Clinical Application of the Next Generation Sequencing for Molecular Classification in Endometrial Carcinomas / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical application of molecular classification in endometrial cancers with the next generation sequencing （NGS）. MethodsTotally 112 cases of endometrial carcinoma diagnosed by pathology in The Sun Yat-sen University Cancer Center were collected. All of them were tested by hybridized-capture second-generation sequencing based on 1，021 gene panel. The molecular variation spectrum of each subtype and its relationship between the clinicopathological features were analyzed. ResultsThe cases were distributed as follows： 8 （7.1%） POLE mutation， 34 （30.4%） mismatch repair deficient， 26 （23.2%） TP53 mutation， 44 （39.3%） non-specific molecular profile. The median tumor mutation burden was respectively 252.0， 38.4， 5.8 and 5.4 Muts/Mb. There were no significantly differences among four subtypes in clinicopathological features such as age， histological grade， lymph node metastasis and clinical stage. PTEN （75.5%）， PIK3CA （66.7%）， ARID1A （55.9%）， TP53 （40.2%）， NF1 （29.4%） were the most common mutations in endometrial cancers. ConclusionsThe utilization of NGS in endometrial cancers can simultaneously identify molecular subgroups， screen Lynch syndrome and obtain molecular variation spectrum， which can provide guidance for immunotherapy and targeted therapy， contribute to further accumulation and exploration of molecular genetic characteristics.

SGK1 as a therapeutic target for central nervous system diseases / 生理学报

Serum and glucocorticoid-regulated kinase 1 (SGK1) plays an important role in the physiological processes of hormone release, neuronal excitation and cell proliferation. SGK1 also participates in the pathophysiological processes of inflammation and apoptosis in the central nervous system (CNS). Increasing evidence demonstrates that SGK1 may serve as a target of the intervention of neurodegenerative diseases. In this article, we summarize the recent progress on the role and molecular mechanisms of SGK1 in the regulation of the function of the CNS. We also discuss the potential of newly discovered SGK1 inhibitors in the treatment of CNS diseases.

Effects of miR-144-3p on Proliferation, Cell Cycle and Apoptosis of K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of miR-144-3p on cell proliferation, cell cycle and apoptosis of blast phase chronic myelogenous leukemia (CML) K562 cells.@*METHODS@#K562 cells were cultured in vitro and mimics negative control, hsa-miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor were respectively transfected into K562 cells with transfection reagents. The cells were divided into five groups including blank control, mimics negative control, miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor. After transfection, the cell proliferation activity was detected by CCK-8 assay. The cell cycle distribution and apoptosis were detected by flow cytometry.@*RESULTS@#Compared with the blank control and mimics negative control groups, the proliferation rate of miR-144-3p mimics group was significantly decreased (P<0.05), the proportion of S phase cells was markedly increased (P<0.05), while the proportion of G1 phase cells was obviously decreased (P<0.05), and the apoptosis rate was significantly increased (P<0.05). Compared with the blank control and inhibitor negative control groups, the proliferation rate of miR-144-3p inhibitor group was obviously increased (P<0.05), the proportion of S phase cells was markedly decreased (P<0.05), while the proportion of G1 phase cells was obviously increased (P<0.05), and the apoptosis rate was significantly decreased (P<0.05).@*CONCLUSION@#miR-144-3p can inhibit the proliferation and promote apoptosis of K562 cells, affect the cell cycle, and block K562 cells in S phase, which indicates that miR-144-3p is involved in the cell cycle activity of CML during blastic phase.

The Structure and Assembly Pathway of MitochondrialRespiratory Chain Complex I / 中国生物化学与分子生物学报

Mitochondria, originated from the last eukaryotic common ancestor by endosymbiosis, are semi-autonomous double-membrane organelles. The oxidative phosphorylation system consists of five complexes that are coordinately encoded by the nuclear and mitochondrial genomes, and establishes the electron transport chain in the mitochondrial inner membrane, concurrently generating ATP using the proton gradient. The proton-pumping Complex I (NADH:ubiquinone oxidoreductase) is the first, large stand most complicated enzyme required in this process. Complex I is an L-shaped multimeric enzyme harbouring over 40 subunits, one FMN molecule and eight Fe-S clusters. In recent years, biochemical, genetic, proteomic and crysta-structure analyses of Complex I in several model systems have provided valuable insights into its function and biogenesis. This review summarizes our current understanding of Complex I structural modules, assembly pathway and factors, discusses their similarities and distinctions between animals and plants, as well as the evolution of Complex I. And we proposes some potentially important but yet unsolved questions of Complex I. Therefore, this review provides a relevant reference for further comprehensively deepening the function and evolution of mitochondrial Complex I.

Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. @*Materials and Methods@#TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. @*Results@#The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. @*Conclusion@#Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

Relationship of Ventilatory Efficiency to Cardiac Function after Exercise in Patients with Chronic Obstructive Pulmonary Disease / 中国康复理论与实践

Objective:To observe the relationship of ventilatory efficiency to cardiac function, especially heart rate recovery after exercise for patients with chronic obstructive pulmonary disease (COPD). Methods:From January, 2019 to December, 2020, 190 patients with COPD were recruited for Cardiopulmonary Exercise Testing. The general condition, medical history and medication history, lung function test and parameters of Cardiopulmonary Exercise Testing were recorded. They were divided into normal group and delay group according to whether the heart rate decline more than twelve beats within a minute after Cardiopulmonary Exercise Testing. Results:There were 89 patients (46.84%) in the delay group. Compared with the normal group, the delay group were older (Z = 2.282, P < 0.05), with less ratio of force exiratory volume in the first second in prediction (FEV1.0%) (Z = 3.626, P < 0.001), maximum power (t = 5.547, P < 0.001), breath reserve (BR) (t = 2.122, P < 0.05) and higher minimum ventilation equivalent of carbon dioxide (VE/VCO2nadir) (Z = 3.296, P = 0.001). Logistic regression showed that the COPD severity, VE/VCO2nadir and BR correlated with heart rate recovery. After adjusting for gender, age, body mass index and COPD severity, VE/VCO2nadir was an independent risk factor for delayed heart rate recovery (OR = 1.203, 95%CI 1.032 to 1.873, P = 0.004), and the best cut-off point was 33.15 (AUC = 0.6387, 95%CI 0.5595 to 0.7178, P = 0.001). Conclusion:The ventilatory inefficiency may increase the risk of abnormal heart rate recovery after exercise in COPD patients.

Prevalence and risk factors of renal function decline in elderly people in a community in Shanghai / 上海预防医学

Objective:To determine the prevalence of renal function decline in the elderly population in a community and risk factors. Methods:Data in the physical examination of the elderly population aged over 60 years old in a community in 2018 were collected and analyzed. Estimated glomerular filtration rate was calculated by modified modification of diet in renal disease （MDRD） formula. Association between renal function decline and risk factors were determined. Results:Among the 9 626 elderly people， the prevalence of renal function decline was 10.71%， which increased with age. Multivariate logistic regression showed that men， age， anemia， abnormal uric acid， hypertension， hyperlipidemia， diabetes， glutamine transaminase， and the history of stroke were the independent risk factors associated with renal function decline. Conclusion:The prevalence of renal function decline in elderly people in a community in Shanghai is relatively high. It is necessary to pay attention to early screening and take effective preventive measures， such as health education， scientific exercise and reasonable diet， chronic disease management and other measures.

Identification of radix et rhizoma clematidis and its adulterants using DNA barcoding / 药学学报

This study provides the candidate sequences in the identification of Radix et Rhizoma Clematidis and its adulterants using DNA barcoding. We amplified and sequenced the region psbA-trnH, with the data of 284 sequences from GenBank, the differential intra- and inter-specific divergences, genetic distance, barcoding gap were used to evaluate five barcodes, and the identification efficiency was assessed using BLAST1 and Nearest Distance methods. The results showed that psbA-trnH barcodes performed high identification efficiency and inter-specific divergences among the five different DNA barcodes. Analysis of the barcoding gap and NJ tree showed psbA-trnH was superior to other barcodes. Based on the identification and PCR amplification efficiency, psbA-trnH can be the ideal barcode to identify Radix et Rhizoma Clematidis and its adulterants accurately.

Molecular identification in genus of Lilium based on DNA barcoding / 药学学报

To establish a new method for identifying genus of Lilium by DNA barcoding technology, ITS, ITS2, psbA-trnH, matK and rbcL sequences were analyzed in term of variation of inter- and intra-species, barcoding gap, neighbor-joining tree to distinguish genus of Lilium based on 978 sequences from experimental and GenBank database, and identification efficiency was evaluated by Nearest distance and BLAST1 methods. The results showed that DNA barcoding could identify different species in genus of Lilium. ITS sequence performed higher identification efficiency, and had significant difference between intra- and inter-species. And NJ tree could also divide species into different clades. Results indicate that DNA barcoding can identify genus of Lilium accurately. ITS sequence can be the optimal barcode to identify species of Lilium.

Surgical treatment and pathological findings of hematological malignancies patients complicated with lung diseases / 中华血液学杂志

<p><b>OBJECTIVE</b>To determine the pulmonary pathological changes in hematological malignancy patients with pulmonary complications.</p><p><b>METHODS</b>17 hematological malignancy patients underwent surgical treatment were evaluated retrospectively. The pathological changes of all the surgical specimens were examined postoperatively by standard hematoxylin and eosin (HE) staining.</p><p><b>RESULTS</b>Pathological examination confirmed: aspergillus infection in 9 patients, sub-acute inflammation (fibrosis and hematoma formation) in 3, and each in 1 of pulmonary infarction with granulomatous tissue in the periphery; granulomatous inflammation with calcified tubercle; alveolar dilation and hemorrhage, interstitial fibrosis and focal vasculitis; intercostal neurilemmoma; and moderate-differentiated adenocarcinoma accompanied by intrapulmonary metastasis. And several operative complications (1 case of fungal implantation, 3 pleural effusion and adhesions and 2 pulmonary hematoma) were occurred. The coincidence rate of pre- and post-operative diagnosis was 9/14 (64.3%). After surgery, 8 patients were received hematopoietic stem cell transplantation (HSCT, allo-gene or autologous), with 7 succeeded. On effective secondary antifungal prophylaxis, 4 of 5 patients of aspergillosis succeeded in transplantation with free from mycotic relapse, one patient died from fungal relapse.</p><p><b>CONCLUSION</b>Hematological malignancies with persistent and/or resistant pulmonary infection, hemoptysis, or unexplained lung diseases, should be treated in time by surgery operation to effectively eliminate residual disease and obtain a definitive diagnosis, so as to create a prerequisite condition for the following treatments. Moreover, the secondary antifungal prophylaxis can provide active roles for patients scheduled for chemotherapy and/or HSCT.</p>

Comparision of HER2/neu oncogene detected by chromogenic in-situ hybridization and immunohistochemistry in breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>Through comparison of HER2/neu oncogene detected by chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) in breast cancer, to explore the effect of CISH on detecting gene amplification of HER2.</p><p><b>METHODS</b>Selected formalin-fixed paraffin-embedded breast samples whose pathological types were infiltrating ductal carcinomas (255 retrospective samples, 271 prospective samples), and these samples were detected by IHC and CISH.</p><p><b>RESULTS</b>(1) In the retrospective study, CISH identified gene amplification in 91.6% of IHC score 3+ tumors (120/131) and in 56.5% of IHC score 2+ tumors (39/69), thus the concordant ratio between IHC and CISH was 81.2% (207/255). The two results showed significant correlation (P<0.01). (2) In the prospective study, the ratio of HER2 protein over expression detected by IHC was 31.7%, the ratio of HER2 gene amplification detected by CISH was 27.3%. CISH identified gene amplification in 91.4% of IHC score 3+ tumors (53/58) and in 46.4% of IHC score 2+ tumors (13/28), Concordant ratio between IHC and CISH was 89.7% (243/271). Two results showed significant correlation (P<0.01). (3) Paired CISH/FISH results were concordant in 14 of 15 cases. The remaining case was detected by FISH, but showed no HER2 gene amplification by CISH. (4) The gene amplification by CISH had a significantly reverse correlation with ER and PR expression (P<0.01).</p><p><b>CONCLUSIONS</b>The results of HER2 gene amplification detected by CISH have high concordance with the results detectd by IHC and FISH. CISH is a novel technique for detecting HER2 gene amplification.</p>