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 preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P＜0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.

Objective:To investigate the relationship between Ig class switch recombination(CSR)and mismatch repair(MMR)protein,microsatellite phenotype in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue(MALT lymphoma).Methods:Forty cases of MALT lymphoma archived in the Department of Pathology,Jiading District Central Hospital,Shanghai University of Medicine & Health Sciences were selected as the observation group,and twenty cases of benign lymphoid tissue hyperplasia were as the control group.The expressions of IgG,IgM,IgD,and IgA in both groups were detected by immunohistochemical double staining,and MMR proteins including MLH1,MSH2,MSH6,and PMS2 in both groups were detected by immunohistochemistry.Multiplex fluorescence PCR capillary electrophoresis was used to detect microsatellite phenotype in tumor and adjacent tissues of the experimental group.Results:In the observation group,the proportions of single Ig heavy chain expression(mode Ⅰ),negative expression(mode Ⅱ),and multiple expression(mode Ⅲ)were 65％(26/40),27.5％(11/40),and 7.5％(3/40),respectively,while in the control group were 0(0/20),5％(1/20),and 95％(19/20).The proportion of Ig heavy chain expression mode Ⅰ+Ⅱ in the observation group was 92.5％,which was significantly higher than 5％in the control group(P＜0.0 1).In the observation group,partial deletion of MMR protein was observed in 3 cases(7.5％),including 2 cases of MSH6 deletion and 1 case of both MSH6 and PMS2 deletion.In the control group,there was 1 case(5％)with PMS2 deletion.There was no significant difference in the deletion rate of MMR protein between the two groups(P＞0.05).A total of 5 cases of microsatellite instability(MSI)were detected in the observation group,including 1 case of low-frequency MSI(MSI-L),4 cases of high-frequency MSI(MSI-H),and 2 cases of MSI-H with MSH6 deletion.When the loss expression of MSI-H or MMR protein was counted as a positive result,the MSI-H rate detected by PCR capillary electrophoresis was 10％(4/40),which was slightly higher than the MMR protein deletion rate detected by immunohistochemistry(7.5％,3/40),but there was no statistically significant difference between the two groups(P＞0.05).The MMR protein deletion rates among the Ig heavy chain protein expression mode Ⅰ,mode Ⅱ,and mode Ⅲ groups were 0(0/26),18.2％(2/11),and 33.3％(1/3),respectively.There was a statistically significant difference in the constituent ratios among the three groups(P＜0.05).The MMR protein deletion rates among the MSS,MSI-L,and MSI-H groups were 2.9％(1/35),0(0/1),and 50％(2/4),respectively.There was a statistically significant difference in the constituent ratios among the three groups(P＜0.05).MMR protein deficiency was positively correlated with Ig heavy chain expression pattern and MSI(r=0.41,P＜0.05;r=0.48,P＜0.05),but Ig heavy chain expression pattern was not correlated with MSI(r=0.02,P＞0.05).Conclusion:Ig heavy chain CSR detection is helpful for the differential diagnosis of MALT lymphoma.Low frequency MMR protein deletion and MSI-H phenotype exist in MALT lymphoma,which may be of certain value for the study of its occurrence,development and clinical treatment.

Objective:Based on value orientation,it aimed to scientifically define the concept and connotation of accessibility to novel anticancer drugs,in order to deeply understand the nature and current status of the accessibility issues of novel anticancer drugs,and to provide a reference for the formulation and optimization of policies related to novel anticancer drugs.Methods:Data was collected through literature review and expert interviews,and the concept of drug accessibility was defined using the atomic diagram method.Results:The core images include"affordability","availability","high quality"and"patients".The concept of accessibility to novel anticancer drugs is defined as"the process of ensuring the sustainable supply,equitable access,affordability,and rational use of high-quality anticancer drugs to safeguard the realization of patient benefit goals."The connotation of the value orientation in policies on the accessibility of novel anticancer drugs is profoundly reflected in the multi-dimensional value-driven approach to ensure the ultimate benefit of patients,which includes quality,sustainability,equity,affordability,and rational use.Conclusion:The proposal of the concept and connotation of accessibility provides a theoretical basis for a deep understanding of the accessibility of novel anticancer drugs and offers valuable references for subsequent policy-making and practical operations.

Objective:To establish a TaqMan-MGB probe-based method for detecting the polymorphic loci C677T and A1298C of the MTHFR gene.Methods:Specific primers and TaqMan-MGB probes targeting the C677T and A1298C polymorphic loci of the MTHFR gene were designed and optimized based on the gene sequence information.A real-time quantitative PCR detection system was established.Gradient dilution experiments were conducted to determine the limit of detection,and reproducibility experiments were performed to evaluate detection consistency.Specificity was validated using wild-type and mutant plasmid templates.The method was applied to detect 56 clinical samples,and its accuracy and practicality were assessed through comparison with traditional Sanger sequencing.Results:The TaqMan-MGB probe method demonstrated high specificity for detecting the C677T and A1298C loci,with no cross-reactivity between wild-type and mutant probes,enabling accurate genotype differentiation.Sensitivity experiments revealed detection limits of 1.13 × 103 copies/μL for C677T and 8.39 × 101 copies/μL for A1298C.Reproducibility experiments showed coefficients of variation below 1％,indicating stable and reliable results.Among the 56 clinical samples,the overall detection rate for the C677T locus was 86.99％,and for the A1298C locus,it was 97.92％.The TaqMan-MGB method exhibited good concordance with Sanger sequencing results.Conclusion:The TaqMan-MGB method exhibits high specificity,sensitivity,and excellent reproducibility in detecting the polymorphic loci C677T and A1298C of the MTHFR gene,making it suitable for rapid detection in large-scale clinical samples.This method provides an effective molecular diagnostic tool for the early diagnosis and prevention of folate-related diseases.

Objective To analyze the disability level and long-term care needs assessment policies issued by 49 pilot cities in China's long-term care insurance system,providing insights for further improvement of the system.Methods Policy documents related to long-term care insurance,published between June 2016 and December 2024 on official platforms of local governments,the Ministry of Human Resources and Social Security,the National Healthcare Security Administration,and the National Public Service Platform for Standards Information,were retrieved.A comparative analysis was used to summarize and compare the content of these policy texts.Results Currently,there are 49 pilot cities implementing the long-term care insurance system in China.47 cities have issued disability level assessment standards,with 38 cities adopting the trial standards issued by the National Healthcare Security Administration.In 42 pilot cities,the disability level assessment includes indicators such as activities of daily living,cognitive function,and sensory and communication abilities.22 cities have issued policies related to care needs assessment.In most cities,the care needs assessment partially or fully includes indicators from the disability level assessment.Conclusion There is no national uniformity in disability level assessment standards,and the care needs assessment framework needs further improvement.It is recommended to standardize disability level assessment criteria,clearly delineate the boundaries and content of disability level and care needs assessments,and enhance the development of the care needs assessment system.

Aim To investigate the protective effect of Gualou Guizhi granules(GLGZG)on neuronal injury induced by LPS-activated microglia based on Notch signaling pathway.Methods LPS-activated microglia were co-cultured with neurons to construct neuron inju-ry models,and the cells were divided into the control group,model group,Notch inhibitor(DAPT)group,GLGZG(50,100,200 mg·L-1)group,DAPT+100 mg·L-1GLGZG group.After intervention,the activity of HT22 cells was detected by CCK-8 method,and rel-ative mRNA expression was detected by real-time PCR.The relative protein expression was detected by Western blot.Results Compared with the model group,after GLGZG intervention,the cell activity was significantly improved,GLGZG decreased IL-6,IL-12,Bax,Notch 1,caspase-3,Delta-1,NICD,RBPSUH,HES1 expression,and increased Bcl-2 expression(P＜0.05).Compared with the model group,the NICD,RBPSUH and HES1 mRNA and protein expressions significantly decreased after DAPT treatment(P＜0.05),and there was no superposition effect with GLG-ZG.Conclusion GLGZG may play a neuroprotective role by inhibiting inflammatory factors and apoptosis,and inhibiting Notch signaling pathway.

Objective:Based on value orientation,it aimed to scientifically define the concept and connotation of accessibility to novel anticancer drugs,in order to deeply understand the nature and current status of the accessibility issues of novel anticancer drugs,and to provide a reference for the formulation and optimization of policies related to novel anticancer drugs.Methods:Data was collected through literature review and expert interviews,and the concept of drug accessibility was defined using the atomic diagram method.Results:The core images include"affordability","availability","high quality"and"patients".The concept of accessibility to novel anticancer drugs is defined as"the process of ensuring the sustainable supply,equitable access,affordability,and rational use of high-quality anticancer drugs to safeguard the realization of patient benefit goals."The connotation of the value orientation in policies on the accessibility of novel anticancer drugs is profoundly reflected in the multi-dimensional value-driven approach to ensure the ultimate benefit of patients,which includes quality,sustainability,equity,affordability,and rational use.Conclusion:The proposal of the concept and connotation of accessibility provides a theoretical basis for a deep understanding of the accessibility of novel anticancer drugs and offers valuable references for subsequent policy-making and practical operations.

Objective To analyze the policy texts related to pediatric medications in China over the past decade,to explore the deficiencies in existing policy formulation from the perspective of stakeholders,and to propose reasonable optimization suggestions based on the current situation.Methods Collecting national-level policies related to pediatric drugs in China from 2013 to 2023,a two-dimensional policy analysis framework of"Policy tools-Stakeholder"were established.And the content analysis method was used to code,categorize,and statistically analyze the policy texts.Results A total of 54 pediatric drug policies were included in the analysis.In terms of policy tools,a total of 197 policy codes were formed,with environmental tools being the most prevalent with 92 codes(46.70％),primarily consisting of regulatory management tools(28 codes,30.43％).This was followed by supply-oriented tools with 53 codes(26.90％),mainly focused on the issuance of technical guidelines(21 codes,39.62％).Demand-oriented tools accounted for the least with 52 codes(26.40％),with inter-departmental collaboration tools having the highest proportion(17 codes,32.69％).In the dimension of stakeholders,a total of 223 policy codes were formed,with the government having the highest number of codes at 133(59.64％),followed by medical institutions with 56 codes(25.11％).The proportions for medical personnel,pharmaceutical companies,and patients were similar,with 14 codes(6.28％),11 codes(4.93％),and 9 codes(4.04％),respectively.Conclusions Pediatric drugs face challenges with policy tools where supply-oriented tools,particularly those providing financial support,suffer from insufficient policy depth and customization.The demand-oriented tools have a low proportion,leading to structural imbalance and underutilized effectiveness;the environment-oriented tools focus more on regulation than incentives,restricting the accessibility of pediatric drugs;the potential of multiple stakeholders is not fully activated,and there is a lack of policies centered around pediatric patients.To address these issues,supply-oriented policy tools need to establish a diversified financial support model and clearly define the scope of coverage.Demand-oriented policy tools require further adjustments to the catalog,procurement upgrades,and international collaborative research to reshape the pediatric drug security system.Environmental policy tools should enhance economic support,strengthen intellectual property rights,and implement targeted education to build a development ecosystem for pediatric drugs.Regarding stakeholders,it is essential to strengthen multi-stakeholder collaboration and optimize pediatric drug policy tools with a patient-centered approach.

Objective To analyze the policy texts related to pediatric medications in China over the past decade,to explore the deficiencies in existing policy formulation from the perspective of stakeholders,and to propose reasonable optimization suggestions based on the current situation.Methods Collecting national-level policies related to pediatric drugs in China from 2013 to 2023,a two-dimensional policy analysis framework of"Policy tools-Stakeholder"were established.And the content analysis method was used to code,categorize,and statistically analyze the policy texts.Results A total of 54 pediatric drug policies were included in the analysis.In terms of policy tools,a total of 197 policy codes were formed,with environmental tools being the most prevalent with 92 codes(46.70％),primarily consisting of regulatory management tools(28 codes,30.43％).This was followed by supply-oriented tools with 53 codes(26.90％),mainly focused on the issuance of technical guidelines(21 codes,39.62％).Demand-oriented tools accounted for the least with 52 codes(26.40％),with inter-departmental collaboration tools having the highest proportion(17 codes,32.69％).In the dimension of stakeholders,a total of 223 policy codes were formed,with the government having the highest number of codes at 133(59.64％),followed by medical institutions with 56 codes(25.11％).The proportions for medical personnel,pharmaceutical companies,and patients were similar,with 14 codes(6.28％),11 codes(4.93％),and 9 codes(4.04％),respectively.Conclusions Pediatric drugs face challenges with policy tools where supply-oriented tools,particularly those providing financial support,suffer from insufficient policy depth and customization.The demand-oriented tools have a low proportion,leading to structural imbalance and underutilized effectiveness;the environment-oriented tools focus more on regulation than incentives,restricting the accessibility of pediatric drugs;the potential of multiple stakeholders is not fully activated,and there is a lack of policies centered around pediatric patients.To address these issues,supply-oriented policy tools need to establish a diversified financial support model and clearly define the scope of coverage.Demand-oriented policy tools require further adjustments to the catalog,procurement upgrades,and international collaborative research to reshape the pediatric drug security system.Environmental policy tools should enhance economic support,strengthen intellectual property rights,and implement targeted education to build a development ecosystem for pediatric drugs.Regarding stakeholders,it is essential to strengthen multi-stakeholder collaboration and optimize pediatric drug policy tools with a patient-centered approach.