OBJECTIVE: To explore the application value of artificial intelligence (AI)-assisted chromosomal karyotype analysis in the diagnosis of prenatal chromosomal mosaicism. METHODS: A retrospective analysis was conducted on 172 pregnant women who underwent amniocentesis at the Department of Medical Genetics and Prenatal Diagnosis, the Third Affiliated Hospital of Zhengzhou University between January 2019 and December 2024. All cases whose fetuses were diagnosed with chromosomal mosaicism via karyotype analysis and stratified into two groups based on the analytical software employed: the conventional analysis group (n = 70), which utilized Leica analysis software for karyotype image recognition and cell counting; and the AI-assisted analysis group (n = 102), which utilized AI-assisted software for the same procedures. The clinical performance of AI-assisted karyotype analysis in diagnosing chromosomal mosaicism was comprehensively evaluated by comparing the types of mosaic karyotypes, distribution of mosaic ratios, and verification outcomes of different detection modalities between the two groups. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-406-01). RESULTS: No statistically significant difference was observed in baseline characteristics (maternal age, gestational week, and indications for prenatal diagnosis) between the two groups. Regarding the detection efficacy for numerical and structural mosaicisms, no significant difference was found in the detection of numerical mosaicism. However, the conventional analysis group exhibited a significantly higher detection rate of autosomal structural mosaicism compared to the AI-assisted group (11.43% vs. 0.98%, P < 0.05). Numerical mosaicism cases were further verified using copy number variation sequencing (CNV-seq) and/or fluorescence in situ hybridization (FISH). The AI-assisted group demonstrated a significantly lower inconsistency rate (5.56% vs. 20.41%, P < 0.05) compared to the conventional group. For low-proportion (< 10%) chromosomal mosaicism, the AI-assisted group had a significantly lower detection rate (13.25% vs. 29.69%, P < 0.05). Subsequent validation of low-proportion mosaicism by CNV-seq and/or FISH showed a higher consistency rate in the AI-assisted group (81.82% vs. 54.55%), though the difference did not reach statistical significance (P = 0.360). CONCLUSION For the karyotyping analysis of prenatal chromosomal mosaicism, AI-assisted karyotype analysis shows high accuracy and consistency in identifying numerical chromosomal mosaicism, particularly in reducing the detection of low-proportion (< 10%) mosaicism while improving verification accuracy. AI-assisted analysis can significantly improve the detection accuracy of numerical mosaicism and mitigate the risk of misclassification for low-proportion (< 10%) mosaicism, thereby providing more precise clinical evidence for the prenatal diagnosis of chromosomal mosaicisms.
Humans ; Female ; Mosaicism ; Pregnancy ; Karyotyping/methods* ; Artificial Intelligence ; Prenatal Diagnosis/methods* ; Adult ; Retrospective Studies ; Chromosome Disorders/genetics* ; Amniocentesis

Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

[Objective]To study etiology and pathogenesis,treatment and prescription of"head sweating",based on the theory of"opening,closing and pivoting six meridians"from Huangdi Neijing.[Methods]Based on the provisions of"head sweating"in the classic works,the dynamic correlation between the imbalance of"opening,closing and pivoting six meridians"and"head sweating"was explored,and the pathogenesis classification and corresponding treatment were summarized.[Results]The pathogenesis of"head sweating"primarily involves Yangming heat obstruction and Shaoyang pivot stagnation.The treatment principle focuses on purging heat and promoting descent,and unblocking the pivot mechanism.If coexisting with Taiyin dampness retention,Taiyang exterior constraint or hyperactivity,the treatment is supplemented by transforming and transporting dampness,unblocking Yang and venting the exterior,or securing the exterior to arrest sweating.When the exterior constraint is pronounced,the primary focus should be on resolving the exterior constraint.When it is not pronounced,treatment should focus directly on the main channels.In severe cases,it may manifest as Jueyin Yin-Yang conflict or Shaoyin pivot mechanism disruption.The treatment principle focuses primarily on reconnecting Yin and Yang,or consolidating Yang while preserving Yin.Additionally,when the pattern pertains to Jueyin but the symptoms are not severe,treatment can be approached from the Shaoyang perspective.For refractory cases of"head sweating"with prolonged duration,adjunct therapy employing resolve phlegm and dissipate stasis methods can significantly enhance therapeutic efficacy.[Conclusion]The treatment of"head sweating"takes"regulating the Qi dynamic and restoring the balance between opening and closing functions"as its guiding principle.The Taiyang and Taiyin systems emphasize the opening function.The Yangming and Jueyin systems value the closing function.The Shaoyang and Shaoyin systems excel in their subtle pivoting function.When the three Yin and three Yang meridians each fulfill their respective duties,the head sweating will be spontaneously resolved.The theory of"opening,closing and pivoting six meridians"provides a dynamic and holistic conceptual framework for the precise pattern differentiation and treatment of"head sweating",while offering novel diagnostic and therapeutic strategies for clinical management of this condition.

AIM To prepare the oral lyophilized tablets of gastrodin-coated micropowder.METHODS Fluidized bed bottom spray method was adopted in the preparation of coated micropowder,after which the oral lyophilized tablets were further prepared.With mannitol consumption,pullulan consumption and xanthan gum consumption as influencing factors,comprehensive score for appearance traits,moisture,disintegration time and the sedimentation volume ratio as an evaluation index,the formulation was optimized by Box-Behnken method,then the taste-masking effect,appearance traits,moisture,disintegration time,content uniformity and dissolution rate were investigated.RESULTS The optimal formulation was determined to be 44.20 mg/tablet for mannitol consumption,3.70 mg/tablet for pullulan consumption,1.30 mg/tablet for xanthan gum consumption,66.67 mg/tablet for coated micropowder,and 1.5 mg/tablet for sucralose micropowder,the comprehensive score was 17.43.The obtained oral lyophilized tablets demonstrated good taste-masking effect,appearance traits and content uniformity with the disintegration time of 3-5 s,whose dissolution rates were less than 5％within 3 min in the simulated oral environment(phosphate buffer solution at pH 6.8)and more than 85％within 15 min in the simulated gastric environment(hydrochloric acid solution at pH 1.2).CONCLUSION The oral lyophilized tablets of gastrodin-coated micropowder display good taste,ease of swallowing and simple and feasible preparation process,which can provide a new idea for the taste improvement of other oral lyophilized tablets and unpleasant-smelling raw medicines.

OBJECTIVE To explore the effect of tracking methodology on investigation of contamination incidents of bronchoalveolar lavage fluid(BALF)specimens from the children.METHODS The onsite tracking was carried out for the contamination incidents of BALF specimens of the children through the tracking methodology,the quality control processes of cleaning and disinfection of bronchofiberscopes and the tracking routes were determined.The quality control process of cleaning and disinfection of bronchofiberscopes were evaluated,the existing risks were found out,and the specific improvement measures were formulated.RESULTS The onsite tracking was carried out for the incident of carbapenem-resistant Klebsiella pneumoniae(CRKP)that was caused by the contamination of 12 BALF specimens from pediatrics department wards before and after Nov.1,2021.No.2180014C bronchofiber-scope without biological surveillance was determined as the high-risk point of contamination of BALF specimens,the monitoring procedure of cleaning and disinfection of the bronchofiberscopes was revised.The BALF specimens that were submitted from Dec.1,2021 to Dec.31,2021 were tracked,and no CRKP was detected among the 23 submitted specimens.Totally 12 bronchofiberscope specimens were collected for biological surveillance,and the qualified rate was 100.00％.The treatment rooms of pediatrics department,hand disinfection effect of health care workers of cleaning and disinfection rooms and disinfection effect of object surfaces were monitored,and the quali-fied rate was increased from 98.39％to 100.00％.CONCLUSIONS The tracking methodology is an effective tool for quality management and can be used for evaluation of quality process of cleaning and disinfection of bronchofi-berscopes,which may find out the causes for adverse events in a timely manner and raise the medical safety.

Hemodialysis patients exhibit compromised immune function and require long-term repeated vascular punctures as therapeutic approach,the risk of infection increases.Hospital-associated infection in hemodialysis de-partment(center)happens from time to time,which has already become a concern for the medical community,patients and social media.This paper outlines the task origin of China's"Standard for infection prevention and control in hemodialysis department(center)"(WS/T854-2025),the compilation basis and explanations for its key content,feasibility and implementation recommendations,as well as the clarifications on common issues encoun-tered during its promotion and enforcement.

Transcatheter arterial embolization(TAE)is the mainstay for treating advanced hepatocellular carcinoma(HCC),and the performance of the embolization material is crucial in TAE.With the development of medical imaging and the birth of"X-ray-free"technologies,we designed a new dual-mode imaging material of dimethoxy tetraphenyl ethylene(DMTPE)via emulsification by mixing poly(N-iso-propylacrylamide-co-acrylic acid)(PNA)with lipiodol and fluorocarbons,which was evaluated for temperature sensitivity,stability,and dual-mode visualization in vitro.Additionally,blood vessel casting embolization and renal artery imaging were assessed in healthy rabbits.In a rabbit model with a VX2 tumor,the effectiveness of TAE for treating HCC was examined,with an emphasis on evaluating long-term outcomes of embolization and its effects on tumor growth,necrosis,and proliferation through imaging techniques.In vitro experiments confirmed that the temperature-sensitive dual-oil-phase Pickering emulsion had good flow,stable contrast,and embolism when the oil-to-oil ratio and water-to-oil ratio were both 7∶3(v/v)and stabilized with 8％PNA.Similarly,in vivo,arterial embolization confirmed the excellent properties of DMTPE prepared at the abovementioned ratios.It was observed that DMTPE not only has an antitumor effect but can also achieve dual imaging using X-rays and ultrasound,making it a promising excellent vascular embolization material for TAE in tumor treatment.

Objective To explore the mechanism of Qingda Granules(QDG)for alleviating brain damage in spontaneously hypertensive rats(SHRs).Methods Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks.The control rats,along with 6 age-matched WKY rats,were treated with saline only.Blood pressure changes of the rats were monitored,and pathologies and neuronal apoptosis in the cerebral cortex were examined with HE staining and TUNEL staining.Cerebral cortical expressions of miR-124 and STAT3 mRNA were detected using RT-qPCR,and the protein expressions of NeuN,STAT3,Bcl-2,Bax,and cleaved caspase-3 were detected with immunohistochemistry and Western blotting.In a HT22 cell model of oxygen and glucose deprivation/reoxygenation(OGD/R),the effects of QDG on cell viability and apoptosis,expressions of miR-124 and STAT3 mRNA,and protein expressions of STAT3,Bcl-2,Bax,and cleaved caspase-3 were evaluated using CCK8 assay,Hoechst 33342 staining,RT-qPCR,and Western blotting.Results Compared with WKY rats,SHRs had significantly elevated systolic blood pressure,diastolic blood pressure and mean arterial pressure with significantly increased neuronal apoptosis in the cerebral cortex,reduced expressions of NeuN,miR-124 and Bcl-2,and enhanced expressions of STAT3,Bax and cleaved caspase-3(P＜0.05).All these changes in the SHRs were significantly ameliorated by treatment with QDG(P＜0.05).In the HT22 cell model,QDG treatment obviously reduced OGD/R-induced cell apoptosis,increased the expressions of miR-124 and Bcl-2,and suppressed the elevation of protein expressions of STAT3,Bax and cleaved caspase-3.Conclusion QDG inhibits cerebral cortical neuronal apoptosis and thereby attenuates brain damage in SHR rats by modulating the miR-124/STAT3 signaling axis.

OBJECTIVE: To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously. METHODS: Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01). RESULTS: Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c.1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright's hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c.2T>C (p.Met1?) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. CONCLUSION When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of co-morbid genetic diseases.
Child, Preschool ; Female ; Humans ; Male ; Class Ia Phosphatidylinositol 3-Kinase/genetics* ; Comorbidity ; Exome Sequencing ; Mutation ; Rare Diseases/genetics* ; Retrospective Studies ; Adolescent

OBJECTIVE: To explore the genetic etiology of Pontocerebellar Hypoplasia Type 2D (PCH2D) due to compound heterozygous variants of the SEPSECS gene and to conduct a literature review. METHODS: A child with PCH2D diagnosed at the Children's Hospital of Nanjing Medical University due to "motor and cognitive retardation" in June 2022 was selected as the study subject. Clinical and imaging data were collected. Genomic DNA was extracted from the peripheral blood samples of the child and her parents. Whole-exome sequencing (WES) was conducted using capture-based high-throughput sequencing technology. Candidate variants were confirmed by Sanger sequencing and bioinformatics analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG). Additionally, relevant literature on PCH2D caused by SEPSECS gene variants was reviewed to assess the genotype-phenotype correlation. This study was approved by the Medical Ethics Committee of the hospital (Ethical No.: 202402022-1). RESULTS: The child, a 1-year-and-3-month-old girl, had presented with global developmental delay, progressive microcephaly, hypotonia, elevated blood lactic acid, feeding difficulties, and absent tendon reflexes. Cranial MRI indicated thinning of the splenium of the corpus callosum. Electromyography suggested peripheral neurogenic changes primarily affecting sensory nerves. WES revealed the she has harbored compound heterozygous variants of the SEPSECS gene, namely c.194A>G (p.N65S) and c.896_c.897insA (p.N299fs*2) (NM_016955), which were inherited from her father and mother, respectively. Neither of her parents had related clinical manifestations. According to the ACMG guidelines, the c.194A>G (p.N65S) variant was classified as pathogenic (PM1+PM2_Supporting+PM3+PP3), and the c.896_c.897insA (p.N299fs*2) variant was as likely pathogenic (PVS1+PM2_Supporting). A total of 18 relevant literature were retrieved, which have involved 32 patients (including this case). The p.N65S variant has been reported previously, while the p.N299fs*2 variant is novel. CONCLUSION Compound heterozygous variants in the SEPSECS gene probably underlay the pathogenesis of PCH2D in this child. Above finding has expanded the mutational and phenotypic spectrum of the SEPSECS gene.
Humans ; Female ; Infant ; Heterozygote ; Cerebellar Diseases/genetics* ; Membrane Proteins/genetics* ; Exome Sequencing ; Mutation