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.

Aim To investigate the mechanism of ultra-fine garlic powder(UGP)in ameliorating dyslipidemia and aortic inflammation and fibrosis in atherosclerotic(AS)mice.Methods A 10-week ApoE-/-mouse AS model was constructed,cardiac index was meas-ured,and aortic histopathological changes were ob-served by oil red O staining.Serum inflammatory factor levels were detected by ELISA,and the expression of JNK,NF-κB,ERK and their phosphorylated proteins were detected by Western blot.Results Cardiac in-dex and other indicators as well as aortic lesions were worsened in the AS group,as compared with the normal control group.Compared with the AS group,the UGP treatment group and the traditional garlic grinding pow-der(TGP)treatment group significantly decreased total cholesterol(TC),triglyceride(TG),low-density lipo-protein cholesterol(LDL-C),atherosclerosis index(AI1,AI2),and coronary cardiac index and restored high-density lipoprotein cholesterol(HDL-C)levels,and the area of aortic lesions,inflammation and fibrosis were significantly improved,and at the same time,sig-nificantly inhibited the expression of TNF-α,IL-1β,and IL-6,as well as the expression of p-JNK,p-NF-κB and p-ERK proteins.The therapeutic effect of the UGP group was superior to that of the TGP group.Conclu-sion UGP can significantly inhibit the formation of aortic endothelial AS plaques,reduce the levels of in-flammation and fibrosis,and regulate blood lipids in a-orta of AS mice.

Objective:To construct a decision tree model to predict the risk of breast cancer in patients with pathological nipple discharge.Methods:A total of 157 patients with pathological nipple discharge,who were diagnosed and treated at Weifang Municipal Hospital of Traditional Chinese Medicine from January 2019 to April 2024 and met the inclusion criteria,were selected.A risk prediction model for concurrent breast cancer in patients with pathological nipple discharge was developed using Logistic regression analysis.A decision tree was then constructed,and the predictive performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC).Re-sults:The incidence of concurrent breast cancer among patients with pathological nipple discharge was 24.2%.Accord-ing to the results of binary Logistic regression analysis,elevated CEA and CA 153 levels in nipple discharge,as well as bloody discharge,emerged as independent risk factors for the development of breast cancer in such patients(P<0.05).Based on these findings,a decision tree model was constructed to predict the risk of concurrent breast cancer in patients with pathological nipple discharge.The validation results showed that the Logistic regression model had an AUC value of 0.800,while the decision tree model achieved an AUC value of 0.889.Conclusions:The decision tree model,built upon the identified influencing factors,exhibits strong predictive power for the risk of developing concurrent breast can-cer in patients with pathological nipple discharge,thus facilitating more precise preoperative diagnoses by clinicians for these patients.

OBJECTIVE To design and synthesize rifamycin S derivatives and load them into milk exosomes to evaluate their in vitro antimicrobial activity.METHODS Rifamycin S derivatives were synthe-sized and characterized by mass spectrometry and NMR.Using the dilution assay method,the inhibitory activity of each rifamycin S derivatives molecule against Staphylococcus aureus and Pseudomonas aerugi-nosa was determined,and the IC50 was calculated.Derivatives molecules with excellent antimicrobial activity were selected and loaded into milk exosomes using the ultrasonication method,resulting in the preparation of milk exosome-loaded rifamycin S derivatives.The antimicrobial activity against Staphylo-coccus aureus was determined using the dilution assay method.The inhibitory effect of the exosome-loaded rifamycin S derivatives on Staphylococcus aureus residing within macrophages was detected using the plate colony counting method.RESULTS Three rifamycin S derivatives were successfully designed and synthesized,which demonstrated superior antimicrobial activity against Staphylococcus aureus(the parent compound's antimicrobial activity is merely from 1/20 to 1/80 of that of the three rifamycin S derivatives)and Pseudomonas aeruginosa(the parent compound's antimicrobial activity is only 1/14 and 1/9 of that of compound 1 and compound 3)compared to the parent compound.The loading of milk exosomes with the rifamycin S derivatives compound 3 was successfully achieved,with a loading efficiency of 10.9％.The antimicrobial activity of the compound after exosome loading was significantly enhanced against Staphylococcus aureus in vitro and against Staphylococcus aureus residing within macrophages(P＜0.01).CONCLUSION The designed and synthesized derivatives of rifamycin S possess stronger anti-microbial activity,and their antibacterial efficacy against both extracellular and intracellular bacteria can be further enhanced after loading into exosomes.

BACKGROUND:Bone microenvironment is also rich in various immune cells and cytokines,which are closely related to bone cells and form an interactive network.Therefore,bone aging is not only caused by the senescence of osteocytes,but also accelerated by age-related changes in the immune system.OBJECTIVE:To review the age-related changes of bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,and immune cells in the bone microenvironment,emphasize the key role of the immune microenvironment in bone aging,and the potential of immunotherapy in the treatment of bone aging.METHODS:We searched PubMed and China National Knowledge Infrastructure for articles on the interaction between bone cell senescence and immune cell senescence using"osteocytes,bone aging,immune microenvironment,immune cells,cytokines,immunosenescence,immunotherapy"as Chinese and English search terms.According to the inclusion and exclusion criteria,128 articles were finally included in the review.RESULTS AND CONCLUSION:Bone aging is a common pathological condition in the elderly,characterized by the interaction of multiple biological processes,among which immune factors play a key role.The cells,molecules,and signaling pathways in the immune microenvironment together constitute a complex network,and the imbalance of this network will accelerate the process of bone aging.The combination of anti-cellular aging and immunotherapy may bring new methods for the treatment of bone aging diseases,including the removal of senescent cells,targeted drugs for senescence-related secretory phenotypes,targeted therapy of inflammatory cytokines,immune cell regulation therapy,stem cell therapy,and molecular therapy.To more effectively and reasonably remove senescent cells,a deeper understanding of the mechanism of senescent cells is needed,which will help to identify senescent cells more accurately.Immunotherapy shows great potential and prospects in the treatment of bone aging,but there are some potential risks.It is believed that with the advancement of science and technology,people can more accurately understand the genetic information and immune status of the human body and develop more personalized immunotherapy plans.

Objective To investigate the effect of fumigation decoction on the expression of aggrecan(AGG)and type Ⅱ collagen(COL2A1)in an intervertebral disc degeneration(IDD)model,and to gain an in-depth understanding of the cellular and molecular mechanisms underlying traditional Chinese medicine fumigation therapy.Methods An IDD model was established using Sprague-Dawley rats by inducing disc injury via needle puncture.The rats were divided into three groups:normal control(CON),model(PUN),and fumigation(CHF).Only the CHF group received treatment with fumigation decoction for 4 weeks.Imaging analysis was conducted to assess the relative height of intervertebral discs,while Masson's trichrome staining was used to observe structural changes in the discs.The expression of NLRP3 inflammasome was detected by immunohistochemistry.Quantitative RT-PCR and Western blotting were employed to evaluate the expression levels of AGG and COL2A1 genes and proteins.Results A total of 12 rats were randomly divided into 3 groups,with 4 rats in each group.Compared with the CON group,disc height was significantly lost in the PUN group(P＜0.05),and disc height could be partially restored in the CHF group(P＜0.05).In the PUN group,the expression levels of AGG mRNA and COL2A1 mRNA and protein in the nucleus pulposus tissue were significantly lower than those in the CON group(P＜0.05).Compared with the PUN group,the CHF group showed significantly increased expression levels of AGG mRNA and COL2A1 mRNA and protein in the nucleus pulposus tissue(P＜0.05).Histological analysis revealed that,compared with the PUN group,the CHF group exhibited partial restoration of the gel-like properties of the nucleus pulposus and an increase in proteoglycan content.Additionally,NLRP3 expression in the nucleus pulposus tissue of the CHF group was markedly reduced.Conclusion Fumigation decoction treatment can enhance the expression of AGG and COL2A1 and decrease the expression of NLRP3 in IDD models,which may be one of its mechanisms for treating lumbar degenerative diseases.This research provides new insights into the treatment of IDD.

OBJECTIVE To design and synthesize rifamycin S derivatives and load them into milk exosomes to evaluate their in vitro antimicrobial activity.METHODS Rifamycin S derivatives were synthe-sized and characterized by mass spectrometry and NMR.Using the dilution assay method,the inhibitory activity of each rifamycin S derivatives molecule against Staphylococcus aureus and Pseudomonas aerugi-nosa was determined,and the IC50 was calculated.Derivatives molecules with excellent antimicrobial activity were selected and loaded into milk exosomes using the ultrasonication method,resulting in the preparation of milk exosome-loaded rifamycin S derivatives.The antimicrobial activity against Staphylo-coccus aureus was determined using the dilution assay method.The inhibitory effect of the exosome-loaded rifamycin S derivatives on Staphylococcus aureus residing within macrophages was detected using the plate colony counting method.RESULTS Three rifamycin S derivatives were successfully designed and synthesized,which demonstrated superior antimicrobial activity against Staphylococcus aureus(the parent compound's antimicrobial activity is merely from 1/20 to 1/80 of that of the three rifamycin S derivatives)and Pseudomonas aeruginosa(the parent compound's antimicrobial activity is only 1/14 and 1/9 of that of compound 1 and compound 3)compared to the parent compound.The loading of milk exosomes with the rifamycin S derivatives compound 3 was successfully achieved,with a loading efficiency of 10.9％.The antimicrobial activity of the compound after exosome loading was significantly enhanced against Staphylococcus aureus in vitro and against Staphylococcus aureus residing within macrophages(P＜0.01).CONCLUSION The designed and synthesized derivatives of rifamycin S possess stronger anti-microbial activity,and their antibacterial efficacy against both extracellular and intracellular bacteria can be further enhanced after loading into exosomes.

BACKGROUND:Bone microenvironment is also rich in various immune cells and cytokines,which are closely related to bone cells and form an interactive network.Therefore,bone aging is not only caused by the senescence of osteocytes,but also accelerated by age-related changes in the immune system.OBJECTIVE:To review the age-related changes of bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,and immune cells in the bone microenvironment,emphasize the key role of the immune microenvironment in bone aging,and the potential of immunotherapy in the treatment of bone aging.METHODS:We searched PubMed and China National Knowledge Infrastructure for articles on the interaction between bone cell senescence and immune cell senescence using"osteocytes,bone aging,immune microenvironment,immune cells,cytokines,immunosenescence,immunotherapy"as Chinese and English search terms.According to the inclusion and exclusion criteria,128 articles were finally included in the review.RESULTS AND CONCLUSION:Bone aging is a common pathological condition in the elderly,characterized by the interaction of multiple biological processes,among which immune factors play a key role.The cells,molecules,and signaling pathways in the immune microenvironment together constitute a complex network,and the imbalance of this network will accelerate the process of bone aging.The combination of anti-cellular aging and immunotherapy may bring new methods for the treatment of bone aging diseases,including the removal of senescent cells,targeted drugs for senescence-related secretory phenotypes,targeted therapy of inflammatory cytokines,immune cell regulation therapy,stem cell therapy,and molecular therapy.To more effectively and reasonably remove senescent cells,a deeper understanding of the mechanism of senescent cells is needed,which will help to identify senescent cells more accurately.Immunotherapy shows great potential and prospects in the treatment of bone aging,but there are some potential risks.It is believed that with the advancement of science and technology,people can more accurately understand the genetic information and immune status of the human body and develop more personalized immunotherapy plans.

Aim To investigate the mechanism of ultra-fine garlic powder(UGP)in ameliorating dyslipidemia and aortic inflammation and fibrosis in atherosclerotic(AS)mice.Methods A 10-week ApoE-/-mouse AS model was constructed,cardiac index was meas-ured,and aortic histopathological changes were ob-served by oil red O staining.Serum inflammatory factor levels were detected by ELISA,and the expression of JNK,NF-κB,ERK and their phosphorylated proteins were detected by Western blot.Results Cardiac in-dex and other indicators as well as aortic lesions were worsened in the AS group,as compared with the normal control group.Compared with the AS group,the UGP treatment group and the traditional garlic grinding pow-der(TGP)treatment group significantly decreased total cholesterol(TC),triglyceride(TG),low-density lipo-protein cholesterol(LDL-C),atherosclerosis index(AI1,AI2),and coronary cardiac index and restored high-density lipoprotein cholesterol(HDL-C)levels,and the area of aortic lesions,inflammation and fibrosis were significantly improved,and at the same time,sig-nificantly inhibited the expression of TNF-α,IL-1β,and IL-6,as well as the expression of p-JNK,p-NF-κB and p-ERK proteins.The therapeutic effect of the UGP group was superior to that of the TGP group.Conclu-sion UGP can significantly inhibit the formation of aortic endothelial AS plaques,reduce the levels of in-flammation and fibrosis,and regulate blood lipids in a-orta of AS mice.

Objective To investigate the effect of fumigation decoction on the expression of aggrecan(AGG)and type Ⅱ collagen(COL2A1)in an intervertebral disc degeneration(IDD)model,and to gain an in-depth understanding of the cellular and molecular mechanisms underlying traditional Chinese medicine fumigation therapy.Methods An IDD model was established using Sprague-Dawley rats by inducing disc injury via needle puncture.The rats were divided into three groups:normal control(CON),model(PUN),and fumigation(CHF).Only the CHF group received treatment with fumigation decoction for 4 weeks.Imaging analysis was conducted to assess the relative height of intervertebral discs,while Masson's trichrome staining was used to observe structural changes in the discs.The expression of NLRP3 inflammasome was detected by immunohistochemistry.Quantitative RT-PCR and Western blotting were employed to evaluate the expression levels of AGG and COL2A1 genes and proteins.Results A total of 12 rats were randomly divided into 3 groups,with 4 rats in each group.Compared with the CON group,disc height was significantly lost in the PUN group(P＜0.05),and disc height could be partially restored in the CHF group(P＜0.05).In the PUN group,the expression levels of AGG mRNA and COL2A1 mRNA and protein in the nucleus pulposus tissue were significantly lower than those in the CON group(P＜0.05).Compared with the PUN group,the CHF group showed significantly increased expression levels of AGG mRNA and COL2A1 mRNA and protein in the nucleus pulposus tissue(P＜0.05).Histological analysis revealed that,compared with the PUN group,the CHF group exhibited partial restoration of the gel-like properties of the nucleus pulposus and an increase in proteoglycan content.Additionally,NLRP3 expression in the nucleus pulposus tissue of the CHF group was markedly reduced.Conclusion Fumigation decoction treatment can enhance the expression of AGG and COL2A1 and decrease the expression of NLRP3 in IDD models,which may be one of its mechanisms for treating lumbar degenerative diseases.This research provides new insights into the treatment of IDD.