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.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

Objective This study aimed to investigate the efficacy of modified endoscopic autologous cartilage eustachian tube pharyngeal orifice tuboplasty(MEACETT)in patients with patulous eustachian tube(PET).Meth-ods A retrospective analysis was conducted on the clinical data of 27 patients(30 ears)diagnosed with PET who underwent MEACETT.Autologous cartilage was used through the incision at the posterior end of the inferior turbi-nate and filled into the lateral wall of the pharyngeal orifice of the eustachian tube.Without affecting the movement function of the eustachian tube during swallowing,the collapse of the pharyngeal orifice was fully filled.Before and after the surgery,the visual analogue scale(VAS),the eustachian tube dysfunction questionnaire-7(ETDQ-7)and hospital anxiety and depression scale(HADS)was used for assessment to evaluate the surgical efficacy.Results There was no significant difference in depression scores before and after surgery(P＞0.05).However,postopera-tive anxiety scores,ETDQ-7 scores,and VAS scores were significantly lower than preoperative scores(P＜0.05).Among the 27 patients,9 showed significant symptom relief,13 exhibited partial relief,and 5 had no significant change compared to preoperative symptoms.The overall response rate of the treatment(significant relief and partial relief)was 81.48％(22/27).All surgeries were successfully performed.Except for secretory otitis media occurring in 2 cases,no major complications were observed.Conclusion MEACETT demonstrates significant symptom relief in PET patients,with high surgical safety and low complication rates,making it worthy of clinical promotion.

Objective To evaluate the diagnostic efficacy of the R value in tubomanometry(TMM)for the di-agnosis of patulous eustachian tube(PET).Methods The clinical data of 58 patients with PET and 65 controls were retrospectively analyzed.TMM was performed on both groups under nasopharyngeal pressures of 30,40,and 50 mbar respectively.The diagnostic efficacy of the R value for PET was evaluated through receiver operating char-acteristic(ROC)curves.Results In the control group,the average R values under nasopharyngeal pressures of 30,40,and 50 mbar were 0.86±0.50,0.76±0.41,and 0.68±0.34 respectively.In contrast,the corresponding R values in the PET group were significantly lower,which were 0.56±0.38,0.50±0.36,and 0.46±0.38 respec-tively.According to the ROC curve analysis,the areas under the curve(AUC)at these pressures were 0.62,0.74,and 0.74 respectively.The specificity and sensitivity of the R value under nasopharyngeal pressures of 30,40,and 50 mbar were 76.90％and 54.30％,74.60％and 68.10％,86.90％and 54.30％,respectively.Under pressures of 30,40,and 50 mbar,the incidence rates of R＞1 in the control group and the PET group were 29.23％(38/130)and 12.77％(12/94)(x2=8.69,P=0.003),20.00％(26/130)and 6.38％(6/94)(x2=7.20,P=0.007),10.00％(13/130)and 3.19％(3/94)(x2=2.87,P=0.09)respectively.Conclusion Although the low R value in TMM reflects the presence of PET to some extent,it does not provide adequate sensitivity and specificity to serve as an independent diagnostic criterion for PET.

Age-related macular degeneration(AMD)is a chronic degenerative retinal disease that severely impairs pa-tients central vision.Research indicates that the complement system is closely associated with the onset and progression of AMD,playing a key role in its pathogenesis,involving various factors such as genetic risk,inflammatory responses,and oxidative stress.This review summarizes the relationship between complement system activation and AMD,as well as re-cent clinical trials targeting complement-based therapies for AMD,with the aim of providing insights for both basic research and clinical treatment of AMD.

Objective:To explore the clinical characteristics and prognostic risk factors of Mycoplasma pneumoniae pneumonia(MPP)in adults across different age groups,providing evidence for age-stratified management strategies.Methods:A retrospective analysis was conducted on 80 MPP patients admitted to the Respiratory Department of a hospital between January 2023 and December 2024.Patients were divided into three groups based on age:young adults(18-40 years),middle-aged adults(41-60 years),and elderly adults(≥ 61 years).Demographic features,clinical indicators,and mixed infections were analyzed.Univariate and multivariate Logistic regression were used to identify risk factors for disease severity.Results:The severity rate was significantly higher in the elderly group(41.2％)compared to the young adult group(7.1％)and middle-aged group(20.0％)(P=0.022).Elderly patients also exhibited significantly higher rates of underlying diseases(chronic lung disease:35.3％vs.3.6％in young adults),elevated inflammatory markers(C-reactive protein:68.3±19.5 mg/L vs.32.5±8.4 mg/L in young adults),mixed infections(52.9％vs.14.3％),and prolonged hospital stays(8.61±2.22 days vs.5.01±1.11 days)(P＜0.05).Multivariate analysis identified age(OR=1.79 per 10 years),chronic lung disease(OR=3.25),blood urea nitrogen ≥6 mmol/L(OR=2.44),and mixed infections(OR=4.26)as independent risk factors for severe MPP(P＜0.05).Conclusion:Clinical manifestations and prognoses of MPP in adults vary significantly across age groups.Elderly patients are characterized by high mixed infection rates,intense inflammatory responses,and renal function impairment,necessitating individualized monitoring and intervention strategies.

Objective To explore the causal relationship between breast cancer and free fatty acid receptor 4(FFAR4)by using two-sample Mendelian randomization.Methods By using Genome-wide Association Studies and expression quantitative trait locus(eQTL)data,single nucleotide polymorphism sites closely related to breast cancer and FFAR4 were extracted.Causal effect values were calculated by using five methods:inverse variance weighting(IVW),MR-Egger,weighted median,simple mode and weighted mode.Cochran Q tests were used to detect heterogeneity,MR-Egger intercept tests and MR-PRESSO tests were used to assess level multiplicity,and the hold-out method was employed for sensitivity analysis to ensure robustness of the results.Additionally,Bayesian co-location analysis was used to evaluate whether FFAR4 expression shares the same causal genetic variant with breast cancer in given genomic region.Results A total of 12 eQTLs closely related to FFAR4 expression levels were included in this study.The results of IVW analysis showed that increased FFAR4 expression levels increased the risk of overall breast cancer,Luminal A,Luminal B/HER2-negative,and HER2-enhanced subtypes of breast cancer.The co-location analysis showed that the posterior probability of FFAR4 expression level and total breast cancer shared causal variation was 0.889.Conclusion There may be a causal relationship between FFAR4 expression and breast cancer.

Background: Bushen Zhuanggu Formula (BZF), derived from the classic Yougui Pills, has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head (NONFH), particularly by promoting bone repair. However, its underlying mechanisms remain unclear. Objective: This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH. Materials and methods: A total of 518 potential BZF targets were identified from the ETCM v2.0 database. Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls. A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis. In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH. Results: Network analysis identified key pathways associated with blood circulation obstruction, immune-inflammatory imbalance, and abnormal bone metabolism. Protein kinase C alpha (PKCA), Ras proto-oncogene (RAS), mitogen-activated protein kinase 3(ERK), ETS proto-oncogene 1 (ETS1), and receptor activator of nuclear factor-κB ligand (RANKL) formed a signaling axis implicated in NONFH pathogenesis. BZF treatment alleviated joint inflammation, preserved trabecular bone morphology, reduced bone loss, and promoted bone repair. Mechanistically, BZF significantly downregulated the expression of PKCA, RAS, ERK, ETS1, and RANKL, improved blood circulation, and inhibited osteoclast activation while promoting osteoblast activation. Conclusion: BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis, thereby reversing dysregulated bone metabolism.

Objective To explore the causal relationship between breast cancer and free fatty acid receptor 4(FFAR4)by using two-sample Mendelian randomization.Methods By using Genome-wide Association Studies and expression quantitative trait locus(eQTL)data,single nucleotide polymorphism sites closely related to breast cancer and FFAR4 were extracted.Causal effect values were calculated by using five methods:inverse variance weighting(IVW),MR-Egger,weighted median,simple mode and weighted mode.Cochran Q tests were used to detect heterogeneity,MR-Egger intercept tests and MR-PRESSO tests were used to assess level multiplicity,and the hold-out method was employed for sensitivity analysis to ensure robustness of the results.Additionally,Bayesian co-location analysis was used to evaluate whether FFAR4 expression shares the same causal genetic variant with breast cancer in given genomic region.Results A total of 12 eQTLs closely related to FFAR4 expression levels were included in this study.The results of IVW analysis showed that increased FFAR4 expression levels increased the risk of overall breast cancer,Luminal A,Luminal B/HER2-negative,and HER2-enhanced subtypes of breast cancer.The co-location analysis showed that the posterior probability of FFAR4 expression level and total breast cancer shared causal variation was 0.889.Conclusion There may be a causal relationship between FFAR4 expression and breast cancer.