Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.
Humans ; B-Lymphocytes/immunology* ; Neoplasms/therapy* ; Carcinogenesis/immunology* ; Immunotherapy/methods* ; Animals

Adult-onset Still's disease(AOSD)is a rare autoinflammatory disease characterized by fever,rash,arthritis,liver,spleen and lymph node enlargement,increased total number of peripheral white blood cells and neutrophil ratio.This paper reported a case of AOSD with dermal lymphadenitis(DL)complicated with hemophagocytic syndrome(HPS),in order to improve the clinicians'understanding for this complicated complication.The patient was a 48-year-old female who was admitted to the hospital with the complant of"intermittent fever with rash for 15 d".After 10 d of active anti-infection treatment,the symptoms were not improved,and there were new large congestive edematous erythema on the face and trunk,muscle pain in limbs and joints,and spleen enlargement.Laboratory tests showed increased white blood cell count,significantly decreased platelet count,hypofibrinogenemia,elevated serum ferritin,and elevated soluble interleukin-2 receptor sCD25;DL was pathologically diagnosed by axillary lymph node biopsy.After excluding other diseases,the diagnosis was confirmed as AOSD with DL complicated with HPS.After diagnosis of HPS,the patient was treated with hemophagocytic lymphohistiocytosis(HLH)-1994 regimen combined with rucotinib for 6 weeks,and the symptoms were improved;the patrent was discharged.The diagnosis of AOSD is particularly complex when complicated with the complications such as HPS,which requires carefully differential diagnosis,especially to exclude lymphoma.The cases of AOSD with DL are rare,and its etiology and pathogenesis need further study;early diagnosis and multidisciplinary collaboration are essential to improve the patient's prognosis.

OBJECTIVE: To apply optical genome mapping (OGM) technique for the analysis of genetic etiology in two rare families with complex chromosomal rearrangements (CCRs) and to provide precise reproductive guidance to them. METHODS: Two Chinese families diagnosed with chromosomal rearrangements by chromosomal microarray analysis (CMA) or whole-exome sequencing (WES) between June and December 2023 at the Affiliated Women and Children's Hospital of Ningbo University were selected as the study subjects. In both cases, unbalanced chromosomal translocations were suspected. Clinical data were collected, and peripheral blood from the couple, amniotic fluid sample and aborted fetal tissue was subjected to combined G-banding karyotyping and OGM for comprehensive genetic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2023-094). RESULTS: In family 1, the fetus was signaled to have abnormal chromosome 7 by non-invasive prenatal testing (NIPT), prompting amniocentesis and CMA detection. In family 2, a pregnancy loss had occurred at 10 weeks' gestation, and trio-WES was carried out. Both fetuses were found to harbor copy number variations (CNVs) suggestive of unbalanced CCRs. Further analysis with OGM has revealed that, in family 1, an unbalanced rearrangement involving chromosomes 7, 8, and 10 was carried by the fetus and the pregnant woman, which has formed der(8) and der(10) derivative chromosomes. In family 2, a maternal CCR was found, which involved chromosomes 2 and 13 with seven breakpoints, resulting in unbalanced fetal CNVs. After genetic counseling, family 1 opted to continue with the pregnancy, considering the woman's normal appearance and inheritance of the rearrangement. For both families remained to have a risk for unbalanced rearrangements in subsequent pregnancies, preimplantation genetic testing (PGT) was recommended. CONCLUSION In both families, the OGM has precisely delineated the genetic basis of fetal CNVs and mapped the maternal CCR breakpoints, providing critical insights for genetic counseling and reproductive decision-making.
Adult ; Female ; Humans ; Male ; Pregnancy ; Chromosome Aberrations ; Chromosome Disorders/genetics* ; Chromosome Mapping/methods* ; Genetic Testing/methods* ; Pedigree ; Prenatal Diagnosis/methods* ; Translocation, Genetic

OBJECTIVE: To assess the value of Optical genome mapping (OGM) for the verification of chromosomal structural variations among patients undergoing assisting reproduction. METHODS: A retrospective analysis was carried out on the clinical data of 12 patients presented at the Reproductive Center of Ningbo University Women and Children's Hospital from October 2022 to October 2024. All patients had undergone OGM testing due to suspection of structural variants by chromosomal karyotyping or a suggestive medical history. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2024-148). RESULTS: Among the 12 patients verified by OGM, one (8.3%) was in keeping with the result of chromosomal karyotyping. Revised karyotypes were confirmed in seven cases (58.3%), including four with complex chromosomal rearrangements. Structural variation was excluded in three cases (25.0%). Of note, OGM has identified a previously undetected cryptic balanced translocation, i.e., ogm[GRCh38] t(7;12)(q36.3;q24.23)(157511190_157523142;119205703_119198409). CONCLUSION OGM can serve as an auxiliary diagnostic technique to conventional karyotyping and enable validation of suspected structural variations in those with ambiguous karyotype results or a history of adverse pregnancies. This can provide more precise genetic diagnosis for patients undergoing assisted reproduction and selection of clinical intervention strategies.
Humans ; Female ; Adult ; Retrospective Studies ; Karyotyping ; Reproductive Techniques, Assisted ; Chromosome Mapping/methods* ; Chromosome Aberrations

OBJECTIVE: To investigate the genetic characteristics and clinical utility of Optical genome mapping (OGM) in resolving complex genomic rearrangements in families with recurrent pregnancy loss. METHODS: A recurrent miscarriage family which presented at both the People's Hospital of Qianxinan Buyi and Miao Autonomous Prefecture and the Affiliated Women and Children's Hospital of Ningbo University in September 2024 was selected as the study subject. Relevant clinical information was collected. Peripheral blood samples of the couple were collected for G banding karyotyping analysis, and copy number variation sequencing (CNV-seq) and OGM were used for verification. This study was approved by the Medical Ethics Committee of the Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2024-148). RESULTS: CNV-seq in an external hospital detected a 10.67 Mb deletion in the 16q12.1q21 region, a 142.4 kb deletion in the 5p15.2 region, and a 359.55 kb duplication in the 7p22.2 region. No abnormality was found in the chromosomal karyotype of the male partner, and the initial karyotyping of the female partner suggested 46,XX,?del(16)(q12.1q22). The CNV-seq verification of her indicated only variations in the 5p15.2 and 7p22.2 fragments, and no deletion of 16q was detected. As indicated by precise OGM analysis, multiple intrachromosomal and interchromosomal translocation variations had occurred between chromosomes 10 and 16 in the female partner, with complex balanced rearrangements (including 5 transchromosomal breakpoints). CONCLUSION The complex balanced rearrangements of the female partner's chromosomes had occurred during meiosis, the resultant unbalanced gametes may be the cause of repeated miscarriage in this family. OGM can delineate complex rearrangement breakpoints and directions that are difficult to reveal by conventional karyotyping analysis and provide a basis for accurate reproductive genetic counseling.
Humans ; Abortion, Habitual/etiology* ; Female ; Pregnancy ; Male ; DNA Copy Number Variations/genetics* ; Adult ; Karyotyping ; Pedigree ; Gene Rearrangement ; Chromosome Mapping

Background::Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.Methods::Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.Results::The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking.Conclusion::With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

Objective:To explore the molecular basis for a Chinese pedigree affected with Achromatopsia (ACHM).Methods:A pedigree with ACHM which was admitted to the Women and Children′s Hospital of Ningbo University on April 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. Related literature was reviewed, and clinical and genetic features of Chinese patients with ACHM due to variants of CNGA3 gene were summarized. This study was approved by the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048). Results:WES revealed that the proband and his younger brother had both harbored compound heterozygous variants of the CNGA3 gene, namely c. 1190G>T (p.Gly397Val) and c. 2013del (p.Gly672ValfsTer69), which were respectively inherited from their mother and father. The c. 1190G>T was a known pathogenic variant, while the c.2013del was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2013del variant was predicted to be likely pathogenic (PM2_Supporting+ PVS1_Moderate+ PM3+ PP4). Literature review has identified 41 CNGA3 gene variants among 43 patients from 38 pedigrees, most of which were missense variants and had located in exon 8. Most patients were males, with nystagmus, photophobia, amblyopia and other symptoms during infancy/childhood as the main clinical manifestations, and there was a lack of genotype-phenotype correlation. Conclusion:The c. 1190G>T (p.Gly397Val) and c. 2013del (p.Gly672ValfsTer69) variants of the CNGA3 gene probably underlay the ACHM in the proband. Discovery of the c. 2013del variant has enriched the mutational spectrum of the CNGA3 gene and provided a basis for genetic counseling and reproduction guidance for this pedigree.