total of 137 strains of Yersinia pestis isolated from the natural foci of plague in Inner Mongolia Autonomous Region at different times, regions, hosts and vectors were collected. According to Clinical and Laboratory Standard Institute (CLSI), the agar plate dilution method was used to determine the minimum inhibitory concentration (MIC) of the 11 kinds of antibiotics against 137 strains of Yersinia pestis, including ofloxacin, ciprofloxacin, kanamycin, streptomycin, ceftriaxone, ampicillin, chloramphenicol, spectinomycin, cefuroxime, tetracycline and sulfamethoxazole-trimethoprim. The MIC 50 and MIC 90 (the minimum concentration of drug which could inhibit 50% and 90% of bacterial growth) were calculated, and their sensitivity was determined according to CLSI standards. Results:Among 137 strains of Yersinia pestis tested, no strains of Yersinia pestis had single or multiple resistance to ofloxacin, ciprofloxacin, kanamycin, streptomycin, ceftriaxone, ampicillin, chloramphenicol, spectinomycin, cefuroxime, tetracycline and sulfamethoxazole-trimethoprim. According to CLSI standards, 137 strains of Yersinia pestis were all sensitive to the 11 kinds of antibiotics; among them, ofloxacin, ciprofloxacin, ceftriaxone and sulfamethoxazole-trimethoprim had higher antibacterial activity, with MIC 90 < 0.250 μg/ ml; the antibacterial activity of spectinomycin was the lowest, with MIC 90 of 16.000 μg/ml. Conclusions:The Yersinia pestis isolated from the natural foci of plague in Inner Mongolia Autonomous Region is not found to have single or multiple resistance to the 11 kinds of antibiotics. Continuous drug resistance monitoring of Yersinia pestis should be carried out to provide a basis for clinical medication.

Objective To investigate the biological characteristics and epidemiological significance of Yersinia pestis strains in Qilian County,Qinghai Province,in order to provide a scientific basis for plague prevention and control.Method Totally 67 strains were separated from kinds of host in Qilian County,Qinghai Province from 1958 to 2011,to do biochemical test,toxicity test,virulence factors evaluation,plasmid analysis and different region (DFR) genotyping.Results According to biochemical typing,48 of the 50 strains tested were Qing-Tibet Plateau ecotype,15 were Qilian Mountain ecotype,and the remaining 4 were different ecotypes from the plague foci in Qinghai plateau.The strains had 8 genomovars,and were given priority to genomovar8 (42 strains),secondly,genomovar44 (15 strains),genomovar5 (4 strains),genomovar7 (2 strains),genomovar19 (1 strain),genomovar30 (1 strain),genomovar32 (1 strain),and genomovar34 (1 strain).A proportion of 95.52％ (64/67) of the strains contained 3 kinds of plasmid-6 × 106,45 × 106,and 52 × 106;85.07％ (57/67) contained all the four virulence factors,and 96.00％ (48/50) were velogenic strains.Conclusion The strains separated in Qilian County,Qinghai Province have the characteristics of Qinghai-Tibet Plateau plague's pathogen and have strong toxicity,so we should enhance the plague monitoring and give more publicity to plague prevention to prevent animal plague spreading to human.

Objective To understand the epidemic trend of Tibetan sheep plague in Guoluo Prefecture,Qinghai Province,we detected the plague F1 antibody in Tibetan sheep serum in this area.Methods Indirect hemagglutination test (IHA) and colloidal gold immunochromatography (GICA) were applied to test serum samples of Tibetan sheep which were separated from 5 ml whole blood drew from jugular vein in Maqin County,Maduo County,Gande County,Banma County,Jiuzhi County and Dari County in 2014 and 2015.Results We collected 1 481 serum samples,566 from Maqin County,315 from Maduo County,150 from Gande County,150 from Banma County,150 from Jiuzhi County and 150 from Dari County.Totally 14 serum samples showed F1 antibody positive,the positive rate was 0.95％ (14/1 481),and they were all from Maqin County.Conclusions This area has the prevalence of Tibetan sheep plague.Therefore,the monitoring work of Tibetan sheep plague should be strengthened.

Objective To study the biological characteristics and epidemiological significance of Yersinia pestis in Chengduo County of Qinghai Province,in order to provide scientific basis for plague prevention and control in this area.Methods Thirty one strains of Yersinia pestis isolated from Chengduo County of Qinghai Province from 1980 to 2011 were selected as study subjects.Biochemical test,virulence factors evaluation [Fra1 (F1),pesticin Ⅱ (Pst Ⅱ),virulence antigen (VW),pigmentation (Pgm)] and different region (DFR) genotyping were carried out.Nineteen of the 31 strains Yersinia pestis were selected according to different time,different areas and different hosts to determine their toxicity in mice,MLD ≤ 10 000 was strong toxic strain,10 000 ＜ MLD ＜ 100 000 was moderate toxic strain.Results Among thirty one strains of Yersinia pestis,23 strains were isolated from human,the Himalaya marmot and its fleas and lice,and their biological type was classical,biochemical type was Qinghai-Tibet plateau;21 strains genotype was type 5,1 was type 16,1 was type 32,and they contained all four kinds of virulence factors (F1,Pgm,Pst Ⅱ,VW),and toxicity test showed all strains (14) were strong toxic strains.The rest 8 strains of Yersinia pestis isolated from the Microtus fuscus and its fleas,and their biological type was Microtus,biochemical type was Chuanqing plateau;they could produce F1 and Pgm,of which 87.5％ (7/8) strains could produce Pst Ⅱ,but could not produce VW antigen factor,the genotype was 14,and the toxicity results showed that they were strong (3)and moderate (2) toxic strains.Conclusion The strains separated in Chengduo County of Qinghai Province from 1980 to 2011 have the pathogen characteristics of Qinghai-Tibet plateau plague,they are mainly strong toxic strains;the work on prevention and control of plague should not be neglected.

Objective To establishment a method for detection of multiple drug resistance gene of Yersina pestis using polymerase chain reaction(PCR), to provide a guidance for treatment of plague. Methods According to National Center for Biotechnology Information (NCBI) released sequences of aminoglycoside resistant genes of streptomycin resistant,strB,strA,beta lactam antibiotics resistant genes tem,shv,and ctx-m,sulfamilamide resistant genes sul1, sul2, and sul3, a pair of primers of each gene was designed. DNAs of 282 strains isolated from plague natural foci in Qinghai Province were amplified by PCR using every pair of primers. The products were separated using gel electrophoresis, and the results were visualized through a gel imaging system. The susceptibility of 282 Yersina pestis to streptomycin, sulfamethoxazole and ceftriaxone was tested by drug sensitivity test. Results The PCR amplification results of all samples were negative,and strains with streptomycin,sulfamilamide and beta lactam antimicrobial drug resistance genes were not found. Drug sensitivity test showed that 282 strains were highly sensitive to streptomycin,sulfamethoxazole and ceftriaxone sodium.The diameter of bacteriostasis ring>19,17,21 mm, respectively. Conclusions It is a feasible method to use PCR technology to detect the multiple drug resistance genes of Yersinia pestis. Using this method to systematically monitor the resistance gene of Yersinia pestis is an efficient, economical and practical experimental method, which can provide guidance for the treatment of plague disease.

Objective To investigate the etiology and the epidemiologic features of drug resistance and disinfectant resistance of Yersinia pestis in Hainan,Qinghai Province,in order to provide a scientific basis for prevention and control of the plague in this area.Methods Totally 75 strains were isolated from vary kinds of host in Hainan from 1960 to 2009,and biochemical test,virulence factors evaluation [Fra1 (F1),pesticin Ⅰ (Pst Ⅰ),virulence antigen (VW),pigmentation (Pgm)],plasmid analysis,different region (DFR) genotyping,drug resistance and disinfectant resistance gene test were carried out.Forty-five strains of Yersinia pestis were selected to determine their toxicity in mice,median lethal dose (LD50) was calculated,and LD50 ＜ 1 000 was defined as strongly toxic.Results Sixty of the 75 strains were Qing-Tibet Plateau ecotype,7 strains were Qilian Mountain ecotype,and the remaining 8 were different ecotypes from the plague foci in Qinghai Plateau.Eighty percent (60/75) contained all the four virulence factors;and 97.78％ (44/45) of the strains were velogenic strains;96.00％ (72/75) of the strains contained 3 kinds of plasmids (Mr:6 × 106,45 × 106 and 52 × 106);the DFR strains had 3 genomovars,which were genomovar 8 (65 strains),genomovar 5 (8 strains) and genomovar 21 (2 strains).No strains related to streptomycin,sulfonamides,β-lactam antibiotics and disinfectants had been found in the 75 strains of Yersinia pestis.Conclusions The strains isolated in Hainan have the characteristics of Qinghai-Tibet Plateau plague's pathogen,and they have strong toxicity.In view of high mortality of plague,drug resistance and disinfectant resistance gene test should be put into routine monitoring of the plague.

Objective:To observe the efficacy of levofloxacin and moxifloxacin in the treatment of experimental plague in guinea pigs.Methods:A total of 70 SPF guinea pigs, female, weighing 250 to 300 g, were selected and randomly divided into 7 groups according to body weight by random number table. There were 10 guinea pigs in each group: levofloxacin 24, 48, 72 h groups, moxifloxacin 24, 48, 72 h groups (drug treatment was carried out after being infected with Yersinia pestis for 24, 48 and 72 h, respectively) and control group (without treatment). Experimentally infected plague model was established through guinea pigs subcutaneous injection of 141 strains of Yersinia pestis [1 × 10 7 colony forming unit (CFU)]; referring to the adult dose in the "National Pharmacopoeia of the People's Republic of China", the daily dose of guinea pigs was converted by Shi Xinyou's animal conversion coefficient method for treatment, the doses of levofloxacin and moxifloxacin in each guinea pig were 12.0 and 9.6 mg/d, respectively for 9 days. The guinea pigs were killed 9 days after drug withdrawal for bacteriological examination and pathological observation, and the cure rate was calculated. Results:The cure rates of levofloxacin 24, 48 and 72 h groups were 100.0% (10/10), 70.0% (7/10) and 6/6, respectively. The cure rates of moxifloxacin 24, 48 and 72 h groups were 100.0% (10/10), 100.0% (10/10) and 5/7, respectively, and the cure rate of animals in the control group was 0 (0/10). Compared with the control group, there were significant differences in the efficacy of moxifloxacin 24, 48 and 72 h groups and levofloxacin 24, 48 and 72 h groups ( P < 0.05). There was no significant difference between the two drugs at the same starting time ( P > 0.05). Conclusion:The effects of levofloxacin and moxifloxacin on animal plague infection are ideal and the two drugs can be used as a substitute for streptomycin in plague treatment under special circumstances.

BACKGROUND:The key to preventing the recurrence of intrauterine adhesions is to reconstruct the endometrium with normal function.The latest breakthrough in the treatment of recurrent intrauterine adhesions in and outside China is the use of degradable materials to prepare hydrogels to prevent the recurrence of adhesions. OBJECTIVE:To review the research advance in hydrogel-promoted endometrial repair in intrauterine adhesions. METHODS:PubMed,Web of Science,China National Knowledge Infrastructure(CNKI),and WanFang databases were searched systematically,with the keywords"intrauterine adhesions,endometrial injury,endometrium regeneration,hydrogel"in Chinese and English.Relevant articles published in each database from January 1990 to March 2023 were collected. RESULTS AND CONCLUSION:In recent years,research on hydrogel-promoted endometrial repair in uterine adhesions in and outside China has made some progress and plays an important role in the prevention and treatment of intrauterine adhesions and the promotion of endometrial repair:(1)As an important carrier in tissue engineering,hydrogel itself has excellent biocompatibility,biodegradability and three-dimensional network structure,which can be better applied in the treatment of intrauterine adhesions.(2)The hydrogel-based carrier system can promote the proliferation and differentiation of endometrial epithelial cells by transporting drugs/biologics/stem cells,and restore normal uterine morphology to prevent adhesion recurrence.(3)Hyaluronic acid hydrogels can not only meet good biocompatibility,but also promote the proliferation and differentiation of endometrial epithelial cells,and will be hydrolyzed by corresponding enzymes in utero,without affecting the normal metabolism of the body.They are currently commonly used uterine anti-adhesion agents in the clinic and are also the most commonly used hydrogel carriers in tissue engineering research.(4)Poloxamer hydrogel with excellent temperature-sensitive properties can rapidly gelate into the body,quickly form a physical barrier,and can play a slow-release effect on carrying substances and provide a platform for cell growth/adhesion.(5)There are broad prospects for the preparation of therapeutic hydrogels using materials with different characteristics,such as temperature-sensitive hydrogels,pH-responsive hydrogels and photosensitive hydrogels,but there are still many problems to be solved,such as the safety of the hydrogel system,whether the degradation products cause immune reactions,and whether they have an impact on the normal body's menstrual period.A large number of animal experiments and clinical trials are needed to verify its safety and efficacy,and continuously improve the treatment strategy.

Objective To analyze the biological characteristics of Yersinia pestis strains in Haixi Prefecture,Qinghai Province,in order to provide a scientific basis for plague prevention and control in future.Methods Totally 181 strains were separated from variety kinds of host in Haixi Prefecture,Qinghai Province from 1957 to 2011,and these strains were conducted biochemical test,virulence factor evaluation,plasmid analysis,different region (DFR) genotyping,drug and disinfectant resistant genes detection;79 of the 181 strains were examined by toxicity test and classified according to the criteria (minimum lethal dose:MLD≤ 10 000 was velogenic strain,10 000 ＜ MLD ＜ 100 000 was moderate virulence strain,MLD ≥ 100 000 was hypovirulent strain).Results According to six biochemical typing about gelatin candy,rhamnose,maltose,melibiose,glycerin and denitrification,the 181 strains of Yersinia pestis were antique biovar and Qing-Tibet Plateau ecotype.Aproportion of 81.22％ (147/181) of Yersiniapestis strains contained all the four virulence factors (F1,Pst Ⅰ,VW,Pgm).Totally 63.54％ (115/181) of the strains contained 3 kinds of plasmid-6 × 106,45 × 106,and 52 × 106;31.49％ (57/181) of the strains contained 3 kinds of plasmid-6 × 106,45 × 106,and 65 × 106.The strains had 8 genomovars,and were given priority to genomovar 8 (109 strains),secondly,genomovar 32 (33 strains),genomovar 5 (20 strains),genomovar 1b(i4 strains),genomovar 44 (2 strains),genomovar 7 (1 strain),genomovar 37 (1 strain),and genomovar 49 (1 strain).Among the 181 Yersinia pestis strains,strains with genes related to streptomycin resistance,sulfanilamide resistance,beta lactam resistance and disinfectant resistance were not found;and 75 of 79 strains were velogenic strains by toxicity test (MLD ≤ 10 000),accounted for 94.94％ (75/79).Conclusion The strains separated in Haixi Prefecture,Qinghai Province have the characteristics of Qinghai-Tibet Plateau plague's pathogen and have strong toxicity;all strains don't have the characteristics of drug and disinfectant resistance genes.

Objective In order to acquaint with the prevalence of Tibetan sheep plague in this area, we conducted a serum epidemiological investigation of Tibetan sheep plague in Qinghai Province. Methods Indirect hemagglutination assay (IHA) and colloidal gold immunochromatography (GICA) were applied to test serum samples of Tibetan sheep and whole blood samples from jugular vein of Tibetan sheep were collected in 8 Prefectures of Qinghai Province from 2013 to 2016. Results A total of 86 positive Tibetan sheep serum samples with plague F1 antibody were detected by both methods, and the positive rate was 0.68％ (86/12710), the samples collected in Xinghai County Hainan Prefecture had the highest positive rate, which was 5.20％ (27/519). The Haixi Prefecture and Yushu Prefecture were historical epidemic areas, the positive rates were 0.65％(15/2313) and 0.26％(6/2293), respectively. Hainan Prefecture, Guoluo Prefacture and Huangnan Prefecture were newly confirmed epidemic areas, the positive rates were 1.61％ (28/1741), 1.01％ (15/1481), and 1.44％(19/1316), respectively. The antibody titers were 1:20 to 1:5120, the samples collected in Maqin County Guoluo Prefecture had the highest titer, namely 1 :5120. Conclusions In Qinghai Province, Tibetan sheep plague is endemic, and there are outbreaks in some regions. So we have to enhance the Tibetan sheep plague monitoring especially in Marmot plague epidemic area.