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 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 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 explore the induction of basic fibroblast growth factor (bFGF)-chitosan carrier transforming the adult rat bone marrow mesenchymal stem cells (rMSCs) into nerve cells. Methods rMSCs were detected qualitatively and counted quantitatively by immunohistochemistry after they were induced into nerve cells, such as neural stem cells neurons and astrocytes. The methyl thiazolyl tetrazolium (MTT) chromometry assay was carried out to determine the cell viability. Results rMSCs induced by bFGF-chitosan carrier expressed neural stem cell marker nestin, neuron marker β-tubulin Ⅲ and astrocytes marker glial fibrillary acidic protein (GFAP). Nestin expressed more in the bFGF-chitosan group, and reached its maximum (49.40%) at the 9th day. Conclusion bFGF-chitosan carrier can induce the adult rMSCs differentiate into neural stem cells in a high proportion.

Objective Comparing the influence of neoadjuvant chemotherapy on sentinel lymph node biopsy and axillary lymph nodal staging. Methods From June 2005 to June 2007 one hundred and sixty five breast cancer patients of stage Ⅰ,Ⅱa,Ⅱb and Ⅲ underwent sentinel lymph node biopsy(SLNB) using 99mTc combining methylene blue dye as tracer to help axillary lymph node dissection(AND) were retrospectively reviewed. Sixty five patients staged Ⅱb or Ⅲ were treated with three circles neoadjuvant chemotherapy prior to SLNB and AND , another one hundred patients staged ⅠorⅡa had SLNB and AND directly without neoadjuvant chemotherapy.Results Average 14.60 axillary lymph nodes were retrieved in patients had neoadjuvant chemotherapy and 14.74 lymph nodes in patients did not have neoadjuvant chemotherapy(P>0.05),a mean number of 1.46 sentinel lymph nodes in neoadjuvant chemotherapy group and 1.5 sentinel lymph nodes in non-neoadjuvant chemotherapy(P>0.05), sentinel lymph node identification rate 96.9% in neoadjuvant chemotherapy group and 97% in non-neoadjuvant chemotherapy(P>0.05), the false negative rate was 4.6% in neoadjuvant chemotherapy group and 4% in non-neoadjuvant chemotherapy group(P>0.05). Conclusions The mean number of lymph nodes,sentinel lymph nodes,SLN identification rate and false-negative rates after neoadjuvant chemotherapy are similar to those seen in patients without neoadjuvant chemotherapy.The SLNB can accurately predict lymph node status of axillary lymph node following neoadjuvant chemotherapy.

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 explore the value of non-invasive prenatal test (NIPT) in pregnant women with intermediate risk after traditional Down syndrome screening. Methods From March 1 2015 to March 31 2016, a total of 2 949 pregnant women with intermediate risk after traditional Down syndrome screening who received NIPT as the second-line screening method at Shenzhen Maternity and Child Healthcare Hospital after informed consent were recruited for this study. Retrospective data analysis including the results of traditional Down syndrome screening, ultrasound, NIPT and invasive amniocentesis to fetal karyotype analysis were conducted, and pregnant outcomes were followed up. Results NIPT results were all obtained in 2 949 pregnant women with intermediate risk after traditional Down syndrome screening. Of 25 NIPT-positive cases, 24 cases received invasive amniocentesis to fetal karyotype analysis. Thirteen cases were confirmed with fetal chromosomal abnormalities including 5 cases of trisomy 21, 2 cases of trisomy 13, 4 cases of sex chromosomal abnormalities and 2 cases of other chromosomal abnormalities. In addition, 1 NIPT-positive case refused prenatal diagnosis was confirmed normal result after birth. The postnatal follow-up in NIPT-negative women did not find any newborn with chromosomal abnormality. The incidence of fetal chromosomal abnormalities in women with intermediate risk was 0.44% (13/2 949). Conclusion NIPT can be used as second-line screening method in pregnant women with intermediate risk after Down syndrome screening, which could lead to the prenatal detection of a higher proportion of fetal chromosomal abnormalities and a lower invasive-testing rate.

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 .

23 cases of the patients with supraorbital neuralgia were treated by puncturing Yangbai (GB 14) toward Yuyao (Extra), Zanzhu (BL 2), Taiyang (Extra), Touwei (ST 8),Zhongzhu (TE 3) and Neiting (ST 44) on the sick side, plus laser radiation on a site about 1 cm apart from the midpoint of the eyebrow of the sick side. After 10 treatments, the results showed cure in 19 cases and remarkable effect in 4 cases.