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.

Objective: To conduct screening for rare blood types within important blood group systems for the Chinese population, such as Rh, Duffy, Kidd, P1Pk, Diego, and MNS, in the Guangzhou region, and to establish a corresponding rare blood type database and physical repository. Methods: The saline medium microplate method was used to screen blood donors with the ccDEE phenotype combined with either Jk(a-) or Jk(b-). The polybrene microplate method was employed to screen for donors with Fy(a-), s(-), Lu(b-), Di(b-), k(-), and p phenotypes. The urea lysis microplate method was applied to screen for the Jk(a-b-) phenotype. A high-resolution melting (HRM) curve method was established for screening some donors with the Di(b-) phenotype. Subsequently, expanded phenotyping of antigens in the Rh, Kidd, MNS, Duffy, P1Pk, Lewis, Kell, and Lutheran blood group systems was performed on identified rare blood type donors using monoclonal antibodies. The test results are entered into the Rare Blood Type Bank Management System of the Guangzhou Blood Center, enabling functions such as confirmation reminders and cryopreservation storage when the donor donates again. Red blood cells of rare blood types are processed into frozen red blood cells for long-term storage. Results: Among voluntary blood donors, 16 cases of the ccDEE combined with Jk(a-) phenotype were identified (0.221 7%, 16/7 216); 10 cases of the ccDEE combined with Jk(b-) phenotype (0.138 6%, 10/7 216); 78 cases of the Fy(a-) phenotype (0.169 5%, 78/46 012); 39 cases of the Lu(b-) phenotype (0.138 2%, 39/28 214); 31 cases of the s(-) phenotype (0.081 8%, 31/37 913); 22 cases of the Di(b-) phenotype (0.029 9%, 22/73 691); 30 cases of the Jk(a-b-) phenotype (0.010 1%, 30/298 250); and 1 case of the k(-) phenotype (0.001 3%, 1/77 382), which was further identified as KELnull phenotype (K0). No p phenotype donors were identified (0/88 528). A total of 228 units of frozen red blood cells were prepared. The screening results were compared and analyzed with rare blood type data from other regions. Conclusion: This study, through a combination of different screening methods, significantly improved the efficiency of rare blood type screening while remaining cost-effective. By conducting large-scale screening and performing data informatization processing, a database and physical repository of rare blood types in the Guangzhou region were successfully established. This provides a strong guarantee for the timely supply of blood to patients with difficult-to-match and rare blood types in the region, effectively enhances the level of transfusion safety in the region, and offers a practical paradigm for constructing a comprehensive blood transfusion support system.

Objective To investigate the in vitro antiviral effects of Blumea balsamifera(L.)DC.extract against Coxsackievirus B5(CVB5).Methods A series of dilutions of Coxsackievirus were prepared and co-cultured with RD cells to determine the TCID50 value.Subsequently,different concentrations of the extract were added to a 96-well plate containing RD cells to evaluate their impact on cell viability.The ability of Blumea balsamifera extract to inhibit Coxsackievirus was further observed in the 96-well plate containing RD cells and the extract.Results The TCID50 value of Coxsackie virus solution was 10-7.67.The inhibition rate of Blumea balsamifera extract against Coxsackievirus increased with concentration,with an IC50 value of 7.26 mg/L.At a concen-tration of 50 mg/L,the extract caused a decrease in RD cell viability(P＜0.05),but within the concentration range of 6.25 to 50 mg/L,it increased the viability of virus-infected RD cells(P＜0.05),with a selectivity index(SI)exceeding 6.89.Conclusion Blumea balsamifera(L.)DC.extract exhibits in vitro activity against Coxsackievirus.

Purpose: This study aimed to evaluate the contrast-enhanced ultrasound with Sonazoid (Sonazoid-CEUS) features of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: In this retrospective study, patients who underwent surgical resection and were histopathologically diagnosed with NAFLD or cirrhosis-related HCC were included. All patients received Sonazoid-CEUS examinations within 1 week prior to hepatic surgery. The enhancement patterns of HCC lesions were evaluated and compared between the two groups according to the current World Federation for Ultrasound in Medicine and Biology guidelines. Multivariate logistic regression analysis was used to assess the correlations between Sonazoid-CEUS enhancement patterns and clinicopathologic characteristics. Results: From March 2022 to April 2023, a total of 151 patients with HCC were included, comprising 72 with NAFLD-related HCC and 79 with hepatitis B virus (HBV) cirrhosis–related HCC. On Sonazoid-CEUS, more than half of the NAFLD-related HCCs exhibited relatively early and mild washout within 60 seconds (54.2%, 39/72), whereas most HBV cirrhosis–related HCCs displayed washout between 60 and 120 seconds (46.8%, 37/79) or after 120 seconds (39.2%, 31/79) (P<0.001). In the patients with NAFLD-related HCC, multivariate analysis revealed that international normalized ratio (odds ratio [OR], 0.002; 95% confidence interval [CI], 0.000 to 0.899; P=0.046) and poor tumor differentiation (OR, 21.930; 95% CI, 1.960 to 245.319; P=0.012) were significantly associated with washout occurring within 60 seconds. Conclusion Characteristic Sonazoid-CEUS features are useful for diagnosing HCC in patients with NAFLD.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

BACKGROUND: Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. METHODS: Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. RESULTS: UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. CONCLUSIONS Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL