[Clinicopathological features of colorectal amphicrine carcinoma].

Objective: To investigate the clinicopathological, immunophenotypic and molecular features of colorectal amphicrine carcinoma (AC). Methods: Eight cases of colorectal AC were collected at the Nanjing Drum Tower Hospital and Nanjing First Hospital, Nanjing, China from 2013 to 2020. The histopathological, immunohistochemical and molecular features were analyzed. The relevant literature was reviewed. Results: There were 6 males and 2 females, with an average age of 56 years (range 28-80 years). The tumor sites were as follows: 4 cases in sigmoid colon, 3 cases in rectum, and 1 case in transverse colon. Microscopically, there were three different patterns in the tumors, including nests with collagen hyperplasia, sheets of cells with scant stroma, and glandular or cribriform growth of goblet- or signet ring-like cells. The tumor cells generally had abundant cytoplasm with abundant mucin or eosinophilic granules. The nuclei were oval or irregular with fine chromatin and inconspicuous nucleoli. Mitotic figures were common. Neuroendocrine granules and mucin granules could be identified clearly under electron microscope. All cases showed frequent perineural and lymphovascular invasions, lymphatic metastasis, and advanced stage. Regarding immunohistochemical and specific stains, the tumor cells expressed more than two neuroendocrine markers, particularly CD56 and synaptophysin which were diffusely positive in 7 of the 8 cases. They also showed intracellular mucin in the amphicrine components which was positive for D-PAS. KRAS G12C or NRAS Q61 gene mutations were found in 2 patients. Among the six cases with complete follow-up, four of them died of the disease within three years of the diagnoses, while two were alive without known disease progression. Conclusions: Colorectal AC is a rare, distinct entity with both epithelial and neuroendocrine differentiation. It mainly occurs in the sigmoid colon and rectum. It typically has aggressive clinical courses, dismal prognosis and characteristic histological features and immunophenotype, which highlight the importance of recognizing this entity for clinicians and pathologists.

[Bioinformatics screening and analysis of key differentially expressed genes characteristics in nonalcoholic fatty liver disease].

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.

[Efficacy of vertical control by using mini-implant anchorage in maxillary posterior buccal area for Angle class â ¡ extraction patients].

OBJECTIVE: To investigate the efficacy of vertical control by using conventional mini-implant anchorage in maxillary posterior buccal area for Angle class Ⅱ extraction patients. METHODS: Twenty-eight Angle class Ⅱ patients [9 males, 19 females, and age (22.6±2.8) years] were selected in this study. All of these patients were treated by using straight wire appliance with 4 premolars extraction and 2 mini-implant anchorage in maxillary posterior buccal area. In this study, the self-control method was used to measure and analyze the lateral radiographs taken before and after orthodontic treatment in each case, the main cephalometric analysis items were related to vertical changes. The digitized lateral radiographs were imported into Dolphin Imaging Software (version 11.5: Dolphin Imaging and Management Solutions, Chatsworth, California, USA), and marked points were traced. Each marked point was confirmed by two orthodontists. The same orthodontist performed measurement on the lateral radiographs over a period of time. All measurement items were required to be measured 3 times, and the average value was taken as the final measurement result. RESULTS: Analysis of the cephalometric radiographs showed that, for vertical measurements after treatment, the differences of the following measurements were highly statistically significant (P < 0.001): SN-MP decreased by (1.40±1.45) degrees on average, FMA decreased by (1.58±1.32) degrees on average, the back-to-front height ratio (S-Go/N-Me) decreased by 1.42%±1.43% on average, Y-axis angle decreased by (1.03±0.99) degrees on average, face angle increases by (1.37±1.05) degree on average; The following measurements were statistically significant (P < 0.05): the average depression of the upper molars was (0.68±1.40) mm, and the average depression of the upper anterior teeth was (1.07±1.55) mm. The outcomes indicated that there was a certain degree of upper molar depression after the treatment, which produced a certain degree of counterclockwise rotation of the mandibular plane, resulting in a positive effect on the improvement of the profile. CONCLUSION: The conventional micro-implant anchorage in maxillary posterior buccal area has a certain vertical control ability, and can give rise to a certain counterclockwise rotation of the mandible, which would improve the profile of Angle Class Ⅱ patients.

[Feasibility multi-center study of artificial intelligence assistance in cervical fluid-based cytology diagnosis].

Objective: To propose a method of cervical cytology screening based on deep convolutional neural network and compare it with the diagnosis of cytologists. Method: The deep segmentation network was used to extract 618 333 regions of interest (ROI) from 5, 516 cytological pathological images. Combined with the experience of physicians, the deep classification network with the ability to analyze ROI was trained. The classification results were used to construct features, and the decision model was used to complete the classification of cytopathological images. Results: The sensitivity and specificity were 89.72%, 58.48%, 33.95% and 95.94% respectively. Among the smears derived from four different preparation methods, this algorithm had the best effect on natural fallout with a sensitivity of 91.10%, specificity of 69.32%, positive predictive rate of 41.41%, and negative predictive rate of 97.03%. Conclusion: Deep convolutional neural network image recognition technology can be applied to cervical cytology screening.

[Clinicopathological significance of poorly differentiated clusters in colorectal adenocarcinoma].

Objective: To investigate the correlation between poorly differentiated clusters (PDCs) in colorectal adenocarcinomas with clinicopathological parameters and its clinicopathological significance. Methods: One hundred and eighty-three colorectal adenocarcinomas resected by radical proctocolecomy were collected at Nanjing Hospital(Nanjing First Hospital), Nanjing Medical University, from January to December 2017. There were 122 male and 61 female patients with age ranging from 42 to 89 years (mean of 68 years). Tumor diameter ranged from 2 to 14 cm (mean 4.5 cm). There were 124 colon cancers and 59 rectal cancers. The number and grade of PDCs in the colorectal adenocarcinoma were evaluated by H-E staining. The overall peritumoural inflammatory reaction was also evaluated. The relationship between PDCs and tumor grades and clinicopathological features and overall peritumoural inflammatory reaction of colorectal adenocarcinoma was analyzed. Results: Of 183 cases of colorectal adenocarcinoma, PDCs were seen in 104 cases (56.8%), of which 36 cases (19.7%) were grade 1, 28 cases (15.3%) were grade 2, and 40 cases (21.9%) were grade 3. PDCs were positively correlated with lymph node metastasis, vascular invasion, degree of differentiation, depth of invasion, and pTNM staging(P<0.05). The detection rate of PDCs in colon cancer was higher than that of rectal cancer(P<0.05). PDCs was unrelated to age, gender, tumor size, and degree of overall peritumoural inflammatory reaction (P>0.05). Among clinicopathological parameters, the grade of PDCs was correlated with lymph node metastasis and vascular invasion (higher than those without lymph node metastasis and vascular invasion, P<0.05); There was a positive correlation between the grade of PDCs and age, tumor differentiation and pTNM staging(P<0.05), and no significant difference between the grade of PDCs and gender, tumor size, tumor location, and depth of invasion was seen (P>0.05). There was no correlation between the grade of PDCs and the degree of overall peritumoural inflammatory reaction (P>0.05). Conclusions: PDC is a histological feature that predicts the aggressiveness of colorectal adenocarcinoma. Evaluation of PDC grade can better predict the biological behavior of colorectal cancer and more accurately guide the treatment and evaluate prognosis.

A novel mutation links to von Hippel-Lindau syndrome in a Chinese family with hemangioblastoma.

Hemangioblastoma of the central nervous system occurs as sporadic tumors or as a part of von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary tumor syndrome caused by a germline mutation in the VHL tumor suppressor gene. We screened a Chinese family with VHL for mutations in the VHL gene and evaluated a genetic test for diagnosing VHL disease and clinical screening of family members. DNA extracted from the peripheral blood of all live members and from tissue of deceased family members with VHL disease was amplified by polymerase chain reaction to 3 VHL gene exons. Mutations in the amplification products were compared against the Human Gene Mutation Database. The involvement of multiple organs among the kindred with VHL disease was confirmed by medical history and radiography. Of the 12 members of the 4-generation family, 5 were diagnosed with VHL disease. Patient age at the initial diagnosis was 26-36 years (mean = 31 years). The mean time was 15 (11-19 months) from symptom appearance to the first patient visit to the hospital. Sequence analysis revealed that the frameshift mutation 327del C (p.Gly39Alafs*26) in exon 1 affected all family members, but not the healthy individuals or 16 unrelated controls. Members without gene mutation showed no clinical manifestation of VHL disease. We detected a conserved novel frameshift mutation in the VHL gene of the family members that contributes to VHL. DNA analysis of VHL is advantageous for VHL diagnosis. We developed a quick and reliable method for VHL diagnosis.

Isolation and molecular characterization of the porcine SLC6A14 gene excludes it as a candidate gene for fat deposition and growth.

The gene encoding solute carrier family 6 member 14 (SLC6A14) has been considered as a candidate gene affecting human obesity. In this study, full-length cDNA (2237 bp) and DNA sequence (24 541 bp) of the porcine SLC6A14 gene were isolated. The porcine SLC6A14 cDNA contains a 5’-untranslated region of 57 bp, a 3’-untranslated region of 254 bp, and an open reading frame of 1926 bp, encoding a deduced protein of 642 amino acids with a molecular mass of 72. 475 kDa and an isoelectric point of 7.82. The genomic structure of the porcine SLC6A14 gene is similar to mammalian orthologs, particularly in terms of exon size and exon/intron boundaries. It comprises 14 exons and 13 introns. A semi-quantitative RT-PCR showed that the porcine SLC6A14 mRNA expression was tissue-specific. Four SLC6A14 single-nucleotide polymorphisms (SNPs) were identified, and 3 informative SNPs were chosen for genotyping in a White Duroc × Erhualian resource population with phenotype data of growth and fatness traits. The association analysis showed that the c.1438 G>A nonsynonymous polymorphism was associated with birth weight and 21-day body weight (P < 0.05), while g.7944 A>T was associated with 46-day body weight. Linkage and radiation hybrid mapping assigned SLC6A14 to a region around SW1522 on SSCXp13, which did not fall in the confidence interval of the quantitative trait locus (QTL) for growth and fatness traits on SSCX in the resource population. These results indicate that SLC6A14 is not a positional candidate gene for the QTL affecting fatness and growth traits in pigs.

Risk of relapse in leprosy after fixed-duration multidrug therapy.

Between 1986 and 1995, 8307 leprosy patients have completed fixed-duration multidrug therapy (FD-MDT) and were followed annually for possible relapse. The mean relapse rate for multibacillary (MB) leprosy is 0.15/1000 person-years (py) and for paucibacillary (PB) 0.55/1000 py. There is no difference in the relapse rates between patients with or without chemotherapy before FD-MDT. In MB patients, the five relapses occurred between 4 and 7 years; in PB patients, five relapses occurred at 4-5 years after FD-MDT. Six additional PB relapses self-reported 1-4 years after the 5-year surveillance period and were not included in the relapse rates. Most PB patients relapsed into MB due to wrong classification and insufficient therapy. For the known 62 irregular MB patients the cumulative relapse rate is 6.5%.

Short-term multidrug therapy in multibacillary leprosy--review of 80 cases in two provinces of China (1983-1988).

Thirty-three active multibacillary patients from nine counties of Weifang Prefecture, Shandong Province, and 47 active cases from Menla County, Yunnan Province, People's Republic of China, were treated with 24 and 27 months of multidrug therapy (MDT), respectively, in 1983. Clinical assessments, smears, and histopathologic examinations were carried out independently by study teams from the Institutes of Dermatology of these two provinces. Reexaminations at 12-14 months and at termination of therapy showed marked improvement, and there was continued improvement at 12-18 and 33 months on follow up. Conversion of the bacterial index to negativity was 0/33, 5/47 for the patients from Shandong and Yunnan provinces, respectively, at the end of MDT and 2/33 at 12 months' and 17/47 at 18 months' follow up, which increased to 21/33 and 26/44 at 33 months' follow up. Regression of specific infiltration was about 21%-100% after 24-27 months of MDT; further regression to 95%-100% occurred at 33 months' follow up.