OBJECTIVE:The rabbit model of steroid-induced osteonecrosis of femoral head is the most commonly used animal model of femoral head necrosis.The pathological changes of the femoral head are close to clinical practice,however,the conditions,methods and evaluation standards of animal models reported in and outside China are not uniform,which leads to the low scientific value of animal models and is difficult to popularize.This study aimed to clarify the influence of different mold-making conditions on the establishment of steroid-induced osteonecrosis of femoral head rabbit model and analyze the appropriate conditions for the successful model establishment. METHODS:We searched the CNKI,WanFang,VIP,CBM,WoS,PubMed and EMbsae databases for the literature on the modeling of steroid-induced osteonecrosis of femoral head rabbits up to April 1,2022,completed the screening of the literature according to the inclusion and exclusion criteria and literature quality evaluation,and extracted the outcome index data in the literature.RevMan Stata and ADDIS statistical software were used to conduct a meta-analysis of the included data. RESULTS:(1)A total of 82 articles with 1 366 rabbits were included in the study.The steroid-induced osteonecrosis of femoral head modeling methods were divided into three types:steroid-alone method,steroid combined lipopolysaccharide method and steroid combined serum method.Among these,33 articles used steroid-alone method;20 articles used steroid combined lipopolysaccharide method;29 articles used steroid combined serum method.(2)Meta-analysis results showed that the three modeling methods significantly increased the rate of empty bone lacunae in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001),and significantly decreased the ratio of the trabecular bone area in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001).The order of empty bone lacunae rate of each modeling method was:steroid combined with lipopolysaccharide method>steroid-alone method>steroid combined with serum method>normal group,and the order of trabecular bone area rate of each modeling method was:normal group>steroid combined with serum method>steroid-alone method>steroid combined with lipopolysaccharide method.(3)The results of subgroup analysis suggested that the rate of empty bone lacunae in the rabbit model induced by steroid alone might be related to the rabbit variety and the type of steroid used for modeling(difference between groups P<0.05),in which the combined effect amount of New Zealand white rabbits was higher than that of Chinese white rabbits(P<0.05)and Japanese white rabbits,and the combined effect amount of dexamethasone was higher than that of other steroids.The rate of empty bone lacunae induced by steroid combined with lipopolysaccharide was related to the administration mode of lipopolysaccharide and the type of steroid(P<0.05),among which the combined effect of methylprednisolone sodium succinate was significantly higher than that of other steroids(P<0.05),and the combined effect of prednisolone was significantly lower than that of other steroids(P<0.05).The combined effect of lipopolysaccharide 100 μg/kg×twice was significantly lower than 10 μg/kg×twice and 50 μg/kg×twice(P<0.05).The rate of empty bone lacunae in the model induced by steroid combined with serum was related to serum dose and steroid type(P<0.05),among which the combined effect amount of dexamethasone sodium phosphate was significantly higher than other steroid types(P<0.05),and the combined effect amount of dexamethasone was significantly lower than other steroid types(P<0.05);the combined effect amount of serum"10 mL/kg+6 mL/kg"combined dose was lower than other serum doses(P<0.05). CONCLUSION:(1)With the rate of empty bone lacunae and the ratio of trabecular bone area as the judgment standard for the successful establishment of the model,the three modeling methods can successfully construct the rabbit steroid-induced osteonecrosis of femoral head model,of which the steroid combined with lipopolysaccharide method is the best.(2)New Zealand white rabbits and dexamethasone are recommended when selecting the steroid-alone method.Methylprednisolone sodium succinate and low-dose lipopolysaccharide are recommended when selecting the steroid combined with lipopolysaccharide method.Dexamethasone sodium phosphate is recommended when selecting the steroid combined with serum modeling method.

Objective:To understand the impact of diet on glycemic control in community-managed patients with type 2 diabetes mellitus (T2DM) and provide evidence for implementing prevention strategies and measures for diabetes patients.Methods:Eight communities were randomly selected from Changshu and Wuhan in 2015, and T2DM patients managed in the community were selected to conduct questionnaire surveys, physical measurements, and blood glucose testing. Factor analysis was used to obtain dietary patterns. A binary logistic regression model was used to analyze the factors affecting glycemic control.Results:Finally, 1 818 T2DM patients were included, and the control rate of FPG was 57.59% (95% CI: 55.30%-59.86%), and the control rate of 2 h postprandial blood glucose (2 h PBG) was 24.90% (95% CI: 22.93%- 26.91%). Five dietary patterns were obtained by factor analysis: animal food pattern, fruit-aquatic products-potato patterns, vegetable-grain pattern, egg-milk-bean pattern, and oil-salt patterns. No-conditional multivariate logistic regression analysis showed that after adjusting for confounding factors, the reduced probability of FPG control was related to animal food pattern ( OR=0.71, 95% CI: 0.52-0.98) and fruit-aquatic products-potato patterns ( OR=0.71, 95% CI: 0.51-0.97). The decrease in the 2 h PBG control probability was related to fruit-aquatic products-potato patterns ( OR=0.60, 95% CI: 0.40-0.90). The increased probability of FPG and 2 h postprandial glucose control were both related to vegetable-grain pattern ( OR=1.41, 95% CI: 1.03-1.94; OR=1.68, 95% CI: 1.13-2.51) and egg-milk-bean pattern ( OR=1.75, 95% CI: 1.25-2.46; OR=1.56, 95% CI: 1.00-2.42). Compared with the Q4 group of egg-milk-bean pattern, the FPG control rate of the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q2 group), egg-milk-bean pattern ( Q3 group)" was higher ( OR=6.79, 95% CI: 1.15-40.23, P=0.035). Compared with the Q4 group of vegetable-grain pattern, the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q3 group), egg-milk-bean pattern ( Q2 group), oil-salt pattern ( Q2 group)" had higher control rate of 2 h PBG ( OR=12.78, 95% CI: 1.26-130.05, P=0.031). Conclusions:A proper combination of dietary patterns and dietary patterns are more conducive to the control of FPG and 2 h PBG in T2DM patients managed in the communities of Wuhan and Changshu. Patient nutrition education should be strengthened, and the food-matching ability of patients should be improved.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in patients with type 2 diabetic retinopathy(T2DR)and to explore the correlation of TCM syndromes with serum inflammatory factors and adiponectin(APN)levels,so as to provide evidence for TCM syndrome differentiation of T2DR.Methods A cross-sectional case-control study was conducted in 42 patients(involving 84 eyes)diagnosed as T2DR in the Department of Ophthalmology,Ganzhou People's Hospital from September 2022 to March 2023.The correlation between fundus fluorescein angiography(FFA)staging and TCM syndrome differentiation in patients with T2DR was explored.The relationship between TCM syndrome types and serum levels of inflammatory factors and APN,as well as the differences in serum inflammatory factors and APN levels of the patients with various FFA stages were analyzed.The correlation between each variable and TCM syndrome types in patients with T2DR was investigated.Results(1)Among the 42 patients with T2DR,27 cases were male and 15 cases were female,and their age averaged(54.0±12.0)years old.Among them,14 cases(33.3％)were differentiated as liver-kidney deficiency with malnutrition of eye collateral syndrome,15 cases(35.7％)were differentiated as yin-essence deficiency with internal dry-heat syndrome,9 cases(21.4％)were differentiated as qi-yin deficiency with collateral stasis and obstruction syndrome,4 cases(9.5％)were differentiated as yin-yang deficiency with blood stasis and phlegm coagulation syndrome,and none case(0.0％)was differentiated as spleen dysfunction and water-damp obstruction syndrome.(2)FFA staging showed that FFA staging ≥ 4[i.e.,having proliferative diabetic retinopathy(PDR)]was found in 78.6％(11/14)of the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome,73.3％(11/15)of the patients with yin-essence deficiency with internal dry-heat syndrome,100％(9/9)of the patients with qi-yin deficiency with collateral stasis and obstruction syndrome,and 100％(4/4)of the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome.But the intergroup comparison showed no significant differences among various syndrome types(P=0.272).(3)Among the 42 patients with T2DR,35 patients(83.3％)had higher level of tumor necrosis factor-α(TNF-α),28 patients(68.3％)had higher level of C-reactive protein(CRP)and 38 patients(90.5％)had higher level of glycosylated hemoglobin(HbA1c)than the normal.However,there was no significant difference in the levels of serum inflammatory factors of TNF-α,CRP,interleukin-6(IL-6)and vascular endothelial growth factor(VEGF),APN and HbA1c among the patients with different FFA stages(P＞0.05),neither did the difference in serum APN,TNF-α,CRP,IL-6 and VEGF levels among the patients with different TCM syndrome types(P＞0.05).(4)The correlation analysis showed that the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome had a shorter course of eye diseases than the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome(r=-0.467,P=0.051),had higher CRP level than the patients with yin-essence deficiency with internal dry-heat syndrome(r=0.592,P=0.010),and had higher CRP level(r=0.668,P=0.013)and a longer course of diabetes(r=0.629,P=0.021)than the patients with qi-yin deficiency with collateral stasis and obstruction syndrome.Conclusion Increased serum TNF-α and CRP expressions are presented in the patients with T2DR.Liver-kidney deficiency with malnutrition of eye collaterals syndrome and yin-essence deficiency with internal dry-heat syndrome are the common syndromes in T2DR.Yin-yang deficiency with blood stasis and phlegm coagulation syndrome is closely correlated with CRP level,and the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome have a longer course of diabetes.

Objective:To establish a new classification system for distal clavicle fracture and evaluate its clinical effectiveness.Methods:A retrospective case series study was conducted to analyze the clinical data of 101 patients with distal clavicle fracture admitted to First Affiliated Hospital of Nanjing Medical University from January 2015 to March 2022, including 57 males and 44 females, aged 19-86 years [(53.8±14.0)years]. Before treatment, patients were routinely subjected to bilateral anteroposterior radiography of the shoulder joints to measure the length of the fractured fragments, coracoclavicular distance, and acromioclavicular distance. According to the correlation between the location of the fracture line and the insertion of the coracoclavicular ligament, distal clavicle fracture was divided into three types: type I, with the fracture line lateral to the coracoclavicular ligament region; type II, with the fracture line in the coracoclavicular ligament region; type III, with the fracture line medial to the coracoclavicular ligament region. According to the injury severity of the coracoclavicular ligament and acromioclavicular ligament, type I was further subdivided into type IA, IB, IC and ID, and type II fracture was further subdivided into type IIA, IIB, IIC, IID and IIE. All the 101 patients were classified and randomly reclassified at an interval of 3 months by 10 senior and 10 junior shoulder surgeons according to the new classification method. Kappa coefficients were used to evaluate the inter- and intra-observer consistency of the new classification. Fifty-two patients with stable fracture (types IA, IB, IIC, and IID) were treated non-surgically, while 49 patients with unstable fracture (types IC, ID, IIA, IIB, IIE, and III) were treated surgically, including 26 patients with anatomic coracoclavicular ligament reconstruction, 9 with locking plate fixation, 8 with clavicle hook plate fixation, 4 with anatomic coracoclavicular ligament reconstruction combined with locking plate fixation, and 2 with anatomic coracoclavicular ligament reconstruction combined with tension screw fixation. The patients were assessed using the visual analogue scale (VAS) and Constant-Murley shoulder score before treatment and at 3, 6, 12, and 18 months after treatment. The coracoclavicular distance and acromioclavicular distance on the anteroposterior radiographs of the healthy and affected shoulder joints were measured at 3, 6, 12, and 18 months after treatment, and fracture healing time and complications were observed.Results:The length of the fractured fragments was 12.9 (9.7, 17.6)mm in patients with type I fracture, 24.7 (21.8, 27.8)mm in patients with type II fracture, and 43.6 (41.2, 46.9)mm in patients with type III fracture ( P<0.01). There were no significant differences in the coracoclavicular distance and acromioclavicular distance of the affected and healthy shoulders among the patients with types IA, IB, IIC, IID, and III fracture ( P>0.05); For the patients with types IC, IIA, IIB and IIE fracture, the coracoclavicular distance of the affected shoulder was significantly increased compared with that of the healthy shoulder ( P<0.01), while there was no significant difference in the acromioclavicular distance of the affected and healthy shoulders ( P>0.05). Both of the inter- and intra-observer consistency of the new classification was good. The inter- and intra-observer Kappa values were 0.69 and 0.71 respectively among the senior shoulder surgeons, and 0.61 and 0.64 respectively among the junior shoulder surgeons. All the patients were followed up for 18-104 months [28(23, 32)months]. At 3, 6, 12 and 18 months after treatment, the VAS scores of non-surgical patients were 3(2, 3)points, 2(1, 2)points, 1(0, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 6)points before treatment ( P<0.01); the VAS scores of surgical patients were 3(2, 3)points, 2(1, 2)points, 1(1, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 7)points before treatment ( P<0.01); the Constant-Murley shoulder scores of non-surgical patients were (76.6±5.3)points, (84.3±5.0)points, (88.4±4.0)points and (91.9±3.8)points respectively, significantly higher than (42.7±5.2)points before treatment ( P<0.01); the Constant-Murley shoulder scores of surgical patients were (77.4±4.6)points, (84.4±4.7)points, (87.6±3.7)points and (91.7±4.0)points respectively, significantly higher than (42.8±5.3)points before treatment ( P<0.01). At 3, 6, 12 and 18 months after treatment, the coracoclavicular distance of the affected shoulder in non-surgical patients was not significantly different from that before treatment ( P>0.05), while the acromioclavicular distance of the affected shoulder in surgical patients was significantly reduced compared with that before treatment ( P<0.01). There were no significant differences in the coracoclavicular distance of the healthy shoulder or bilateral acromioclavicular distance in non-surgical and surgical patients at 3, 6, 12, and 18 months after treatment compared with those before treatment ( P>0.05). Fractures were healed within 12 months after treatment in all the patients, without dislocation or subluxation of the acromioclavicular joint, internal fixation failure or internal fixator breakage. Eight patients treated with clavicular hook plate fixation had shoulder pain associated with limited mobility after operation, and all underwent a second operation to remove the clavicular hook plate at 12 months after operation. Conclusions:The new classification system for distal clavicle fracture is established, which comprehensively considers the position of the fracture line, injury of the coracoclavicular and acromioclavicular ligaments, and fracture stability. The new classification system exhibits good inter- and intra- observer consistency, and the effectiveness of its preliminary clinical application is satisfactory.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To explore the knowledge, attitude, and practice of insulin injection among nurses in Beijing and analyze its influencing factors.Methods:From July to August 2019, stratified-random-cluster multi-stage sampling was used to select 7 448 nurses from 30 hospitals of different levels in Beijing as the research subject. The survey was conducted using the General Information Questionnaire and the Insulin Injection Knowledge, Attitude, and Practice Questionnaire. Multiple linear regression was used to analyze the influencing factors of nurses' knowledge, attitude, and practice on insulin injection.Results:A total of 7 448 questionnaires were distributed and 7 448 valid questionnaires were collected, with an effective response rate of 100.00% (7 448/7 448). Among 7 448 nurses, 6 942 had no positions, and the scores of the belief dimension, behavior dimension, and the total score of questionnaire were calculated; the knowledge dimension score was calculated based on the overall sample. The total score of the Insulin Injection Knowledge, Attitude, and Practice Questionnaire was (115.22±10.75), and the scores for each dimension of the questionnaire were (14.14±2.97), (17.29±2.73), and (83.82±7.72), respectively. The proportion of nurses who scored well in all questionnaire dimensions was 19.01% (1 320/6 942). The excellent score rates of each dimension in the questionnaire, from high to low, were the practice dimension [92.71% (6 436/6 942) ], attitude dimension [76.40% (5 304/6 942) ], and knowledge dimension [22.35% (1 665/7 448) ]. Multiple linear regression analysis showed that the influencing factors of insulin injection knowledge, attitude, and practice among nurses were gender, age, professional title and department ( P<0.05). The influencing factors of knowledge were gender, age, years of work, education level, professional title, and department ( P<0.05). The influencing factors of attitude were gender, professional title, and department ( P<0.05). The influencing factors of practice were gender and age ( P<0.05). The above differences were statistically significant. Conclusions:Nurses at all levels of hospitals in Beijing have great beliefs and behaviors in insulin injection but lack knowledge. The knowledge of insulin injection among clinical nurses can be enhanced by improving the training and education standards on insulin injection, regularly providing insulin injection knowledge training and skill assessment to clinical nurses and other methods.

MethodIn the experiment， 46% vol Red Star Erguotou （10 mL·kg·d^-1） was used to establish the AONFH rat model， and the intervention effect of JPHGP at different doses （2.5， 5.0， 10.0 g·kg^-1） was observed. Jiangusheng pill （JGS， 1.53 g·kg^-1） was selected as the positive control. After 8 weeks of administration， the bone histomorphometry of the femoral head was analyzed by Micro-CT imaging， and the area of medullary microvessels in the femoral head was detected by ink perfusion. The pathological change was observed by hematoxylin and eosin （HE） staining. The protein expressions of Platelet endothelial cell adhesion molecule-1 （CD31）， VEGF， VEGFR2， PI3K， phosphor-Akt （p-Akt） and phosphatase and Tensin homologue deleted on chromosome 10 （PTEN） in the femoral head were determined by immunohistochemistry and Western blot. ResultCompared with normal group， the model group presented the fracture and thinning of trabeculae in the femoral head， increased empty bone lacunae， and elevated number and diameter of adipocytes （P<0.01）. Micro-CT imaging revealed a decrease in bone mineral density （BMD）， bone volume fraction （BV/TV）， trabecular thickness （Tb.Th） and trabecular number （Tb.N） （P<0.05， P<0.01） while an increase in bone surface-to-volume ratio （BS/BV） and trabecular separation （Tb.Sp） （P<0.01）. The results of ink perfusion showed that the area of medullary microvessels in the femoral head was reduced （P<0.01）. Compared with model group， JPHGP lowered the empty bone lacunae rate as well as the number and diameter of adipocytes in the femoral head of AONFH rats. Micro-CT imaging indicated that JPHGP low-dose group had elevated BV/TV， Tb.Th and Tb.N （P<0.05， P<0.01） while decreased BS/BV （P<0.01）， and there was an upward trend in BMD while a downward trend in Tb.Sp， but without statistical difference. In addition， JPHGP medium- and high-dose groups had a rise in BMD， BV/TV， Tb.Th and Tb.N （P<0.05， P<0.01）， a decrease in BS/BV and Tb.Sp （P<0.05， P<0.01） and enlarged area of medullary microvessels in the femoral head （P<0.05， P<0.01）. The expressions of CD31， VEGF， VEGFR2， PI3K， p-Akt in the model group were lower than those in the normal group （P<0.01）， and after medium and high doses of JPHGP treatment， the expressions of CD31， PI3K and p-Akt in the femoral head of rats were up-regulated （P<0.01） while the protein expression of PTEN was down-regulated （P<0.01）. Moreover， JPHGP up-regulated the expressions of VEGF and VEGFR2 （P<0.05， P<0.01）. ConclusionJPHGP can repair the vascular injury in AONFH， and its mechanism may be related to the activation of VEGF/VEGFR2/PI3K/Akt signaling pathway. This study provides certain scientific basis and reference for the clinical application of JPHGP. ObjecctiveTo observe the repair effect of Jianpi Huogu prescription （JPHGP） on vascular injury in experimental alcohol-induced osteonecrosis of femoral head （AONFH）， and to explore its mechanism based on vascular endothelial growth factor （VEGF）/VEGFR2/phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway.

OBJECTIVE To understand the safety of Ilaprazole sodium for injection in clinical practice. METHODS From Jan. 1st 2019 to Feb. 29th 2020， the data of 3 926 valid hospitalized patients receiving Ilaprazole sodium for injection were collected prospectively from 5 third-level hospitals through CHPS， and the post-marketing safety analysis was performed by using retrospective multicenter single cohort study. At the same time， a nested case-control study （the ratio of trial group and control group was 1∶4） was used to confirm the baseline stability of this study cohort and the correlation between adverse reactions and Ilaprazole sodium for injection. RESULTS Among 3 926 patients， 3 patients experienced 5 adverse drug events after using Ilaprazole sodium for injection， with the incidence of 0.076%. There was no serious adverse event， and the occurrence time was 2 days after medication； adverse drug events mainly include elevated liver function indicators （alanine transaminase， aspartate transaminase， total bilirubin）， which were mild and untreated， and all adverse drug events were improved. The results of the nested case-control study showed that the trial group and the control group belonged to the same background baseline， and the occurrence of adverse drug events was more closely related to Ilaprazole sodium for injection. CONCLUSIONS The overall safety of Ilaprazole sodium for injection is relatively high， and the occurrence of adverse events is more related to it.

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

ObjectiveTo investigate the protective effect of Jianpi Huogu prescription （JPHGP） on the functional injury of vascular endothelial cells caused by alcohol and explore its mechanism based on protein kinase B/c-Jun amino-terminal kinase/p38 MAPK （Akt/JNK/p38 MAPK） signaling pathway. MethodThrough chick embryo allantoic membrane， thoracic aortic ring， and migration， invasion， adhesion， and lumen formation of human umbilical vein endothelial cells （HUVEC）， the effect of JPHGP with different concentrations （8， 16 and 32 μg·L^-1） on angiogenesis was observed in the presence or absence of alcohol. The expression levels of phosphorylation of Akt， JNK， and p38 MAPK were determined by Western blot. ResultAs compared with the normal group， the number and length of capillaries around the arterial ring in the model group were decreased， and the migration， invasion， and lumen formation capacity of HUVEC were decreased （P<0.05， P<0.01）. After treatment with 16 and 32 μg·L^-1 JPHGP， the length of neovascularization in chick embryo allantoic membrane was significantly increased （P<0.05， P<0.01）. Compared with the model group， the 8， 16， and 32 μg·L^-1 JPHGP groups increased the number of capillaries around the thoracic aortic ring in a concentration-dependent manner （P<0.05， P<0.01）， and the 32 μg·L^-1 JPHGP group increased the length of capillaries around the thoracic aortic ring （P<0.05）. The 16 and 32 μg·L^-1 JPHGP groups enhanced the migration， invasion， and lumen formation capacity of HUVEC. The results of Western blot showed that， as compared with the normal group， the protein expression levels of p-JNK/JNK， p-p38 MAPK/p38 MAPK， and p-Akt/Akt were significantly decreased in the model group （P<0.01）， and as compared with the model group， the protein expression levels of p-p38 MAPK/p38 MAPK and p-Akt/Akt were significantly increased in the 8， 16， and 32 μg·L^-1 JPHGP groups （P<0.01） and the protein expression level of p-JNK/JNK was increased significantly in the 16 and 32 μg·L^-1 JPHGP groups （P<0.01）. ConclusionJPHGP has a protective effect on the functional injury of vascular endothelial cells caused by alcohol， and its mechanism may be related to the activation of Akt/JNK/p38 MAPK signaling pathway. Relevant research results will provide certain scientific basis for clarifying the effect of JPHGP on 'invigorating spleen and promoting blood circulation'.