[Diagnosis of lung biopsy employing the 2015 WHO criteria and detection of related oncogenic driver mutations].

Objective: The diagnostic criteria of lung biopsy specimens by 2015 WHO lung tumor classification were used to evaluate lung biopsy specimens along with detection of genetic alterations of major tumor driving genes including epidermal growth factor receptor (EGFR). Methods: The clinical data, histological slides, immunohistochemical stains and special stains of 806 lung biopsy specimens at Beijing Hospital from July 2015 to July 2018 were retrospectively analyzed. Diagnosis of lung cancer was reclassified according to the 2015 WHO lung tumor classification and related gene mutation data were analyzed. Results: During a three-year period, the total number of lung cancer diagnosis was 483 cases, including 221 female and 262 male patients with age ranging from 37 to 85 years (median age of 65 years). There were 40 cases(8.28%) of small cell carcinoma,11 cases (2.28%) of large cell neuroendocrine carcinoma, 3 cases (0.62%) of combined neuroendocrine carcinoma, 2 cases(0.41%) of atypical carcinoid, 208 cases (43.06%) of adenocarcinoma, 92 cases(19.05%) of non-small cell carcinoma, favor adenocarcinoma, 66 cases (13.66%) of squamous cell carcinoma, 42 cases(8.70%) of non-small cell carcinoma, favor squamous cell carcinoma, 16 cases(3.31%) of non-small cell carcinoma, not otherwise specified, and 3 cases (0.62%) of non-small cell carcinoma, possible adenosquamous carcinoma. Among 202 cases tested, 107 cases (52.97%) showed EGFR mutations, including 86 of 133 cases (64.66%) of adenocarcinoma and 18 of 52 cases (34.62%) of non-small cell carcinoma, favor adenocarcinoma. Twenty two cases were found to have T790M mutation among 27 patients after EGFR TKI targeted drug therapy. Immunohistochemical staining of ALK (D5F3) was positive in 3 of 354 cases of non-small cell lung cancer, confirmed by EML4-ALK fusion gene fluorescence PCR. ROS1 gene fusion was found in 1 of 38 cases. Splicing mutations in exon 14 of MET gene were seen in one case of non-small cell carcinoma with spindle cell differentiation. Conclusion: The new diagnostic criteria by the 2015 WHO lung tumor classification is better suited for diagnosing lung biopsy specimens and providing accurate treatment guidance and improving the patient outcome.

[An analysis of clinical features of celiac disease patients in different ethnic].

OBJECTIVE: To summarize the clinical features of different racial patients with celiac disease (CD) and analyze the disease prevalence, diagnosis and treatment in Chinese population. METHODS: All the patients were diagnosed as CD and enrolled in Beijing United Family Hospital between January 2005 and July 2015.Clinical data including nationality, age, symptoms, endoscopic and pathological findings, outcome were collected and compared in patients from different countries. RESULTS: A total of 87 patients were enrolled including 63 Caucasians, 18 Asian patients and 6 Middle East patients.The peak age of disease onset was 40-60 years old.Patients with typical symptoms such as chronic diarrhea and weight loss only accounted for 20.7%(18/87) and 9.2%(8/87) respectively.Some patients presented with nonspecific symptoms such as abdominal pain and bloating [32.2%(28/87)], even constipation [5.7%(5/87)].13.8%(12/87) patients were previously diagnosed as irritable bowel syndrome.The incidence of abdominal pain, bloating, diarrhea and constipation between Asians and Caucasians had no statistical significance (P>0.05); but the proportions of weight loss, growth retardation, iron deficiency anemia and dermatitis herpetiformis in Asian group were significantly higher than that in Caucasian group (P<0.05). IgA type of anti-gliadin antibody (AGA), endomysium antibody (EMA) and tissue transglutaminase antibody (tTGA) were dominant autoimmune antibodies in patients with CD, which accounted for 58.6%(51/87), 44.8%(39/87) and 36.8%(32/87) respectively.The endoscopy showed that the lesion of CD was mainly located in small intestine, with reducing severity from the proximal to the distal small intestine.The lesions of duodenal bulb and descending duodenum appeared more significant in Asian group.Accordingly pathological intestinal atrophy and the degree of intraepithelial lymphocytosis were more severe in Asian patients.All 87 cases took the gluten-free diet (GFD). Eighty-one cases received serological follow up and 8 with endoscopic intestinal biopsy.The celiac disease antibodies in 47 patients turned negative from 6-9 months after GFD treatment, while 34 patients turned negative from 12-18 months after GFD.All patients reported disease remission to some extent.After 1 year GFD treatment, the pathology of endoscopic intestinal biopsy in 8 patients showed significant improvement of villous atrophy and lymphocyte infiltration. CONCLUSIONS: CD patients with typical clinical manifestations are not the majority.Serological celiac disease antibodies (AGA, EMA and tTGA) have a high diagnostic value.GFD treatment is effective on majority of celiac patients.Clinical manifestations, endoscopy, intestinal pathology, and response to GFD in Chinese patients are not the same as Caucasians.Clinicians need to pay attention to the differential diagnosis.

Rabbit MSTN gene polymorphisms and genetic effect analysis.

We analyzed meat samples of nine pure lines of rabbit and its 37 hybrid combinations by sequencing and single-strand conformation polymorphism techniques to explore genetic polymorphisms of all the three exon regions and part of the 5'-regulatory region of the myostatin (MSTN) gene. Thus, we detected a single nucleotide mutation (T→C) on the 476 locus of the 5'-regulatory region, but no mutation sites were detected in the exon areas. The correlation analysis showed that the mutation had some favorable genetic effects, and it resulted in increased liver weight, carcass weight, forelegs weight, back and waist weight, ham weight, and tare weight, whereas it decreased muscle drip loss and cooking loss (P < 0.05). These results suggest that the mutations in the upstream regulatory region of the MSTN gene are beneficial to the rabbit soma development, and the mutations can be used as molecular markers for the selection of the meat quality of rabbits.

ADME evaluation in drug discovery. 5. Correlation of Caco-2 permeation with simple molecular properties.

The correlations between Caco-2 permeability (logPapp) and molecular properties have been investigated. A training set of 77 structurally diverse organic molecules was used to construct significant QSAR models for Caco-2 cell permeation. Cellular permeation was found to depend primarily upon experimental distribution coefficient (logD) at pH = 7.4, high charged polar surface area (HCPSA), and radius of gyration (rgyr). Among these three descriptors, logD may have the largest impact on diffusion through Caco-2 cell because logD shows obvious linear correlation with logPapp (r=0.703) when logD is smaller than 2.0. High polar surface area will be unfavorable to achieve good Caco-2 permeability because higher polar surface area will introduce stronger H-bonding interactions between Caco-2 cells and drugs. The comparison among HCPSA, PSA (polar surface area), and TPSA (topological polar surface area) implies that high-charged atoms may be more important to the interactions between Caco-2 cell and drugs. Besides logD and HCPSA, rgyr is also closely connected with Caco-2 permeabilities. The molecules with larger rgyr are more difficult to cross Caco-2 monolayers than those with smaller rgyr. The descriptors included in the prediction models permit the interpretation in structural terms of the passive permeability process, evidencing the main role of lipholiphicity, H-bonding, and bulk properties. Besides these three molecular descriptors, the influence of other molecular descriptors was also investigated. From the calculated results, it can be found that introducing descriptors concerned with molecular flexibility can improve the linear correlation. The resulting model with four descriptors bears good statistical significance, n = 77, r = 0.82, q = 0.79, s = 0.45, F = 35.7. The actual predictive abilities of the QSAR model were validated through an external validation test set of 23 diverse compounds. The predictions for the tested compounds are as the same accuracy as the compounds of the training set and significantly better than those predicted by using the model reported. The good predictive ability suggests that the proposed model may be a good tool for fast screening of logPapp for compound libraries or large sets of new chemical entities via combinatorial chemistry synthesis.