Objective:To retrospectively analyze the results of second-trimester serological prenatal screening and explore the factors which may influence the false-positive rate (FPR).Methods:From January 2013 to December 2022, false-positive samples with follow-up outcomes from 632, 825 second-trimester serological prenatal screening samples tested at Sichuan Provincial Maternity and Child Health Care Hospital were selected as the study group, while true-negative samples were 1 : 1 matched as the control group by propensity-score matching (PSM). Univariate and Multivariate Logistic Regression Models were used to analyze the influencing factors. The study has approved by the Medical Ethics Committee of the Sichuan Provincial Maternity and Child Health Care Hospital (Ethic No.20240607-270).Results:The study and control groups were each matched with 305, 998 cases. Univariate analysis showed that sampling season, the difference between ultrasound and gestational weeks calculated by last menstrual period (LMP), monthly median multiple of the median (mMoM) of alpha-fetoprotein (AFP), and monthly mMoM of free β-human chorionic gonadotropin (free β-hCG) were significantly different between the two groups ( P<0.05). Multivariate Logistic Regression analysis showed that winter ( OR=0.938; 95% CI: 0.893~0.985), monthly AFP mMoM ≥ 1.11 ( OR=0.846; 95% CI: 0.761~0.941), monthly free β-hCG mMoM ≤ 0.89 ( OR=0.827; 95% CI: 0.737~0.929) are protective factors for FPR increase, whilst spring ( OR=1.124; 95% CI: 1.072~1.179), summer ( OR=1.121; 95% CI: 1.062~1.183), the difference between ultrasound and gestational weeks calculated by LMP of 8~14 days ( OR=1.319; 95% CI: 1.241~1.402), > 14 days ( OR=1.689; 95% CI: 1.542~1.850), monthly AFP mMoM of 0.90~0.94 ( OR=1.088; 95% CI: 1.046~1.131), and monthly free β-hCG mMoM of 1.05~1.10 ( OR=1.046; 95% CI: 1.000~1.094), ≥ 1.11 ( OR=1.062; 95% CI: 1.002~1.126) are risk factors for FPR increase. Conclusion:Sampling season, difference between ultrasound and gestational weeks by LMP, monthly AFP mMoM, and monthly free β-hCG mMoM are risk factors for FPR during serological prenatal screening. Screening laboratories should look for the cause of abnormal FPR through such factors and adjust them accordingly.

OBJECTIVE: To retrospectively analyze the results of second-trimester serological prenatal screening and explore the factors which may influence the false-positive rate (FPR). METHODS: From January 2013 to December 2022, false-positive samples with follow-up outcomes from 632,825 second-trimester serological prenatal screening samples tested at Sichuan Provincial Maternity and Child Health Care Hospital were selected as the study group, while true-negative samples were 1 : 1 matched as the control group by propensity-score matching (PSM). Univariate and binary logistic regression models were used to analyze the influencing factors. This study was approved by the Medical Ethic Committee of Sichuan Provincial Maternity and Child Health Care Hospital (Ethic No. 20240607-270). RESULTS: The study and control groups were each matched with 305,998 cases. Univariate analysis showed that sampling season, the difference between ultrasound and gestational weeks calculated by last menstrual period (LMP), monthly median multiple of the median (mMoM) of alpha-fetoprotein (AFP), and monthly mMoM of free β -human chorionic gonadotropin (free β -hCG) were significantly different between the two groups (P < 0.05). Binary logistic regression analysis showed that Winter (OR = 0.938; 95%CI: 0.893 ~ 0.985), monthly AFP mMoM ≥ 1.11 (OR = 0.846; 95%CI: 0.761 ~ 0.941), monthly free β -hCG mMoM ≥ 0.89 (OR = 0.827; 95%CI: 0.737 ~ 0.929) are protective factors for FPR increase, whilst Spring (OR = 1.124; 95%CI: 1.072 ~ 1.179), Summer (OR = 1.121; 95%CI: 1.062 ~ 1.183), the difference between ultrasound and gestational weeks calculated by LMP of 8 ~ 14 days (OR = 1.319; 95%CI: 1.241 ~ 1.402), < 14 days (OR = 1.689; 95%CI: 1.542 ~ 1.850), monthly AFP mMoM of 0.90 ~ 0.94 (OR = 1.088; 95%CI: 1.046 ~ 1.131), and monthly free β -hCG mMoM of 1.05 ~ 1.10 (OR = 1.046; 95%CI: 1.000 ~ 1.094), ≥ 1.11 (OR = 1.062; 95%CI: 1.002 ~ 1.126) are risk factors for FPR increase. CONCLUSION Sampling season, difference between ultrasound and gestational weeks by LMP, monthly AFP mMoM, and monthly free β -hCG mMoM are risk factors for FPR during serological prenatal screening. Screening laboratories should look for the cause of abnormal FPR through such factors and adjust them accordingly.
Humans ; Female ; Pregnancy ; Propensity Score ; Pregnancy Trimester, Second/blood* ; Retrospective Studies ; China ; False Positive Reactions ; Adult ; Prenatal Diagnosis/methods* ; alpha-Fetoproteins/analysis* ; Logistic Models ; Chorionic Gonadotropin, beta Subunit, Human/blood*

Objective:To retrospectively analyze the results of second-trimester serological prenatal screening and explore the factors which may influence the false-positive rate (FPR).Methods:From January 2013 to December 2022, false-positive samples with follow-up outcomes from 632, 825 second-trimester serological prenatal screening samples tested at Sichuan Provincial Maternity and Child Health Care Hospital were selected as the study group, while true-negative samples were 1 : 1 matched as the control group by propensity-score matching (PSM). Univariate and Multivariate Logistic Regression Models were used to analyze the influencing factors. The study has approved by the Medical Ethics Committee of the Sichuan Provincial Maternity and Child Health Care Hospital (Ethic No.20240607-270).Results:The study and control groups were each matched with 305, 998 cases. Univariate analysis showed that sampling season, the difference between ultrasound and gestational weeks calculated by last menstrual period (LMP), monthly median multiple of the median (mMoM) of alpha-fetoprotein (AFP), and monthly mMoM of free β-human chorionic gonadotropin (free β-hCG) were significantly different between the two groups ( P<0.05). Multivariate Logistic Regression analysis showed that winter ( OR=0.938; 95% CI: 0.893~0.985), monthly AFP mMoM ≥ 1.11 ( OR=0.846; 95% CI: 0.761~0.941), monthly free β-hCG mMoM ≤ 0.89 ( OR=0.827; 95% CI: 0.737~0.929) are protective factors for FPR increase, whilst spring ( OR=1.124; 95% CI: 1.072~1.179), summer ( OR=1.121; 95% CI: 1.062~1.183), the difference between ultrasound and gestational weeks calculated by LMP of 8~14 days ( OR=1.319; 95% CI: 1.241~1.402), > 14 days ( OR=1.689; 95% CI: 1.542~1.850), monthly AFP mMoM of 0.90~0.94 ( OR=1.088; 95% CI: 1.046~1.131), and monthly free β-hCG mMoM of 1.05~1.10 ( OR=1.046; 95% CI: 1.000~1.094), ≥ 1.11 ( OR=1.062; 95% CI: 1.002~1.126) are risk factors for FPR increase. Conclusion:Sampling season, difference between ultrasound and gestational weeks by LMP, monthly AFP mMoM, and monthly free β-hCG mMoM are risk factors for FPR during serological prenatal screening. Screening laboratories should look for the cause of abnormal FPR through such factors and adjust them accordingly.

Objective To characterize the distribution and assess the exposure to phthalic acid esters （PAEs） in the indoor dust of Shanghai City. Methods Samples were collected from 33 sampling sites， including homes， hotels， offices and public places， in Shanghai in 2018， 2019， and 2020. The samples were pretreated by 100 sieves， extracted and concentrated， and then analyzed by gas chromatography-mass spectrometry in selected ion mode （SIM）. Results Results on the characteristics of PAEs in indoor dust in different places showed that concentrations of PAEs were in a range of <0.01-2 464 mg·kg^-1.The average concentration of 16 PAEs was 613 mg·kg^-1. Bis（2-ethylhexyl） phthalate （DEHP）， di-iso-butyl phthalate （DiBP）， di-n-butyl phthalate （DBP） and di-n-octyl phthalate （DnOP） were the main components of PAEs in indoor dust， accounting for approximately 99.5% of 16 PAEs. The intake of DEHP， DBP， DEP and BBP was lower than the tolerable daily intake （TDI） and reference doses （RfD） set by EU CSTEE and U.S. EPA. Conclusion Average daily dose （ADD） via indoor dust is estimated， and the order of intake through different pathways is hand-oral intake>skin contact>respiratory inhalation. Exposure risk of PAEs in children is greater than that in adults.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Objective To investigate the risk factors predicting pathology grade upgrading after radical prostatectomy using the 2014 International Society of Urologic Pathology (ISUP) grading system.Methods A total of 205 patients who underwent biopsy and radical prostatectomy from January 2017 to December 2018 were reviewed retrospectively.The median and range of the patients' age,PSA level,prostate volume,number of biopsy core examined,Gleason score and ISUP grade were 66 (45-81) years old,17.16(0.89-1254.00)ng/ml,36.4(4.1-152.1) rnl,10(1-15),7(6-10),and 3(1-5) respectively.The patients were divided into group of upgrading ISUP grade and group without upgrading ISUP grade.Multivariate Logistic regression analysis and receiving operating characteristic curve analysis were performed to identify predictors of ISUP upgrading and determine the optimal cut off value respectively.Result The median and range of Gleason score and ISUP grade after radical prostatectomy were 7 (6-10),and 3 (1-5) respectively.The radical prostatectomy ISUP grade upgraded in 73 (35.6％) out of 205 cases when compared with biopsy ISUP grade.Radical prostatectomy ISUP grades were concordant in 91 cases (44.4％) and downgraded in 41 cases(20.0％).Of 101 with biopsy ISUP grades less than or equal to 2,the ISUP grade of radical prostatectomy upgraded in 58 cases (57.4％),while radical prostatectomy ISUP grade upgraded in only 18 (26.9％) of 67 patients with biopsy ISUP grades of 3 or 4.Biopsy ISUP grades represent an independent predictor for ISUP grade upgrading after radical prostatectomy (OR =0.496,P ＜ 0.001).Conclusion Patients with biopsy ISUP grades less than or equal to 2 are at great risk of ISUP grade upgrading after radical prostatectomy.

Objective:To investigate the characteristics of senile neurodegenerative diseases (NDDs) inpatients in south China, especially in Guangdong province, and explore the influencing factors for their medical expenses.Methods:The medical records of 7231 patients with NDDs≥65 years were collected in the electronic health database of our hospital from January 2010 to December 2019, including gender, age, admission ways, chief complaints, length of hospital stays and medical expenses. On the basis of median of the medical expenses (21 345 yuan) of these patients, they were divided into low cost (<21 345 yuan) group and high cost (≥21 345 yuan) group. Univariate Logistic analysis and multivariate Logistic regression analysis were conducted to screen the influencing factors for medical expenses and the independent influencing factors.Results:(1) The main age group of geriatric inpatients with NDDs were 70-79 years (40.96%); the admission source was mainly outpatient (56.70%), and length of hospital stays of a large percent of patients (44.50%) were 8-14 d. (2) From 2010 to 2019, the number of hospitalized geriatric patients with NDDs showed an increasing trend year by year, the overall trend of length of hospital stays was shortened, and the medical expenses showed gradual increase; the causes of hospitalization, percentages of patients caused by infection, abnormal blood pressure and water-electrolyte metabolism disturbances showed decreased trend, percentages of patients caused by heart diseases, cerebrovascular accidents and mental-psychological diseases showed increased trend, and the proportions of patients caused by fracture/trauma/wound injuries were generally stable. The proportion of patients returning home and mortality rate after hospital discharge were declined, and the proportion of patients returning to other medical or community institutions was increased. (3) Living in ICU, length of hospital stays, diabetes, nosocomial infection, chronic kidney disease, urinary tract infection, tumble, body mass index, and anticholinergic drugs were independent risk factors influencing the medical expenses ( P<0.05). Conclusions:An aging trend is noted in patients with NDDs; the number of hospitalized patients and medical expenses increase year by year, and the length of hospital stays gradually decreases. In view of the many factors that influence the medical expenses of this disease, it is suggested to develop the corresponding standardized treatment plan for the main influencing factors in clinical practice.

Objective To evaluate the characteristics of left ventricular structure ,function ,myocardial mechanics ,hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy ( HCM ) using state‐of‐the‐art echocardiography . Methods A consecutive series of 85 adult HCM patients w ho were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected . According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography ,the patients were divided into three groups :patients with non‐obstructive HCM ( n ＝28) ,those with labile‐obstructive HCM ( n ＝27) ,and those with obstructive HCM ( n ＝ 30 ) . In addition ,16 normal family members of HCM patients were included as control group . T wo‐dimensional speckle tracking imaging ,tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states . Results ① As compared with the control group ,left ventricular end‐diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups ( all P ＜ 0 .05 ) . Left ventricular maximum wall thickness and left ventricular mass index were the highest in obstructive HCM , followed by labile‐obstructive and non‐obstructive HCM ,and the lowest in the control group ( all P ＜0 .05) . ②A t rest ,the left ventricular global longitudinal ,circumferential and radial strain ( GLS ,GCS and GRS) ,as well as the twist of obstructive HCM were significantly lower than the other three groups ( all P ＜0 .05) . As compared with the control group ,the GLS and twist decreased in the labile‐obstructive and non‐obstructive HCM ( all P ＜0 .05 ) ,but there were no significant changes of GCS and GRS ( all P ＞ 0 .05 ) . T he obstructive HCM had the lowest mitral annular plane systolic excursion ( M APSE ) and s′,and the longest systolic peaking time standard deviation( T s‐SD) and early diastolic peaking time standard deviation ( Te‐SD) ( all P ＜0 .05) . T he left ventricular diastolic function of obstructive HCM ( e′,the E/e′ratio and the left atrial volume index ) was the worst ,labile‐obstruction and non‐obstructive HCM were better ,and the control group was the best ( all P ＜ 0 .001 ) . ③ During exercise ,the GLS ,GCS ,GRS ,twist of the left ventricle and the M APSE were the lowest in the obstructive HCM ,which increased in the labile‐obstructive and non‐obstructive HCM ,and were best in the control group . T he T s‐SD and Te‐SD were the shortest in the control group ,were prolonged in non‐obstructive and labile‐obstruction HCM ,and were longest in obstructive HCM ( all P ＜ 0 .05 ) . Additionally ,the exercise time of the control group was the longest , followed by non‐obstructive and labile‐obstruction HCM ,and the shortest in the obstructive HCM ( all P ＜0 .05) . T he M ET s of obstructive HCM were significantly lower than the other three groups ( all P ＜0 .05) . Conclusions In obstructive HCM ,the left ventricular systolic strain and synchronization ,as well as the M APSE ,are significantly impaired in patients both at rest and during exercise . T he patients with labile‐obstructive and non‐obstructive HCM have reduced left ventricular GLS , twist ,and e′,but normal left ventricular GCS ,GRS ,synchrony ,and M APSE at rest ,which are all impaired during exercise .

Objective: To evaluate the characteristics of left ventricular structure, function, myocardial mechanics, hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy (HCM) using state-of-the-art echocardiography. Methods: A consecutive series of 85 adult HCM patients who were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected. According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography, the patients were divided into three groups: patients with non-obstructive HCM (n=28), those with labile-obstructive HCM (n=27), and those with obstructive HCM (n=30). In addition, 16 normal family members of HCM patients were included as control group. Two-dimensional speckle tracking imaging, tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states. Results: ①As compared with the control group, left ventricular end-diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups(all P<0.05). Left ventricular maximum wall thickness and left ventricular mass index were the highest in obstructive HCM, followed by labile-obstructive and non-obstructive HCM, and the lowest in the control group (all P<0.05). ②At rest, the left ventricular global longitudinal, circumferential and radial strain (GLS, GCS and GRS), as well as the twist of obstructive HCM were significantly lower than the other three groups (all P<0.05). As compared with the control group, the GLS and twist decreased in the labile-obstructive and non-obstructive HCM(all P<0.05), but there were no significant changes of GCS and GRS (all P>0.05). The obstructive HCM had the lowest mitral annular plane systolic excursion (MAPSE) and s′, and the longest systolic peaking time standard deviation(Ts-SD) and early diastolic peaking time standard deviation(Te-SD) (all P<0.05). The left ventricular diastolic function of obstructive HCM (e′, the E/e′ ratio and the left atrial volume index) was the worst, labile-obstruction and non-obstructive HCM were better, and the control group was the best (all P<0.001). ③During exercise, the GLS, GCS, GRS, twist of the left ventricle and the MAPSE were the lowest in the obstructive HCM, which increased in the labile-obstructive and non-obstructive HCM, and were best in the control group. The Ts-SD and Te-SD were the shortest in the control group, were prolonged in non-obstructive and labile-obstruction HCM, and were longest in obstructive HCM (all P<0.05). Additionally, the exercise time of the control group was the longest, followed by non-obstructive and labile-obstruction HCM, and the shortest in the obstructive HCM (all P<0.05). The METs of obstructive HCM were significantly lower than the other three groups (all P<0.05). Conclusions In obstructive HCM, the left ventricular systolic strain and synchronization, as well as the MAPSE, are significantly impaired in patients both at rest and during exercise. The patients with labile-obstructive and non-obstructive HCM have reduced left ventricular GLS, twist, and e′, but normal left ventricular GCS, GRS, synchrony, and MAPSE at rest, which are all impaired during exercise.

OBJECTIVETo explore the relationship between electrocardiographic (ECG) and genetic mutations of patients with hypertrophic cardiomyopathy (HCM), and early ECG changes in HCM patients.

METHODSClinical, 12-lead ECG and echocardiographic examination as well as genetic examinations were made in a three-generation Chinses HCM pedigree with 8 family members (4 males). The clinical characterization and ECG parameters were analyzed and their relationship with genotypes in the family was explored.

RESULTSFour missense mutations (MYH7-H1717Q, MYLK2-K324E, KCNQ1-R190W, TMEM70-I147T) were detected in this pedigree. The proband carried all 4 mutations and 5 members carried 2 mutations. Corrected QTc interval of KCNQ1-H1717Q carriers was significantly prolonged and was consistent with the ECG characterization of long QT syndrome. MYLK2-K324E and KCNQ1-R190W carriers presented with Q wave and(or) depressed ST segment, as well as flatted or reversed T waves in leads from anterolateral and inferior ventricular walls. ECG results showed ST segment depression, flat and inverted T wave in the gene mutation carriers with normal echocardiographic examination results. ECG and echocardiographic results were normal in TMEM70-I147T mutation carrier.

CONCLUSIONSThe combined mutations of the genes associated with cardiac ion channels and HCM are linked with the ECG phenotype changes in this HCM pedigree. The variations in ECG parameters due to the genetic mutation appear earlier than the echocardiography and clinical manifestations. Variation in ECG may become one of the indexes for early diagnostic screening and disease progression of the HCM gene mutation carriers.

Brugada Syndrome ; Cardiac Conduction System Disease ; Cardiac Myosins ; Cardiomyopathy, Hypertrophic ; Echocardiography ; Electrocardiography ; Exons ; Genetic Testing ; Genotype ; Humans ; KCNQ1 Potassium Channel ; Long QT Syndrome ; Mutation ; Mutation, Missense ; Myosin Heavy Chains ; Myosin-Light-Chain Kinase ; Pedigree ; Phenotype