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.

To explore the variation laws of volatile oil during the extraction process of Artemisiae Argyi Folium and its impact on the quality of the medicinal solution, as well as to achieve precise control of the extraction process, this study employed headspace solid phase microextraction gas chromatography-mass spectrometry(HS-SPME-GC-MS) in combination with multiple light scattering techniques to conduct a comprehensive analysis, identification, and characterization of the changes in volatile components and the physical properties of the medicinal solution during the extraction process. A total of 82 volatile compounds were identified using the HS-SPME-GC-MS technique, including 21 alcohols, 15 alkenes, 14 ketones, 9 acids, 6 aldehydes, 5 phenols, 3 esters, and 9 other types of compounds. At different extraction time points(15, 30, 45, and 60 min), 71, 72, 64, and 44 compounds were identified in the medicinal solution, respectively. It was observed that the content of volatile components gradually decreased with the extension of extraction time. Through multivariate statistical analysis, four compounds with significant differences during different extraction time intervals were identified, namely 1,8-cineole, terpinen-4-ol, 3-octanone, and camphor. RESULTS:: from multiple light scattering techniques indicated that at 15 minutes of extraction, the transmittance of the medicinal solution was the lowest(25%), the particle size was the largest(0.325-0.350 nm), and the stability index(turbiscan stability index, TSI) was the highest(0-2.5). With the extension of extraction time, the light transmittance of the medicinal solution improved, stability was enhanced, and the particle size decreased. These laws of physicochemical property changes provide important basis for the control of Artemisiae Argyi Folium extraction process. In addition, the changes in the bioactivity of Artemisiae Argyi Folium extracts during the extraction process were investigated through mouse writhing tests and antimicrobial assays. The results indicated that the analgesic and antimicrobial effects of the medicinal solution were strongest at the 15-minute extracting point. In summary, the findings of this study demonstrate that the content of volatile oil in Artemisiae Argyi Folium extracts gradually decreases with the extension of extraction time, and the variation in volatile oil content directly influences the physicochemical properties and pharmacological efficacy of the medicinal solution. This discovery provides important scientific reference for the optimization of Artemisiae Argyi Folium extraction processes and the development and application of process analytical technologies.
Oils, Volatile/pharmacology* ; Artemisia/chemistry* ; Gas Chromatography-Mass Spectrometry ; Drugs, Chinese Herbal/pharmacology* ; Chlorogenic Acid/pharmacology* ; Solid Phase Microextraction ; Quality Control

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.

OBJECTIVE To evaluate the impact of bundle intervention measures on incidence of catheter-related in-fections in patients of neurosurgery intensive care unit(NICU).METHODS The related data regarding to incidence rates of hospital-associated infections and utilization rates of catheters were collected from the NICU patients of Renji Hospital,Shanghai Jiaotong University from 2007 to 2022.The effect of the bundle intervention measures on reducing the incidence of catheter-related infections was analyzed by means of interrupted tune series(ITS)method.RESULTS There was significant difference in the decline trend of incidence of the infections during the study(the trend x2=91.978,P＜0.001).ITS analysis showed that the utilization rate of catheters only presented the decline trend after the intervention(β2=-0.667,P=0.042),the utilization rate of ventilator tubes only de-clined after the intervention(β3=-26.375,P＜0.001).Th utilization rate of central venous catheters showed a downward trend before the intervention(β1=-2.525,P＜0.001)but did not change significantly after the inter-vention.The incidence of central line-associated bloodstream infection(CLABSI)was decreased(RR=0.268,95％CI:0.124 to 0.581),however,there was significant difference in the change of slope(RR=0.912,95％CI:0.730 to 1.140).The incidence of catheter-associated urinary tract infection(CAUTI)showed a downward trend(RR=0.796,95％CI:0.647 to 0.975),however,there was no significant difference in the change of the level(RR=1.543,95％CI:0.816 to 3.005).The incidence of ventilator-associated pneumonia(VAP)showed a downward trend(RR=0.829,95％CI:0.767 to 0.895),however,there was no significant difference in the change of the level(RR=0.817,95％CI:0.595 to 1.114).CONCLUSIONS The bundle intervention measures may effectively reduce the incidence of catheter-related infections.The incidence rates of the catheter-related infections vary in the chan-ging trends after the interventions are taken,indicating that it is necessary to comprehensively take the character-istics of catheter-related infections into account when carrying out the bundle intervention measures and continu-ously optimize the control strategies.

OBJECTIVE Liver transplantation is an important mean for treatment of the children with end-stage liv-er disease,but the postoperative infections remain a major and potentially fatal complication.Due to the unique physiological and immunological characteristics of the children,the types and risk factors for the postoperative in-fections differ from those in adults.This review summarizes the current status of research on the postoperative in-fections among the liver transplantation children in recent years and focuses on the major risk factors such as pre-operative state,intraoperative procedures,immunosuppression and postoperative management.The prevention and control strategies were put forward to reduce the risk of infection and raise the rate of successful transplanta-tion by optimizing the assessment and strengthening perioperative management,individualized immunization strat-egies and multidisciplinary collaboration.

The incidence rate of kidney diseases in China has always remained high.At present,the clinical treat-ment mainly focuses on symptomatic treatment to delay the progression of the disease,and there is a lack of eco-nomical and effective treatment methods.MicroRNA plays an important regulatory role in the occurrence and devel-opment of diseases.This study aims to explore the role and regulatory mechanism of miR-142a-3p in adriamycin(ADR)-induced renal tubular epithelial cell(TCMK-1)injury,with a focus on its potential as a therapeutic target for ADR nephropathy.First,cell viability was assessed using the CCK-8 kit,and a mouse renal tubular epithelial cell model induced by ADR was established.Subsequently,alterations in miR-142a-3p and its target gene ATG16L1 mRNA levels were quantified using RT-qPCR.Western blotting was used to detect the protein levels of autophagy marker proteins and pyroptosis marker proteins.Monodansylcadaverin(MDC)staining was performed and the autophagy of cells was detected by flow cytometry.The results showed that the relative expression of miR-142a-3p in TCMK-1 cells induced by ADR was increased and the relative expression of its target gene ATG16L1 was decreased(P＜0.0001).Western blotting results showed that the levels of p62(P＜0.001)and pyroptosis-related proteins(P＜0.001)were increased,while the protein levels of autophagy-related proteins were decreased(P＜0.05).The flow cytometry results showed that there was no difference in the mean fluorescence intensity of autoph-agosomes between the ADR group and the autophagosome inhibitor group(3-MA group)(P＞0.05),indicating that after ADR induction,cell autophagy was inhibited and pyroptosis was enhanced.When the expression of miR-142a-3p was inhibited by transfecting miR-142a-3p inhibitor,the relative expression level of the target gene ATG16L1 was restored(P＜0.001).Western blotting showed that the protein level of p62(P＜0.01)and pyropto-sis-related proteins(P＜0.01)were decreased,and the protein level of autophagy-related proteins was restored(P＜0.001).Flow cytometry results further indicated that cell autophagy was restored(P＜0.0001).In conclusion,ADR targets A TG1 6L1 through miR-142a-3p to reduce the autophagy level of TCMK-1,and simultaneously activates GSDMD-mediated pyroptosis.

Objective To investigate the causal relationship between gut microbiota and viral pneumonia,as well as the underlying mechanisms,using two-sample and two-step Mendelian randomization(MR)approaches,thereby providing novel insights for the prevention and treatment of viral pneumonia.Methods All data were obtained from publicly available genome-wide association studies(GWAS)pooled datasets,including gut microbiota data from the MiBioGen Consortium and the Netherlands Microbiome Project,viral pneumonia data from the FinnGen R10 database,and plasma metabolome data from the publicly available GWAS Catalog.Instrumental variables(IVs)were extracted according to the predefined threshold values.MR analyses were conducted using inverse variance weighting(IVW),MR-Egger,weighted median(WME),weighted mode(WM),and Bayesian-weighted Mendelian randomization(BWMR)methods.Reverse MR analysis was performed to determine whether there was a reverse association.Two-step MR analysis was used to explore the potential mediating role of plasma metabolites,and a series of sensitivity analyses were performed to test the stability of the results.Results Among 196 gut microbiota taxa from the MiBioGen consortium GWAS,11 taxa were associated with viral pneumonia.An increase in the abundance of 4 taxa increased the risk of viral pneumonia,while an increase in the abundance of 7 taxa had a protective effect against viral pneumonia.Among the 207 gut microbiota taxa from the Dutch Microbiome Project GWAS data,10 taxa were associated with viral pneumonia,with 6 risk-increasing and 4 protective taxa identified.Mediation analysis results showed that the causal effect of Defluviitaleaceae on viral pneumonia(OR=0.708,95%CI 0.540-0.929,P=0.013)was mediated to some extent by the N6-acetyllysine levels,with a mediation ratio of 18.4%.Sensitivity analyses did not reveal significant heterogeneity or horizontal pleiotropy.Conclusions Specific gut microbiota are causally associated with viral pneumonia and show potential differences across different populations;the protective effect of Defluviitaleaceae against viral pneumonia may be mediated by the N6-acetyllysine levels.Targeting metabolites may become a potential therapeutic approach for viral pneumonia.

Objective Aedes albopictus is the primary vector of the dengue virus.Screening and the analysis of immune-related genes in DENV2-infected Ae.albopictus provides a scientific basis for further research on blocking the extrinsic incubation period of the dengue virus.Methods Through the approach of literature mining,thirty-three potential immune-related genes were screened from species such as Aedes aegypti and Anopheles gambiae,which have a close genetic relationship with Ae.albopictus.The protein—protein interaction(PPI)analysis is employed to explore the interaction relationship of the proteins encoded by genes.The alterations in mRNA expression levels of the relevant genes in DENV2-infected Ae.albopictus midgut were detected using the qRT-PCR method.Results The PPI results indicates that TLR and Spz of Ae.albopictus;Rel1,Rel2,DefC,Spz,PIWI,Ago2,DOME and HOP of Ae.aegypti;and Rel1,Rel2,CACT,STAT and DOME of An.gambiae exhibit PPI relationships.After Ae.albopictus was infected with DENV2,10 genes showed significant difference in expression.Ago3(7.39,P<0.05),DOMEa(1.63,P<0.01),DOMEb(21.29,P<0.001),and TLRb(1.61,P<0.05)were significantly up-regulated.Rel1(0.62,P<0.001),CACTl(0.65,P<0.001),Rel2a(0.65,P<0.01),Rel2b(0.24,P<0.001),GATAa(0.64,P<0.01)and DefC(0.28,P<0.05)were significantly down-regulated.Conclusions The concordance of Ae.albopictus with Ae.aegypti was higher than that with An.gambiae.DOMEb,Ago3,Rel2b and DefC,can serve as the preferred target genes for subsequent studies on DENV2 immune blockade.