Background Carbendazim (CBZ), a widely used benzimidazole fungicide, has raised increasing concerns regarding the health risks associated with its residues. However, the toxic effects and associated mechanisms of CBZ on the skeletal system have not been reported. Objective To elucidate the effects of carbendazim on osteogenic differentiation and its underlying mechanisms. Methods MC3T3-E1 mouse pre-osteoblastic cells were treated with 1, 10, and 100 μmol·L⁻¹ CBZ for 24 h to examine cell viability, alkaline phosphatase (ALP) activity, bone nodule formation, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and nitric oxide synthase (NOS) activity. Transcriptomics was used to identify differentially expressed genes (DEGs) in osteoblasts exposed to CBZ. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were employed to analyze the potential biological pathways of DEGs. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to validate changes in gene and protein expression. Results Exposure to 10 and 100 μmol·L⁻¹ CBZ significantly reduced osteoblast viability, ALP activity, bone nodule formation, and NOS activity, while increasing intracellular ROS levels. CBZ at 100 μmol·L⁻¹ concentration significantly elevated MDA level (P < 0.05). The transcriptomic analysis revealed that 1 μmol·L⁻¹ CBZ treatment resulted in 385 significantly DEGs. The KEGG enrichment analysis revealed that CBZ significantly affects hormone regulation pathways (including parathyroid hormone, growth hormone, dopamine, and oxytocin), mitogen-activated protein kinase (MAPK) and cyclic GMP-dependent protein kinase G (cGMP-PKG) signaling pathways, focal adhesion and adherens junction, as well as the NOD-like receptor signaling pathway and the mRNA surveillance (NMD) pathway. The results of GSEA showed that CBZ significantly inhibited the bile acid metabolism and the Wnt/β-catenin pathway in osteoblasts. The validation results demonstrated that CBZ significantly suppressed the mRNA expression of Wnt3a and β-catenin, as well as the protein expression of Runx2 and Osterix in the Wnt/β-catenin pathway. Conclusion CBZ exposure exhibits potential skeletal toxicity, and its mechanism is through promoting oxidative stress, interfering with the Wnt/β-catenin pathway in osteogenic differentiation, thereby inhibiting the bone formation function of osteoblasts.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

As the only effective treatment for end-stage diseases, organ transplantation has been facing core challenges such as shortage of donor organs, technical bottlenecks, and inadequate system construction. Based on the practical experience of the organ donation and transplantation team of the First Affiliated Hospital of Xi’an Jiaotong University, this article systematically reviews the pathways for the specialization of organ donation and the disciplinary development of Organ Procurement Organization (OPO). It thoroughly analyzes the innovative achievements in kidney transplantation, including key breakthroughs in the establishment of technical standards for donor and organ evaluation, preservation and repair, the research and development of mechanical perfusion repair systems, the creation of an independent human leukocyte antigen (HLA) detection platform, and the improvement of the rejection prevention and control system. Meanwhile, combined with the latest research progress at home and abroad, this paper discusses current issues in the field of organ donation and transplantation such as the utilization of marginal donors, multidisciplinary collaboration, and ethical norms. It proposes a future direction to promote the systematic disciplinary development with "Chinese Technology, Chinese Standards, and Chinese Solutions", providing a reference for the high-quality development of organ transplantation in China.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

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.

To explore the clinical value of a multimodal predictive model based on multiparametric magnetic resonance imaging(MRI) radiomics combined with deep learning(DL) features for the preoperative noninvasive assessment of mismatch repair-deficient(MMRd) status in endometrial cancer(EC).

ObjectiveTo observe the effect and therapeutic effect of Kaixuan Jiedu core prescription （KXJD） on skin homing of Th17 cells in the mouse model of imiquimod （IMQ） combined with restraint stress-induced psoriasis-like skin damage， and to explore its potential mechanism from the perspective of neuro-immune axis. MethodsThirty male C57BL/6J mice were randomly allocated into five groups （n=6）： Control， model （IMQ）， restraint stress model （IMQ+RS）， KXJD， and methotrexate （MTX）. The mouse model of psoriasis-like skin damage was established by 5% IMQ combined with restraint stress. At the same time of modeling， each treatment group was treated with corresponding doses of drugs， and the control， IMQ， and IMQ+RS groups were treated with the same amount of normal saline by gavage once a day for 5 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the skin tissue and Baker scoring was performed. Serum levels of interleukin-1β （IL-1β） and angiopoietin-2 （Ang-2） were measured by enzyme-linked immunosorbent assay （ELISA）. The levels of matrix metalloproteinase-9 （MMP-9）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， C-C motif chemokine ligand 20 （CCL20）， and C-C motif chemokine receptor 6 （CCR6） in the skin tissue were determined. Immunohistochemistry （IHC） was employed to determine the protein expression of cutaneous lymphocyte-associated antigen （CLA）， integrin α_E （CD103）， cytokeratin 10 （CK10）， and nuclear factor-kappa B （NF-κB） in the skin. Immunofluorescence double staining （DIF） was adopted to detect the expression and co-localization of vascular endothelial cadherin （VE-cadherin） and platelet-endothelial cell adhesion molecule （CD31）， CCR6， CD103， substance P （SP）， calcitonin gene-related peptide （CGRP）， and protein gene product 9.5 （PGP9.5） in the skin tissue. Real-time PCR was employed to quantify the mRNA levels of IL-10， IL-17A， and IL-23. ResultsCompared with the control group， the IMQ group and IMQ+RS group showed significant inflammatory cell infiltration， abnormal proliferation of epidermal cells， keratinization and other pathological changes in the skin tissue， and a significant increase in Baker score， elevated levels of IL-1β and Ang-2 in the serum and MMP-9， CCL20 and CCR6 in the skin lesions， upregulated expression of CLA， CD103， CK10， NF-κB， IL-17A mRNA， and IL-23 mRNA in the skin lesions， and downregulated expression of TIMP-1 and IL-10 mRNA. In addition， the fluorescence intensities of VE-cadherin and CD31 co-localization， CCR6 and CD103 co-localization， SP and PGP9.5 co-localization， and CGRP and PGP9.5 co-localization were increased （P<0.05）. Compared with the IMQ group， the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ group， the above indicators in the IMQ+RS group were further aggravated. Compared with the IMQ+RS group， KXJD and MTX significantly alleviated the pathological damage of skin lesions， significantly decreased the Baker score， lowered the levels of IL-1β and Ang-2 in the serum and MMP-9， CCL20 and CCR6 in skin lesions， downregulated the expression of CLA， CD103， CK10， NF-κB， IL-17A mRNA and IL-23 mRNA in skin lesions， and upregulated the expression of TIMP-1 and IL-10 mRNA. Furthermore， KXJD and MTX reduced the fluorescence intensities of VE-cadherin and CD31 co-localization， CCR6 and CD103 co-localization， CGRP and PGP9.5 co-localization， and SP and PGP9.5 co-localization （P<0.05）. ConclusionKXJD can significantly ameliorate the psoriasis-like skin damage induced by IMQ combined with restraint stress in mice by regulating the neural-immune axis and inhibiting the skin homing of Th17 cells.

ObjectiveThis study aimed to provide a scientific basis for the safety management of drinking water by assessing the contamination levels of 21 per- and polyfluoroalkyl substances (PFASs) in water samples collected from the Yangtze River Delta region. MethodsSolid-phase extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to determine 21 PFASs in 6 source water samples, 20 treated water samples, and 60 tap water samples collected from 5 administrative districts in the Yangtze River Delta region across four seasons in 2023. The Kruskal-Wallis H test was used to compare differences in PFAS concentrations among the three types of water samples, followed by post hoc pairwise comparisons with Bonferroni correction. Removal efficiencies of target compounds were also calculated. ResultsAmong the 86 samples, 14 PFASs were detected, with 7 compounds detected in 100% of samples. The total concentrations of PFASs in source water, treated water, and tap water ranged from 63.85 to 190.54 ng·L^-¹, 55.75 to 774.36 ng·L^-¹, and 40.72 to 689.80 ng·L^-¹, respectively. The compounds with the highest median concentrations were perfluorobutanoic acid (PFBA) (40.19, 15.20, and 14.05 ng·L^-¹), perfluorohexanoic acid (PFHxA) (29.69, 32.62, and 34.24 ng·L^-¹), perfluorooctanoic acid (PFOA) (17.65, 39.45, and 36.83 ng·L^-¹), and potassium perfluorobutanesulfonic acid (PFBS) (16.99, 24.38, and 23.89 ng·L^-¹). Notably, concentrations of PFOA (7.71‒71.63 ng·L^-¹) and PFOS (-¹) in tap water were below the regulatory limits specified in GB 5749‒2022 Standards for Drinking Water Quality (PFOA: 0.000 08 mg·L^-1, PFOS: 0.000 04 mg·L^-1). Significant seasonal variations in PFAS concentrations were observed, with total PFAS levels in March being higher than those in September and November (adjusted P<0.001, and P=0.006), and levels in May being higher than those in September (adjusted P=0.037). The removal efficiencies of PFASs in the water treatment plants ranged from -14% to 34%. ConclusionPFAS contamination is widespread in source water, treated water, and tap water in the Yangtze River Delta region, and concentrations of PFOA and PFOS in all tested water samples comply with the Chinese national standards for drinking water quality (GB 5749‒2022). The use of PFASs should be continuously regulated to ensure water safety.

Objective: To evaluate the prevalence and future trend of change of the disease burden of injuries in Chinese children and adolescents from 1990 to 2021, so as to provide reference for injury prevention and control in this population. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021), the trend of change in the disease burden of injuries in children and adolescents in China from 1990 to 2021 was analyzed by the Joinpoint regression model. The Bayesian age period cohort model (BAPC) was used to predict the disease burden of injuries among children and adolescents in China from 2022 to 2031. Results: From 1990 to 2021, the standardized incidence rate, standardized prevalence rate, standardized mortality rate, and standardized disability adjusted life years (DALYs) rate of injuries among children and adolescents in China showed an overall downward trend (AAPC=-1.14%, -0.76%, -5.41%, -5.03%, P <0.05). For different genders, the standardized incidence rate (7 106.00/100 000, 5 388.00/100 000), standardized mortality rate (92.00/100 000, 19.00/ 100 000 ), and standardized DALYs rate (7 834.00/100 000, 1 673.00/100 000) of injuries in boys were higher than the rate of injuries in girls in 1990 and 2021 (5 188.00/100 000, 3 874.00/100 000; 61.00/100 000, 10.00/100 000; 5 398.00/100 000, 945.00/100 000). Compared with Asia and globally, China had the fastest decline in the standardized mortality rate (AAPC= -5.41 ) and the slowest decline in the standardized prevalence rate (AAPC=-0.76) among children and adolescents. The results of the Joinpoint burden trend analysis demonstrated that the standardized incidence rate of injuries showed an increasing trend from 2005 to 2021, and the standardized prevalence rate of injuries showed an increasing trend from 2006 to 2021. Among the different age groups, the disease burden of injuries was highest in the 15-19-year-old group in 2021. For different types of injuries, the standardized incidence rate, standardized mortality rate, and standardized DALYs rate of unintentional injury were higher than those of transport injury, and self harm and interpersonal violence from 1990 to 2021. The BAPC prediction model showed that the standardized incidence rate ( 4 833.05/ 100 000-5 313.70/100 000) and standardized prevalence rate (5 433.90/100 000-5 821.88/100 000) of injury showed an increasing trend, and the standardized mortality rate (13.69/100 000-5.52/100 000) and the standardized DALYs rate ( 1 226.37/ 100 000-510.14/100 000) showed a decreasing trend during 2022-2031. The analysis of influencing factors found that children and adolescents who drank alcohol were at high risk of injury burden. Conclusions From 1990 to 2021, the injury burden of children and adolescents in China generally showed a downward trend. The standardized incidence rate and standardized prevalence rate of injuries are predicted to increase from 2022 to 2031. More targeted and individualized intervention measures should be developed to reduce the injury burden in children and adolescents.

ObjectiveThis study sought to investigate the impact of exosomes derived from LoVo cells (LoVo-Exos) in colorectal cancer (CRC) on tumor angiogenesis, as well as to elucidate the potential molecular mechanisms underlying their pro-angiogenic effects. MethodsLoVo-Exos were isolated via ultracentrifugation, and their internalization into recipient human umbilical vein endothelial cells (HUVECs) was visualized using confocal microscopy. The influence of LoVo-Exos on angiogenesis was assessed through an in vitro tube formation assay. Additionally, the pro-angiogenic effects of LoVo-Exos were evaluated in vivo using a matrix gluing assay in mice. To investigate the molecular mechanisms through which LoVo-Exos facilitate angiogenesis, Western blot analysis was employed to examine the transfer of pEGFR by LoVo-Exos into recipient cells. Both Western blot and ELISA were utilized to assess the expression levels of key signaling proteins within the EGFR-ERK pathway, as well as the expression of downstream angiogenic core molecules. Furthermore, the impact of EGFR knockdown and ERK inhibitor treatment on angiogenesis was evaluated, with subsequent analysis of the expression of downstream angiogenic core molecules following these interventions. ResultsConfocal microscopy demonstrated the internalization of LoVo-Exos into HUVECs. In vitro angiogenesis assays further indicated that LoVo-Exos significantly enhanced the formation of tubular structures in HUVECs. Additionally, macroscopic examination of subcutaneous matrix plug formation in mice revealed a substantial increase in vascular-like structures within the matrix plugs following the administration of LoVo-Exos, compared to the PBS control group. Hematoxylin and eosin (HE) staining revealed the presence of erythrocyte-filled microvessels within the matrix plugs combined with LoVo-Exos. Furthermore, immunohistochemical analysis demonstrated the expression of the endothelial cell marker CD31 in these matrix plugs. The presence of CD31-positive cells in the LoVo-Exos-treated matrix plugs was associated with a significant enhancement in the formation of luminal structures. These findings suggest that LoVo-Exos facilitate the in vivo development of vascular-like structures. Subsequent investigations demonstrated that LoVo-Exos facilitated the delivery of pEGFR to HUVEC, thereby enhancing angiogenesis. Conversely, LoVo-Exos with EGFR knockdown exhibited a diminished capacity to promote angiogenesis, an effect that was further attenuated by the ERK phosphorylation inhibitor U0126. Western blot analysis assessing the activation of the EGFR-ERK signaling pathway in HUVEC indicated that LoVo-Exos augmented angiogenesis through the activation of this pathway. Furthermore, analysis of the impact of LoVo-Exos on the expression of downstream angiogenic core molecules revealed an increase in interleukin-8 (IL-8) secretion in HUVEC. The enhancement observed was diminished in LoVo-Exos following EGFR knockdown, and this reduction was counteracted by the ERK phosphorylation inhibitor U0126. ConclusionThe underlying mechanism may involve the delivery of pEGFR in LoVo-Exos to HUVECs, leading to increased IL-8 secretion via the EGFR-ERK signaling pathway, thereby enhancing the angiogenic potential of HUVECs. This finding may offer new insights into the mechanisms underlying cancer metastasis.