Neurodevelopmental disorders (NDDs) are a group of diseases caused by abnormal development of the brain and nervous system, mainly including global developmental disabilities/intellectual disabilities, autism spectrum disorders, attention deficit hyperactivity disorder, and others; at present, certain progress has been made in the research on common NDDs, and some effective therapeutic approaches have been developed, but for rare NDDs such as fragile X syndrome, Rett syndrome, and Dravet syndrome, the elucidation of their pathogenesis and the development of therapeutic strategies still face major challenges due to insufficient clinical samples, the complexity of the brain structure, and the limitations of existing research models. In recent years, induced pluripotent stem cells (iPSCs) technology has achieved breakthrough progress, where the directed differentiation of patient-derived iPSCs into neurons, glial cells, and cerebral organoids, combined with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) gene-editing technology, provides a novel research model for exploring the pathogenic mechanisms and therapeutic strategies of rare NDDs, and this paper reviews the research advances and challenges of iPSCs technology in the study of rare NDDs.

ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.

Occupational noise-induced hearing loss (NIHL) is an irreversible sensorineural hearing loss that severely endangers workers’ health, making early screening crucial. This article reviewed the research progress on early screening methods for occupational NIHL, introduced the testing mechanisms of three core screening methods—tympanometry, otoacoustic emissions, and extended high-frequency audiometry —and summarized their clinical application advantages and limitations. It is proposed that multimodal combined detection (e.g., the combination of tympanometry, otoacoustic emissions, and extended high-frequency audiometry) can significantly improve the accuracy and comprehensiveness of early screening. Meanwhile, future studies with prospective cohort design are encouraged to verify the long-term monitoring value of each method and to strengthen the joint development of screening technologies with cutting-edge approaches such as machine learning, in order to further improve screening efficiency and provide stronger protection for workers’ hearing health.

IgA nephropathy（IgAN）is a common primary glomerular disease in children，characterized by the deposition of IgA or IgA-dominant immune complexes in the glomeruli.The clinical manifestations are highly heterogeneous，with some children progressing to end-stage renal disease.The prognosis of IgAN is influenced by multiple factors，involving clinical，pathological，and laboratory examinations.Among the clinical factors，persistent proteinuria，reduced baseline estimated glomerular filtration rate（eGFR），hypertension during follow-up，and hyperuricemia are risk factors for poor prognosis.The predictive value of hematuria remains controversial.Pathologically，the Oxford classification highlights that segmental sclerosis，tubular atrophy/interstitial fibrosis，and crescents are significantly associated with disease progression，with tubular atrophy/interstitial fibrosis serving as an independent risk factor for poor outcomes.The prognostic significance of mesangial hypercellularity and endocapillary hypercellularity requires further validation.Among the biomarkers，serum galactose-deficient IgA 1 and complement-related markers（such as IgA/C3 ratio）show potential predictive value，but need to be supported by large samples studies.This article reviews the clinical，pathological，and biomarker-related risk factors influencing the prognosis of pediatric IgAN，aiming to provide basis for developing risk prediction models and guiding individualized treatment strategies.

Objective To analyze the correlations of multimodal ultrasound parameters with Ki-67 and cytokeratin 5/6(CK5/6)in triple-negative breast cancer(TNBC).Methods A retrospec-tive analysis was conducted on 212 breast cancer patients in Jurong Hospital Affiliated to Jiangsu Uni-versity and Jiangsu Provincial People's Hospital from January 2017 to December 2023.The patients were divided into TNBC group(n=95)and non-TNBC group(n=117).Immunohistochemical stai-ning was used to detect the expression of Ki-67 and CK5/6 in both groups,and the correlations of ul-trasound parameters with Ki-67 and CK5/6 were analyzed.Results In the TNBC group,the positive rates of CK5/6 and Ki-67 were 69.47％(66/95)and 75.79％(72/95)respectively,while in the non-TNBC group,the positive rates were 23.93％(28/117)and 14.53％(17/117)respectively,with significant between-group differences(P＜0.05).In the TNBC group,patients with high and low level of CK5/6 showed significant differences in maximum lesion diameter,morphology,margin,aspect ratio,presence of calcifications,posterior acoustic pattern,lymph node metastasis,and distant metastasis(P＜0.05);similarly,patients with high and low level of CK5/6 demonstrated significant differences in distribution,enhancement pattern,and perfusion defects(P＜0.05);patients with high and low level of Ki-67 also exhibited significant differences in maximum lesion diameter,mor-phology,margin,aspect ratio,presence of calcifications,posterior acoustic pattern,lymph node me-tastasis,and distant metastasis(P＜0.05);additionally,patients with high and low level of Ki-67 showed significant differences in the enhanced range,distribution,and enhancement pattern(P＜0.05).Multivariate analysis revealed that clear margin,calcifications,and enhanced range were in-dependent influencing factors for CK5/6 positivity(P＜0.05),while enhancement pattern and en-hanced range were independent influencing factors for Ki-67 positivity(P＜0.05).Conclusion Ki-67 and CK5/6 have higher positive expression rates in TNBC patients,and multimodal ultrasound pa-rameters are correlated with Ki-67 and CK5/6.

Objective:To study the prognosis of congenital bile duct cysts following cyst resection, and to analyze the risk factors associated with the development of postoperative biliary calculus.Methods:Clinical data of 149 patients with congenital bile duct cysts undergoing surgery in the First Affiliated Hospital of Nanjing Medical University from May 2004 to January 2022 were retrospectively analyzed, including 59 males and 90 females, with a median age of 32 (21, 47) years old. Patients were divided into two groups: the stone group ( n=51, biliary calculus occurred during the follow-ups after surgery) and non-stone group ( n=98). Clinical data such as gender, age, medical history, cyst type, biliary calculus, anastomotic stenosis and occurrence of cancer were compared. All patients were followed up via telephone consultations. A logistic regression analysis was used to identify the risk factors associated with the occurrence of biliary calculus after surgery. Results:The duration of the follow-ups was 120 (24, 211) months. The observed incidence of postoperative biliary calculus, anastomotic stricture, and cancer in the patients were 34.2% (51/149), 8.7% (13/149), and 4.7% (7/149), respectively. The logistic regression analysis indicated that incomplete cyst resection ( OR=3.332, 95% CI: 1.221-9.094) and postoperative anastomotic stenosis ( OR=13.300, 95% CI: 2.586-68.401) were associated with a higher risk of biliary calculus formation after cystectomy (all P<0.05). Conclusion:Patients with congenital bile duct cysts suffer a high risk of biliary calculus formation after cystectomy. The residual cyst and postoperative anastomotic stenosis are independent risk factors for biliary calculus after surgery.

Compassion is an important part of nurses'professional quality,and it is also the basis of effective nurse-patient communication and humanistic care.Improving nurses'compassion is helpful to provide high-quality nursing services to patients.This study reviews the definition of compassion,the factors affecting compassion and the training methods to improve compassion,analyzes the shortcomings of existing training methods,and puts forward the prospects for future research,so as to provide a theoretical foundation for future compassion training among nurses.

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Steroid-resistant nephrotic syndrome (SRNS) is the second cause of chronic kidney disease in children. The SRNS has high risk of rapid progression to end-stage renal disease. With the advancement of high-throughput sequencing technology, more than 70 monogenic mutation having the Mendelian inheritance patterns are identified to be associated with SRNS. Most of these genes are involved in podocyte function. Accurate diagnosis of monogenic mutation in SRNS patients helps with guiding clinical treatment protocols and genetic counseling, avoiding the excessive use of steroids/immunosuppressive therapy, and opening up possibilities for targeted therapies in SRNS patients. In this article, our research team summarizes and generalizes the molecular mechanisms, genetic testing, and specific treatment for the major types of monogenic mutations associated with SRNS.

This study aimed at conducting retrospective analysis of the clinical symptoms and genetic mutations in 20 children with Gitelman syndrome treated at the Affiliated Children′s Hospital of Nanjing Medical University from August 2015 to November 2022 and also explored the molecular mechanism of the pathogenic high-frequency mutation D486N in the Chinese population.