Animal models are highly valuable systems that have been extensively used to elucidate human disease pathogenesis and to find therapeutic ways to treat human diseases .Since non-human primates are close to humans,monkeys are important model species in exploring the mechanisms and treatment of human neurodegenerative diseases , neuropsychiatric disorders, cognitive function, and neural circuits.However, due to the lack of embryonic stem cell lines in large animals, the traditional gene targeting technology is difficult to establish primate animal models of human diseases . CRISPR/Cas9, as a recently developed tool for genome modifications , has been successfully used to target genomic loci in mouse, rat, monkey, and other species.Here, we discuss the utilization of CRISPR /Cas9 technology in establishing monkey models for studying human neurodegenerative diseases .

Objective To estimate the application value of dermoscopy in the differential diagnosis of basal cell carcinoma (BCC).Methods Patients who underwent dermoscopic examination and had been definitely diagnosed by pathological examination in the Peking University First Hospital were enrolled in this study.In a blind study,dermoscopic images of 86 BCC lesions from 81 patients (case group) and 68 non-BCC hyperpigmented lesions with similar degree of hyperpigmentation and location from 61 patients (control group) were evaluated for features suggestive of BCC and melanocytic lesions.The diagnostic capability of dermoscopy in patients with BCC was evaluated by diagnostic test.Pathology served as the gold standard method for diagnosis.The frequency of features suggestive of melanocytic lesions was calculated in BCC lesions,and dermatoscopic findings were compared between heavily and lightly pigmented BCC lesions.Results The sensitivity,specificity,positive predictive value,negative predictive value of the classic dermoscopic pattern for the diagnosis of BCC were 98.84％,89.71％,92.39％,98.39％ respectively,with a Youden index of 0.88.The coincidence rate was 94.81％ between pathologic and microscopic diagnosis.Pigment network,multiple brown to black globules/dots,pigmentation around hair follicle openings were observed more frequently in melanocytic lesions compared with BCC lesions (all P ＜0.05).Blue-whitish veil-like structures were observed in 61.63％ of the BCC lesions.The presence of blue-black blotch and blue-whitish veil-like structures was significantly more frequent in heavily pigmented BCC lesions than in lightly pigmented BCC lesions (both P ＜0.01).Conclusions The classic dermoscopic pattern of BCC shows a favorable diagnostic capacity in Chinese population.Large-scale studies are needed to estimate the value of some features proposed in this study,such as peripheral pigment in palisade arrangement,peripheral hyperpigmentation and hypo-or hyperpigrnentation around hair follicle openings,in the differential diagnosis of pigmented diseases.

Objective To investigate the dermoscopic features of palmoplantar melanocytic lesions.Methods The dermoscopic images of palmoplantar melanocytic lesions that underwent examination in the Department of Dermatology in Peking University First Hospital from September 2009 to October 2011,were retrospectively analyzed.Results Totally,155 benign acral melanocytic lesions in 121 patients and 23 acral melanomas in 22 patients were analysed in this study.Among the benign acral melanocytic lesions,the parallel furrow pattern and its variations (34.2％) were the most common,followed by the fibrillar pattern (22.6％).Two benign lesions (1.3％) showed a parallel ridge pattern.Of 23 melanoma lesions,12 (52.2％) exhibited parallel ridge pattern,and 14 (60.9％) showed irregular diffuse pigmentation that was present in all of the invasive melanoma lesions.The fibrillar pattern,as a common benign acral dermoscopic pattern,was also present in 39.1％ of melanoma specimens.Conclusions Dermoscopy is valuable to some extent in the differential diagnosis of benign melanocytic nevi and malignant melanoma in palmoplantar region,and may facilitate the secreening for early melanoma.

Objective To evaluate the roles of signal transducer and activator of transcription 3(STAT3) played in delayed xenograft rejection.Method Mice-to-rats cardiac xenograft model was established and recipients were administrated by inhibitor of phosphorylation of STAT3,5,15-Diphenylporphyrin(DPP),and immunosuppressive agent,ciclosporin A (CsA) alone or both.The survival of graft was analyzed.Immunohistochemistry and immunoblotting were utilized to detect the phosphorylated STAT3 (p-STAT3),and real-time polymerase chain reaction was used to assess STAT3-targeted genes in grafts.Result The expression of p-STAT3 was increased significantly with the prolonged survival in grafts (P ＜ 0.05).Administration of DPP and CsA both significantly prolonged survival of the grafts (P＜0.05),and decreased the expressions of STAT3-targeted genes including Bcl-xl,Bcl-2,Cyclin D1,C-myc and VEGF (P＜0.05).DPP and CsA exerted the synergistic effects.Conclusion STAT3,which is persistently activated in cardiac xenografts,probably up-regulates downstream genes to promote proliferation and to inhibit apoptosis of endothelial cells,leading to the activation of endothelial cells and delayed xenograft rejection.

Objective To evaluate the relationship of peripheral blood Th17 and regulatory T (Treg) cells with disease activity in patients with systemic sclerosis (SSc).Methods This study recruited 21 patients with active SSc,24 patients with inactive SSc and 24 normal human controls with informed consent.Peripheral blood samples were obtained from these subjects.Flow cytometry was used to detect the percentages of Th17 and Treg cells in peripheral blood CD4+ cells,a fluorescence-based quantitative PCR to determine the levels of interleukin (IL)-17A,retinoid-related orphan receptor gamma t (RoRγt),forkhead box P3 (FoxP3) mRNA in peripheral blood mononuclear cells (PMBCs),and enzyme linked immunosorbent assay to measure the serum level of IL-17.Results Increased percentage of Th17 cells in peripheral blood CD4+ cells was observed in patients with active SSc compared with those with inactive SSc and normal human controls (2.34％ ± 1.19％vs.0.68％ ± 0.39％ and 0.57％ ± 0.49％,respectively,both P ＜ 0.05).No statistical difference was noted in the percentage of Treg cells in CD4+ cells or the mRNA expression levels of FoxP3 between the patients with active SSc,inactive SSc and normal human controls (all P ＞ 0.05).There was a significant increase in the mRNA expression of IL-17A,RoRγt in PBMCs and serum levels of IL-17 in patients with active SSc compared with patients with inactive SSc and normal human controls ( 11.73 ± 0.80 vs.9.77 ± 1.30 and 10.79 ± 0.74,respectively,both P ＜ 0.05; 18.48 ± 1.09 vs.15.89 ± 1.48 and 17.77 ± 1.64,respectively,both P ＜ 0.05; 53.60± 9.90 pg/ml vs.15.18 ± 3.24 pg/ml and 15.53 ± 4.12 pg/ml,respectively,both P ＜ 0.05).The percentage of Th17 cells in CD4+ cells and serum IL-17 levels were both positively correlated with disease activity in patients with active SSc (r =0.675,0.644,respectively,both P ＜ 0.05).Conclusions Th17 cells are highly proliferative in patients with active SSc,which may be closely correlated with the activity of SSc.

Objective To investigate the effects of preconditioning with 3-nitropropionie acid on myocardial apoptosis induced by ischemia-reperfusion injury.Method Twenty-four rabbits were randomly divided into control group(group C,n=8),precondition group(group 3-NPA,n=8)and 5-HD group(group 5-HD,n=8).The group 5-HD was treated intravenously with 5 mg·kg-1 5-HD(ATP-sensitive potassium channels blocker),group C and group 3-NPA received normal saline instead of 5-HD.Ten minutes later,5-HD group and 3-NPA group were injected with 3-NPA(3 mg·kg-1)and the group C was injected with normal saline.Twenty-four hours later,the left anterior descending coronary artery was ligated for 30 min and then unclamped for 120 min to estabhsh ischemi-a-reperfitsion injury model.After reperfusion,the infarct sizes of ventricular myocardium,apoptotic myocardial cells and the expressions of Bcl-2 and Bax protein were measured.Results Infarct sizes and apoptotic myocardial cells in group 3-NPA were less than those in the others(P＜0.01).The expressions of Bcl-2 in group 3-NPA.in-creased as compared with group C(P＜0.05)and group 5-HD(P＜0.05),whereas the expressions of Bax in group 3-NPA decreased as compared with group C(P＜0.05)and group 5-HD(P＜0.05).Conclusions Preconditioning with 3-nitmpropionie acid reduces myocardial apoptosis induced by isehemia-reporfusion injury which is attributed to the opening of mitochondrial KATP channels.

A 19-year-old Chinese woman presented with progressive ulcers and recurrent fever for 1 year.The lesions originally began with purplish red maculopapules,then rapidly developed into ulcer with severe pain and spread to the trunk and extremities accompanied by intermittent fever.Histopathology revealed lymphoid infiltration of middle and large atypical T cells throughout the dermis and subcutaneous fat laver along with focal epidermotropism.The lymphoid infiltrates were positive for CD3,CD8,T-cell intercellular antigen(TLA)and T-cell receptor β(TCR-β).Gene analysis showed the rearrangement of T-cell receptor gene.According to the above findings,the patient was diagnosed as primary cutaneous aggressive epidermotropic CD8-positive cytotoxic T-cell lymphoma. Combined thempy with cyclophosphamide,vincristine,prednisone and bleomycin resulted in partial remission of skin lesions,but she eventually died 22 months after the onset of disease.

Objective To explore the diagnosis ,treatment methods and clinical features of primary ureteral polyps.Methods Clinical data of 27 cases with primary ureteral polyps were analyzed retrospectively .The clinical features and treatment of this disease were analyzed .Results 7 cases were treated with polypectomy ,10 cases with basement fulguration by ureteroscopy operation or polyps-removing by ureter forceps ,4 cases with distal ureter resec-tion and termino-terminal anastomosis ,4 cases with lesions ureter resection and bilateral ureteric reimplantaion and 2 cases with nephrectomy due to nonfunctioning kidney .All cases were confirmed to be primary ureter polyp by pathology.All cases were followed up for 6-12 months with no recurrence and canceration ,only 1 case had ureteral stenosis.Conclusion Primary ureteral polyps is a benign disease with rare malignancy .The primary and effective treatment method is surgery which has few complications and good effect .

Objective To investigate the clinical roles of lysine methyltransferase 5A(KMT5A)in human hepatocellular carcinoma(HCC)and its functions in cell migration and invasion. Methods The expression levels of KMT5A of 60 cases were detected by immunohistochemistry(IHC). KMT5A siRNA was used to down-regulate the expression of KMT5A in SMMC-7721 cells. Cell migration and invasion were measured by wound healing assays and transwell assays,respectively. Immunoblotting was used to detect the expression of MMP-2 after siRNA trans-fection. miR-186 mimics were transfected into SMMC-7721 cells and the mRNA levels of KMT5A was detected by qRT-PCR after transfection. Results High expression of KMT5A was associated with large tumor diameter (>5 cm,P=0.047)and advanced TNM stage(Ⅲ+Ⅳ,P=0.035). The expression of KMT5A was knocked down by siRNA in SMMC-7721 cells. Down-regulation of KMT5A suppressed cell migration(P=0.031,P=0.006)and invasion(P=0.010),and impaired MMP-2 expression(P=0.040). Overexpression of miR-186 could significantly inhibit the expression of KMT5A(P = 0.007). Conclusions Over-expression of KMT5A in HCC tissues associ-ates with poor clinical features. KMT5A knockdown inhibits the migration and invasion on HCC cells.

OBJECTIVE To investigate the distribution and drug resistance of pathogenic bacteria which caused respiratory infection among suscepted patients and offer scientific basis for reasonable usage of antibiotics.METHODS Oropharyngeal swabs among 709 cases of respiratory infection neonates were investigated by the routine methods and drug resistance was analyzed by K-B method.RESULTS Totally 438 bacterial strains were isolated from 709 neonates.most of these bacteria were Gram-negative bacilli(70.3%),among which Haemophilus influenzae and Klebsiella pneumoniae were accounted for 39.8% and 10.3%,respectively;fungi and Gram-positive cocci were accounted for 23.5% and 6.2%.CONCLUSIONS Most strains present higher resistance rates to penicillin and ampicillin;but cefoxitin,amikacin,vancomycin,imipenem and the third generation cephalosporins are revealed with higher sensitivity rates for pathogenic bacteria in newborns.