Objective To construct a diagnostic and prognostic model for malignant pleural effusion (MPE) in patients with non-M1b stage (AJCC 7th edition) non-small cell lung cancer (NSCLC) by machine learning. Methods Retrospective analysis was conducted on patients diagnosed with NSCLC in the Surveillance, Epidemiology, and End Results database from 2010 to 2015, excluding those in the M1b stage. Two sets of data were collected: data 1 (patients with non-M1b stage NSCLC, n=47 392) was used to construct the MPE diagnostic model; and data 2 (patients with M1a stage NSCLC and MPE, n=2 422) was used to construct a prognostic model. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to screen feature variables, with a training set and validation set ratio of 7:3. Models were built using eight machine learning algorithms, with evaluation metrics including accuracy, precision, recall, F1 score, area under the ROC curve (AUC), decision curve, calibration curve, and precision recall curve (PR), with ROC-AUC as the main evaluation metric. Results The incidence of MPE in patients with non-M1b stage NSCLC was 5.12%, and the 1-year survival rate of patients with MPE was 32.5%. LASSO regression identified nine diagnostic-related variables and 12 prognostic-related variables. The AUC values of the models constructed by eight machine learning algorithms all exceeded 0.70. The random forest model performed the best in the diagnostic model (training set AUC=0.908, validation set AUC=0.897), and the XGBoost model showed the best performance in the prognostic model (training set AUC=0.905, validation set AUC=0.875). Other evaluation indicators showed good results and balanced distribution. SHAP feature importance analysis showed that tumor size, lymph node metastasis, and histological type were important influencing factors for the occurrence of MPE, and chemotherapy intervention was the most remarkably prognostic factor. Conclusion The random forest diagnostic model constructed in this study can effectively predict the risk of MPE in patients with non-M1b stage NSCLC, and the XGBoost prognostic model can predict the prognosis of M1a-stage NSCLC patients with concurrent MPE.

Epidermal growth factor receptor(EGFR)gene exon 20 insertion(ex20ins)mutation is a common driver gene activation mutation in non-small cell lung cancer(NSCLC).Tumors harboring this gene mutation are characterized by high heterogeneity,high malignancy,low detectability,poor response to conventional therapies,and poor prognosis.In recent years,significant progress has been made in the study of EGFR ex20ins mutation.The wide application of next-generation sequencing has improved the detection rate.The U.S.Food and Drug Administration(FDA)has approved the relevant indications of amivantamab in NSCLC patients with EGFR ex20ins mutation.A variety of new drugs have also achieved good results in previous studies.This article will summarize the structural characteristics,detection methods and clinical treatment progress of NSCLC patients with EGFR ex20ins mutations,hoping to provide help for the choice of clinical treatment for such patients.

Over the past 40 years,gynecological ultrasound in China has evolved from two-dimensional imaging to multi-modal imaging,quantitative analysis,artificial intelligence analysis and minimally invasive treatment,playing more and more important role in diagnosis and treatment of gynecological diseases.The development of diagnostic and therapeutic gynecological ultrasound techniques and relative clinical application advances in China were reviewed,and the future development prospects were looked forward to in this article.

Over the past 40 years,gynecological ultrasound in China has evolved from two-dimensional imaging to multi-modal imaging,quantitative analysis,artificial intelligence analysis and minimally invasive treatment,playing more and more important role in diagnosis and treatment of gynecological diseases.The development of diagnostic and therapeutic gynecological ultrasound techniques and relative clinical application advances in China were reviewed,and the future development prospects were looked forward to in this article.

Epidermal growth factor receptor(EGFR)gene exon 20 insertion(ex20ins)mutation is a common driver gene activation mutation in non-small cell lung cancer(NSCLC).Tumors harboring this gene mutation are characterized by high heterogeneity,high malignancy,low detectability,poor response to conventional therapies,and poor prognosis.In recent years,significant progress has been made in the study of EGFR ex20ins mutation.The wide application of next-generation sequencing has improved the detection rate.The U.S.Food and Drug Administration(FDA)has approved the relevant indications of amivantamab in NSCLC patients with EGFR ex20ins mutation.A variety of new drugs have also achieved good results in previous studies.This article will summarize the structural characteristics,detection methods and clinical treatment progress of NSCLC patients with EGFR ex20ins mutations,hoping to provide help for the choice of clinical treatment for such patients.

Objective To investigate pathogenic genes related to the phenotype of fetus with severely short limbs in the first and second trimester by whole exome sequencing (WES). Methods Thirteen fetuses with severely short limbs detected by ultrasonography in the first and second trimester admitted in Chinese PLA General Hospital from September 2016 to June 2018 were collected. All cases were performed induced abortion, 6 of which were carried out karyotype analysis of amniotic fluid at the same time. WES and copy number variations (CNV) were performed on specimens from fetal tissues after labor induction. The suspected pathogenic mutations were validated by Sanger sequencing reactions. Results No abnormal karyotypes or pathological CNV were found. In 10 fetuses, pathogenic or possibly pathogenic mutations were detected in the following genes: COL2A1, FGFR3, COL1A1, COL1A2, DYNC2LI1 and TRIP11, all of which were essential to skeletal development. The diagnostic yield of WES in the fetuses with severe short limbs was 10/13. Conclusions In the first and second trimester, most of the fetuses with extremely short limbs suffer from monogenic diseases. WES is likely to be a valuable diagnostic testing option for the fetuses with severe short limbs.

Objective To investigate the NPHS1 gene mutations in Finnish type congenital nephrotic syndrome (CNF). Methods Clinical data of one neonate with CNF and the results of NPHS1 gene detection in the neonate and his parents were retrospectively analyzed. Results The male neonate who was born at gestational age of 34 weeks presented with breathing difficulties after birth, and then glycosuria, proteinuria, and hematuria at 3 days of age. The CNF was clinically diagnosed. The neonate carried two heterozygous mutations in NPHS1 gene, c.1699?>?C, p.(Cys567Arg) and c.3523_3524de1TT, p.(Leu1175Valfs). His father carried the heterozygous mutations of c.1699?>?C, p.(Cys567Arg). His mother carried the heterozygous mutations of c.3523_3524de1TT, p.(Leu1175Valfs). Conclusions The NHPSI gene mutation of c.1699?>?C, p.(Cys567Arg) and c.3523_3524de1TT, p.(Leu1175Valfs) may cause CNF. The mutation of c.1699?>?C, P. (Cys567Arg) has not been reported at home and abroad.

OBJECTIVETo investigate the value of maternal plasma cell-free fetal DNA (cff-DNA) examination in detection of fetal chromosomal aneuploidy in pregnant women at advanced maternal ages during the first trimester of pregnancy.

METHODSA total of 136 pregnant women (11 to 13+6 gestational weeks) with advanced maternal ages were screened for fetal chromosomal aneuploidy with ultrasound and maternal plasma cff-DNA examination during March 1, 2011 to August 31, 2013, and the results were then confirmed by karyotype analysis and fluorescence in situ hybridization (FISH).

RESULTSOf the 136 women examined, cff-DNA screening detected chromosomal aneuploidy in 5 cases, including trisome-21 in 3 cases, trisome-18 in 1 case, and 45,X in 1 case as confirmed subsequently by karyotype analysis. Ultrasound screening reported a normal finding in one case of trisomy-21, thickening of the NT in the case of trisomy-18, and fetal anasarca in the case of 45,X. Karyotype analysis and follow-up of the women did not find chromosomal abnormality in the 131 negative cases screened by cff-DNA detection.

CONCLUSIONScreening of material plasma cff-DNA allows accurate and early detection of fetal chromosomal aneuploidy in women of advanced maternal ages to avoid unnecessary invasive antenatal examinations.

Aneuploidy ; Chromosomes, Human, Pair 18 ; DNA ; blood ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Maternal Age ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis ; Trisomy

Aim To investigate the possible mecha-nisms of the levels of NO decrease induced apoptosis in human placental trophoblast cells. Methods Human placental trophoblast cells ( HTR-8 ) were cultured in 5 ml DMEM-F12 culture medium with 37℃ 5% CO2 . Then, the old culture medium was discarded and re-placed with 10,100,500,1 000 μmol·L-1 L-NAME, and the group without L-NAME was set as the control group, cultured for 48h. The effects of L-NAME on the survival of cells were detected by methylthiazolyldiphe-nyl tetrazolium bromide ( MTT); the content of NO in cells was tested by nitrate reductive enzymatic;trans-mission electron microscopy, flow cytometry analysis and Annexin-V FITC dyeing were used to test the effects of L-NAME on apoptosis in HTR-8 cells;restore Fe3+ colorimetric assay was applied for detection of to-tal antioxidant capacity ( T-AOC ) , xanthine oxidase for detection of superoxide dismutase ( SOD) activity, and thiobarbituric acid colorimetry for determination of content of MDA. Results Compared with the control group, the survival rate of HTR-8 cells and the levels of NO in 100,500,1 000 μmol·L-1 L-NAME group were significantly reduced(P<0.05,P<0.01). Flow analysis and Annexin-V FITC staining showed that L-NAME could induce cell apoptosis in a dose-dependent manner. The number of cell apoptosis was negatively correlated with the content of NO ( r = -0.5210 ) in HTR-8 cells. Transmission electron microscopy results showed that compared with the control group, the ex-perimental group's cell nucleus shape was irregular, nuclear pyknosis in irregular shape, the chromatin ag-glutination or side the collection, mitochondrial swell-ing or enrichment, crest fracture or dissolved, even vanished, forming the vacuole, especially in 100 μmol ·L-1 L-NAME group, the apoptotic bodies obviously appeared. At the same time, T-AOC, SOD levels in HTR-8 cells decreased ( P <0.05 ) , and the MDA content increased ( P<0.05 ) . The number of cell ap-optosis was negatively correlated with the level of T-AOC ( r= -0.3212 ) , SOD ( r= -0.2779 ) in HTR-8 cells , while positively correlated with the content of MDA(r=0.2807). Conclusion Oxidative stress may play an important role in the levels of NO decrease in-duced apoptosis in human placental trophoblast cells.

Aim To explore the role of ERO1 αand its DNA methylation in homocysteine (Hcy)-induced in-hibition of hepatocytes proliferation.Methods The hepatocytes stimulated with 0 μmol·L -1 Hcy were set as the normal group (NC group)and the hepatocytes stimulated with 1 00 μmol·L -1 Hcy as the experimen-tal group (Hcy group).Methyl thiazolyl tetrazolium (MTT)reduction assay was used to reflect the prolifer-ation of the hepatocytes;qRT-PCR and Western blot were used to detect the mRNA and protein levels of ERO1 α;the expression of green fluorescence protein was observed in hepatocytes after the recombinant plas-mid of ERO1 α was constructed,which was used to confirm if the recombinant plasmid into hepatocytes was successful,then the mRNA and protein levels of ERO1 αwere assayed and the proliferation of the hepa-tocytes was also detected;ntMSP was used to detect the change of ERO1 αDNA methylation.Results The mRNA and protein levels of ERO1 αwere decreased in Hcy group compared with NC group,and the prolifera-tion activity of hepatocytes in Hcy group was de-creased.Sequencing result showed that the recombi-nant plasmid of ERO1 αwas constructed successfully. QRT-PCR and Western blot revealed that ERO1 αwas overexpressed. The result of MTT suggested that ERO1 αoverexpression restored hepatocyte proliferation inhibited by Hcy.Hcy caused ERO1 αDNA hyperm-ethylation.Conclusions Hcy inhibits hepatocyte pro-liferation by downregulating the expression of ERO1 α, and methylation of ERO1 αpromoter may play a role in this process.