Objective To analyze the related factors of prognosis in patients with primary Sjogren’s syndrome (SS) complicated with renal damage, and to provide reference for clinical development of personalized prevention and treatment measures. Methods A total of 508 patients with primary SS complicated with renal damage in the First Affiliated Hospital of Xinjiang Medical University from February 2020 to February 2022 were enrolled as study subjects. According to the prognosis status within 3 years, the enrolled patients were divided into good prognosis group (n=426) and poor prognosis group (n=82). Univariate and logistic multivariate regression analyses were adopted to analyze the influencing factors of poor prognosis. Results There were significant differences in hypertension, anemia, renal interstitial chronicity grading, and levels of globulin (GLO), immunoglobulin G (IgG) and hemoglobin between the two groups (P<0.05). Logistic multivariate analysis showed that concurrent hypertension, anemia, increased grade of renal interstitial chronicity, and elevated GLO and IgG levels were risk factors of poor prognosis in patients with primary SS complicated with renal damage, while hemoglobin level was a protective factor (OR: 1.962, 95%CI: 1.056-3.645; OR: 2.467, 95%CI: 1.153-5.278; OR: 17.796, 95%CI: 5.157-61.419; OR: 3.655, 95%CI: 1.812-7.372; OR: 5.732, 95%CI: 2.632-12.480; OR: 0.325, 95%CI: 0.165-0.640, P<0.05). Conclusion Patients with primary SS complicated with renal damage have a higher risk of poor prognosis, which is affected by factors such as hypertension, anemia, and GLO, IgG and hemoglobin levels. Clinically, it is necessary to take active prevention and treatment measures to improve the prognosis of patients.

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.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

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.

Height， as one of the crucial indicators for assessing children’s growth and development， has consistently been a global focus. With economic development and improvements in social living standards， the clinical management needs for children with short stature have been increasingly growing. While growth hormone brings hope to children with short stature， it also triggers ethical challenges such as medical standardization， expansion of indications， equitable accessibility， and informed consent. To avoid the ethical issues related to the use of pediatric growth hormone， multidimensional and comprehensive clinical management should be implemented for children with short stature， including strictly adhering to medical standards and ethical guidelines， enhancing public awareness， and promoting the standardized development of recombinant human growth hormone （rhGH） therapy and ethics.

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.