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.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

Glycosylation plays an important role in tumorigenesis and development. Mucoprotein-1 (MUC1), a transmembrane glycoprotein, is overexpressed in a variety of malignant tumors. The biochemical characteristics of tumor-specific short chain O-glycosylation (such as Tn/sialyl Tn (STn) antigens) are significantly different from those of normal tissue MUC1, which provides a molecular basis for precision diagnosis and treatment of tumors. This article systematically reviews the molecular design, clinical transformation progress and technical bottleneck of three types of probes targeting MUC1 glycosylation epitopes in tumors, including aptamers, peptides and monoclonal antibodies, focusing on their tumor uptake efficiency, targeting specificity and the potential of diagnosis and treatment integration, so as to provide theoretical basis for optimizing the clinical transformation path of MUC1 targeting probes.

Objective To investigate the risk factors for ligamentum flavum hypertrophy(LFH)and its correlation with clinical symptoms in patients with degenerative lumbar spinal stenosis(DLSS).Methods The clinical and imaging data of 79 patients with DLSS were collected.Patients were divided into four groups based on LFH severity.Quantitative parameters,including lumbar lordosis(LL),sacral slope(SS),facet tropism,facet joint effusion,intervertebral height index,dural sac cross-sectional area(CSA),epidural fat area,and fat infiltration rate(FIR)of the paraspinal muscle were measured on imaging.One-way analysis of variance was used to compare the differences in these parameters among groups.Multiple linear regression analysis was performed to identify the risk fac-tors for LFH,and the correlation between LFH severity and clinical manifestations was analyzed.Results The results of one-way analy-sis of variance showed that there were statistically significant differences among the four groups of patients in terms of sex,body mass index(BMI),LL,epidural fat area and FIR of the multifidus(MF).Multiple linear regression analysis identified that BMI,LL,and epidural fat area as independent risk factors for LFH.Correlation analysis indicated a weak positive association between LFH and dis-ease duration(r=-0.231,P=0.041).Conclusion In DLSS patients,LFH is weakly correlated with disease duration,while BMI,LL,and epidural fat area are risk factors for LFH.

Objective To study the regulatory effect of Qufeng Xiaodian Formula on serum differential metabolites of allergic purpura,and provide scientific basis for the diagnosis and treatment of allergic purpura in traditional Chinese medicine.Methods Sixty rats were randomly divided into a blank control group(referred to as the blank group),a model group,a compound glycyrrhizin group,a low-dose Qu Feng Xiao Dian Fang group,a medium dose Qu Feng Xiao Dian Fang group,and a high-dose Qu Feng Xiao Dian Fang group according to a random number table method,with 10 rats in each group.The model group was constructed by combining dried ginger,pepper,and long pepper with ovalbumin to create an allergic purpura rat model.After successful modeling,each treatment group was intervened with corresponding drugs for 4 weeks.After 4 weeks,serum was collected and non targeted metabolomics screening of serum differential metabolites was performed using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometer(UPLC-QTOF/MS).Subsequently,data extraction and multivariate statistical analysis will be conducted to identify potential metabolic pathways.Results Compared with the control group,there were 91 possible differential metabolites in the serum of the model group rats,corresponding to 20 metabolic pathways;Compared with the model group,there were a total of 43 possible differential metabolites in the serum of rats in the wind dispelling and disease eliminating group,corresponding to 15 metabolic pathways.Among them,there are a total of 12 metabolic pathways.Inflammatory metabolites such as arachidonic acid and ceramide can damage vascular endothelium.Ten biomarkers,including arachidonic acid and ceramide,were significantly abnormal in the serum of the model group rats compared to the normal group.The Qufeng Xiaodian formula can significantly reverse these metabolites and significantly enrich them in arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion Qufeng Xiaodian Formula has a certain regulatory effect on metabolites such as arachidonic acid and ceramide that affect vascular endothelial injury.

Objective:To describe the prevalence and distributions of mood disorder in Inner Mongolia Au-tonomous Region,and analyze the related risk factors.Methods:The multistage stratified sampling method with un-equal probability was used to select permanent residents aged 18 years and over in Inner Mongolia Autonomous Re-gion.The Composite International Diagnostic Interview 3.0 was used as a diagnostic tool.Mood disorders were di-agnosed according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition(DSM-Ⅳ).Single and multivariate analyses were used to investigate the related factors of mood disorders.Results:Totally,12 315 community residents were interviewed in the survey.The weighted 12-month prevalence and lifetime prevalence of mood disorder were 5.4％and 8.7％,respectively.Weighted 12-month prevalence of depressive disorder was 4.9％,and that of bipolar disorder was 0.3％.Among all subtypes of mood disorder,the 12-month prevalence rate of major depressive disorder(3.1％)was the highest.Multivariate logistic regression analysis showed that female,unmarried,separated or divorced,unemployment,family history,other mental disorders,sleep disorders and chronic diseases(OR=1.56,2.80,2.07,1.42,13.46,7.97,3.23,2.13)were risk factors of mood disorder,while aged 65 years and over(OR=0.44)was protective factor of mood disorders.The lifetime consultation rate in patients with mood disorders was 15.5％,the rate of psychiatric consultation was 3.7％,the rate of medication was 1.8％.Con-clusion:It indicates that female residents and people who are unmarried,separated and divorced,unemployed,with family history,suffering from other mental disorders,suffering from sleep disorders,and suffering from chronic dis-eases may be high risk groups of mood disorders,and the utilization rate of health services is rather low in Inner Mongolia Autonomous Region.

Objective To study the regulatory effect of Qufeng Xiaodian Formula on serum differential metabolites of allergic purpura,and provide scientific basis for the diagnosis and treatment of allergic purpura in traditional Chinese medicine.Methods Sixty rats were randomly divided into a blank control group(referred to as the blank group),a model group,a compound glycyrrhizin group,a low-dose Qu Feng Xiao Dian Fang group,a medium dose Qu Feng Xiao Dian Fang group,and a high-dose Qu Feng Xiao Dian Fang group according to a random number table method,with 10 rats in each group.The model group was constructed by combining dried ginger,pepper,and long pepper with ovalbumin to create an allergic purpura rat model.After successful modeling,each treatment group was intervened with corresponding drugs for 4 weeks.After 4 weeks,serum was collected and non targeted metabolomics screening of serum differential metabolites was performed using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometer(UPLC-QTOF/MS).Subsequently,data extraction and multivariate statistical analysis will be conducted to identify potential metabolic pathways.Results Compared with the control group,there were 91 possible differential metabolites in the serum of the model group rats,corresponding to 20 metabolic pathways;Compared with the model group,there were a total of 43 possible differential metabolites in the serum of rats in the wind dispelling and disease eliminating group,corresponding to 15 metabolic pathways.Among them,there are a total of 12 metabolic pathways.Inflammatory metabolites such as arachidonic acid and ceramide can damage vascular endothelium.Ten biomarkers,including arachidonic acid and ceramide,were significantly abnormal in the serum of the model group rats compared to the normal group.The Qufeng Xiaodian formula can significantly reverse these metabolites and significantly enrich them in arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion Qufeng Xiaodian Formula has a certain regulatory effect on metabolites such as arachidonic acid and ceramide that affect vascular endothelial injury.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.