Myopia is a highly prevalent refractive error worldwide, with scleral remodeling accompanying excessive axial elongation being one of its core pathological features. As the crucial outer layer responsible for maintaining eyeball morphology and biomechanical stability, the sclera plays a decisive role in the pathogenesis and progression of myopia through abnormal alterations in its cellular components, extracellular matrix(ECM)metabolism, and regulatory networks. This review systematically summarizes recent research advances in scleral remodeling. It focuses on elucidating, from cellular and molecular perspectives, the mechanisms by which dysfunction of scleral fibroblasts, dysregulation of ECM metabolism(e.g., decreased collagen content, disrupted MMP-2/TIMP-2 balance), and complex regulatory networks involving multiple signaling pathways such as TGF-β, Wnt/β-catenin, and MAPK drive scleral thinning and reduced mechanical strength. Concurrently, the review provides a comprehensive analysis of the potential roles and existing controversies regarding factors like inflammatory responses and novel regulatory axes(e.g., FOXM1/METTL3/APOA1)in scleral remodeling. Furthermore, it discusses the current research status and application prospects of sclera-targeted intervention strategies(e.g., modulating specific pathways, supplementing exogenous factors), aiming to provide a theoretical basis and directional reference for a deeper understanding of myopia pathogenesis and the development of new prevention and treatment approaches.

Abstract Adolescents are a high risk group for non suicidal self injury (NSSI), and the severity of the issue has been increasing. However, stigma originating from self perceptions, the public, and healthcare professionals poses significant barriers to help seeking and recovery among adolescents with NSSI. The paper systematically reviews the main intervention strategies targeting NSSI related stigma in adolescents, along with their effectiveness, from three perspectives: educational approaches, contact based interventions, and public advocacy against stigma, aiming to inform the development of a scientific, effective, and multi stakeholder collaborative integrated intervention framework to provide a basis for reducing and ultimately eliminating stigma associated with adolescent NSSI.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

OBJECTIVE: To determine the prevalence of GJB2 gene c.109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. METHODS: One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c.109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c.109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2023-009). RESULTS: For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c.109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c.109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined (n = 53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined (n = 24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls (P = 0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1 ± 12.0 dB nHL, P = 0.005). CONCLUSION Infants harboring the GJB2 c.109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c.109G>A variant can confer a more severe hearing loss.
Humans ; Connexin 26/genetics* ; Female ; Male ; Infant, Newborn ; Infant ; Hearing Loss/genetics* ; Retrospective Studies ; Child, Preschool ; Child ; Genotype ; Connexins/genetics* ; Mutation

Objective:To investigate the value of nomogram model based on CT features in differentiating ectopic pancreas (EP) from gastrointestinal stromal tumors (GIST) with a long diameter less than 3 cm.Methods:This study was a case-control study. The clinical and imaging data of 43 patients with EP and 90 patients with GIST confirmed by pathology in the Affiliated Hospital of Guizhou Medical University from August 2013 to March 2024 were retrospectively analyzed. Preoperative CT images were analyzed to obtain qualitative features (number of lesions, location, morphology, growth pattern, borders, cystic degeneration, calcification, ulceration, catheter sign, central umbilication) and quantitative features (lesion long diameter, short diameter, long/short diameter, lesion and normal pancreas arterial-phase and venous-phase CT values, and enhancement ratio). Statistical analyses, including independent sample t-tests, Mann-Whitney U tests, χ2 tests, and Fisher exact tests, were performed to compare CT characteristics between the two groups. Binary logistic regression analysis was used to obtain independent predictors to identify the two groups, to establish a joint model, and to draw a nomogram. The discriminative performance of the independent predictors and the combined model was assessed using receiver operating characteristic (ROC) curves, while calibration curves were used to evaluate model fit. Results:The differences in age, location, morphology, border, catheter sign, central umbilication, short diameter, long/short diameter, arteriovenous phase enhancement CT value and arteriovenous phase enhancement ratio were statistically significant between the EP group and the GIST group (all P<0.05). The logistic analysis showed that the differences in age ( OR=0.920, 95% CI 0.885-0.956, P<0.001), border ( OR=5.994, 95% CI 2.111-17.022, P=0.001), long/short diameter ( OR=7.820, 95% CI 1.841-33.224, P=0.005), and venous phase enhancement ratio ( OR=8.847, 95% CI 1.103-70.972, P=0.040) were the independent predictors for distinguishing EP from GIST, and the area under the ROC curve (AUC) were 0.782 (95% CI 0.698-0.866), 0.684 (95% CI 0.600-0.767), 0.705 (95% CI 0.607-0.803), and 0.693 (95% CI 0.605-0.781), respectively. Combined age, border, long diameter/short diameter and venous phase enhancement ratio were plotted in a nomogram with an AUC of 0.881 (95% CI 0.817-0.945), sensitivity and specificity of 74.4% and 93.3%, respectively. The calibration curve demonstrated a strong agreement between predicted and actual probabilities (Hosmer-Lemeschow test, P=0.267). Conclusions:CT imaging reveals significant differences between EP and small GISTs (<3 cm). EP is more likely when patients are younger and lesions exhibit indistinct borders, a higher long-to-short diameter ratio, and greater venous-phase enhancement. The nomogram derived from CT features provides a valuable tool for differentiating EP from GIST.

Portal vein tumor thrombus (PVTT) is a critical prognostic factor in advanced hepatocellular carcinoma, significantly impacting patient outcomes. Effective management of PVTT is essential for improving survival rates. Current treatment strategies, including vascular interventional therapy, particle implantation therapy, external beam radiotherapy, targeted therapy and immunotherapy, have shown promising outcomes in managing PVTT. Therefore, a thorough understanding of the blood supply to PVTT is crucial for optimizing diagnostic and therapeutic approaches in clinical practice. This review focuses on the establishment and characteristics of PVTT blood supply and its imaging manifestations across various modalities.

Objective:To develop a modified University of Wisconsin preservation solution (UW solution) containing α 2-adrenergic receptor agonists (dexmedetomidine) and noble gases (argon) and investigate its protective effect on the isolated amputated skeletal muscle of rats. Methods:Sixty male SD rats were selected to establish a hindlimb cold preservation/perfusion model and were divided into blank control group, hypothermic storage group, UW solution perfusion group, and modified UW solution perfusion group using a random number table, with 15 rats in each group. Simultaneously, a cold preservation model of rat skeletal muscle myoblasts (L6 cells) was established and the rats were also divided into four groups in the same way. Animal models were prepared in different ways: In the blank control group, the hindlimbs received no special treatment; In the hypothermic storage group, the amputated hindlimbs were stored in a dry centrifuge tube at 4℃ for 18 hours; In the UW solution perfusion group, the amputated hindlimbs were perfused with UW solution and then stored in a centrifuge tube containing UW solution at 4℃ for 18 hours; In the modified UW solution perfusion group, the amputated hindlimbs were perfused with modified UW solution (containing 0.1 nmol/L dexmedetomidine and 50% volume fraction of argon) and then stored in a centrifuge tube containing the modified UW solution at 4℃ for 18 hours. Cell models were treated as follows: In the blank control group, L6 cells were cultured under standard conditions; In the hypothermic storage group and UW solution group, L6 cells were treated with conventional culture medium or UW solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours; In the modified UW solution group, L6 cells were treated with the modified solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours. After sample collection, skeletal muscle morphology, tissue edema and ultrastructure features were assessed by HE staining, wet-to-dry weight ratio, and transmission electron microscopy, respectively. Additionally, L6 cell morphology was examined by light microscopy. L6 cell viability was determined by cell counting kit-8 (CCK-8) assay (expressed as absorbance A value). Expression levels of glutathione peroxidase 4 (GPX4) protein in both skeletal muscle tissue and L6 cells were evaluated by immunofluorescence staining and Western blot, respectively.Results:After 18 hours of in vitro preservation of rat isolated amputated limbs, the following results were obtained: (1) HE staining results showed that the muscle fiber morphology of the modified UW solution perfusion group was close to that of the blank control group. Moreover, the area ratio of skeletal muscle cells in the modified UW solution perfusion group was significantly higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). (2) The wet-dry weight ratio results showed that there was no statistically significant difference among the modified UW solution perfusion group, the blank control group and UW solution group ( P>0.05), with significantly lower ratios in all three groups than that in the hypothermic storage group ( P<0.05). (3) Transmission electron microscopy results revealed that the modified UW solution perfusion group showed no statistically significant differences in ultrastructural metrics, including myofiber diameter, sarcomere length, mitochondrial short-axis/long-axis ratio, and mitochondrial cristae count, compared with those in the blank control group ( P>0.05), and performed significantly better than both the hypothermic storage group and UW solution perfusion group ( P<0.05). (4) Morphological observation of L6 cells showed that the cellular morphology was regular in the modified UW solution perfusion group, close to that in the blank control group, while it was severely damaged in the hypothermic storage group. Moreover, the cells were reduced in number and partially damaged in the UW solution group. The sequence of cell viability expressed as absorbance A value was blank control group >modified UW solution perfusion group > UW solution perfusion group > hypothermic storage group, with statistically significant differences among the four groups ( P<0.05). (5) Immunofluorescence staining showed that there was no statistically significant difference in fluorescence intensity of GPX4 protein expression between the modified UW solution perfusion group and blank control group ( P>0.05), while the fluorescence intensity was higher in the modified UW solution perfusion group than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Western blot analysis showed that the relative expression level of GPX4 in the modified UW solution group was significantly lower than that in the blank control group ( P<0.05), but higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Conclusion:The modified UW solution can stabilize the expression level of GPX4 protein, thereby inhibiting ferroptosis and alleviating cold preservation injury in both rat amputated isolated limb skeletal muscle tissue and L6 cells.

Objective:To investigate the additional value of 99Tc m-hydrazinonicotinamide (HYNIC)-Tyr3-octreotide (TOC) SPECT/CT imaging in the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods:A total of 54 patients (28 males and 26 females, age: (52.6±11.7) years) who underwent enhanced CT (MR) and 99Tc m-HYNIC-TOC SPECT/CT in People′s Hospital of Zhengzhou University between December 2017 and June 2023 were analyzed retrospectively. Surgical pathology or biopsy was the gold standard of patients′ diagnosis (primary tumors), and comprehensive evaluation based on pathology, imaging and follow-up results was used as the diagnostic criteria of lesions. McNemar χ2 test was used to compare the diagnostic efficacy of different imaging methods. Results:Pathological results showed that 43 of the 54 patients were with GEP-NETs and 11 were with non-neuroendocrine tumors (NETs). The sensitivities of enhanced CT and enhanced MR in the diagnosis of patients with GEP-NETs were 65.1%(28/43) and 60.0%(15/25) respectively, which increased to 93.0%(40/43) and 92.0%(23/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 8.64, 4.90, P values: 0.002, 0.021). There were 22 and 15 patients showing atypical enhancement on enhanced CT and enhanced MR respectively. The sensitivities of these two methods for GEP-NETs in patients with atypical enhancement were 54.5%(12/22) and 8/15 respectively, which increased to 95.5%(21/22) and 14/15 with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.82, 4.17, P values: 0.012, 0.031). Compared with enhanced CT, the detection rates of liver and bone metastatic lesions were improved significantly from 90.8%(158/174) and 55.2%(32/58) to 96.6%(168/174) and 87.9%(51/58) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2 values: 5.79, 9.82, P values: 0.013, 0.001). Compared with enhanced MR, the detection rate of bone metastases was improved significantly from 56.0%(14/25) to 88.0%(22/25) with the addition of 99Tc m-HYNIC-TOC imaging ( χ2=4.08, P=0.039). After 99Tc m-HYNIC-TOC imaging, stages were changed in 7.0%(3/43) of patients and a greater number or extent of metastases were detected in 11.6%(5/43) of patients. 99Tc m-HYNIC-TOC imaging detected additional recurrent or metastatic lesions in 40.0%(8/20) of patients during follow-up compared to enhanced CT. Conclusion:99Tc m-HYNIC-TOC imaging can provide an added value for diagnosing GEP-NETs with atypically enhanced CT(MR), and in the detection of liver metastasis and early bone metastasis, thus helping the optimization of clinical treatment strategies.

Objective:To determine the prevalence of GJB2 gene c. 109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. Methods:One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c. 109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c. 109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children′s Hospital of Ningbo University (Ethics No.: EC2023-009). Results:For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c. 109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c. 109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined ( n=53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined ( n=24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls ( P=0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1±12.0 dB nHL, P=0.005). Conclusion:Infants harboring the GJB2 c. 109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c. 109G>A variant can confer a more severe hearing loss.

Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.