Clinical application and evaluation of health economics for non-invasive prenatal testing of fetuses in Tianjin / 中华医学遗传学杂志

OBJECTIVE@#To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies.@*METHODS@#10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13.@*RESULTS@#The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly.@*CONCLUSION@#The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.

Genetic analysis of a fetus with mosaicism Y chromosome aberration / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis for a fetus with mosaicism Yq deletion.@*METHODS@#A fetus with high risk of sex chromosomes indicated by non-invasive prenatal testing (NIPT) at Tianjin Medical University General Hospital in July 2021 was selected as the study subject. Prenatal diagnosis of the fetus was performed with combined G-banded chromosomal karyotyping, fluorescence in situ hybridization (FISH), copy number variation sequencing (CNV-seq), real-time fluorescence PCR (QF-PCR), and ultrasound examination.@*RESULTS@#Analysis of the amniocytes at 23 gestational weeks had yielded a 45,X karyotype. However, FISH had shown signals of Y chromosome. Re-examination by cordocentesis had shown a mosaicism of 46,X,+mar[33]/45,X[17]. FISH showed that 69% of the cells had contained Y chromosome signals. The result of CNV-seq was seq[19]del(Y)(q11.1q12)(mos) chrY: g.13200001_ 28820000del (mosaicism rate = 64%), which suggested mosaicism for a Yq deletion, which encompassed the azoospermia factor (AZF) region. Deletion of the AZF region was verified by QF-PCR. The fetal karyotype was ultimately determined as mos46,X,del(Y)(q11.1)[33]/45,X[17]. Although ultrasound examination had shown no abnormality in the fetus, the couple had opted to terminate the pregnancy, and the induced fetus had a normal male appearance.@*CONCLUSION@#The combined use of multiple techniques is beneficial for accurate and rapid prenatal diagnosis. For fetuses with mosaicism chromosomal abnormalities, it may be difficult to accurately predict the postnatal phenotype. It is therefore necessary to further explore their genotype-phenotype correlation in order to provide better guidance upon genetic counseling.

Prognostic value of left ventricular ejection fraction on admission in patients with septic cardiomyopathy / 中华危重病急救医学

Objective:To investigate the prognostic value of cardiac ultrasound left ventricular ejection fraction (LVEF) on admission in patients with septic cardiomyopathy.Methods:A retrospective cohort study was conducted. The patients with septic cardiomyopathy hospitalized in the intensive care unit of Zhoupu Hospital Affiliated to Shanghai Health College from January 2019 to March 2023 were enrolled. The general information including gender and age, LVEF on admission, severity of illness scores within 24 hours after admission [acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score], procalcitonin (PCT), cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), and MB isoenzyme of creatine kinase (CK-MB)], mitochondria related indicators [aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT) ratio], blood lactate (Lac), the usage of vasoactive drugs and mechanical ventilation, and the prognosis during hospitalization were collected. The differences in above clinical data between the two groups were compared. The variables with statistically significant differences in univariate analysis were incorporated into multivariate Logistic regression analysis to analyze the independent risk factors for death during hospitalization in patients with septic cardiomyopathy. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the prognostic value of LVEF by echocardiography on admission in patients with septic cardiomyopathy during hospitalization.Results:A total of 62 patients were enrolled, including 36 males and 26 females. Thirty-nine cases died and 23 cases survived during hospitalization, and the mortality was 62.90%. Compared with the survival group, the LVEF of patients on admission was lower in the death group [0.51 (0.40, 0.57) vs. 0.56 (0.51, 0.63), P < 0.01], APACHEⅡ score, SOFA score, Lac, NT-proBNP, CK-MB within 24 hours after admission were higher [APACHEⅡ score: 22.18±8.38 vs. 17.39±8.22, SOFA score: 9.90±3.87 vs. 7.09±3.27, Lac (mmol/L): 5.10 (2.63, 11.50) vs. 2.00 (1.40, 5.00), NT-proBNP (μg/L): 5.24 (2.84, 11.29) vs. 2.53 (0.35, 6.63), CK-MB (U/L): 1.88 (0.21, 5.33) vs. 0.17 (0.02, 1.62), all P < 0.05], and the proportion of vasoactive drug application was higher (82.05% vs. 47.83%, P < 0.01). Multivariate Logistic regression analysis showed that LVEF on admission was an independent risk factor for predicting the prognosis of patients with septic cardiomyopathy during hospitalization [odds ratio ( OR) = 0.920, 95% confidence interval (95% CI) was 0.855-0.990, P = 0.025]. ROC curve analysis showed that the area under the ROC curve (AUC) of LVEF on admission for predicting the death of patients with septic cardiomyopathy was 0.715 (95% CI was 0.585-0.845, P = 0.005). When LVEF ≤ 0.52, the sensitivity was 73.9%, and the specificity was 61.5%. Conclusions:The lower cardiac ultrasound LVEF on admission, the worse the prognosis of patients with septic cardiomyopathy. The cardiac ultrasound LVEF on admission can be used as a clinical index to evaluate the severity of the condition and predict the prognosis of patients with septic cardiomyopathy.

Prediction of radiomics-based machine learning in dose verification of intensity-modulated pelvic radiotherapy / 中华放射医学与防护杂志

Objective:Based on radiomics characteristics, different machine learning classification models are constructed to predict the gamma pass rate of dose verification in intensity-modulated radiotherapy for pelvic tumors, and to explore the best prediction model.Methods:The results of three-dimensional dose verification based on phantom measurement were retrospectively analyzed in 196 patients with pelvic tumor intensity-modulated radiotherapy plans. The gamma pass rate standard was 3%/2 mm and 10% dose threshold. Prediction models were constructed by extracting radiomic features based on dose documentation. Four machine learning algorithms, random forest, support vector machine, adaptive boosting, and gradient boosting decision tree were used to calculate the AUC value, sensitivity, and specificity respectively. The classification performance of the four prediction models was evaluated.Results:The sensitivity and specificity of the random forest, support vector machine, adaptive boosting, and gradient boosting decision tree models were 0.93, 0.85, 0.93, 0.96, 0.38, 0.69, 0.46, and 0.46, respectively. The AUC values were 0.81 and 0.82 for the random forest and adaptive boosting models, respectively, and 0.87 for the support vector machine and gradient boosting decision tree models.Conclusions:Machine learning method based on radiomics can be used to construct a prediction model of gamma pass rate for specific dosimetric verification of pelvic intensity-modulated radiotherapy. The classification performance of the support vector machine model and gradient boosting decision tree model is better than that of the random forest model and adaptive boosting model.

Evaluation value of Karnofsky performance score for prognosis of elderly patients with sepsis / 中华急诊医学杂志

Objective:To evaluate the prognostic value of Karnofsky performance scores (KPS) in elderly patients with sepsis, so as provide a basis for clinical evaluation of the condition, prognosis and corresponding treatment measures.Methods:A retrospective cohort study was conducted to collect the general information, clinical data, and follow-up data of limb motor function status and self-care ability of elderly patients with sepsis who were hospitalized in the Intensive Care Unit of our hospital from January 2018 to June 2021. Patients were divided into the survival group and death group according to whether they survived the hospitalization. Statistical analysis was performed using t-test, chi-square test, and Mann-Whitney test. The KPS score before admission, disease severity scores (APACHEⅡ and SOFA), serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and arterial blood lactate level on admission were compared between the two groups. Then, the factors with significance in univariate analysis were analyzed by Logistic regression method, the independent risk factors for predicting in-hospital mortality were determined, and the receiver operating characteristic (ROC) curve was drawn to evaluate the prognostic value of KPS score in elderly patients with sepsis.Results:A total of 135 patients were collected. There were 85 males and 50 females, 60 died and 75 survived during hospitalization, with a mortality rate of 44.4%. The preadmission KPS score of elderly patients with sepsis in the death group was significantly lower than that in the survival group [30 (30, 40) vs. 70 (50, 90), P<0.001]. Multivariate logistic regression analysis showed that KPS score ( OR=0.938, 95% CI: 0.914-0.963, P<0.001), SOFA score ( OR=1.255, 95% CI: 1.066-1.451, P=0.002) and arterial blood lactate ( OR=1.219, 95% CI: 1.059-1.404, P=0.006) were independent risk factors for predicting the prognosis during hospitalization. ROC curve analysis of mortality showed that compared with SOFA score and blood lactate, the area under the curve of KPS score was the largest, with AUC of 0.830 (95% CI: 0.756-0.890, P<0.001). In addition, the combination of KPS, SOFA and blood lactate had a greater predictive value for the prognosis of elderly patients with sepsis than that of the single index, with an AUC of 0.883 (95% CI: 0.826-0.940, P<0.001). Conclusions:The lower the KPS score, the worse the prognosis of elderly patients with sepsis. The KPS score can be used as a clinical indicator to predict the prognosis of elderly patients with sepsis.

Expression of forkhead transcription factor O4 in prostate cancer and its effect on prostate cancer cell invasion / 中南大学学报(医学版)

To examine the expression of forkhead transcription factor O4 (FOXO4) in prostate cancer and to explore its effect on prostate cancer cell invasion.
 Methods: Immunohistochemistry was used to detect the expression of FOXO4 in prostate hyperplasia tissues and prostate cancer tissues. Western blot was used to detect the expression of FOXO4 in prostate hyperplasia cell line BPH-1 and prostate cancer cell lines: PC-3 and DU145. PC-3 cells with high relative expression of FOXO4 were transfected with FOXO4 siRNA and scramble siRNA; DU145 cells with low expression of FOXO4 were transfected with FOXO4 plasmid and blank vector. Matrigel Transwell assay was used to detect the invasive ability of transfected cells. The expression of endothelial-mesenchymal transition (EMT)-related proteins E-cadherin, N-cadherin, and vimentin in the transfected cells was detected by Western blot.
 Results: The expression of FOXO4 in prostate cancer cells and tissues was significantly lower than that in the prostate hyperplasia cells and tissues (both P10 (all P<0.05). The expression of FOXO4 in cancer tissues with Gleason score <8 was significantly higher than that in the cancer tissues with Gleason ≥8 (P<0.05). The expression of FOXO4 in clinical stage T1-T2 prostate cancer tissues was higher than that in the clinical stage T3-T4 prostate cancer tissues (P<0.05). The expression of FOXO4 in prostate cancer tissues without lymph node metastasis was significantly higher than that in the prostate cancer tissues with lymph node metastasis (P<0.05). Down-regulation of FOXO4 in PC-3 cells could significantly promote the EMT and invasion, with the decreased expression of E-cadherin and the increased expression of N-cadherin and vimentin (all P<0.05); Up-regulation of FOXO4 in DU145 cells could inhibit the EMT and invasion of cells, with the increased expression of E-cadherin and the decreased expression of N-cadherin and vimentin (all P<0.05).
 Conclusion: FOXO4 is involved in prostate cancer progression, and it can inhibit prostate cancer cell invasion by regulating EMT of prostate cancer cells.

Genetic polymorphisms of HPRTB, DXS6803 and DXS6809 STR loci in Tianjin Han female population / 天津医药

Objective To investigate genetic polymorphisms of HPRTB, DXS6803 and DXS6809 STR loci in Tianjin Han female population, and to provide experimental data in the prenatal diagnosis of aneuploidies accurately and rapidly. Methods A total of 150 blood samples were collected in Tianjin Han population. QF-PCR and capillary electrophoresis were used in this study. The relevant data were analyzed by ABI Prism GeneMapper v3.0 software. Two homozygotes were se?lected from each locus for sequencing. The frequencies of the genotypes were checked using Chi-square test to verify Hardy-Weinberg Equilibrium. Data of genetic polymorphisms were calculated by PowerStatsV12 software. Results A total of 150 samples were successfully amplified in 24 hours. The 10, 6 and 10 alleles and 22, 12 and 29 genotypes were found respec?tively in HPRTB, DXS6803 and DXS6809 loci. The most common alleles were 14, 13 and 14. The higher frequencies of gen?otypes were 14-14, 12-13 and 13-14. No significant deviations from the Hardy-Weinberg equilibrium were observed in these three STR loci (χ2=10.554, 5.783 and 15.355, respectively, P>0.05). Values of He were 0.748, 0.649 and 0.806 for these three STR loci respectively. Values of Ho were 0.607, 0.700 and 0.713 respectively. Values of PIC were 0.706, 0.599 and 0.775 respectively. Values of PD were 0.894, 0.814 and 0.931 respectively. And values of PE were 0.299, 0.428 and 0.449 respectively. Conclusion HPRTB, DXS6803 and DXS6809 STR loci were highly polymorphic, which are favorable genetic markers on chromosome X and can be used in rapid prenatal genetic diagnosis.

Comparing the performance of temporal model and temporal-spatial model for outbreak detection in China Infectious Diseases Automated-alert and Response System, 2011-2013, China / 中华预防医学杂志

<p><b>OBJECTIVE</b>For providing evidences for further modification of China Infectious Diseases Automated-alert and Response System (CIDARS) by comparing the early-warning performance of the temporal model and temporal-spatial model in CIDARS.</p><p><b>METHODS</b>The application performance for outbreak detection of temporal model and temporal-spatial model simultaneously running among 208 pilot counties in 20 provinces from 2011 to 2013 was compared; the 16 infectious diseases were divided into two classes according to the disease incidence level; cases data in nationwide Notifiable Infectious Diseases Reporting Information System was combined with outbreaks reported to Public Health Emergency Reporting System, by adopting the index of the number of signals, sensitivity, false alarm rate and time for detection.</p><p><b>RESULTS</b>The overall sensitivity of temporal model and temporal-spatial model for 16 diseases was 96.23% (153/159) and 90.57% (144/159) respectively, without significant difference (Z = -1.604, P = 0.109), and the false alarm rate of temporal model (1.57%, 57 068/3 643 279) was significantly higher than that of temporal-spatial model (0.64%, 23 341/3 643 279) (Z = -3.408, P = 0.001), while the median time for detection of these two models was not significantly different, which was 3.0 days and 1.0 day respectively (Z = -1.334, P = 0.182).For 6 diseases of type I which represent the lower incidence, including epidemic hemorrhagic fever,Japanese encephalitis, dengue, meningococcal meningitis, typhus, leptospirosis, the sensitivity was 100% for both models (8/8, 8/8), and the false alarm rate of both temporal model and temporal-spatial model was 0.07% (954/1 367 437, 900/1 367 437), with the median time for detection being 2.5 days and 3.0 days respectively. The number of signals generated by temporal-spatial model was reduced by 2.29% compared with that of temporal model.For 10 diseases of type II which represent the higher incidence, including mumps, dysentery, scarlet fever, influenza, rubella, hepatitis E, acute hemorrhagic conjunctivitis, hepatitis A, typhoid and paratyphoid, and other infectious diarrhea, the sensitivity of temporal model was 96.03% (145/151), and the sensitivity of temporal-spatial model was 90.07% (136/151), the number of signals generated by temporal-spatial model was reduced by 59.36% compared with that of temporal model. Compared to temporal model, temporal-spatial model reduced both the number of signals and the false alarm rate of all the type II diseases;and the median of outbreak detection time of temporal model and temporal-spatial model was 3.0 days and 1.0 day, respectively.</p><p><b>CONCLUSION</b>Overall, the temporal-spatial model had better outbreak detection performance, but the performance of two different models varies for infectious diseases with different incidence levels, and the adjustment and optimization of the temporal model and temporal-spatial model should be conducted according to specific infectious disease in CIDARS.</p>

Genetic Polymorphisms of STR Loci D18S53, D18S59 and D18S488 in Fetus in Tianjin / 天津医药

Objective To investigate the genetic polymorphisms of 3 short tandem repeat (STR) loci D18S53, D18S59 and D18S488 on chromosome 18 in fetus of Tianjin Han population, and to provide basic data in the use of 3 STR lo-ci in the prenatal diagnosis of Edward syndrome (ES). Methods A total of 64 villus samples and 374 amniotic fluid sam-ples were collected from gravida in Tianjin Han population. QF-PCR and ABI PRISM 377 sequence were used in this study. The frequencies of the genotypes were tested with H-W equilibrium. Genetic analysis was performed to conclude some data of population genetics such as the frequency of the alleles, the heterozygosity of observation (Ho), the polymorphism informa-tion content (PIC), the probability of discrimination power (DP), and the probability of exclusion (PE). Results The 15, 13 and 15 alleles of D18S53, D18S59 and D18S488 were observed respectively. The frequencies of the genotypes were in good agreement with H-W equilibrium. The Ho of 3 STR loci were 0.797, 0.847 and 0.792. The PIC was 0.81, 0.75 and 0.73. The DP was 0.944, 0.901 and 0.881. The PE was 0.593, 0.689 and 0.585. Conclusion D18S53, D18S59 and D18S488 STR lo-ci were the favorable genetic markers of chromosome 18, which can be used in prenatal genetic diagnosis of ES.

The expression and correlation of TLR4 and NF-κB p65 in colorectal carcinoma / 中华检验医学杂志

Objective To investigate the expression of TLR4 mRNA and NF-κB p65 in colorectal carcinomas and adjacent normal colon tissue, and evaluate their roles in the pathogenesis and development in colorectal carcinoma. Methods Sixty-three colorectal carcinoma samples and respective adjacent normal colon tissue samples ( well differentiated : 23 cases; moderately differentiated: 17 cases; poorly differentiated:20 cases; other differentiated type: 3 cases; lymph node metastasis: 27 cases; no lymph node metastasis:36 cases; Dukes A: 18cases;Dukes B: 14 cases Dukes C: 22 cases; Dukes D: 9 cases) were collected. The expression of TLR4 mRNA in colorectal carcinomas and adjacent tissue were detected by RT-PCR. The expression of NF-κB p65 was detected by WB. Results The expression of TLR4 mRNA in colorectal carcinomas and adjacent tissue were 86.42 ± 15.16 and 32.74 ± 9.44. It was significantly higher in carcinoma tissue than that in adjacent tissue ( t = 22.354, P ＜ 0.01 ). The expression of TLR4 mRNA in well, moderately and poorly differentiated coiorectal carcinomas were 69.58 ± 11.27, 64.57 ± 13.91 and 97.12 ± 15.44 respectively. TLR4 mRNA in poorly differentiated colorectal carcinomas was significantly higher than that in well, moderately differentiated ones ( t = 11.304 and 12.223, P ＜ 0.01 ). There was no difference between lymph node metastatic carcinomas ( 89.91 ± 13.33 ) and carcinomas without metastasis (81.16±13.59,t =0.959,P＞0.05). The expression of TLR4 mRNA in the Dukes A stage tumors (59.05±11.66) was lower than that in Dukes B(90.34 ±0.08),C(91.41 ± 15.21), D(101.46 ±17.43), respectively ( t = 8.708,9.664,9.525, P ＜ 0.05 ). The expression of NF-κB p65 in colorectal carcinoma(0.63 ±0.11) was significant higher than that in adjacent tissue(0.34 ±0.08,t = 18.266,P ＜0.01 ). The expression of NF-κB p65 in well, moderately and poorly differentiated colorectal carcinomas were 0.46 ± 0.09, 0.72 ± 0.11 and 0.77 ± 0.14, respectively. The experssion of NF-κB p65 in well differentiated colorectal carcinomas was obviously lower than the woderately and poorly differentiated carcinomas (t = 11.223 and 10.875, P ＜0.01 ). There was significant difference between the expression of p65 in lymph node metastatic carcinomas(0.82 ± 0.17) and non-metastatic carcinomas(0.57 ± 0.12, t =18.269,P＜0.05). The expression of NF-κB p65 in Dukes A colorectal carcinomas (0.39 ± 0.06) was lower compared with the Dukes B(0.72 ±0.12), C(0.69 ±0.14) and D carcinomas(0.76 ±0.13,t =10.442, 9.889 and 9.721, P ＜ 0.01 ). Conclusions The enhanced expression of TLR4/NF-κB p65 are closely associate with clinical stage and pathologic grade. NF-κB p65 may be an molecular marker of lymph node metastatic. The increased expression of TLR4/NF-κB p65 promote the pathogenesis and development of colorectal carcinoma.