AIM:To investigate the effect of hypoxia-preconditioned human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSC-Exos)on pulmonary vascular endothelial-mesenchymal transition(EndMT)in hypoxic pulmonary hypertension(HPH).METHODS:(1)Primary hUCMSCs were isolated and cultured by tissue adhesion method,and hUCMSC-Exos were extracted by ultrafiltration and identified.(2)Twenty-four SPF male SD rats were ran-domly divided into normoxia(N)group,hypoxia(H)group,hypoxia+normoxic hUCMSC-Exos group and hypoxia+hypoxia-preconditioned hUCMSC-Exos group,with 6 rats in each group.The rats in H group and intervention groups were placed in a cabin that simulated the hypoxic environment at an altitude of 5 000 m,and normoxic hUCMSC-Exos,hypoxia-precon-ditioned hUCMSC-Exos or equivalent volume of PBS were injected through the tail vein on the 3rd,5th,7th,10th and 14th days in hypoxia environment.After 21 d of modeling,the right ventricular systolic pressure(RVSP)and right ven-tricular hypertrophy index(RVHI)of the rats were detected,and the pathological changes of lung tissues were observed by HE staining.(3)After starvation for 12 h,human pulmonary arteriole endothelial cells(HPAECs)were randomly di-vided into normoxic control(N-Con)group,hypoxic model(H-Con)group,hypoxia+normoxic hUCMSC-Exos group and hypoxia+hypoxia-preconditioned hUCMSC-Exos group.The migration ability and tube formation ability of HPAECs were detected by Transwell assay and tube formation experiment.The expression of CD31 and α-smooth muscle actin(α-SMA)in HPAECs was detected by immunofluorescence double-staining.The protein levels of CD31,VE-cadherin,α-SMA and vimentin in pulmonary vessels and HPAECs were assessed by Western blot.RESULTS:(1)The HPH rat model was suc-cessfully established after 21 d of hypoxia,and EndMT occurred in pulmonary vessels.Compared with N group,the levels of RVSP,RVHI,percentage of vascular wall area(WA%)and percentage of vascular wall thickness(WT%)in H group were significantly increased(P＜0.01),pulmonary vascular wall thickening and the protein levels of CD31 and VE-cad-herin were significantly decreased(P＜0.01),while the protein levels of α-SMA and vimentin were significantly increased in pulmonary vessels(P＜0.05 or P＜0.01).Compared with H group,the RVSP,RVHI,WA%and WT%(P＜0.01)were significantly decreased(P＜0.05 or P＜0.01),and pulmonary vascular remodeling was attenuated after normoxic or hypoxia-preconditioned hUCMSC-Exos intervention.After hypoxia-preconditioned hUCMSC-Exos intervention,HPH pul-monary vascular remodeling and EndMT formation were significantly inhibited.(2)After 48 h of hypoxic treatment,the migration,tubule formation and EndMT of HPAECs were induced.Compared with H-Con group,cell migration and tube formation were significantly decreased after hypoxia-preconditioned hUCMSC-Exos intervention(P＜0.01).The protein levels of CD31 and VE-cadherin were increased,while the protein levels of α-SMA and vimentin were decreased(P＜0.05 or P＜0.01).CONCLUSION:Hypoxia-preconditioned hUCMSC-Exos attenuate the formation of HPH pulmonary vascu-lar remodeling by inhibiting pulmonary vascular EndMT.

Objective: To investigate the distribution characteristics and functional genes of cariogenic bacteria in oral microorganisms of patients with type 2 diabetes mellitus and to improve the understanding of the relationship between type 2 diabetes mellitus and dental caries. Methods: The experimental group included 10 patients with type 2 diabetes treated in the Department of Endocrinology, the First Affiliated Hospital of Air Force Medical University. The normal control group included healthy oral subjects without type 2 diabetes in the community population (10 cases). Samples of supragingival plaque from patients with type 2 diabetes mellitus and normal controls were collected and sequenced. Bioinformatics and statistical analysis of cariogenic bacteria such as Streptococcus mutans, Lactobacillus, Actinomyces viscosus and Candida albicans were carried out. Results: There were slightly fewer cariogenic bacteria such as Streptococcus mutans, Lactobacillus, Actinomyces viscosus and Candida albicans in supragingival plaque samples of type 2 diabetic patients than in normal controls, but the difference was not statistically significant (P>0.05). The results of KEGG pathway functional metabolic differences showed that the metabolic pathways of D-arginine and D-ornithine metabolism, biofilm formation-Escherichia coli, carolactam degradation and arginine biosynthesis were more abundant in the T2DM group than in the normal control group, while metabolic pathways such as tyrosine metabolism, selenocompound metabolism and pyruvate metabolism showed the opposite trend. Conclusion There was no significant difference in the content of cariogenic microorganisms between type 2 diabetic patients and normal control group. The differential metabolic pathways of the functional genes indicated that an increase in the arginine metabolic pathway was beneficial to the maintenance of acid-base balance in the oral microecological environment.

ObjectiveThis study aimed to understand the epidemiological characteristics of hand-foot-mouth disease （HFMD） in Minhang District， Shanghai from 2009 to 2020， and provide a scientific basis for the prevention and control of HFMD. MethodsThe case information of HFMD was collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. We used descriptive epidemiological methods to analyze the population characteristics， temporal and spatial distribution of HFMD， the pathogen composition of the case and its changing trend. ResultsFrom 2009 to 2020， a total of 66，198 cases of HFMD were reported in Minhang District， Shanghai， including 377 severe cases （severe case rate 0.57%） and 3 deaths （severs case fatality rate 0.80%）. There were more cases of HFMD in boys than in girls （1.5∶1）. HFMD patients aged under 5 years predominated， accounting for 88.91% of all cases. Majority of the cases （91.42%） were in scattered children （55.80%） and children in kindergartens （35.62%）. The incidence showed a cyclical trend， with low incidence years and high incidence years appearing alternately. The peak period was from April to July， and sometimes there were small peaks during October to December. A total of 12 years time-space scanning analysis revealed 3 clusters. The cluster centers were located in Wujing Town， Huacao Town and Xinzhuang Town， respectively. The proportion of EV71 in common cases was generally decreasing， and reduced to zero in 2019. The proportion of CoxA6 had increased year by year， and reached 75.00% in 2020. CoxA6 became the dominant pathogen in recent years. The number of severe cases had decreased year by year since 2010， and the dominant pathogen was EV71 （90.03% on average） in severe cases. ConclusionThe incidence of HFMD in Minhang District of Shanghai has a downward trend from 2014. The dominant pathogen changes from EV71 to CoxA6， and the dominant pathogen in severe cases is EV71. The discovered temporal and spatial clustering pattern is helpful for in-depth understanding of the distribution and epidemic trend of HFMD in Minhang District， and provides a scientific basis for epidemic prevention and control.

Objective: Metagenomic sequencing was used to explore the species composition and internal functional metabolic pathway of saliva and supragingival plaque microbial communities in healthy adults to provide a theoretical reference for the biological prevention and treatment of oral diseases. Methods: Saliva and supragingival plaque samples were collected from healthy adults, total DNA was extracted, and a metagenomic library was constructed. The qualified library was sequenced via metagenomics, and the sequencing data were analyzed using bioinformatics and statistics. Results : The main bacterial phyla in healthy oral samples were Proteobacteria (32.51%), Bacteroidetes (30.81%), and Actinobacteria (16.23%), and the main bacterial species were Corynebacterium matruchotii (3.84%), Haemophilus parainfluenzae (2.91%), and Prevotella melaninogenica (2.76%). The alpha diversity of the supragingival plaque group was higher than that of the saliva group, and there was a significant difference in the composition of the microbial community between the two groups (P<0.05). At the species level, Prevotella melaninogenica, Fusobacterium periodonticum, and Prevotella intermedia were more abundant in saliva samples than in supragingival plaque samples, while Corynebacterium matruchotii, Propionibacterium acidifaciens, and Rothia dentocariosa were more abundant in supragingival plaque samples than in saliva samples (P<0.05). High-quality gene sets of saliva and supragingival plaque in healthy adults were constructed based on metagenomic sequencing. The results of KEGG pathway functional metabolic differences showed that starch and sucrose metabolism, leucine and isoleucine degradation, and arginine biosynthesis in salivary microorganisms were more abundant than in supragingival plaque, while glycolysis/gluconeogenesis and carbon metabolism in supragingival plaque were more abundant than in saliva. Conclusion There are significant differences in the species composition and functional gene metabolic pathways of saliva and supragingival plaque microecology in healthy adults. The sensitivity of dominant species in different microecological regions to the identification of oral diseases may be different. In the microbiological study of oral diseases, appropriate samples should be selected according to different diseases.

Objective To evaluate effects of the daily average temperature on the daily number of outpatient visits for eczema in Lanzhou city.Methods Clinical data were obtained from outpatients with eczema in the Department of Dermatology of 2 third-grade class-A hospitals in Lanzhou city from January 1st 2007 to December 31st 2015,and meteorological data during this period were also collected.Controlling for confounding factors like long-term trends and day of the week,a distributed lag non-linear model (DLNM) fitted with quasi-Poisson link function was used to assess the effects of daily average temperature on the daily number of outpatient visits for eczema,and the analysis was stratified by season,age and gender.Results The exposure-response relationship between the daily average temperature and daily number of outpatient visits for eczema could be roughly described by a W-shaped curve.Stratification analysis showed that the effect of the daily average temperature on outpatient visits for eczema was strongest in autumn and winter,followed by summer,and weakest in spring.Low temperature may have lagged,cumulative and persistent effects on the daily number of outpatient visits for eczema,with the maximum relative risk (RR) value (1.12 [95％ CI:1.03-1.22]) observed at-9 ℃ on lag day 14.With a 1 ℃decrease in the temperature,16％ (RR =1.16,95％ CI:1.00-1.03),14％ (RR =1.14,95％ CI:1.02-1.26) and 13％ (RR =1.13,95％ CI:1.02-1.25) increases in the daily number of outpatient visits for eczema were observed in men,teenagers and middle-aged adults respectively (P ＜ 0.05).However,low temperature had no significant effects on outpatient visits for eczema among women or the elderly (P ＞0.05).The effect of high temperature usually occurred following exposure without lag periods,and was gradually weakened over lag time (P ＞ 0.05).Conclusions In Lanzhou,the effect of daily average temperature on outpatient visits for eczema was strongest in autumn and winter.Changes of the daily temperature may be one of risk factors for eczema.Low temperature had lagged effects on the daily number of outpatient visits for eczema,and the effects were strongest on lag day 14.

Objective: To analyze the processing situation of 124 batches of scorpions and optimize the salt-water processing.Methods: The character, extract, moisture, total ash, acid insoluble ash, amino acids content and heavy metals in the marketed scorpions were determined.Using extract and amino acids contents as the indices, the salt-water processing was optimized.Results: The results of the above determinations showed that the quality difference was very obvious for the marketed scorpion, and the extract and amino acids contents were the highest in scorpion boiled in 2% sodium chloride aqueous solution for 5 min.Conclusion: The item of extract test should be revised in the current standard, and the items such as moisture, total ash, acid insoluble ash, amino acids content and heavy metals should be taken into consideration in order to control the quality of scorpion more comprehensively.The best salt-water processing of scorpion is boiled in 2% sodium chloride aqueous solution for 5 min.

Objective To study the antipyretic,anti-inflammatory and analgesic effects of Chaigeshubiao granules. Methods Animals were randomly divided into 6 groups:blank control group,indomethacin group,Fengreganmao granules group and the high, the medium and the low dosage groups of Chaigeshubiao granules ( 26, 13, 6. 5 g . kg-1 ) . Each group was administered via intragastric administration once a day for 5 days.Rat model suffering from fever by dried yeast,relieving fever of Chaigeshubiao granules was investigated;Rats with toe swelling by 1% carrageenin and mice with ear swelling by dimethylbenzene were applied to observe anti-inflammatory effects of Chaigeshubiao granules were observed;The pain models induced by 0. 6%acetic acid and the hot-plate tests in mice were used to observe the analgesic effects of Chaigeshubiao granules. Results Compared with negative control group,Chaigeshubiao granules in high dosage could obviously decrease the temperature of rat with fever induced by dried yeast 0.5 h later,and the medium dosage group decreased 4-6 h later. Moreover,Chaigeshubiao granules in high dosage could inhibit inflammatory reaction of rat with toe swelling caused by albumen at 1 h,2 h,3 h,when the medium dosage group inhibited at 2 h,3 h,4 h. The inhibition ratio of the mice with ear swelling induced by dimethylbenzene was 58.2%, 52.0% and 53.9%,respectively at the high,medium and low dose groups. And the inhibition ratio of retortion of mice by 0.6%acetic acid was 50.5%,68.8%,58.1%,respectively, at the high,medium and low dose groups. In addition,the high,medium and low dose groups reduced the pain reaction latency of mice in the hot-plate tests. Conclusion Chaigeshubiao granules have antipyretic,anti-inflammatory and analgesic actions.

Objective To evaluate the effect of hypoxic-ischemic time on reduction of hypoxic-ischemic brain injury by sevoflurane postconditioning in neonatal rats.Methods Two hundred and ten 7-day-old Sprague-Dawley rats (105 male,105 female),weighing 13-17 g,were randomly divided into 7groups (n=30 each) using a random number table:sham operation group (group Sham),hypoxia-ischemia group (group HI),and sevoflurane postconditioning at different hypoxic-ischemic time point groups (P0,P3,P6,P 12 and P24 groups).Immediately after ligation of the left common carotid artery,and at 3,6,12 and 24 h after ligation,the rats inhaled the mixed gas containing 2％ sevoflurane for 30 min in P0,P3,P6,P13 and P24 groups,respectively.The fatality was recorded within 7 days after establishment of the model.At 7 days after establishment of the model,the rats were sacrificed,the brains were removed,and the right and left cerebral hemispheres were weighed separately,and the left/right cerebral hemisphere weight ratio was calculated.The hippocampal CA1 region and posterior cingulate gyrus were isolated,and the ratio of density of normal neurons in the left to the right was calculated.Results Compared with group Sham,the left cerebral hemisphere weight,left/right cerebral hemisphere weight ratio,and ratio of density of normal neurons were significantly decreased,and the fatality rate was increased in the other six groups (P＜0.05).Compared with group HI,the left cerebral hemisphere weight,left/right cerebral hemisphere weight ratio,and ratio of density of normal ncurons were significantly increased in P0,P3 and P6 groups (P＜0.05),and no significant change was found in the parameters mentioned above in P12 and P24 groups (P＞0.05).Compared with group P6,the left cerebral hemisphere weight,left/right cerebral hemisphere weight ratio,and ratio of density of normal neurons were significantly increased in P0 and P3 groups (P＜ 0.05).There was no significant difference in the parameters mentioned above between group P0 and group P3 (P＞0.05).Conclusion Sevoflurane postconditioning performed within 6 h of hypoxia-ischemia can reduce hypoxic-ischemic brain injury,and it provides no cerebral protection if exceeding 12 h.

Objective To evaluate effects of daily average temperature on the occurrence of urticaria in Lanzhou city,and to analyze differences in the effects between different populations.Methods Time-series data on daily outpatient visits for urticaria between January 1,2007 and December 31,2013 were collected from the First Hospital of Lanzhou University and Lanzhou University Second Hospital.Daily meteorological data during this peroid were obtained from the Gansu Meteorological Bureau.Distributed lag non-linear models were used to analyze the association between daily average temperature and occurrence of urticaria,and the analysis was stratified by age and gender.Results The association between daily average temperature and daily number of outpatient visits for urticaria was nonlinear.Low temperature had significant lag effects on the daily number of outpatient visits for urticaria,with the maximum relative risk (RR) value (1.014 [95％ CI 1.000-1.023]) observed at 6 ℃ on lag day 18.Stratification analysis demonstrated that the effects of high temperature on the number of outpatient visits for urticaria were apparent on the day of exposure in age groups of 0-18 and 19-64 years,but decreased on the day of exposure in the age group ≥ 65 years.The effects of low temperature,which showed similar trends along with the increment of lag days in all groups,were relatively delayed and occurred 2 to 4 days after exposure.Conclusions Air temperature affects the occurrence of urticaria in Lanzhou city.Low temperature has evident lag effects on the occurrence of urticaria,while high temperature does not have.

OBJECTIVE To evaluate the long-term toxicity of fully human anti-human tumor necrosis factor-α monoclonal antibody(anti-hTNF-α FHMA)for injection in cynomolgus monkeys. METHODS Forty cynomolgus monkeys were randomly divided into 5 groups (4 males and 4 females in each group):negative control group,adalimumab 10 mg·kg-1 group,anti-hTNF-αFHMA 2,10 and 50 mg·kg-1 groups. Cynomolgus monkeys in each group were injected sc once a week for 5 consecutive times, followed by 4 weeks of recovery. During the test,general clinical observation,body mass,body temperature,electrocardiogram(ECG),hematology,coagulation function,blood biochemistry,urine, ophthalmology,immune index,and pathological changes in organs and tissues were observed. At the same time,plasma drug concentrations were detected and the toxicokinetics parameters were analyzed. RESULTS No significant toxicological changes related to drugs were observed in general clinical observation,body mass,body temperature,ECG,ophthalmic examination,blood cell counts,coagu?lation function,blood biochemistry,urine analysis,lymphocyte subsets,cytokines,serum immuno?globulin,serum complement. Neutralizing anti-drug antibody(ADA)could be detected in adalimumab group and anti-hTNF-αFHMA groups. Anti-hTNF-αFHMA showed linear dynamic characteristics in cyno?molgus monkeys. At the same dose(10 mg·kg-1),anti-hTNF-αFHMA had similar immunogenicity and kinetics characteristics to adalimumab. CONCLUSION The level of anti-hTNF-α FHMA at which no adverse effect was observed was 50 mg · kg-1,which is equivalent to 75 times clinical dosage of quasi (0.67 mg·kg-1),which suggests that anti-hTNF-αFHMA be safe in clinical use.