Association between clinicopathological characteristics and gene mutations in 94 cases of cutaneous melanoma / 中华皮肤科杂志

Objective:To investigate associations between clinicopathological characteristics and mutations in susceptibility genes in cutaneous melanoma (CMM) .Methods:A total of 94 patients with confirmed CMM were collected from People′s Hospital of Xinjiang Uygur Autonomous Region from January to December in 2019, and their clinical and histopathological characteristics were retrospectively analyzed. In 48 paraffin-embedded melanoma tissue specimens, Sanger sequencing was performed to detect mutations in the BRAF, NRAS, c-KIT genes and the promoter region of human telomerase reverse transcriptase (hTERT) gene, and the association between gene mutations and clinicopathological characteristics was analyzed. Measurement data were compared using t test, and enumeration data were compared using chi-square test or Fisher′s exact test. Results:Among the 94 patients with CMM, there were 46 (48.9%) males and 48 (51.1%) females, with the age being 58.5 ± 16.0 years; 41 (43.6%) patients were of Han nationality, and 53 (56.4%) were of ethnic minorities. Skin lesions were located at the acral sites in 50 (53.2%) patients, including 27 (28.7%) of Han nationality; non-acral skin lesions occurred in 44 (46.8%) , including 14 (31.8%) of Han nationality; there was a significant difference in the nationality distribution between the acral CMM group and non-acral CMM group ( χ2 = 5.25, P = 0.022) . Histopathological examination showed CMM of Clark grades Ⅳ or Ⅴ in 41 (43.6%) cases, ulcers in 52 (55.3%) cases, and lymph node metastasis in 32 (34.04%) cases at the first clinic visit. Gene sequencing revealed BRAF gene mutations in 11 (22.9%) of 48 cases, including c.1799 T>A (p.V600E) , c.1790 T>A (p.L597Q) and c.1394 C>T (p.S465F) ; NRAS gene mutation c.182 A>G (p.Q61R) was identified in 5 (10.4%) cases; c-KIT gene mutations were identified in 6 (12.5%) cases, including c.1727 T>C (p.L576P) and c.1669 T>C (p.W557R) ; mutations in the promoter region of hTERT gene were identified in 7 (14.6%) cases, including 4 cases with a mutation at 124 bp upstream of the ATG start codon (C228T) and 3 cases with a mutation at 146 bp upstream of the ATG start codon (C250T) . Among 26 patients aged < 60 years, BRAF gene mutations were found in 9, and the incidence of BRAF gene mutations was significantly higher in the patients aged < 60 years than in those aged ≥ 60 years (2/22, P < 0.05) , but significantly lower in the patients with acral CMM (3/27) than in those with non-acral CMM (8/21, P < 0.05) ; the incidences of the NRAS, c-KIT and hTERT gene mutations were all significantly higher in the patients with lymph node metastases (3/10, 4/10, 4/10, respectively) than in those without (2/38, 2/38, 3/38, respectively, all P < 0.05) . Conclusion:CMM lesion locations significantly differed among different ethnic groups; the BRAF gene mutation was associated with the age of patients and lesion locations of CMM; NRAS, c-KIT gene mutations and hTERT promoter mutations were closely related to lymph node metastasis.

A clinical study of preoperative endoscopic assessment of the invasion depth of colorectal laterally spreading tumor / 中华消化内镜杂志

Objective To compare the diagnostic accuracy of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for preoperative endoscopic assessment of the invasion depth of colorectal laterally spreading tumour(LST).Methods Data of 104 cases of colorectal LST were included.With the final pathological diagnosis as the golden standard,the accuracies of MCE and EUS for preoperative assessment of the invasion depth of colorectal LST were compared.Results The diagnostic accuracies of MCE and EUS for evaluating the invasion depth of LST were 89.4％ (93/104) and 73.1％ (76/104),respectively(P＜0.05).The lesion size and the endoscopist could affect the accuracy of the EUS evaluation (P=0.017,OR=3.561;P=0.035,OR =1.399).The accuracy of EUS seemed to show a downward trend for colorectal LST of larger diameters.Conclusion Both MCE and EUS are effective for evaluating the invasion depth of colorectal LST,but the accuracy of MCE may be higher than that of EUS.Large diameter of the lesion and the doctor's experience inadequacy may be the risk factors for the accuracy of EUS.

Research on PEGylated uricase by periodate oxidation and reductive- amination / 中国药科大学学报

@#PEGylated uricase was prepared with the N-terminal amino site-specific modification by periodate oxidation followed by reductive-amination. A monomethoxy poly(ethylene glycol)intermediate was synthesized by amidation from monomethoxy poly(ethylene glycol)amine hydrochloride 20000(mPEG20000-NH2 ·HCl)with the relative molecular mass of 20 kD and N-(tert-butoxycarbonyl)-L-serine(Boc-Ser-OH), and then the Boc group of the intermediate was removed by trifluoroacetic acid(TFA)to produce the desired product Ser-mPEG20000. This compound could be oxidated by periodate to obtain a new poly(ethylene glycol)aldehyde derivative with high activity, which could be used to modify proteins with the N-terminal amino site-specific PEGylation after ultrafiltration, and the modification conditions to uricase by Ser-mPEG20000 were optimized. The structures of poly(ethylene glycol)intermediate and the target product were characterized by IR and 1H NMR, and the overall yield of the target product was 72. 8%. The preliminary modification to uricase indicated that the desired product Ser-mPEG20000 could modify proteins easily and efficiently. The optimal modification conditions of uricase PEGylated by Ser-mPEG20000 were obtained as follows: the molar ratio of Ser-mPEG20000 to uricase was 2 ∶1; the pH value of solution was 5. 0; the reaction temperature was 25 °C and the reaction time was 6 h.

Diagnosis and treatment of huge gastrointestinal stromal tumor combined with large inguinal hernia / 中华消化外科杂志

Gastrointestinal stromal tumors (GISTs) are relatively common mesenchymal tumors of the digestive tract characterized by c-kit mutations and the stomach is the commonly involved site.Clinical and pathological diagnosis of GISTs can be achieved by B sonography,computed tomography and immunohistochemical detection of marker CD117.Surgical resection of GISTs has been the most effective therapy.Target therapy with tyrosine kinase inhibitors may reduce the development of recurrence or progression of GISTs.The optimized method of diagnosis and treatment of huge GISTs is still controversial.In this paper,the diagnosis and treatment for huge GIST combined with large right inguinal hernia were discussed.