Objective: To investigate the changes of microorganisms and metabolites in joint effusion of patients with Rheumatoid arthritis(RA), Osteoarthritis(OA) and Urarthritis(UA). To provide new ideas for the study of the effect of microbiota on the pathogenesis of arthritis. Methods: Joint effusion samples were collected from 20 patients with RA, 20 patients with OA, and 20 patients with UA. 16S rRNA gene sequencing and untargeted ultra-high performance Liquid chromatography-mass spectrometry(LC-MS) were used to explore the differences in microorganisms and metabolites among the three groups. Pearson correlation analysis was used to detect the correlation between effusion microbiota and metabolites. Results: There were differences in microbial diversity and microbiota composition among the three groups. Combined with VIP>1 from OPLS-DA andP<0.05 from two-tailed Students t-test, 45 differential metabolites(Between RA and OA groups), 38 differential metabolites(Between UA and OA groups) and 16 differential metabolites(Between RA and UA groups), were identified. GO analysis and KEGG pathway analysis showed that the differential metabolic pathways among the three groups were mainly concentrated in citric acid cycle(TCA cycle), nucleotide metabolism, amino acid metabolism and glycolysis pathway. Correlation analysis of joint effusion microbiota and metabolites suggested that bacteria enriched in the three groups of joint effusion, such asPrevotella,Clostridium ruminosus,Prevotellaceae＿UCG-001, were related to many key metabolites such as lysozyme, uric acid, glucose, and L-glutamine. Conclusion This study shows that there are a variety of bacterial flora in joint cavity effusion of RA, OA, and UA patients, and the differential metabolites produced by them are involved in the pathogenesis of the three types of arthritis by affecting a variety of metabolic pathways.

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

Dalian Medical University, aiming at cultivating innovative talents, has formulated and implemented a "5+3" innovative talents training reform plan. In the whole process of medical undergraduate education, tutorial system is used as the carrier to develop a phased innovative ability training system, which covers basic scientific research ability training such as courses, lectures, experimental design, papers and so on, and strengthens the cultivation of undergraduate scientific research ability. Through statistical analysis of the results of the first "5+3" students' periodic training, it is found that the proportion of "5+3" students publishing Chinese periodicals and SCI, and hosting national innovation projects and provincial innovation projects is significantly higher than that of ordinary 5-year students ( P<0.05). Although there are some problems and deficiencies in the implementation process, the basic scientific research training with tutorial system as the core has a significant effect on improving students' scientific research thinking and innovation ability, and is feasible for training medical innovative talents.

Objective Most common infected bacteria were found to analyze their effects on clinical characteristics and 3-year outcome of patients with diabetic foot ulcer ( DFU ) . Methods Materials of cases with positive bacterial culture were selected from DFU patients. 203 cases were infected with the most common 6 strains of mono-bacteria, and 62 cases were infected with multi-bacteria. Data were grouped according to the most common 6 infected bacteria. The outcomes of healing, recurrence, amputation, cardiac events, cerebrovascular events and death were calculated of 3 years after hospitalization. Clinical characteristics of mono-and multi-infected groups and these 6 mono-bacterial infection groups, and risk factors to outcome were analyzed. Results No significant difference was found in baseline clinical characteristics, cardiac and cerebrovascular events, and death during follow-up between mono-and multi-infected groups. The most common 6 infected bacteria were staphylococcus aureus, pseudomonas aeruginosa, proteus, enterococcus faecalis, escherichia coli and klebsiella pneumoniae. Among these groups, there were no significant differences of baseline clinical characteristics and recurrence, cardiac and cerebrovascular events, and death except for the foot ulcer and foot ulcer related prognosis. In staphylococcus aureus infected group, severe lower extremity arterial disease (8.5％), Wagner grade 3-5 (48.9％), moderate and severe infection rate (34.0％) were significantly lower than other groups, and the healing rate ( 93. 6％) was higher than other groups ( all P<0.05). Severe lower extremity arterial disease, cardiac function grading over 3(NYHA), eGFR<60 ml·min-1· (1.73 m2)-1, duration of DFU over 30 days were the main risk factors for ulcers′healing. Wagner grade over 3 was main risk factor for minor amputation. Severe lower extremity arterial disease, Hb<90g/L were the main risk factors for major amputation. Cardiac function grading over 3 ( NYHA ) was main risk factor for cardiac events, and also for death. ALB<30 g/L was main risk factor for death (all P<0.05). Conclusion DFU patients infected with different strains of bacteria were significantly different in foot ulcer and healing rate, while not in cardiac and cerebrovascular events and death.

OBJECTIVE:To prepare Carbinoxamine maleate sustained-release suspension,and evaluate its quality. METH-ODS:Using carbinoxamine maleate as raw material,drug-loaded resin was prepared by cation exchange resin;surface coating method was used to finally prepare sustained-release suspension,using Eudragit RS100 as sustained-release coating material to pre-pare sustained-release microparticles. HPLC was conducted to determine the content of carbinoxamine maleate,release degree of original preparations and self-made suspensions was compared,drug-loading capacity was calculated. RESULTS:The drug amount in preparing drug-loaded resin was 2%,reaction temperature was 25 ℃,and reaction time was 4 h;the drug-loading capacity in surface coating was 35%,amount of coating material was 10%,and reaction temperature was 40 ℃. The drug-loading capacities of sustained particles before and after coating were 35.23%,32.72%,respectively;the yield was 96.82%. The carbinoxamine ma-leate in prepared sustained-release suspension accounted for 98.76% of the labeled amount;release degree in 10 h reached about 80%,f2 was 65.73. CONCLUSIONS:Carbinoxamine maleate sustained-release suspension is prepared successfully,and its release is similar to the original preparation.

Objective To investigate the association of serum C peptide concentration with the severity and the outcome of diabetic foot ulcer (DFU). Methods The clinical data of 257 inpatients with DFU were collected, including fasting and postprandial 2h C peptide levels and C peptide area under curve (AUCCP ). The patients were followed up on the outcomes of ulcers and death. The associations of serum C peptide concentration with the Wagner degree, infection severity, and healing rate were analyzed. Results The medians of fasting and 2h postprandial serum C peptide as well as AUCCP were 1. 37(0. 02 ~ 9. 00) nmol/ L, 3. 22(0. 02 ~ 29. 61) nmol/ L, and 511. 65 (3. 60 ~ 2 691. 30)nmol·min-1 ·L-1 respectively, which were lower than general levels. The time of follow-up in our study was 2. 8 (1. 0 ~ 5. 1) years. By the end of study, the wound of 75. 88% patients was healed, 3. 5%undergone major amputation, and 23. 74% died. After adjusting for relative factors, there were no significant associations of serum fasting and postprandial C peptide levels and AUCCP with Wagner degree and infection severity (P>0. 05). Cox regression analysis showed that the fasting plasma C peptide and hemoglobin were the independent protective factors for the healing of ulcers; old age, male, higher infection degree, and diabetes family history were their independent risk factors ( all P < 0. 05). Conclusions The lower plasma fasting C peptide concentration in patients with DFU is not correlated with Wagner degree and infection severity, but closely related with healing rate.

Under the guidance of strengthening medical undergraduates' practical ability and their competence in future jobs, Dalian Medical University has established a clinical medical talents practical ability training mode. This model has implementedThree Turnsclinical skills training pattern to strengthen the three stage (before, during and after practice) clinical skills training and concentrated on humanistic quality education through overall evaluations and set up clinical skill examination system to evaluate teach-ing effectiveness comprehensively and truly , which has effectively improved the quality of education by perfecting safeguard mechanisms and guaranteeing teaching quality.

Objective To investigate the clinical characteristics and risk factors for healthcare-associated infection (HAI)in patients with severe chronic hepatitis B (CHB),and provide theoretical basis for preventing and controlling HAI.Methods Retrospective survey was used to investigate the occurrence of HAI in hospitalized patients with severe CHB in a hospital between January 2012 and January 2015,risk factors for HAI were analyzed. Results A total of 126 patients with severe CHB were investigated,49 patients developed 106 times of HAI, incidence of HAI was 38.89%.The main HAI site was respiratory tract (n=47,44.34%),the next was abdominal cavity (n=34,32.08%).A total of 76 isolates of pathogens were detected,gram-negative bacteria,gram-positive bacteria,and fungi accounted for 53.95%(n =41 ),43.42%(n =33),and 2.63%(n =2)respectively.Risk factors for HAI in patients with severe CHB were patients ’ age ≥ 60 years, length of hospital stay ≥ 30 days, complications,invasive operation,serum albumin < 35 g/L,and white blood cell count (WBC)< 4 × 109/L. Conclusion Incidence of HAI in patients with severe CHB is high,the majority are respiratory tract and abdominal cavity infection,risk factors are old age,long length of hospital stay,invasive operation,hypoalbuminemia,and low WBC count.

Objective To explore the distribution of pathogenic micro-organisms in the diabetic patients with foot infection,and to investigate the characteristics of the pathogen distribution and its relationship with the severity of diabetic foot ulcer( DFU ).Methods Ninety diabetic foot patients with positive culture of micro-organisms were classified into Wagner 1-5 grades according to the severity of DFU,which was ranked as mild,moderate,and severe infection based on the gradient of infection.The family,genus,and strain of micro-organisms were analyzed,and associated factors were discussed in regard to the kinds and severity of DFU and infection.Results With rising Wagner's grades and aggravating infection,the bacterial floras were transformed from gram-positive cocci( 61.1％ in Wagner 1 ) to gram-negative rods( 80.0％ in Wagner 5),at the same time,composite( 10.0％ to 28.6％ ) and opportunist ( 83.3％ to 100％ ) infections were increased.Wagner's grade,severity of infection,previous treatment,patients' age,control of blood glucose,course of DFU,etc,were all related to types of infection and opportunist infection ( P＜0.05 ).Conclusions Proportion of gram-negative bacilli with opportunist composite infection seems to increase in patients with severe DFU and severe infection requiring appropriate application of antibiotics.

Objective To estimate heart function among patients with diabetic foot ulcer,and to investigate the characteristics of heart failure(HF) before and after treatment of ulcer. Methods Items associated with diabetes and some physiological and biochemical indicators were observed in patients with diabetic foot ulcer(162 cases) and with high risk factors of ulcer(75 cases). Heart function was evaluated at patients′ admission, during ulcer related treatment, and prior to discharge. Left ventricular ejection fraction and other cardiac assessment were measured with ultrasonic scan.Results During hospitalization, 23.6%(56/237) patients underwent HF with normal left ventricular ejection fraction, and it was 27.2%(44/162) in patients with foot ulcers. The prevalence of HF was 8.9%(21/237) in all patients studied on admission, and that was 10.5%(17/162) in patients with foot ulcer, more than that without foot ulcer(P＜0.01). More patients with HF were found, being 14.8%(35/237) during 2-7 days after ulcer related treatment initiated, and peak was on the 4th day. There was statistical difference among different Wagner grades(P＜0.05) about the morbidity rate of HF. All patients with HF were improved and tolerant to ulcer related treatment. Conclusion The prevalence of HF with normal left ventricular ejection fraction was relatively high in patients with diabetic foot ulcer, especially after ulcer treatment.