Objective:To understand the current and integrated disease burden and economic burden caused by breast cancer in females in China.Methods:Based on six updated data sources, including the series of Chinese Cancer Registry Annual Report, China Death Cause Surveillance Datasets, China Health Statistical Yearbook, GLOBOCAN, Cancer Incidence in Five Continents, Global Burden of Disease Study (GBD), the information about incidence, mortality and disability adjusted life years (DALY) of breast cancer were extracted for the analysis on the current incidence and time trend of breast cancer and predicted disease burden of breast cancer in females in China. Software Joinpoint was used for time trend analysis. The data of economic burden were systematically updated and analyzed by literature review.Results:1) GLOBOCAN 2022 estimated that the age-standardized incidence rate (ASIR) age-standardized mortality rate (ASMR) and one- year prevalence rate of breast cancer in females were 33.0/100 000, 6.1/100 000 and 40.1/100 000, respectively, in China in 2022. According to Chinese Cancer Registry Annual Report, the ASIR and ASMR were 28.4/100 000 and 5.8/100 000, respectively, in 2018. The China Death Cause Surveillance Datasets showed that the ASMR was 4.5/100 000 in 2021, and the urban to rural area mortality ratio was 1.2∶1. GBD reported that the DALYs of breast cancer were 2.921 million in China in 2021, accounting for 14.4% of the global total. 2) Chinese Cancer Registry Annual Report data showed that the ASIR and ASMR of breast cancer decreased by 2.1% and 11.4%, respectively, in China from 2009 to 2018, while increased by 43.9% and 8.2% in rural area, respectively. The Joinpoint analysis showed that the average annual percentage change (AAPC) of ASIR and ASMR in China were -0.2% ( P>0.05) and -1.6% ( P<0.05). The AAPC of ASIR and ASMR in rural area were 3.9% ( P<0.05) and 0.6% ( P>0.05), and -0.3% ( P>0.05) and -1.2% ( P<0.05) in urban area, respectively. China Health Statistical Yearbook data showed that the urban ASMR decreased by 12.3% from 2014 to 2021 with AAPC of -2.6% ( P<0.05). 3) The GLOBOCAN 2022 predicted that, the breast cancer case count and death count in China would be 387 776 and 111 133 by 2050, an increase of 8.6% and 48.2%, respectively, compared with 2022, the increases would be more obvious in people over 65 years old, an increase of 80.8% and 124.9%, respectively. 4) Thirteen individual- based studies reported that the median medical expenditure per patient ( M=21 000 to 39 000 Yuan) and length of hospital stay ( M=11.0 to 30.5 days) for breast cancer treatment decreased from 2010 to 2019, while the average medical expenditure per visit ( M=9 000 to 23 000 Yuan) showed an upward trend. There was only one national-level analysis, which showed that the treatment cost of breast cancer was 25.24 billion Yuan in China in 2018, accounting for 6.4% of the total cancer treatment cost. Conclusions:According to the above updated multi-source data, the incidence and mortality of female breast cancer in China were stable in the past ten years, but the increasing trend in rural area should be noted. The direct medical expenditure of breast cancer treatment per case might decrease, but the population-level economic burden would remain heavy due to population aging.

Objective To analyze the predictive value of serum micro RNA(miR)-411-5p and micro RNA(miR)-485-5p levels in preeclampsia(PE)pregnant women combined with ultrasound blood flow indicators for perinatal outcomes.Methods A total of 88 pregnant women with PE who were enrolled in the obstetric card and underwent cesarean section in Beijing Nuclear Industry Hospital from January 2020 to December 2021 were selected as the study subjects(PE group).In addition,90 normal pregnant women who delivered by cesarean section due to other reasons in the same period were regarded as the control group.The differences of pulsitility index(PI)and resistance index(RI)were compared between the two groups.The serum levels of miR-411-5p and miR-485-5p were measured and compared between the two groups by real time fluorescent quantitative PCR(qRT-PCR).According to the different perinatal outcomes of PE patients,they were grouped into good outcome group and poor outcome group.The differences of PI,RI,miR-411-5p and miR-485-5p between the two groups were compared.The predictive effect of PI,RI,miR-411-5p,miR-485-5p and combined detection on the adverse perinatal outcome of PE patients was analyzed by the receiver operating characteristic(ROC)curve method.Results The RI(0.79±0.08)and PI values(1.82±0.08)of pregnant women in the PE group were higher than those in the control group(0.66±0.06,1.38±0.15),the serum levels of miR-411-5p(0.32±0.09)and miR-485-5p(0.26±0.03)were lower than those in the control group(1.01±0.08,1.02±0.09),and the differences were statistically significant(t=12.283,24.339,54.091,75.231,all P＜0.001).The RI(0.83±0.08)and PI(1.86±0.09)values of PE patients in the poor outcome group were higher than those in the good outcome group(0.70±0.07,1.71±0.07),the serum levels of miR-411-5p(0.27±0.02)and miR-485-5p(0.24±0.02)were lower than those in the good outcome group(0.45±0.04,0.31±0.04),and the differences were statistically significant(t=11.545,12.428,37.840,14.716,all P＜0.001).The areas under the curve of ultrasound blood flow index RI and PI to predict the adverse perinatal outcome of PE patients were 0.838(sensitivity was 90.8％,specificity was 65.2％),and 0.758(sensitivity was 50.8％,specificity was 91.3％),respectively.The areas under the curve of serum miR-411-5p and miR-485-5p in predicting adverse perinatal outcome of PE patients were 0.830(sensitivity was 90.8％,specificity was 73.9％),and 0.769(sensitivity was 95.4％,specificity was 61.9％),respectively.The area under the curve of the four combined tests to predict the adverse perinatal outcome of PE patients was 0.976(sensitivity was 98.5％,specificity was 91.3％).Conclusion The levels of miR-411-5p and miR-485-5p in serum of PE pregnant women were decreased,and the combination of miR-411-5p and miR-485-5p and ultrasound blood flow indicators PI and RI may predict the perinatal fetal outcome of PE pregnant women.

Objective To explore the genetic polymorphism and mutation rate of 36 Y-STR loci in Sichuan Han population and provide basic data for their forensic applications.Methods Blood samples were collected from 307 unrelated male individuals and 367 father-son pairs in Sichuan Han population using FTA blood sampling cards.The Y41SE-v1.2 kit was used to type 36 Y-STR loci,and the population genetic parameters and mutation rates of each locus were calculated.The genetic relationship between Sichuan Han population and other ethnic populations was analyzed in combination with 19 other populations in China.Results A total of 79 mutations were observed in 36 Y-STR loci in 367 father-son pairs of Sichuan Han population,with an average mutation rate of 6.00×10-3.There were 74(93.67%)one-step mutations and 5(6.33%)multi-step mutations.A total of 383 alleles were found at 36 Y-STR loci in 307 Sichuan Han males.The number of alleles at each locus ranged from 5(0.016 29)to 56(0.182 41),GD ranged from 0.100 02(DYS645)to 0.959 99(DYS385),and 306 haplotypes were found.The HD,DC and HMP values were 0.999 973,99.67%and 0.003 284,respectively.The results of genetic distance(Fst)analysis showed that the Sichuan Han population had the closest genetic distance with the Chongqing Han population(0.000 9)and the furthest genetic distance with the Xinjiang Mongolian group(0.032 0).The MDS based on genetic distance was basically consistent with the results of cluster analysis.Conclusion The 36 Y-STR loci have high genetic polymorphism in the Sichuan Han population.The study data can provide data support for the construction of the Y-STR database in this region,and also provide basic genetic information for forensic investigation and population genetics research.

Objective:To investigate the study on the diagnostic value of multimodal ultrasound technique for the lesion of extensor carpi ulnaris(ECU)tendon in patients with rheumatoid arthritis(RA).Methods:A total of 175 RA patients who were confirmed by the department of rheumatology of Yantaishan Hospital of Yantai city from December 2021 to January 2023 were selected,and them were included into the RA group.Other 50 patients without RA but with clinical symptoms of wrist were included into the non-RA group,and 50 healthy volunteers were included into the healthy control group.All subjects underwent routine ultrasound and shear wave elastography(SWE)examination on wrist,and then,the characteristics of ultrasound images of wrists and the blood flow distribution of ECU power Doppler ultrasonography(PDUS)were recorded.SWE was used to measure ECU to obtain elastic modulus index(EI)and velocity modulus index(VI).The differences between three groups were compared,and the receiver operating characteristic(ROC)value of RA patients were drawn,so as to confirm the area under curve(AUC)value and optimize cutoff value.Results:There were significant differences in EI and VI of the ECU tendon among three groups(F=61.15,61.28,P<0.05),respectively.The optimal cut-off values of EI and VI were respectively 319.35 kPa and 10.55 m/s in RA patients.In RA patients,age and disease course had significant influences on EI(r=0.19,0.21,P<0.05),and age,disease course,ultrasound score of wrist joint,and grade of power Doppler ultrasonography PDUS of the ECU tendon(ECUPDUS)had significant influences on VI(r=0.19,0.15,-0.16,-0.17,P<0.05).Conclusion:SWE is able to quantitatively and non-invasively assess the stiffness information of the ECU tendon in RA patients.After the supplement of gray-scale ultrasound and PDUS,multimodal ultrasound technique can clearly judge the correlation of the lesions of ECU tendon of RA patients.

Objective To investigate the progress of two-dimensional echocardiographic parameters in patients with different severity of aortic stenosis.Methods A retrospective analysis was per-formed on 96 patients diagnosed with aortic stenosis with at least 2 times of transthoracic echo-cardiography(interval ≥1 year)in Department of Cardiology,Fourth Medical Center of Chinese PLA General Hospital from March 2017 to December 2023.According to aortic stenosis severity,they were divided into a mild group(72 cases),a moderate group(14 cases)and a severe group(10 cases).Peak pressure gradient(PPG)across aortic valve,Vmax,mean aortic valve pressure gradient(ΔPm),pulmonary artery systolic pressure(PASP)were collected,and the changes and annual progress of these echocardiographic parameters at baseline and before and after follow-up were analyzed.Results The values of IVST,LVPWT,Vmax,aortic valve PPG and ΔPm were sig-nificantly increased in the mild,moderate and severe stenosis groups in turn(P＜0.05,P＜0.01).The values of Vmax,PPG and ΔPm were significantly lower in the mild stenosis group than the moderate and severe stenosis groups,and the LVPWT value was obviously lower in the mild ste-nosis group than the severe stenosis group(P＜0.05).The aortic valve PPG and ΔPm values at follow-up were significantly higher than those before the follow-up in the three stenosis groups(P＜0.05,P＜0.01).After follow-up,the Vmax values in mild and moderate stenosis groups were notably higher than before(P＜0.01).The PASP value at follow-up was significantly higher than before in the severe stenosis group(P＜0.05).The annual progression rate of Vmax,PASP,LVEF were gradually increased in the mild,moderate,and severe stenosis groups(P＞0.05).The annual progression rate of ΔPm was gradually increased in the three groups in turn(2.30±1.77 mm Hg/year vs 2.40±1.18 mm Hg/year vs 6.08±1.70 mm Hg/year,P＜0.05).Conclusion As the severity of baseline aortic stenosis increases,obvious changes are observed in cardiac structure and function.Before and after follow-up,the serious the aortic stenosis severity is,the faster the annual progression rates of Vmax,PPG,LVEF and PASP are.

Objective Explore the feasibility and accuracy of using deep learning techniques for gender inference in panoramic dental radiography images of Chinese Han population.Methods A total of 10,600 OPG images from Han individuals aged 18 to 70(5,300 males and 5,300 females)were collected and randomly divided into training set,validation set,and test set in an 8:1:1 ratio.MobileNetV2,Swin Transformer Small,and Swin Transformer Tiny models were trained,and the classification performance of the models was evaluated and visually displayed using accuracy,F1 score,and Grad-CAM algorithm.Results The accuracy of MobileNetV2,Swin Transformer Small,and Swin Transformer Tiny models was 97.57%,95.13%,and 96.28%respectively,with MobileNetV2 model showing the best overall performance.The Grad-CAM algorithm revealed that male OPG images mainly focused on the left and right mandibular branches and alveolar bone,while female OPG images mainly focused on the maxillary sinus,left mandibular branch,and posterior alveolar bone.Conclusion This study demonstrates that the gender inference model based on deep learning techniques for OPG images of Chinese Han population has high accuracy and generalization ability,providing a new approach for forensic gender determination in forensic medicine.

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). METHODS: From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. RESULTS: Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. CONCLUSION Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular/genetics* ; 22q11 Deletion Syndrome ; Fetus

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID). METHODS: The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs. RESULTS: The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18⁺³ weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA. CONCLUSION The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.
Female ; Humans ; Pregnancy ; Young Adult ; Disks Large Homolog 4 Protein ; DNA Copy Number Variations ; Fetus ; Genetic Testing ; Intellectual Disability/genetics* ; Pregnant Women

Objective:To analyze the radiographic improvements after Halo-gravity traction in severe kyphoscoliosis patientswith type III spinal cord on preoperative apex MRI, and to assess the clinical outcomes and surgical safety of Halo-gravity traction in this cohort.Methods:A total of 47 severe thoracic kyphoscoliosis patients with type III spinal cord on preoperative apex MRI who underwent preoperative Halo-gravity traction followed by one-stage posterior spinal fusion from February 2019 to June 2021 in the Nanjing Drum Tower Hospital were retrospectively analyzed. There were 18 males and 29 females with an average age of 22.5±12.8 years (range, 9-60 years). The average duration of traction was 7.4±3.9 weeks (range, 4-16 weeks). Radiographic parameters were measured including the coronal Cobb angle, distance between C 7 plumb line and center sacral vertical line (C 7PL-CSVL), sagittalglobal kyphosis (GK) and sagittal vertical axis (SVA) atpre-traction, post-traction and post-operation, respectively. The traction correction rate was measured as "traction degree before traction-traction degree after traction)/traction degree before traction" and the surgical correction rate was represented as "traction degree before traction-postoperative degree)/ traction degree before traction". The Frankel scoring system was used for the evaluation of neurological status at pre-traction, post-traction and post-operation. Results:All of 47 patients underwent the Halo-gravity traction and posterior spinal correction surgery. The C 7PL-CSVL was 35.7±16.9 mm at initial visit. At post-operation, C 7PL-CSVL was improved to 22.0±13.7 mm ( t=13.75, P<0.001), and the improvement rate was 39.9%±15.5%. The GK was 110.9°±22.1° at initial visit, which was improved to 84.1°±19.9° ( t=8.84, P<0.001) after Halo-gravity traction with an average correction of 23.7%±8.9%. At post-operation, GK was improved to 65.3°±19.3° ( t=10.63, P<0.001), and the improvement rate were 40.1%±20.7%. The SVA was 43.8±19.5 mm at initial visit. At post-operation, SVA was improved to 21.1±14.9 mm ( t=10.32, P<0.001), and the improvement rate were 53.1%±27.0%. A total of 14 patients showed neurological deficits of lower limbs at pre-traction, of which 8 patients had significant neurological improvement after Halo gravity traction; 3 patients had significant neurological improvement after surgery, and the remaining 3 patients had no significant neurological improvement during treatment. No new neurological deficits were observed after Halo-gravity traction or surgery. Conclusion:For severe kyphoscoliosis patients with type III spinal cord on preoperative apex MRI, the Halo-gravity traction could effectively correct the deformity, improve neurological function, enhance the tolerance of spinal cord to surgery and reduce the risk of intraoperative iatrogenic neurological deficit.

Objective:To summarize initial experience of applying nanopore third-generation sequencing detection method (nanopore sequencing) for genetic diagnosis of non-classical 21 hydroxylase deficiency (NC 21-OHD), and to explore its performance and application prospects.Methods:Clinical data of the two NC 21-OHD patients, who were hospitalized at the First Affiliated Hospital of Zhengzhou University in May 2019, were collected. Peripheral venous blood was collected and genome DNA extracted. Genetic variants was detected by nanopore sequencing and underwent bioinformatic analysis. Pathogenetic mutations in CYP21A2 gene were validated with PCR-sanger sequencing in the two patients and their parents.Results:The average reads length and sequence depth in the patient one was 12, 792 bp and 27.19×. The average reads length and sequence depth in the patient two was 13, 123 bp and 21.34×. Compound variants of c.293-13C>G/c.844G>T (p.Val282Leu) and c.332_339delGAGACTAC (p.Gly111Valfs)/c.844G>T (p.Val282Leu) were detected in these two patients, which were consistent with clinical phenotype of NC 21-OHD. Further analysis showed that c.293-13C>G mutation was inherited from her father and c.844G>T (p.Val282Leu) mutation was inherited from her mother for the patient one. The c.844G>T (p.Val282Leu) mutation was inherited from her father and c.332_339delGAGACTAC (p.Gly111Valfs) mutation from her mother.Conclusions:The heterozygous mutations in CYP21A2 gene are the cause of NC 21-OHD in these two patients. Nanopore sequencing technique is a reliable new detection method for patients with NC 21-OHD.