Objective: To investigate the distribution characteristics of ABO and Rh blood group antigen phenotypes among blood donors in the Yantai, Shandong. Methods: Blood samples from 310 180 voluntary blood donors in Yantai collected from January 2019 to December 2023 were tested for ABO and Rh blood group antigens using standard serological methods. RhD-negative samples were further typed for C, c, E, and e antigens. Population genetic analysis of blood groups was performed: allele frequencies were inferred from ABO phenotypes, and Rh allele/haplotype frequencies were estimated based on the proportion of RhD-negative donors and CcEe antigen typing, followed by Hardy-Weinberg equilibrium testing. Results: The phenotypic distribution frequency of ABO blood groups was B(32.72%)>O(28.93%)>A(27.65%)>AB(10.70%). The inferred allele frequencies were r(53.74%)>q(24.78%)>p(21.48%), consistent with Hardy-Weinberg equilibrium (P>0.05). A total of 1 872 Rh-negative donors (0.603%) were identified. The most common Rh phenotypes were ccdee (59.56%) and Ccdee (30.18%). The distribution of Rh antigen phenotypes deviated significantly from Hardy-Weinberg equilibrium (χ =37.15, P<0.001), with the cde haplotype showing the highest frequency. There was no statistically significant difference in ABO blood group distribution between RhD-positive and RhD-negative donors (P>0.05). Conclusion: The ABO blood group distribution among voluntary blood donors in Yantai is generally stable and consistent with population genetic equilibrium, whereas the Rh antigen phenotype distribution deviates from equilibrium, indicating potential underlying genetic structural differences.

AIM: To investigate the diagnostic and prognostic value of differential expression of Cyclin D1 and p53 in eyelid tumors.METHODS: This retrospective study enrolled patients who underwent surgical resection for eyelid tumors at our hospital between March 2018 and March 2023. Participants were categorized into benign and malignant groups based on tumor characteristics. Clinical data were collected. Genetic data for eyelid tumors were obtained from the GEO database, and differential gene analysis, including volcano plot visualization and KEGG pathway enrichment analysis, was performed using the Sangerbox 3.0 platform. Immunohistochemistry was used to detect the expression levels of Cyclin D1, p53, and BAX in tissue samples. Correlations with clinical features were analyzed using Spearman analysis, and prognostic factors were identified via Logistic regression analysis.RESULTS: This study included 69 patients with eyelid tumors(78 eyes), categorized into a benign group(37 patients, 41 eyes)and a malignant group(32 patients, 37 eyes)based on tumor characteristics. There were significant differences between the two groups in histological subtype, TNM staging, vascular invasion, differentiation status, and local infiltration(all P<0.05). Among benign tumors: pigmented nevi in 11 eyes(27%), hemangiomas in 9 eyes(22%), squamous cell papillomas in 5 eyes(12%), epidermoid cysts in 5 eyes(12%), seborrheic keratoses in 4 eyes(10%), neurofibromas in 3 eyes(7%), and both calcifying epithelioma and xanthelasma in 2 eyes each(5%); among malignant tumors: basal cell carcinoma in 18 eyes(49%), meibomian gland carcinoma in 8 eyes(22%), squamous cell carcinoma in 5 eyes(14%), sebaceous gland carcinoma in 4 eyes(11%), lymphoma and malignant melanoma each in 1 eye(3%). At the follow-up cutoff date of March 2025, the 2-year survival rate in the benign group(95%)was significantly higher than that in the malignant group(78%; P<0.05). Bioinformatics analysis identified 4 103 differentially expressed genes, including Cyclin D1, p53, and BAX, which were predominantly involved in pathways such as the p53 signaling pathway and calcium-related signaling. Spearman analysis revealed that local invasion(rs=0.71, P<0.05)and TNM stage(rs=0.73, P<0.05)correlated with Cyclin D1 expression; local invasion(rs=0.76, P<0.05)and histological subtype(rs=0.65, P<0.05)correlated with p53 expression. Logistic regression results indicated that Cyclin D1, p53, TNM staging, and local invasion were prognostic risk factors. ROC curve analysis demonstrated that the combined detection of these four indicators had the highest predictive value for prognosis(AUC=0.83).CONCLUSION: High expression of cyclin D1 and p53 serves as molecular markers for distinguishing benign from malignant eyelid tumors and assessing prognosis. Combined detection of these markers with TNM staging and local invasion demonstrates high predictive value for prognosis.

Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

Objective: To report the antibody identification, blood management during pregnancy and the monitoring process of fetal hemolytic disease of fetus and newborn (HDFN) in a pregnant woman with a history of blood transfusion and pregnancy who developed anti-Jr . Methods: Saline tube technique and anti-human globulin technique were used for maternal blood typing, unexpected antibody screening and identification, as well as for determining antibody titer and IgG subclasses. PCR-SSP was employed for genotyping of 18 blood group systems. Next-generation sequencing (NGS) was utilized for gene sequencing of 38 blood group systems. Sanger sequencing was applied to verify rare blood group mutations detected by NGS and to investigate the corresponding rare blood group genes in family members. Blood preparation was achieved through anemia management in prenatal clinics and autologous blood collection during pregnancy. The newborn underwent the three primary tests for HDFN and plasma IgG subclass testing. Results: The pregnant woman's blood type was B, RhD positive, with a positive unexpected antibody screen, and the antibody identification pattern was consistent with a high-frequency antigen antibody. Gene sequencing revealed a homozygous ABCG2 c.376C>T mutation in the woman, resulting in the Jr(a-) phenotype, and anti-Jr antibody was present in her plasma. No compatible Jr(a-) blood was found among family members. The maternal anti-Jr IgG titer remained stable at 256 during pregnancy, with no detectable IgG1 or IgG3 subclasses against the Jr antigen. A total of 800 mL of autologous blood was collected in two stages during pregnancy. The newborn was B, RhD positive, Jr(a+), with a positive unexpected antibody screen (anti-Jr ). IgG subclass typing detected no IgG1 or IgG3. The direct antiglobulin test was positive, while the acid elution test was negative. Conclusion: The combination of serology and blood group genetic analysis provides a diagnostic basis for identifying antibodies to high-frequency antigens. Managing perinatal anemia and implementing staged autologous blood storage can secure blood supply for the perioperative period. IgG antibody subclass typing offers a reference for clinical assessment and prevention of HDFN.

Intravitreal anti-vascular endothelial growth factor(anti-VEGF)therapy has been widely used, but the variability in its therapeutic efficacy limits individualized treatment. In recent years, the application of artificial intelligence(AI)has opened up new avenues for personalized treatment response prediction, and its core branches include machine learning(ML)and deep learning(DL). This review systematically retrieved and analyzed 41 relevant studies published up to April 2025. Comprehensive analysis reveals that AI predictive models are evolving from forecasting single endpoints(such as visual acuity or central retinal thickness)to integrating multi-dimensional endpoints(encompassing anatomical, functional, and treatment demand parameters)and generating predictive imaging outputs. In terms of technical approaches, DL models(28 studies, accounting for 68.3%)dominate this field due to their robust image interpretation capabilities, while ML models(10 studies, 24.4%)retain significant value in the analysis of structured clinical data. Cross-disease comparisons indicate that research efforts are most concentrated on age-related macular degeneration(ARMD)and diabetic macular edema(DME), with shared conceptual frameworks for model construction, yet distinct anatomical and functional indicators are prioritized for each disease. Currently, the field confronts several key challenges, including insufficient prospective clinical validation, limited model interpretability(the “black box problem”), and a scarcity of high-quality multi-center datasets. Moving forward, it is imperative to advance real-world validation and develop explainable AI techniques to expedite the clinical translation of these predictive models.

BackgroundFamily functioning is one of the factors influencing non-suicidal self-injury （NSSI） behaviors in adolescents with depressive disorders. Previous studies have treated family functioning as a unitary construct， which may obscure the differential impacts of specific dimensions on NSSI behaviors. ObjectiveTo explore the relationships between various dimensions of family functioning and NSSI behaviors in adolescents with depressive disorders， aiming to provide precise targets for family-based interventions for adolescents with depressive disorders who exhibit NSSI behaviors. MethodsIn this cross-sectional study， 217 adolescent patients who were treated at the outpatient or inpatient department of The First Psychiatric Hospital of Harbin from January to July 2025 and met the diagnostic criteria for depressive disorders as stipulated in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were included as the research subjects. Assessments included a self-designed questionnaire， the Hamilton Depression Scale-17 item （HAMD-17）， and the Family Assessment Device （FAD）. Univariate Logistic regression analysis was employed to investigate the association between each dimension of family functioning and the NSSI behaviors， and multivariate Logistic regression was used to test the independent effect of each dimension of family functioning on the NSSI behaviors. ResultsA total of 204 cases （94.01%） of adolescent patients with depressive disorders completed the valid questionnaire survey. Among them， 134 cases （65.69%） exhibited NSSI behaviors （NSSI group）， and 70 cases （34.31%） did not exhibit NSSI behaviors （non-NSSI group）. Compared with the non-NSSI group， the NSSI group had a higher HAMD-17 score ［（20.97±7.50） vs. （17.79±6.95）， t=8.705， P=0.004］， a higher FAD total score ［（155.68±21.84） vs. （148.87±22.72）， t=4.348， P=0.038］， and a higher problem-solving dimension score ［（2.54±0.49） vs. （2.34±0.51）， t=7.399， P=0.007］. All the differences were statistically significant. The results of the Logistic regression analysis showed that the FAD total score （OR=1.014， 95% CI： 1.001–1.028， P=0.041） and the problem-solving dimension score （OR=2.241， 95% CI： 1.228–4.090， P=0.009） were both risk factors for NSSI behaviors. After adjusting for gender， age， residence， educational level， monthly family income， and whether being an only child， the correlation between the FAD total score and NSSI behaviors was not statistically significant （OR=1.010， 95% CI： 0.995–1.025， P=0.185）， while the correlation between the FAD problem-solving dimension score and NSSI behaviors remained statistically significant （OR=2.000， 95% CI： 1.028–3.889， P=0.041）. ConclusionImpaired problem-solving capacity within family functioning may constitute a risk factor for NSSI behaviors in adolescents with depressive disorders. ［Funded by Research Project of Heilongjiang Provincial Health Commission （number， 20240303090148， 20230303090154）］

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

ObjectiveThis study focused on the marketed Chinese patent medicines for the treatment of Functional Diarrhea （FDr） in China and their prescription characteristics， in order to provide support for the clinical application and research and development of anti-FDr Chinese patent medicines. MethodsCollect the information of Chinese patent medicines that have been marketed to treat FDr， use Microsoft Excel 2021 software to conduct preliminary data collation and statistical analysis， and use the ancient and modern medical record cloud platform （V2.3.9） to analyze the standardized Chinese patent medicine prescriptions from the aspects of drug nature and taste， medication characteristics and prescription rules. Results147 kinds of FDr Chinese patent medicines were included in this study. There are a total of 40 varieties of FDr Chinese patent medicines suitable for children； The distribution of dosage forms is mainly pills， tablets， and capsules. 110 prescriptions were screened， among which the proportion of Chinese patent medicines for the treatment of spleen deficiency syndrome was the highest； The top three drug use frequency were licorice， Atractylodes macrocephala， and Poria cocos； The medicinal properties are mainly warm and flat， and the medicinal taste is mostly pungent， sweet and bitter， and most of them belong to the two meridians of the spleen and stomach； The association rules analysis obtains 20 strong association pairing sets； Three drug combinations were obtained by cluster analysis. ConclusionFDr Chinese patent medicine shows unique value in clinical application， especially in the field of children. However， there are still problems such as strong professionalism in the indication expression of drug instructions， limited coverage of the medical insurance catalog， and lack of high-level evidence-based medicine and pharmacoeconomic evidence. To this end， in the future， efforts should be made to build a multi-level evidence-based evidence system， improve medication compliance， and deepen research on syndrome-based medication laws， so as to enhance the clinical application value and scientific connotation of FDr Chinese patent medicines.