BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

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.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

Objective To conduct Monte Carlo simulations on the microselectro-HDR¹⁹²Ir radiation source, investigate dose distributions under various conditions, and provide assistance in optimizing radiotherapy plans. Methods A microselectro-HDR¹⁹²Ir radiation source model was established based on the MCNP5 software. Theoretical calculation formulas were used to validate the simulation results. The dose distributions under different activities and positions were obtained through simulations using the MCNP5 transport program. By fitting the simulation data, the relationship between the safe distance for at-risk organs and treatment time was analyzed. Results As the distance from the origin increased in the X-direction, the distance required for the absorbed dose rate to decrease to half its original value increased, and the isodose lines became sparser. The shapes of the dose distribution diagrams under different activities were consistent, presenting concentric polygons and concentric circles at different distances. Under the condition of the same lethal dose, the difference in the safe distance between two organs increased with time; under different lethal dose conditions, the differences were not significant whether between similar organs or between different organs. Conclusion The Monte Carlo method can accurately describe the radiation field generated by the microselectro-HDR¹⁹²Ir radioactive source during high-dose-rate brachytherapy. Quantitative analysis of the radiation field will help optimize the radiotherapy plan.

Objective To conduct Monte Carlo simulations on the microselectro-HDR¹⁹²Ir radiation source, investigate dose distributions under various conditions, and provide assistance in optimizing radiotherapy plans. Methods A microselectro-HDR¹⁹²Ir radiation source model was established based on the MCNP5 software. Theoretical calculation formulas were used to validate the simulation results. The dose distributions under different activities and positions were obtained through simulations using the MCNP5 transport program. By fitting the simulation data, the relationship between the safe distance for at-risk organs and treatment time was analyzed. Results As the distance from the origin increased in the X-direction, the distance required for the absorbed dose rate to decrease to half its original value increased, and the isodose lines became sparser. The shapes of the dose distribution diagrams under different activities were consistent, presenting concentric polygons and concentric circles at different distances. Under the condition of the same lethal dose, the difference in the safe distance between two organs increased with time; under different lethal dose conditions, the differences were not significant whether between similar organs or between different organs. Conclusion The Monte Carlo method can accurately describe the radiation field generated by the microselectro-HDR¹⁹²Ir radioactive source during high-dose-rate brachytherapy. Quantitative analysis of the radiation field will help optimize the radiotherapy plan.

Objective To conduct Monte Carlo simulations on the microselectro-HDR¹⁹²Ir radiation source, investigate dose distributions under various conditions, and provide assistance in optimizing radiotherapy plans. Methods A microselectro-HDR¹⁹²Ir radiation source model was established based on the MCNP5 software. Theoretical calculation formulas were used to validate the simulation results. The dose distributions under different activities and positions were obtained through simulations using the MCNP5 transport program. By fitting the simulation data, the relationship between the safe distance for at-risk organs and treatment time was analyzed. Results As the distance from the origin increased in the X-direction, the distance required for the absorbed dose rate to decrease to half its original value increased, and the isodose lines became sparser. The shapes of the dose distribution diagrams under different activities were consistent, presenting concentric polygons and concentric circles at different distances. Under the condition of the same lethal dose, the difference in the safe distance between two organs increased with time; under different lethal dose conditions, the differences were not significant whether between similar organs or between different organs. Conclusion The Monte Carlo method can accurately describe the radiation field generated by the microselectro-HDR¹⁹²Ir radioactive source during high-dose-rate brachytherapy. Quantitative analysis of the radiation field will help optimize the radiotherapy plan.

OBJECTIVE To establish the fingerprint of Gerbera delavayi and the methods for the content determination of 11 components in G. delavayi. METHODS High-performance liquid chromatography（HPLC）was adopted to establish the fingerprints of 13 batches of G. delavayi（No. S1-S13）， and the similarities were evaluated according to Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）， while the common peaks were identified. Hierarchical clustering analysis （HCA）， principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were carried out by using SPSS 25.0 software and SIMCA 14.1 software. The contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， 3，8-dihydroxy-4-methoxy-2-oxo-2H-1-benzopyran-5-carboxylic acid， caffeic acid， 3-hydroxy-4-methoxy-2- oxo-2H-1-benzopyran- 5-carboxylic acid， luteolin-7-O-β-D-glucoside， isochlorogenic acid A， apigenin-7-O-β-D-glucoside， isochlorogenic acid C and xanthotoxin were determined by HPLC. RESULTS The similarities in HPLC fingerprint of 13 batches of G. delavayi were 0.801-0.994； a total of 38 common peaks were identified and 13 common peaks were identified. The results of HCA showed that S1-S5 and S7 were clustered into one group， S6 into one category， S8 into one category， S9 and S11 into one category， S10， S12 and S13 into one category， and the results of PCA were consistent with them. The results of OPLS-DA showed that variable importance values for the projection of peak 7 （chlorogenic acid）， peak 21 （isochlorogenic acid A）， peak 26 （xanthotoxin）， peak 19 （isochlorogenic acid B）， peak 33， peak 13， peak 23 （isochlorogenic acid C）， peak 2 （new chlorogenic acid）， peak 17 （luteolin-7-O-β-D- glucoside） were greater than 1. The above 11 components had good linearity in their respective detection concentration ranges （r was greater than 0.999）. RSDs of precision， repeatability， and stability tests were not more than 2% （n＝6）. The average recovery rates were 92.54%-105.55%， and the RSDs were 0.83%-1.93% （n＝6）. The average contents of 11 components were 0.744， 5.014， 0.646， 0.431， 0.069， 0.582， 0.979， 2.754， 0.157， 1.284 and 2.943 mg/g， respectively. CONCLUSIONS The constructed HPLC fingerprint and content determination methods are simple， accurate and stable， which can provide reference for quality control of G. delavayi. Xanthotoxin， chlorogenic acid， isochlorogenic acid A， luteolin-7-O- β -D-glucoside， isochlorogenic acid C and new chlorogenic acid can be used as markers for G. delavayi.

BACKGROUND:It is urgent to improve the study on the molecular mechanism of Ban's Culuan Zhuyun Decoction improving oocyte quality in polycystic ovary syndrome.OBJECTIVE:To observe the effects of Ban's Culuan Zhuyun Decoction on oocyte quality in a mouse model of polycystic ovary syndrome and to explore the underlying mechanisms of its intervention in polycystic ovary syndrome.METHODS:Subcutaneous injection of dehydroepiandrosterone sulfate was used to establish the polycystic ovary syndrome model in 21-day-old female Kunming mice,and the treatment was conducted for 21 consecutive days.The estrous cycle and pregnancy was recorded.ELISA was used to detect serum sex hormone levels.The rate of apoptosis in oocytes was detected using Annexin V staining.The level of reactive oxygen species in oocytes was detected using dichlorodihydrofluorescein diacetate.The condition of spindle bodies and chromosomes in oocytes were detected using the immunofluorescence method.Network pharmacology and molecular docking were used to verify the binding properties of Ban's Culuan Zhuyun Decoction core active components and oocyte maturation-related factors(growth differentiation factor 9 and bone morphogenetic protein 15).Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression levels of growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes,respectively.RESULTS AND CONCLUSION:(1)Ban's Culuan Zhuyun Decoction core active components(quercetin,kaempferol,and β-sitosterol)showed good binding activities with growth differentiation factor 9 and bone morphogenetic protein 15.(2)Ban's Culuan Zhuyun Decoction ameliorated the estrous cycle,regulated serum hormone,increased the pregnancy,decreased the rate of apoptosis,declined the level of reactive oxygen species,diminished the rate of abnormal spindle assembly and chromosome loss(P<0.01,P<0.05);and promoted the mRNA and protein expression of growth differentiation factor 9 and bone morphogenetic protein 15(P<0.05).Therefore,Ban's Culuan Zhuyun Decoction may improve the oocyte quality and increase the fertility of polycystic ovary syndrome mice by regulating the gene expression of growth differentiation factor 9 and bone morphogenetic protein 15.

To summarize experience in the diagnosis and treatment of adolescent non-freezing cold injury (NFCI).Methods:Retrospective case summary.The clinical data of 7 children with NFCI treated at the First Affiliated Hospital of Zhengzhou University from December 2023 to January 2024 were reviewed.Results:Among the 7 children, including 2 boys and 5 girls, the main clinical manifestations were persistent pain with stiffness in feet, involving metatarsophalangeal joint, interphalangeal joint, and plantar surface, with toe pain the severest, and the pain worsened at night.All 7 children had magnetic resonance imaging of the foot, and among them, 4 cases showed multiple patchy fat-suppressed high signals on talus, medial tarsal bone, metatarsal bone, and phalangeal bone, suggesting ischemia, and 3 cases showed long T1 long T2 fluid signals on ankle joint cavity, some tarsal joint space, and metatarsophalangeal joint space, suggesting bone marrow edema with joint effusion.Four children received intravenous infusion of 10 mg Hydroprednisone injection once a day for 5 consecutive days, with loss of pain and complete resolution of stiffness.Conclusions:NFCI is a rare cold injury but not frostbite disease.Pathogenic conditions and clinical manifestations are the main basis for its diagnosis, and low-dose hydroprednisone is effective for the treatment of this disease.

Objective:To analyze and summarize clinical phenotypic characteristics and genetic variations in patients with intellectual disability and pathogenic variations of the DYNC1H1 gene across 4 generations within a single family. Methods:Retrospective case analysis.Clinical data of a child with epilepsy and intellectual disability and her family members were collected from the Children′s Medical Center, Peking University First Hospital on December 2019.The child was followed up regularly.DNA was extracted from the peripheral blood of the child′s family members.Then whole-exome sequencing and Sanger sequencing were performed to identify the genetic variation type in the proband and her family members.The relationship between genotype and phenotype was further analyzed.Results:A total of 13 patients across 4 generations in the family had intellectual disability, and the proband also had drug-resistant epilepsy.The variation c. 13556C> A (p.A4519E) of the DYNC1H1 gene was confirmed by gene testing in 8 patients (no blood samples were obtained from the remaining patients). Conclusions:DYNC1H1 gene-related intellectual disability in most previously reported cases are caused by novel variations of this gene.In this study, a large family of 13 intellectual disability patients across 4 generations caused by a pathogenic mutation in the DYNC1H1 gene was summarized.The findings make precise genetic counseling possible for this family and provide a basis for further studies on the relationship between the genotype and phenotype of the DYNC1H1 gene.