Objective To investigate the clinical significance of the combined screening of thyroid stimulating hormone(TSH)and seven candidate pathogenic genes of congenital hypothyroidism(CH)for CH.Methods 16 645 newborns delivered in Nanjing Women and Children's Healthcare Hospital from July 2022 to July 2023 were performed the screening of TSH.Their DNA was extracted from dried blood spots and the chip capture second-generation sequencing technology was used to detect the candidate pathogenic genes,in-cluding dual oxidase 2(DUOX2),dual oxidase maturation factor 2(DUOXA2),prophet of pit-1(PROP1),thyroid-stimulating hor-mone receptor(TSHR),thyroid peroxidase(TPO),thyroglobulin(TG),and paired box 8(PAX8).The sensitivity,specificity,pos-itive predictive value(PPV),and negative predictive value(NPV)of the screening of TSH,candidate genes,and their combination for CH were analyzed.Results A total of 13 CH patients were screened out based on sensitive thyroid stimulating hormone(sTSH)and free thyroxine(FT4),including 3 patients with hyperthyrotropinemia.Among them,11 were screened out by TSH alone,4 were screened out by candidate genes alone,and 2 were screened out by the combination of TSH and candidate genes.The sensitivity,speci-ficity,PPV,and NPV of TSH for screening CH were 84.62％,99.23％,7.91％,and 99.97％,respectively.The sensitivity,specifici-ty,PPV,and NPV of candidate genes for screening CH were 30.77％,99.87％,15.38％,and 99.87％,respectively.The sensitivity,specificity,PPV,and NPV of the combination of TSH and candidate genes for screening CH were 100％,99.09％,7.88％,and 100％,respectively.The primary mutant gene in the samples with positive candidate genes was DUOX2(85.71％),mainly point muta-tions,among which the c.1588A>T variant was the most common(16.67％).PAX8(14.29％)was the second most common variation,and all of the variation point were c.280G>A.No positive samples for the pathogenic variants of DUOXA2,TSHR,PROP1,TPO,and TG were detected.Conclusion The combined screening of TSH and candidate genes helps to improve the screening efficacy of CH.The genetic etiology of CH in Nanjing area may be mainly the variation of DUOX2 and PAX8 genes.

Objective:Objective To analyze the carrier rates and mutational spectrum of pathogenic variants in deafness-associated genes among newborns in Nanjing.Methods:In this cross-sectional study, heel blood samples were collected from 30 043 neonates born at Nanjing Maternity and Child Health Care Hospital between March 2022 and April 2024. DNA was extracted from dried blood spots and subjected to targeted next-generation sequencing of the full coding regions of deafness-associated genes GJB2, SLC26A4, USH2A, MT-RNR1, and MYO15A. Descriptive statistics were used to analyze carrier rates and variant characteristics, with pathogenicity classified according to American College of Medical Genetics and Genomics guidelines. Results:(1) Carrier rates: The overall carrier rate for deafness-associated gene variants was 19.196% (5 767/30 043). GJB2 showed the highest carrier rate at 13.174% (3 958/30 043), followed by SLC26A4 (2.912%, 875/30 043), USH2A (1.524%, 458/30 043), MT- RNR1 (0.959%, 288/30 043), and MYO15A (0.626%, 188/30 043). MT-RNR1 follows mitochondrial inheritance, while others are autosomal recessive. (2) Variant analysis revealed: 25 GJB2 variants with c.109G>A being most frequent (allele frequency 4.925%, 2 959/60 086), followed by c.235delC (1.127%, 677/60 086) and c.299_300delAT (0.261%, 157/60 086); 85 SLC26A4 variants dominated by c.919-2A>G (0.621%, 373/60 086), c.2009T>C (0.165%, 99/60 086), and c.2168A>G (0.100%, 60/60 086); 118 USH2A variants with c.2802T>G (0.218%, 131/60 086) and c.8559-2A>G (0.165%, 99/60 086) most prevalent; three MT-RNR1 variants including m.1095T>C (230 cases), m.1555A>G (52 cases), and m.1494C>T (six cases); and 81 MYO15A variants with c.10250_10252delCCT (0.043%, 26/60 086) being most common. Conclusion:The predominant pathogenic variants in deafness-associated genes among Nanjing neonates are GJB2 c.109G>A and SLC26A4 c.919-2A>G, with MT- RNR1 m.1095T>C representing a significant mitochondrial variant.

Objective:To analyze the carrier rates and profiles of pathogenic and likely pathogenic variants for hearing loss-related genes MYO7A, PCDH15, and CDH23 among neonates in Nanjing city through targeted next-generation sequencing (NGS). Methods:Heel-prick blood samples were collected from 30 043 newborns delivered at Nanjing Women and Children′s Health Care Hospital between March 2022 and April 2024. Dried blood spots were prepared, and genomic DNA was extracted. Targeted NGS was applied to detect variants across the full coding regions of the MYO7A, PCDH15, and CDH23 genes. The carrier rates and profiles of pathogenic and likely pathogenic variants of the three genes were analyzed. This study was approved by the Medical Ethics Committee of Nanjing Maternal and Child Health Care Hospital (Ethics No.: 2021KY-071). Results:The carrier rates of pathogenic and likely pathogenic variants (with ≥ 1 variant site) for the MYO7A, PCDH15, and CDH23 genes were 0.340%, 0.226%, and 0.156%, respectively. A total of 65, 49, and 30 variant types were detected in the MYO7A, PCDH15, and CDH23 genes, respectively. For MYO7A, single base variants were predominant, with the most common variant being c. 5581C>T, followed by c. 1343+ 1G>A, c. 2837T>G, and c. 5660C>T, with allelic frequencies of 0.013% (8/60 086), 0.007% (4/60 086), 0.007% (4/60 086), and 0.007% (4/60 086), respectively. PCDH15 variants were mainly deletions, with the most common variant site being c. 4699_4715dupAGAGAAAAGATTCAGAG, followed by c. 3441delA, c. 440T>G, and c. 4733_4736delTCAG, with allelic frequencies of 0.015% (9/60 086), 0.005% (3/60 086), 0.005% (3/60 086), and 0.005% (3/60 086), respectively. For CDH23, single base variants were predominant, with c. 6604G>A being the most common, followed by c. 6085C>T, c. 6050+ 9G>A, and c. 6253+ 1G>A, with allelic frequencies of 0.013% (8/60 086), 0.012% (7/60 086), 0.005% (3/60 086), and 0.005% (3/60 086). Conclusion:This study analyzed the carrier rates and profiles of pathogenic and likely pathogenic variants of the MYO7A, PCDH15, and CDH23 genes, which can provide more evidence for the prevention and management of deafness in the region.

Objective:To explore the influencing factors of multiple bronchoscopic lavage in children with lobar pneumonia and evaluate its predictive value.Methods:The clinical data of 184 children with lobar pneumonia who underwent bronchoscopic lavage in the Hubei Medical College Affiliated People′s Hospital from September 2018 to June 2022 were retrospectively analyzed. According to the number of lavage, they were divided into the single lavage group (108 cases) and the multiple (≥ 2 times) lavage group (76 cases). The two groups was matched in a 1∶1 ratio by using propensity score matching (PSM), and the influencing factors for multiple lavage after matching was analyzed by multivariate Logistic regression analysis. The predictive effect of risk factors on multiple lavage was analyzed by the receiver operating characteristic (ROC) curve.Results:After PSM matching, a total of 68 pairs of children were successfully matched. According to multivariate Logistic regression analysis, the duration of preoperative fever ≥7 d, pleural effusion, procalcitonin (PCT) ≥2.0 μg/L, white blood cell (WBC) ≥12.0 × 10 9/L, C-reactive protein (CRP) ≥10.0 mg/L, neutrophil ratio (N%) ≥70%, lactate dehydrogenase (LDH) ≥300 U/L, erythrocyte sedimentation rate (ESR) ≥35.0 mm/1 h, serum alanine aminotransferase (ALT)>40 U/L, serum albumin (ALB)<35 g/L and mucus thrombus were risk factors for multiple bronchoscopic lavage in children with lobar pneumonia ( OR = 3.031, 2.230, 2.125, 3.050, 2.735, 3.043, 3.025, 3.360, 2.962, 2.989, 3.108, P<0.05). According to ROC curve analysis, the sensitivity and specificity of the combination of 11 influencing factors in predicting multiple bronchoscopic lavage in children with lobar pneumonia were 72.10% and 63.20% respectively, and the area under the curve was 0.733. Conclusions:The duration of preoperative fever, pleural effusion, PCT, WBC, CRP, N%, LDH, ESR, ALT, ALB and mucus thrombus are all influencing factors for multiple bronchoscopic lavage in children with lobar pneumonia, and comprehensive evaluation of the above influencing factors has predictive effect on multiple bronchoscopic lavage in children.

BACKGROUND:Mesenchymal stem cells have been widely used in the treatment of various diseases due to their wide range of sources,their ease of proliferation in vitro and their ability to secrete a range of immunomodulatory factors to suppress inflammation and promote tissue repair and regeneration.However,in the treatment of many diseases,the therapeutic effect is limited.The effort to engineer and modify mesenchymal stem cells for specific disease pathogenesis or intervention targets is an important development for cell therapy in the future.OBJECTIVE:Interleukin-10 is a typical anti-inflammatory cytokine that helps to modulate the immune response and induces macrophage polarization towards an anti-inflammatory phenotype.This study investigated the therapeutic effect of interleukin-10 engineered human umbilical cord mesenchymal stem cells on inflammatory bowel disease.METHODS:Human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were established by electro-transfection,and screened for clinical-grade cells based on the cell therapy product criteria.C57BL/6J mice were given 5%aqueous dextran sulfate sodium ad libitum to establish a model of acute colitis.Empty plasmid-transfected human umbilical cord mesenchymal stem cells or interleukin-10-human umbilical cord mesenchymal stem cells(1×106 cells/each mouse)were injected on day 1 before modeling(tail vein injection)and day 4(intraperitoneal injection)after modeling,respectively.On day 6 after modeling,colon tissue sections were taken for hematoxylin-eosin staining to assess histological changes.Immunofluorescence staining was performed to detect the expression of proliferating cell nuclear antigen and CD31.RESULTS AND CONCLUSION:The engineered human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were constructed,and met the quality standard of clinical-grade human umbilical cord mesenchymal stem cells.Human umbilical cord mesenchymal stem cells could repair acute colitis in mice.The therapeutic effect of interleukin-10-human umbilical cord mesenchymal stem cells was more efficacious,which more significantly suppressed body weight loss(P<0.05),colon shortening(P<0.05),and damage of colonic tissues(P<0.05)in acute colitis mice.In interleukin-10-human umbilical cord mesenchymal stem cell treatment group,there were significantly more proliferating cell nuclear antigen-positive cells and CD31-positive cells in the colon sections than in the human umbilical cord mesenchymal stem cell treatment group,suggesting that interleukin-10-overexpressing human umbilical cord mesenchymal stem cells contributed to the repair of colon tissue by significantly promoting the proliferation of intestinal tissues and angiogenesis.

Transient perivascular inflammation of the carotid artery(TIPIC)syndrome is a relatively rare disease,and ultrasound is the first screening method for initial diagnosis of the disease.Contrast-enhanced ultrasound(CEUS)has unique advantages in the follow-up of patients with TIPIC syndrome.This paper reports a patient with TIPIC syndrome who was treated with acute left neck pain.The inflammation was significantly re-lieved and subsided after treatment with non-steroidal anti-inflammatory drugs.The ultrasound changes of carotid artery lesions in this patient during follow-up were analyzed,and the application value of CEUS in the follow-up diagnosis of this disease was summarized,in the hope of providing clinical reference.

OBJECTIVE: To analyze the carrier rates and profiles of pathogenic and likely pathogenic variants for hearing loss-related genes MYO7A, PCDH15, and CDH23 among neonates in Nanjing city through targeted next-generation sequencing (NGS). METHODS: Heel-prick blood samples were collected from 30 043 newborns delivered at Nanjing Women and Children's Health Care Hospital between March 2022 and April 2024. Dried blood spots were prepared, and genomic DNA was extracted. Targeted NGS was applied to detect variants across the full coding regions of the MYO7A, PCDH15, and CDH23 genes. The carrier rates and profiles of pathogenic and likely pathogenic variants of the three genes were analyzed. This study was approved by the Medical Ethics Committee of Nanjing Maternal and Child Health Care Hospital (Ethics No.: 2021KY-071). RESULTS: The carrier rates of pathogenic and likely pathogenic variants (with ≥ 1 variant site) for the MYO7A, PCDH15, and CDH23 genes were 0.340%, 0.226%, and 0.156%, respectively. A total of 65, 49, and 30 variant types were detected in the MYO7A, PCDH15, and CDH23 genes, respectively. For MYO7A, single base variants were predominant, with the most common variant being c.5581C>T, followed by c.1343+1G>A, c.2837T>G, and c.5660C>T, with allelic frequencies of 0.013% (8/60 086), 0.007% (4/60 086), 0.007% (4/60 086), and 0.007% (4/60 086), respectively. PCDH15 variants were mainly deletions, with the most common variant site being c.4699_4715dupAGAGAAAAGATTCAGAG, followed by c.3441delA, c.440T>G, and c.4733_4736delTCAG, with allelic frequencies of 0.015% (9/60 086), 0.005% (3/60 086), 0.005% (3/60 086), and 0.005% (3/60 086), respectively. For CDH23, single base variants were predominant, with c.6604G>A being the most common, followed by c.6085C>T, c.6050+9G>A, and c.6253+1G>A, with allelic frequencies of 0.013% (8/60 086), 0.012% (7/60 086), 0.005% (3/60 086), and 0.005% (3/60 086). CONCLUSION This study analyzed the carrier rates and profiles of pathogenic and likely pathogenic variants of the MYO7A, PCDH15, and CDH23 genes, which can provide more evidence for the prevention and management of deafness in the region.
Humans ; Cadherins/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; Infant, Newborn ; Female ; Myosin VIIa/genetics* ; Cadherin Related Proteins ; Male ; Hearing Loss/genetics* ; Myosins/genetics* ; Heterozygote

Objective:To analyze the carrier rates and profiles of pathogenic and likely pathogenic variants for hearing loss-related genes MYO7A, PCDH15, and CDH23 among neonates in Nanjing city through targeted next-generation sequencing (NGS). Methods:Heel-prick blood samples were collected from 30 043 newborns delivered at Nanjing Women and Children′s Health Care Hospital between March 2022 and April 2024. Dried blood spots were prepared, and genomic DNA was extracted. Targeted NGS was applied to detect variants across the full coding regions of the MYO7A, PCDH15, and CDH23 genes. The carrier rates and profiles of pathogenic and likely pathogenic variants of the three genes were analyzed. This study was approved by the Medical Ethics Committee of Nanjing Maternal and Child Health Care Hospital (Ethics No.: 2021KY-071). Results:The carrier rates of pathogenic and likely pathogenic variants (with ≥ 1 variant site) for the MYO7A, PCDH15, and CDH23 genes were 0.340%, 0.226%, and 0.156%, respectively. A total of 65, 49, and 30 variant types were detected in the MYO7A, PCDH15, and CDH23 genes, respectively. For MYO7A, single base variants were predominant, with the most common variant being c. 5581C>T, followed by c. 1343+ 1G>A, c. 2837T>G, and c. 5660C>T, with allelic frequencies of 0.013% (8/60 086), 0.007% (4/60 086), 0.007% (4/60 086), and 0.007% (4/60 086), respectively. PCDH15 variants were mainly deletions, with the most common variant site being c. 4699_4715dupAGAGAAAAGATTCAGAG, followed by c. 3441delA, c. 440T>G, and c. 4733_4736delTCAG, with allelic frequencies of 0.015% (9/60 086), 0.005% (3/60 086), 0.005% (3/60 086), and 0.005% (3/60 086), respectively. For CDH23, single base variants were predominant, with c. 6604G>A being the most common, followed by c. 6085C>T, c. 6050+ 9G>A, and c. 6253+ 1G>A, with allelic frequencies of 0.013% (8/60 086), 0.012% (7/60 086), 0.005% (3/60 086), and 0.005% (3/60 086). Conclusion:This study analyzed the carrier rates and profiles of pathogenic and likely pathogenic variants of the MYO7A, PCDH15, and CDH23 genes, which can provide more evidence for the prevention and management of deafness in the region.

Objective To evaluate the results of anorectal dynamics in patients with severe rec-tocele.Methods A retrospective analysis was conducted on the clinical data of 38 patients defini-tively diagnosed with severe rectocele at the pelvic floor center of the anorectal department of Nanjing Hospital of Traditional Chinese Medicine from January 2020 to January 2023.All patients underwent anorectal manometry,and the results of anorectal dynamics were analyzed.Results A total of 15 pa-tients(39.47％)had elevated anal resting pressure(ARP),20(52.63％)had normal ARP,and 3(7.89％)had decreased ARP.Five patients(13.16％)had elevated maximum anal sphincter pressure(MASP),9(23.68％)had normal MASP,and 24(63.16％)had decreased MASP.Nor-mal defecation relaxation reflex was observed in 15 patients(39.47％),and abnormal defecation re-laxation reflex was observed in 23 patients(60.53％).Ten patients(26.32％)had normal rectal defecation pressure,and 28(73.68％)had decreased rectal defecation pressure.Eleven patients(28.95％)had elevated rectal initial sensory threshold(RIST),27(71.05％)had normal RIST.Fifteen patients(39.47％)had elevated rectal defecation sensory threshold,21(55.26％)had normal rectal defecation sensory threshold,and 2(5.26％)had decreased rectal defecation sensory threshold.Three patients(7.89％)had elevated rectal maximum tolerable volume,26(68.42％)had normal rectal maximum tolerable volume,and 9(23.68％)had decreased rectal maximum tolerable vol-ume.ARP was moderately positively correlated with the chronic constipation severity(CSS)score(P=0.007,r=0.429),and abnormal defecation relaxation reflex was moderately negatively correla-ted with the CSS score(P=0.019,r=-0.329).In 3 patients(7.89％),both ARP and MASP were decreased,and both ARP and MASP were elevated in 5 patients(13.16％).Conclusion Pre-operative anorectal dynamics analysis is necessary for patients with severe rectocele to formulate a reasonable individualized surgical plan and postoperative rehabilitation program.

Objective To analyze the efficacy of modified transvaginal rectal repair(MTVRR)in patients with moderate to severe rectocele(RC).Methods A retrospective analysis was conducted on the clinical data of 21 female patients with RC who underwent MTVRR.The Constipation Scoring System(CSS)scale was used to assess patients'constipation symptoms before surgery and at 3,6,12 and 24 months after surgery,and the efficiency of symptom improvement was recorded.The occurrence of postoperative complications in RC patients was observed.Results All 21 patients successfully un-derwent the surgery,with surgical duration ranging from 25 to 135 minutes,with average of(83.14±30.39)minutes,and hospital stay ranging from 10 to 21 days,with average of(14.10±2.34)days.Postoperatively,one patient was lost during follow-up among 21 patients.The CSS scores of the remai-ning 20 patients were lower than those before surgery,with a statistically significant difference(P＜0.05).The overall effective rates of constipation symptom improvement at 3,6 and 12 months postop-eratively were 100.00％,90.00％and 80.00％,respectively.Among 20 patients,15 patients com-pleted 24-month follow-up after surgery,and the CSS score after surgery was lower than that before sur-gery,the difference was statistically significant(P＜0.05).The CSS scores of the remaining 15 pa-tients were lower than those before surgery,with a statistically significant difference(P＜0.05).The overall effective rate of constipation symptom improvement at 24 months postoperatively was 80.00％among 15 patients.During postoperative follow-up,it revealed that no complications occurred in any patient.Conclusion MTVRR can improve constipation symptoms in patients with RC,demonstra-ting good therapeutic efficacy.