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

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Despite therapeutic advancements over recent decades, the prognosis for patients with metastatic CRC (mCRC) remains poor. Approximately 2%-4% of mCRC cases exhibit human epidermal growth factor receptor 2 (HER2) amplification or overexpression, defining a distinct molecular subtype. This HER2-positive status is strongly associated with primary resistance to anti-epidermal growth factor receptor (EGFR) therapies, which are the standard of care for patients with RAS wild-type tumors. Beyond its well-established role in breast and gastric cancers, HER2 has emerged as a pivotal biomarker and actionable therapeutic target in mCRC. However, selecting appropriate treatment strategies remains challenging due to patient heterogeneity and diverse molecular subtypes. This review systematically summarizes the molecular biology, diagnostic strategies, and advances in targeted therapies for HER2-positive mCRC. On the diagnostic front, we discuss the applications of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and circulating tumor DNA (ctDNA) detection technologies. We highlight discrepancies in diagnostic criteria across key clinical trials—such as HERACLES, DESTINY, and MOUNTAINEER—underscoring the urgent need for standardized, CRC-specific definitions to ensure consistent patient selection and comparability of efficacy data across studies. Although NGS enables comprehensive genomic profiling, its cost-effectiveness relative to traditional methods must be carefully considered. Therapeutically, we summarize clinical trial data for HER2-directed agents, including tyrosine kinase inhibitors (TKIs) such as tucatinib and lapatinib, monoclonal antibodies like trastuzumab, bispecific antibodies, and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan. We review dual-targeting strategies and note recent FDA approvals that represent significant milestones in second-line treatment. Additionally, we explore the potential of combining immune checkpoint inhibitors with HER2-targeted therapies to enhance antitumor immunity through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and modulation of the tumor microenvironment. ADCs enable precise delivery of cytotoxic payloads, reducing off-target toxicity while effectively inhibiting oncogenic pathways. A substantial portion of this review is dedicated to dissecting the molecular mechanisms underlying primary and acquired resistance to HER2-targeted therapies—persistent challenges that limit clinical benefit. These mechanisms include reactivation of downstream signaling pathways such as PI3K/AKT/mTOR and MAPK, concurrent mutations in genes like KRAS or BRAF, and alterations in HER2 expression that compromise treatment efficacy. For instance, specific HER2 mutations (e.g., L755S) can reduce drug binding affinity, while ctDNA monitoring facilitates early detection of emerging resistance clones during disease progression, thereby enabling timely therapeutic adjustments. Tumor heterogeneity and dynamic interactions with the microenvironment further complicate resistance patterns observed in clinical practice. HER2-targeted therapy represents a new frontier in precision oncology for mCRC, offering renewed hope for improving patient outcomes. Realizing this potential will require continued optimization of diagnostic algorithms and treatment workflows. Future efforts must focus on overcoming resistance, validating liquid biopsy approaches for dynamic monitoring, and establishing unified clinical guidelines. HER2 has become an essential biomarker for stratifying mCRC patients beyond traditional RAS and BRAF status, underscoring the shift from empiric treatment to biomarker-driven precision medicine. International, multidisciplinary collaboration will be critical to validate emerging biomarkers and refine treatment algorithms globally.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

AIM: To explore the risk factors associated with diabetic retinopathy(DR)based on ultra-widefield swept-source optical coherence tomography angiography(UWF-SS-OCTA), and to establish a clinical prediction model.METHODS:A total of 235 patients(235 eyes)with type 2 diabetes mellitus who were treated in the Affiliated Hospital of Xuzhou Medical University from July to November 2024 were selected as the research objects. According to the presence or absence of DR, they were divided into 120 cases(120 eyes)in non-DR group(NDR group)and 115 cases(115 eyes)in non-proliferative DR group(NPDR group). Data on general characteristics, laboratory tests, and OCTA results were collected for both groups. Univariate analysis was employed to identify DR-related risk factors. Logistic regression analysis was conducted to analyze these risk factors and to establish a DR prediction model. The efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve, calibration curve, and decision curve analysis(DCA).RESULTS: The duration of diabetes, fasting blood glucose, blood urea nitrogen(BUN), history of hypertension, and the choroidal vascular index(CVI)were found to be statistically significant in the model(all P<0.05). Specifically, the duration of diabetes, fasting blood glucose, BUN, and history of hypertension were identified as risk factors for DR among diabetic patients, while CVI was recognized as a protective factor. The area under the curve for the model predicting the probability of DR was 0.898(0.859-0.938), with a diagnostic threshold of 0.438. The corresponding sensitivity and specificity were 87.8% and 78.3%, respectively, indicating that the model possesses high predictive value for the occurrence of DR.CONCLUSION: The duration of diabetes, fasting blood glucose, BUN, history of hypertension, and CVI are significantly correlated with DR. The established prediction model demonstrates a substantial screening capability for DR.

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

To establish a double fluorescent RT-LAMP that can distinguish between chicken astro-virus(CAstV)and avian nephritis virus(ANV),two sets of specific primers and probes labeled with fluorescent groups were designed by comparing the conserved sequences of CAstV ORF1b gene and ANV ORF1b gene downloaded from GenBank.The CAstV probe was labeled with CY3 fluorophore at the 3'end and the quencher BHQ2 at the 5'end.The ANV probe was labeled with CY3 fluorophore at the 3'end and the quencher BHQ2 at the 5'end.The reaction system of the method was optimized,and specificity,repeatability,interference,sensitivity,and clinical sample detection were performed.The results were compared with RT-qPCR and RT-PCR to verify the ef-fectiveness of the method.The experimental results showed that the established double fluorescence RT-LAMP method could complete the reaction within 60 min,and the optimal reac-tion temperature was 65 ℃.This method only detects ANV and CAstV,with no cross-reactivity to other common avian pathogens.The minimum detection limit of CAstV was 1.4 ×10 2 copies/μL,and the minimum detection limit of ANV was 1.5×10 2 copies/μL.The interference and reproduc-ibility tests were good.Compared with RT-qPCR,the coincidence rates of CAstV and ANV were 97.97％and 98.85％,respectively.In conclusion,the double fluorescence RT-LAMP method estab-lished in this study has the characteristics of rapidity,accuracy,good specificity,high sensitivity and good reproducibility,which is suitable for clinical diagnosis and provides technical support for the epidemiological investigation of CAstV and ANV.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

Through a comprehensive analysis of four cases involving repeated forensic clinical identification on the degree of human injury,disability grade,causal relationship of injury and disease,medical damage liability dispute,the reasons for the emergence of different appraisal opinions are explored.According to the reasons for the disputed conclusion,the deviation or error of the appraisal opinion can be classified in a variety of ways.Among them,the inherent limitations of theories and methods used as appraisal bases,the lack of operational skills or cognitive ability of appraisers,the unclear provisions of appraisal standards and the lack of adequacy and validity in the process of analysis and reasoning are the key reasons for the deviation or error of appraisal opinions.In light of these findings,it is necessary to strengthen the review of expert opinions in judicial practice and form a powerful error correction mechanism.

The essential public health services is an important component of China's health risk governance system.It possesses both institutional and emotional attributes and addresses potential risk factors in health risk governance by forming a rational pathway and an emotional pathway:essential public health services guide-trust in government enhancement-improve health risk governance capacity.The rational pathway strengthens calculative trust through institutional reinforcement mechanisms,fostering the public's cognitive trust in government departments.The emotional pathway follows the principle of satisfaction,strengthening non-calculative trust through emotional communication and cultivating the public's emotional trust in government departments.By reinforcing both cognitive and emotional trust among the public,essential public health services improved the level of health information reserves and the guidance of medical service order,thereby improving health risk governance capacity.

Objective:To evaluate the toxicity of foscarnet sodium injection into the anterior chamber and intravitreal cavity on the cornea and retina.Methods:Thirty-six adult New Zealand White rabbits were randomly divided into control group, intravitreal injection group, and intracameral injection group, with 12 rabbits in each group.In the control group, 0.1 ml of balanced salt solution (BSS) was injected into the vitreous cavity of one eye, and an equal volume of BSS was injected into the anterior chamber of the other eye.In the intracameral injection group and intravitreal injection group, 0.1 ml of sodium foscarnet 1.2 mg was injected into the anterior chamber and vitreous cavity of one eye, respectively.Slit-lamp microscopy, ophthalmoscope, optical coherence tomography (OCT), and in vivo confocal laser scanning microscopy were performed on 3 experimental rabbits from each group on days 1, 7, 14, and 28 after injection.After sacrifice, both eyeballs were removed, and the corneas and retinas were examined using optical microscopy, scanning electron microscopy and transmission electron microscopy to evaluate the toxicity to the cornea and retina comprehensively.The use and care of the animals complied with the ARVO Statement.The study protocol was approved by an Ethics Committee of Peking University Third Hospital (No.IRB00006761-2015197). Results:Slit-lamp microscopy and OCT showed no corneal edema, intraocular inflammation, or other abnormalities in the intravitreal injection and control groups.Mild corneal edema was observed in intracameral injection group 1 day after injection, which resolved 7 days after injection. In vivo confocal laser scanning microscopy revealed normal hexagonal corneal endothelial cell morphology in the intravitreal injection and control groups.There was no significant difference in endothelial cell density at baseline and 1, 7, and 14 days after injection among the three groups ( Fgroup=1.21, P=0.32; Ftime=1.21, P=0.32).Light microscopy revealed no obvious corneal abnormalities.On days 1 and 7 after injection, retinal nerve fiber layer vacuolization and inflammatory cell infiltration were observed in the intravitreal injection and control groups.In the intravitreal injection of BSS group, inflammatory cell infiltration occurred in the retina without vacuolization 1 day after injection.There were no structural changes in the photoreceptor layer, and the nuclear layer was well-organized.Scanning electron microscopy showed no significant abnormalities in the corneal endothelium in the intravitreal injection group 1 day after injection.In the intracameral injection group, a large number of inflammatory cells were deposited and adhered to the corneal endothelium 1 day after injection and disappeared 7 days after injection.Transmission electron microscopy revealed that in the intravitreal injection group, 1 day after injection swelling of corneal endothelial cells, dilatation of the endoplasmic reticulum, and partial mitochondrial swelling were observed, which normalized 14 days after injection and vacuolization was present in the retina and interstitial fluid accumulation persisted until the 28 days after injection.In the intracameral injection group, swollen mitochondrial and endoplasmic reticulum of corneal endothelial cells was observed and resolved by 14 days after injection.However, structural abnormalities in the membranous discs of the photoreceptor outer segments and interstitial fluid accumulation in the optic nerve fiber layer persisted 1 day after injection and did not fully recover 28 days after injection. Conclusions:Intracameral intravitreal and injection of foscarnet sodium have transient toxic effects on the retina, which gradually weaken over time.Intracameral injection of foscarnet sodium was more toxic to corneal endothelial cells than intravitreal injection.