Objective To explore the inhibition of different immunosuppressive drugs or immunosuppressive combination regiments on the development of de novo donor specific antibodies (dnDSA).Methods We used BABL/c mice and C57BL/6 mice alloimmunized using donor splenocytes for establishing model of producing dnDSA.After that,mice were divided into 10 groups,and were administrated with mycophenolate mofetil (MMF,300 mg· kg-1 · d-1);sirolimus (0.3 mg·kg-1 ·d-1);tacrolimus(0.9 mg· kg-1 · d-1);cyclosporine A (45 mg· kg-1 · d-1);MMF (150 mg· kg-1· d-1) + tacrolimus(0.45 mg · kg-1 · d-1);MMF (150 mg · kg-1 · d-1) + cyclosporine A (22.5 mg·kg-1 ·d-1);MMF (150 mg·kg-1 ·d-1) + sirolimus (0.15 mg·kg-1 ·d-1);sirolimus (0.15 mg· kg-1 · d-1) + tacrolimus (0.45 mg· kg-1 · d-1);sirolimus (0.15 mg· kg-1 · d-1) + cyclosporine A (22.5 mg· kg-1 · d-1);and placebo;respectively.Anti-serum was harvested and tested using flow cytometry.Results (1) Four weeks after sensitization,the dnDSA level in BALB/c and C57BL/6 group was 88.86％ and 25.58％.Comparing with control group(25.33％),there was a significant increase in BALB/c group(89.23％ versus 25.33％;P＜0.001),whereas no change was found in C57BL/6 group (25.58％ versus 25.33％;P =0.259),that we chose BABL/c mice as the model for sensitization.(2)After 4 weeks of sensitization and immunosupression,dnDSA level was 29.31％,46.33％,57.10％ and 66.35％ in MMF,sirolimus,cyclosporine A and tacrolimus monotherapy group respectively.In comparison to sensitization group,dnDSA level in all monotherapy arm reduced significantly.Intra-group analysis found MMF monotherapy had the most effective inhibition of dnDSA production,sirolimus came the second,and tacrolimus and cyelosporine A had equivalent effectiveness.dnDSA level was 31.00％,33.12％,45.18％,44.62％ and 61.60％ in MMF+ sirolimus,MMF+ tacrolimus,MMF+ cyclosporine A,sirolimus + cyclosporine A and sirolimus + tacrolimus combination treatment arm,respectively,which was much lower than that of sensitization group (P＜0.001,P＜0.001,P＜0.001,P＜0.001,P =0.015).MMF + tacrolimus and MMF+ sirolimus combination treatment had comparable effectiveness in dnDSA inhibition,which is greater than that of the rest of three combination.Conclusion Our data show that the effects of single immunosuppressive drugs on the level of dnDSA is MMF＞sirolimus＞cyclosporine A =tacrolimus,and that in combination regimens is MMF + tacrolimus =MMF + sirolimus＞MMF + cyclosporine A =sirolimus + cyclosporine A =sirolimus + tacrolimus.In conclusion,this study demonstrates that MMF+ tacrolimus combination treatment arm can minimize the development of dnDSA.But,this conclusion remains to be confirmed by future clinical studies.

Objective This study aimed to establish the leukemia mouse model by using EL4/DsRed cell line expressing red fluorescent protein (DsRed) and to evaluate the model. Methods After total body irradiation with X-ray of 7.0 Gy, C57BL/6 mice were inoculated 5×106 bone marrow cells mixed different numbers of EL4/DsRed cells via tail vein. The model was evaluated by flow cytometry (FCM), reverse transcriptase-polymerase chain reaction (RT-PCR), and histopathology. Results The incidence of leukemia was 100 %. The presence of EL4/DsRed cells was found in liver, spleen, bone marrow and peripheral blood of recipients by FCM two weeks after transplantation. Pathological section revealed that all recipients had several organs infiltration apparently. With the increase in the number of inoculated tumor cells, the survival time of recipients was reduced and the infiltration of leukemia cells in organs was more serious. Conclusion Mouse leukemia model was successfully established when C57BL/6 mouse was intravenously transplanted with ≥5×102 EL4/DsRed cells. The model could be employed usefully in the future research such as the pathogenesis of leukemia and minimal residual disease (MRD).

Objective To investigate the effect of birth order on outcomes of renal transplantation from siblings.Method We conducted a retrospective study to examine the immune effect exerted by birth order in kidney transplantation between siblings.227 kidney transplants were included and we stratified the cohort by birth order,old to young parings (group A,104 pairs) and young to old pairings (group B,123 pairs),using old to young parings as reference group.Result During the follow-up period,4 recipients suffered graft failure and 2 died.The survival rate of recipients and grafts was 98％ and 95％,respectively.After adjusting the effect of confounding factors in demography,young to old pairings were found at a higher risk of developing death uncensored graft failure (Hazards ratio,HR =2.77,95％ CI..0.23,33.00),which was not significantly different from group A (P =0.42).And group B had a higher risk of developing death censored graft failure (HR =10.79,95％ CI:0.30-389.43),with no statistically significant difference (P＞0.05).Most rejections occurred in two months after transplantation,and the rejection-free rate in 3 years post-transplantation was 86％.Similarly,no significant difference was detected between the two groups in terms of death censored graft failure,and no benefit of birth order was found in rejection protection (HR =1.266,95％ CI:0.391,4.103,P =0.694).Conclusion Birth order may not be taken into consideration in kidney transplantation between siblings.

Objective To formulate an evidence-based nursing scheme of a pin site nursing method to reduce the incidence of pin site infection among patients with bone pin surgery. Methods Under the principle of PICO, the issue was put forward aiming directly at patient′s clinical manifestations. By some database retrieval and evaluate the retrieval of literature evidence, the optimal evidence will be applied to the patients and the curative effect were observed. Results A total of 1 systematic review, 1 cohort study and 9 randomized controlled trials (RCTs) were included. According to the available evidence mentioned herein and patient′s conditions, they developed a new pin site nursing method and applied to patients. Seven days later, the two pin sites with infection symptoms obviously improved, with decreasing secretion, without skin redness and pain, and the temperature of skin was normal. The other six pin sites without infection did not occur infection. Conclusions The patients with pin sites using based iodine disinfection and sterile gauze strip winding better than the conventional alcohol drop pin site in reducing infection.

OBJECTIVETo study the expression of fascin-1 protein in breast cancer and to evaluate its correlation with clinicopathologic features of the tumor.

METHODSImmunohistochemical EnVision method was performed to evaluate the expression of fascin-1 in 23 cases of normal breast tissues, 69 cases of benign breast lesions, 58 cases of usual ductal hyperplasia (UDH), 61 cases of ductal carcinoma in situ (DCIS) and 221 cases of breast cancer from March 2007 to December 2011.

RESULTSFascin-1 protein expression rates in normal breast tissues, benign breast lesions, UDH, DCIS and breast cancer were 100.0% (23/23), 89.9% (62/69), 13.8% (8/58), 19.7% (12/61), and 42.1% (93/221), respectively. Fascin-1 expression in normal breast tissues and benign breast lesions was significantly higher than those in UDH, DCIS and breast cancer (P < 0.01); Fascin-1 expression in breast cancer was significantly higher than those in UDH and DCIS (P < 0.01). There was a tendency of increased fascin-1 expression in DCIS compared to UDH, but the difference was not statistically significant (P > 0.05). Fascin-1 positive rates in patients with DCIS grade III (26.8%, 11/41) was significantly higher than that in patients with DCIS grade I-II (1/20, P < 0.05). Fascin-1 protein expression in breast cancer increased with increasing histologic grade and clinical stage (P < 0.01). Fascin-1 protein expression was also significantly higher in tumors with negative estrogen receptor (ER) and progestone receptor (PR) status and > 3 axillary lymph node metastases compared to tumors that were ER and PR positive and ≤ 3 axillary lymph node metastases (P < 0.01 and P < 0.05, respectively). Logistic regression analysis showed that fascin-1 expression correlated positively with high clinical stage (OR = 1.568, 95% CI = 1.029-2.387, P < 0.05) , but negatively with ER expression (OR = 0.149, 95% CI = 0.079-0.281, P < 0.01) .

CONCLUSIONSFascin-1 is highly expressed in normal breast tissues and benign breast lesions, suggesting that it may be a biological marker of mature mammary ductal epithelium. Fascin-1 protein expression shows a significantly increasing trend from UDH, DCIS to invasive breast cancer, suggesting that fascin-1 plays an important role in breast carcinogenesis and may be a potential target for therapy.

Axilla ; Breast ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carrier Proteins ; metabolism ; Estrogen Receptor alpha ; metabolism ; Female ; Humans ; Hyperplasia ; metabolism ; Lymph Nodes ; metabolism ; Lymphatic Metastasis ; Microfilament Proteins ; metabolism ; Receptors, Estrogen ; metabolism

Objective To understand adolescent with type 1 diabetes on disease knowledge and experience and provide a scientific reference for the design and implement effective interventions. Methods Phenomenological research design and semi-structural interviews were conducted to 9 adolescent with type 1 diabetes, and used the method of phenomenological analysis for data. Results The adolescent patients were unsure about the causes and treatments of type 1 diabetes,and the cognition of the importance and necessity were vague to treatment compliance. The own experience of disease compose of negative physical and mental experience significantly, living a normal life,a desire to cure, seeking social and professional support demand strongly. Conclusions adolescent with type 1 diabetes and their family or the hospital are under inadequate treatment and disease management.It is suggested to pay attention to patients′ motivation and psychological,individual needs and effective medical communication in delivering intervention programs for adolescent with type 1 diabetes so that individualized treatment and management are performed.

Objective:To investigate the surgical method and clinical effect in the repair of thumb tip defect with radial thenar fasciocutaneous flap.Methods:From March, 2016 to January, 2019, 15 patients with thumb tip defect were treated by radial thenar fasciocutaneous flap. There were 6 defects in left thumb and 9 in right thumb. All the thumbtip defects had the exposure of digital bone, and some had defects of digital bone itself. The size of defects ranged from 1.0 cm×2.0 cm to 1.5 cm×3.0 cm, and the size of the flaps ranged from 1.2 cm×2.5 cm to 1.8 cm×4.0 cm. All of the donor sites were directly closed. The patients entered follow-up by outpatient visit, telephone calls or WeChat reviews to evaluate the quality of the flaps and the clinical effects of the surgery.Results:All flaps survived with good quality. All the donor sites achieved primary healing. The follow-ups lasted for 6 to 18 months with an average of 10.5 months. At the final follow-up review, the appearance of flaps was satisfactory in natural colour, flexible and wear-resistant. There were various degrees of sensation recovery of the flaps, with TPD from 6 mm to 12 mm. The sensation around the donor site was close to normal. Function of the thumbs was evaluated according to the total active movement (TAM) evaluation system. Twelve thumbs were graded excellent and 3 in good.Conclusion:The radial thenar fasciocutaneous flap achieved satisfactory clinical effect in the repair of thumb tip defect. The texture of the flaps is close to the recipient site and the damage to the donor site is minimal.

Objective: To screen for hotspot gene mutations associated with genetic deafness in Chinese pregnant women, and to perform risk assessment and prenatal diagnosis in high-risk families. Methods: Between November 2012 and October 2017, 26 117 pregnant women were screened by molecular hybridization microarray for 9 hot-spot mutations in 4 hereditary deafness related genes (GJB2 c. 35 del G, c. 176_191 del 16 bp, c. 235 del G, c. 299_300 del AT, GJB3 c. 538 C>T, SLC26A4 c. 2168 A>G, IVS 7-2 A>G, mitochondrial DNA 12S rRNA m. 1494 C>T, m. 1555 A>G). Genotype analysis was carried out in husbands of women carrying mutations, and prenatal diagnosis was carried out in the fetuses with high risk of deafness. Results: Among all women tested, 1 208(4.63%) were carriers of genetic deafness mutations, 7 with hearing impairment were affected by homozygous or compound heterozygous mutations, 51 were mitochondrial gene mutation carriers, 103 were carriers of GJB3 c. 538 C>T heterozygous mutation, 1 026 were carriers of GJB2 or SLC26A4 heterozygous mutations, and 21 carried heterozygous mutations in two genes simultaneously. In 394 families, the husbands accepted gene sequence testing, and 27 in which were determined as carriers of mutations in identical genes as their wives. Among which, 18 families received prenatal diagnosis, and 5 fetuses were diagnosed as hereditary deafness. In 9 families who did not receive prenatal diagnosis, 1 neonate was diagnosed as compound heterozygote after delivery. Conclusion In order to prevent birth defects with congenital hearing problems, it is effective to provide screening for hotspot mutations in pregnant women and to perform prenatal diagnosis on high risk pregnancies.

Objective To translate the Water Orientation Test of Alyn 2 (WOTA2) into Chinese, and to study its reliability and validity for patients with spinal cord injury. Methods After authorizing, the English version WOTA2 scale and its training package were translated into Chinese. From January to September, 2018, 137 patients with spinal cord injury were evaluated with the Chinese version WOTA2 by two evaluators independently, and evaluated again three days later by one of the evaluators. The Cronbach's α, Spearman-Brown coefficient, intra-group correlation coefficient (ICC) and Kappa coefficient were calculated to evaluate the reliability. Content Validity Index (CVI) of items (I-CVI) and scale (S-CVI) were used to evaluate the content validity, and factors analysis was used to evaluate the structure validity. Results The Cronbach's α was 0.947 in all items of the scale, 0.890 in mental adjustment items and 0.954 in aquatic skills items. Pearson correlation coefficient of the half scales separated by odd and even items was 0.948, and the Spearman-Brown coefficient was 0.973. The ICC of test-retest was 0.965 in total score, 0.965 in centesimal system total score, 0.847 in mental adjustment score and 0.970 in aquatic skills score. The ICC of inter-testers was 0.964 in total score, 0.965 in centesimal system total score, 0.847 in mental adjustment score and 0.970 in aquatic skills score. The Kappa coefficient was 0.528 to 0.927 in test-retest and 0.528 to 0.927 in inter-testers. The I-CVI was 0.8 to 1.0 and S-CVI was 0.63. Factors analysis extracted four factors, which met the theory, and contributed 67% of cumulative variance. Conclusion The Chinese version WOTA2 is good in reliability and validity for patients with spinal cord injury, and can be used in the clinical practice of aquatic therapeutic exercise in China.