1.Quality Evaluation of Naomaili Granules Based on Multi-component Content Determination and Fingerprint and Screening of Its Anti-neuroinflammatory Substance Basis
Ya WANG ; Yanan KANG ; Bo LIU ; Zimo WANG ; Xuan ZHANG ; Wei LAN ; Wen ZHANG ; Lu YANG ; Yi SUN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):170-178
ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics, and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography (UPLC) fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated, and 23 of them were identified and assigned. In 27 batches of Naomaili granules, the mass fractions of 14 components that were stachydrine hydrochloride, leonurine hydrochloride, calycosin-7-O-glucoside, calycosin,tanshinoneⅠ, cryptotanshinone, tanshinoneⅡA, ginsenoside Rb1, notoginsenoside R1, ginsenoside Rg1, paeoniflorin, albiflorin, lactiflorin, and salvianolic acid B were found to be 2.902-3.498, 0.233-0.343, 0.111-0.301, 0.07-0.152, 0.136-0.228, 0.195-0.390, 0.324-0.482, 1.056-1.435, 0.271-0.397, 1.318-1.649, 3.038-4.059, 2.263-3.455, 0.152-0.232, 2.931-3.991 mg∙g-1, respectively. Multivariate statistical analysis showed that paeoniflorin, ginsenoside Rg1, ginsenoside Rb1 and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them, salvianolic acid B and ginsenoside Rb1 had strong anti-inflammatory activity, with IC50 values of (36.11±0.15) mg∙L-1 and (27.24±0.54) mg∙L-1, respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out, and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.
2.Study on the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep
Ming QIAO ; Yao ZHAO ; Yi ZHU ; Yexia CAO ; Limei WEN ; Yuehong GONG ; Xiang LI ; Juanchen WANG ; Tao WANG ; Jianhua YANG ; Junping HU
China Pharmacy 2026;37(1):24-29
OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets, followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established , and the zebrafish were treated with L. ruthenicum Murr. extract (LRME) at concentrations of 0.1, 0.2 and 0.4 mg/mL, respectively; 24 h later, behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 (IL-6), IL-1β, IL-10, tumor necrosis factor-α (TNF-α)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT)], and neurotransmitters [5- hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), glutamic acid (Glu), dopamine (DA), and norepinephrine (NE)] were measured. The protein expression levels of protein kinase B1 (AKT1), phosphorylated AKT1 (p-AKT1), epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), sarcoma proto-oncogene,non-receptor tyrosine kinase (SRC), and heat shock protein 90α family class A member 1 (HSP90AA1) in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these, apigenin, naringenin and others were recognized as core active compounds, while AKT1, EGFR and others served as key targets; EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-, medium-, and high-dose groups were 54.60%, 69.03% and 77.97%, 开发。E-mail:hjp_yft@163.com respectively, while the inhibition ratios of locomotor distance were 0.57, 0.83 and 0.95, respectively. Compared with the model group, the number of resting counts, resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups (P<0.05). Neuronal damage in the brain was alleviated. Additionally, the levels of IL-6, IL-1β, TNF-α, MDA, Glu, DA and NE, as well as the protein expression levels of AKT1, p-AKT1, EGFR, SRC and HSP90AA1, were markedly reduced (P<0.05), while the levels of IL-10, SOD, GSH-Px, CAT, 5-HT and GABA, as well as Bcl-2 protein expression, were significantly elevated (P<0.05). CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects, and its specific mechanism may be related to the regulation of inflammatory responses, oxidative stress, neurotransmitter balance, and the EGFR tyrosine kinase inhibitor resistance signaling pathway.
3.Construction and efficacy verification of an intelligent pharmaceutical Q&A platform based on AI hallucination-suppression
Zhengwang WEN ; Jiaying WANG ; Wenyue YANG ; Haoyu YANG ; Xiao MA ; Yun LIU
China Pharmacy 2026;37(2):226-231
OBJECTIVE To construct an intelligent pharmaceutical Q&A platform for precision medication with low “artificial intelligence (AI) hallucination”, aiming to enhance the accuracy, consistency, and traceability of medication consultations. METHODS Medication package inserts were batch-processed and converted into structured data through Python programming to build a local pharmaceutical knowledge base. The retrieval and question-answering processes were designed based on large language models, and system integration and localized deployment were completed on Dify platform. By designing typical clinical medication questions and comparing the output of the intelligent pharmaceutical Q&A platform with the online version of DeepSeek across dimensions such as peak time retrieval, half-life, and dosage adjustment reasoning for patients with renal impairment, the accuracy and reliability of its retrieval and reasoning results were evaluated. RESULTS The intelligent pharmaceutical Q&A platform, constructed based on local drug package inserts, achieved 100% accuracy in retrieval and reasoning for peak time, half-life, and dosage adjustment schemes. In comparison, the online version of DeepSeek demonstrated accuracies of 30%(6/20), 50%(10/20), and 38%(23/60) across these three dimensions, respectively. CONCLUSIONS The constructed intelligent pharmaceutical Q&A platform is capable of accurately retrieving and extracting information from the local knowledge base based on clinical inquiries, thereby avoiding the occurrence of AI hallucinations and providing reliable medication decision support for healthcare professionals.
4.Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells
Ruijia LI ; Zixuan WANG ; Shilong GUO ; Sen YANG ; Jing LI ; Qianqian ZHANG ; Wen DONG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):28-35
ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan (DSS) on renal injury in db/db mice and its impact on endoplasmic reticulum stress (ERS) in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week, after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease (DKD) model. The model mice were randomly divided into a model group, an irbesartan group, and three DSS treatment groups with different doses (16.77, 33.54, and 67.08 g·kg-1·d-1). A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention, general conditions were observed. Serum cystatin C (Cys-C), 24-hour urinary total protein (24 h-UTP), 24-hour urinary microalbumin (24 h-UMA), urinary creatinine (Ucr), and urea nitrogen (UUN) were measured. Transmission electron microscopy (TEM) was used to observe glomerular basement membrane (GBM) and ultrastructural changes of the endoplasmic reticulum (ER) in glomerular endothelial cells. Western blot, real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78, CHOP, and related markers. ResultsCompared with the normal group, the mice in the model group showed curled posture, sluggish response, poor fur condition, increased levels of Cys-C, 24 h-UTP, 24 h-UMA, and UUN (P<0.05), while Ucr decreased (P<0.05). The GBM was significantly thickened, with podocyte and foot process fusion. The protein expressions of GRP78, CHOP, and ATF6 were significantly upregulated (P<0.05), the mRNA levels of GRP78 and CHOP increased (P<0.05), and immunohistochemistry showed an enhanced GRP78 signal (P<0.05). After treatment, the mice exhibited improved behavior, normalized GBM and podocyte structure, improved ER morphology and markedly better biochemical indicators. Western blot, Real-time PCR, and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups (P<0.05), suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice, possibly by regulating ERS in glomerular endothelial cells, although the underlying signaling mechanisms require further investigation.
5.Herbal Textual Research on Quisqualis Fructus in Famous Classical Formulas
Xiuping WEN ; Shiying CHEN ; Ying TAN ; Guanwen ZHENG ; Huilong XU ; Wen XU ; Chengzi YANG ; Zehao HUANG ; Yu LIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):225-237
This article systematically analyzed the historical evolution of the origin, scientific name, producing area, quality evaluation, harvesting and processing, and other aspects of Quisqualis Fructus by consulting the ancient materia medica, medical books, prescription books, local literature and combining with the modern literature and standards, summarized and explored the development rules of its medicinal properties and efficacy along with their underlying causes, in order to provide support for the development and utilization of famous classical formulas containing this herb. According to the textual research, Shijunzi was first recorded as Liuqiuzi in Nanfang Caomuzhuang of the Jin dynasty, and the name of Shijunzi was first used in Kaibao Bencao of the Song dynasty, which has been consistently used throughout subsequent dynasties, and there were also aliases such as Junziren, Sijunzi, and Dujilizi. The mainstream source of Quisqualis Fructus used in the past dynasties has been the dried mature fruits of Quisqualis indica, a plant belonging to the family Combretaceae. In modern times, its variety Q. indica var. villosa has also been recorded as the medicinal material of Quisqualis Fructus. In 2007, the Flora of China(English edition) designated Q. indica var. villosa as a synonym of Q. indica. Today, the accepted name of Shijunzi is updated to Combretum indicum. According to ancient herbal records, the producing areas of Quisqualis Fructus were Guangdong, Hong Kong, Macao, Guangxi, Hainan, Sichuan and Fujian, and then gradually expanded to Yunnan, Taiwan, Jiangxi and Guizhou. Since the Song dynasty, two major production regions have gradually emerged in Sichuan, Chongqing and Fujian. Currently, it is primarily cultivated in Chongqing, Guangxi and other areas, with Chongqing yielding the highest output. Since modern times, superior quality has been defined by large size, a purple-black surface, plump grains, and a yellowish-white kernel. According to ancient herbal records, the harvesting period of Quisqualis Fructus was the July and August of the lunar calendar, mostly used raw after shelling or with the shell intact, it underwent processing methods such as cleaning, slicing, mixing, steaming, roasting, stewing, and frying. Currently, the harvesting period is autumn, followed by sun-drying or low-heat drying, with processing methods including cleaning, stir-frying, and stewing. In ancient and modern literature, the records of the properties, functions and indications of Quisqualis Fructus are basically the same, that is, sweet in taste, warm in nature, predominantly non-toxic, belonging to the spleen and stomach meridians. It possesses effects of insecticide, decontamination and invigorating spleen for ascariasis, enterobiasis, abdominal pain due to worm accumulation and infantile malnutrition.The contraindications for use primarily include avoiding consumption by individuals without parasitic infestations, limiting use for those with spleen-stomach deficiency-cold, refraining from drinking hot tea during medication, and avoiding excessive intake. Based on the textual research, it is suggested that the dried mature fruits of Q. indica should be used as the medicinal material for the development of famous classical formulas containing Quisqualis Fructus. Processing methods may be chosen according to prescription requirements, and the raw products is recommended for medicinal use if not specified.
6.Establishment of a new predictive model for esophagogastric variceal rebleeding in liver cirrhosis based on clinical features
Wen GUO ; Xuyulin YANG ; Run GAO ; Yaxin CHEN ; Kun YIN ; Qian LI ; Manli CUI ; Mingxin ZHANG
Journal of Clinical Hepatology 2026;42(1):101-110
ObjectiveTo establish a new noninvasive, simple, and convenient clinical predictive model by identifying independent predictive factors for rebleeding after endoscopic therapy in cirrhotic patients with esophagogastric variceal bleeding (EGVB), and to provide a basis for individualized risk assessment and development of clinical intervention strategies. MethodsCirrhotic patients with EGVB who were diagnosed and treated in The First Affiliated Hospital of Xi’an Medical University from September 2018 to October 2023 were enrolled as subjects, and according to whether the patient experienced rebleeding within 1 year after endoscopic therapy, they were divided into rebleeding group with 93 patients and non-rebleeding group with 84 patients. Clinical data were collected and analyzed. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Logistic model was established based on the results of the univariate and multivariate analyses, and the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to assess the accuracy of the model. R software was used to visualize the model by plotting a nomogram, and the Bootstrap method was used for internal validation of the model. ResultsThe multivariate analysis showed that red blood cell count (RBC), cholinesterase (ChE), alkaline phosphatase (ALP), albumin (Alb), thrombin time (TT), portal vein trunk diameter, sequential therapy, and primary prevention were independent predictive factors for rebleeding. Based on the results of the multivariate analysis, a logistic model was established as logit(P)=-0.805-1.978×(RBC)+0.001×(ChE)-0.020×(ALP)-0.314×(Alb)+0.567×(TT)+0.428×(portal vein trunk diameter)-2.303×[sequential therapy (yes=1, no=0)]-2.368×[primary prevention (yes=1, no=0)]. The logistic model (AUC=0.928, 95% confidence interval [CI]: 0.893—0.964, P<0.001) had a better performance in predicting rebleeding than MELD score (AUC=0.603, 95%CI: 0.520—0.687, P=0.003), Child-Pugh class (AUC=0.650, 95%CI: 0.578—0.722, P=0.001), and FIB-4 index (AUC=0.587, 95%CI: 0.503—0.671, P=0.045). The model had an optimal cut-off value of 0.607, a sensitivity of 0.817, and a specificity of 0.817. Internal validation confirmed that the model had good predictive performance and accuracy. ConclusionSequential therapy, implementation of primary prevention, an increase in RBC, and an increase in Alb are protective factors against rebleeding, while prolonged TT and widened main portal vein diameter are risk factors. The logistic model based on these independent predictive factors can predict rebleeding and thus holds promise for clinical application.
7.Prenatal diagnosis of 22q11.2 microduplication syndrome in a three-generation family: Clinical-genetic characteristics and literature review.
Yifan LIAO ; Yidong WEN ; Xiaoqin DENG ; Cimo WANG ; Zhirong SHANG ; Jinghong YANG ; Jiabing LI
Chinese Journal of Medical Genetics 2026;43(1):57-63
OBJECTIVE:
To explore the genetic etiology for a pregnant woman with a history of multiple adverse pregnancies and assess the phenotype-genotype correlation of 22q11.2 microduplication syndrome in her family.
METHODS:
Amniotic fluid sample was taken from a pregnant woman for whom non-invasive prenatal screening indicated chromosome 22 abnormalities in the fetus. Peripheral blood samples from the woman, her brother and parents were collected for high-throughput low-depth whole genome sequencing (CNV-seq). A pedigree traceability analysis of the results was conducted in conjunction with analysis of clinical manifestation. Relevant literature (from establishment to March 2025) was systematically searched. This study was approved by the Medical Ethics Committee of Mianyang Maternal and Child Health Care Hospital (Ethics No.: Lun Shen [2024]009).
RESULTS:
CNV-seq revealed that the fetus had harbored a 6.02 Mb duplication at 22q11.21q11.23. Karyotyping confirmed it as 46,X?dup(22)(q11.2). Pedigree verification demonstrated that the pregnant woman, her brother and mother had all carried the same duplication. Phenotypic analysis of the affected family members showed classic features of 22q11.2 microduplication syndrome, including hypernasal speech, low nasal bridge, congenital heart disease, and cognitive impairment. A total of 44 cases with full information (including three patients from this pedigree) were included in the analysis. The penetrance of 22q11.2 duplication was approximately 29.5% (13/44), and 52.3% (23/44) of the cases had inherited the variant from a phenotypically normal parent.
CONCLUSION
This study has identified the genetic basis for the woman's recurrent adverse pregnancies and phenotypic abnormalities in her family members. The scoliosis identified in her younger brother has not been previously reported, thereby may enrich the clinical phenotype of this syndrome. For fetuses identified with a 22q11.2 microduplication, detailed fetal imaging is recommended, and genetic counseling should be provided to the couples.
Humans
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Female
;
Pregnancy
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Prenatal Diagnosis/methods*
;
Chromosome Duplication/genetics*
;
Male
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Pedigree
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DiGeorge Syndrome/diagnosis*
;
Adult
;
Chromosomes, Human, Pair 22/genetics*
;
Abnormalities, Multiple
8.Association between sunshine duration and hospitalization risk for mental and behavioral disorders in Zigong City, Sichuan Province
Xianyan JIANG ; Fengyuan TIAN ; Yang LI ; Shijuan RUAN ; Yue WEN ; Chunli SHI
Journal of Environmental and Occupational Medicine 2026;43(4):485-492
Background Sunshine duration is closely associated with population mental health and emotional states, although its relationship with mental and behavioral disorders (MBD) remains insufficiently studied. Objective To analyze the effect of sunshine duration on hospital admissions for MBD in Zigong City, Sichuan Province. Methods Hospital admission records for MBD from 10 medical institutions, meteorological data, and ambient air pollutant concentrations were collected in Zigong City from January 1, 2019 to December 31, 2024. A distributed lag non-linear model (DLNM) was employed to calculate single-day and cumulative lag effects of different sunshine duration exposures—0 h (P0, P5, P25), 6 h (P75), and 10.4 h (P95)—on hospitalization risks for MBD, stratified by diagnostic category, sex, and age groups. Results This study analyzed
9.Fibroblast Growth Factors in Parkinson’s Disease: Multi-target Neuroprotective Mechanisms Involving Neuroinflammation, Cellular Stress, and Ferroptosis
Hui WANG ; Zi-Gui ZHOU ; Teng-Teng HAN ; Chang-Zhi YANG ; Xue-Wen TIAN
Progress in Biochemistry and Biophysics 2026;53(4):855-874
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.
10.Compact Fundus Imaging System Using Shack-Hartmann Wavefront Sensing for High-speed Auto-focus
Zhe-Kai LIN ; Long CHEN ; Geng-Yong ZHENG ; Jin-Tian HUANG ; Jia-Xin DONG ; Shang-Pan YANG ; Wen-Zheng DING ; Ding-An HAN ; Xue-Hua WANG ; Ya-Guang ZENG
Progress in Biochemistry and Biophysics 2026;53(4):1076-1086
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.

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