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.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

To investigate the association between neutrophil to lymphocyte ratio (NLR) andestimated glomerular filtration rate (eGFR) in patients with diabetes using large-scale data.

Epilepsy is a chronic neurological disorder caused by an imbalance between excitation and inhibition in the central nervous system.Recently,the role of the orexin system in the pathogenesis of epilepsy has garnered significant attention.Orex-in primarily regulates arousal states and enhances neuronal excit-ability through activation of OX1-R/OX2-R receptors.Studies have shown that elevated orexin levels lower the seizure thresh-old,while orexin receptor antagonists(ORAs)exhibit potential antiepileptic effects.ORAs suppress epileptiform discharges by reducing glutamate release,enhancing GABAergic inhibitory effects,and modulating the thalamocortical circuit.Animal ex-periments and preliminary clinical studies demonstrate that OX1R antagonists decrease excitatory synaptic transmission,whereas OX2 R antagonists primarily strengthen GABA-mediated inhibition.With the widespread application of ORAs in sleep disorders,exploring their clinical value as antiepileptic drugs will become a key focus for future research.This review summa-rizes the role of the orexin system in epileptogenesis and discus-ses the research progress and future directions of ORAs as poten-tial antiepileptic agents.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objective To evaluate the diagnostic value of preoperative positron emission computed-tomography(PET-CT)examination for lymph node metastasis in early non-small cell lung cancer(NSCLC).Methods A total of 232 early-stage NSCLC patients who underwent preoperative PET-CT examination and radical surgery for lung cancer in the hospital from January 2019 to April 2023 were selected.Clinical data,PET-CT examination results,and lymph node dissection pathology were collected to calculate the sensitivity,specificity,accuracy,positive predictive value and negative predictive value of PET-CT diagnosis of NSCLC lymph node metastasis.The maximum standard uptake value(SUVmax)of the primary lesion and the predic-tive value of lymph node SUVmax for early NSCLC lymph node metastasis were evaluated by the receiver op-erating characteristic(ROC)curve.Results The accuracy of PET-CT examination in the diagnosis of NSCLC was 95.69％,the accuracy of lymph node metastasis diagnosis was 85.78％,the sensitivity was 35.56％,the specificity was 97.86％,the positive predictive value was 80.00％,and the negative predictive value was 86.32％.There was a statistically significant difference in the detection rate of PET-CT examination and path-ological results among pulmonary nodules of different natures and sizes(P＜0.01).For predicting lymph node metastasis in NSCLC,the cutoff point of SUVmax in the primary lesion was 3.83(P＜0.001),and the cutoff point of SUVmax in lymph nodes was 3.07(P＜0.001).Conclusion In early NSCLC,preoperative PET-CT examination has a high diagnostic accuracy for ground glass nodule lymph node metastasis,but its di-agnostic value for solid nodule lymph node metastasis is limited and insufficient to guide lymph node dissec-tion.Primary lesion SUVmax≥3.83 or lymph node SUVmax≥3.07 are high-risk factors for early lymph node metastasis in lung cancer.

Objective To explore the application value of ultrasound combined with elastography in grading inflammation in patients with chronic liver disease at S2 stage of liver fibrosis.Methods Totally 51 patients who were hospitalized at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from Jan.2022 to Mar.2024 and underwent liver biopsy with pathological results indicating a stage of S2 liver fibrosis in chronic liver disease were enrolled.All patients underwent ultrasound-guided liver biopsy to obtain the stage of pathological liver fibrosis(S1 to S4)and the grade of liver inflammation(G0 to G4).In addition,all the patients were examined by ultrasound combined with elastography;and shear wave velocity(Vs),acoustic attenuation coefficient(ATT),liver fibrosis index(LFI),fibrosis-related index(F index),and inflammatory activity index(A index)were obtained.The correlation between ultrasound combined with elastography parameters and pathological inflammation grading was analyzed.Results According to the pathological inflammation grading,there were 15 cases in group G1,28 cases in group G2,and 8 cases in group G3.There were significant differences in F index,A index,Vs and ATT among the 3 groups(all P＜0.05).Among them,F index,A index and Vs in group G1 were significantly lower than those in group G3(P=0.007,0.006,0.040),while ATT was significantly higher than that in group G3(P=0.005);and there was no significant difference in LFI among the 3 groups(P=0.373).Vs,ATT,F index and A index were correlated with pathological inflammation grade(r=0.404,-0.417,0.379,0.383;P=0.003,0.002,0.006,0.006).The mean plot showed that with the increase of pathological inflammation grade,the age of patients showed a linear upward trend,ATT showed a linear downward trend,and A index showed a linear upward trend.Vs was positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),γ-glutamyltransferase(GGT),total bilirubin,and direct bilirubin(DBil)(all P＜0.05).ATT was negatively correlated with ALT,AST,GGT,and DBil(all P＜0.05);and both F index and A index were positively correlated with ALT,AST,ALP,GGT,and DBil(all P＜0.05).Conclusion Ultrasound combined with elastography can be used to evaluate the degree of inflammation in patients with chronic liver disease at S2 stage of liver fibrosis.

Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.

Objective To study the epidemiological characteristics of special pathogenic infection in Wenchang area following the super typhoon"Yagi"disaster,and provide basis for the diagnosis,treatment,prevention and control of infectious diseases in disaster-affected areas.Methods Clinical characteristics and pathogenic data of 7 groups of patients infected with 9 species of zoonotic pathogens and opportunistic pathogens were analyzed retrospectively.The 7 groups included:pre-typhoon landfall group(August 6 to September 5,2024),post-typhoon landfall group(September 6 to October 5,2024),and groups in the past years of the same period(A2023,B2022,C2021,D2020,E2019,September 6 to October 5 of each year in 2019-2023).Epidemiological characteristics of patients as well as distribution and resistance of pathogens were compared and analyzed.Results In post-typhoon landfall group,26 patients were infected.The overall infection rate of the post-typhoon landfall group was higher than all groups except B2022 group(all P＜0.05).The infected cases mainly distributed in coastal areas.The main route of infection was outside the hospital(88.5％).Male accounted for 80.8％,agricultural workers accounted for 53.9％,and 69.2％of the cases occurred within 10 days after the typhoon.The major infection sites were multiple site co-infection,bloodstream infection,and soft tissue infection.The main pathogens maintained high sensitivity to commonly used antimicrobial agents.The accuracy of clinical initial empirical antimicrobial use was relatively low(45.5％in post-typhoon landfall group vs 62.8％in the groups of the same period in the past).The clinical cure rate decreased to 76.9％,and mortality increased to 7.7％.The mortality of patients infected with Burkholderia pseudomallei and kidney infected with Leptospira were 25.0％and 50.0％,respectively.Conclusion After ty-phoon disaster,special pathogen infection significantly increases and the prognosis is poor.It is recommended to emphasize blood culture and molecular biology testing to facilitate early diagnosis and precise treatment,optimize prevention and control measures,and enhance the accuracy of clinical empirical medication.

OBJECTIVE To summarize the clinical data of 2 cases of multiple organ dysfunction syndrome(MODS)induced by infection with renal leptospira so as to provide bases for prevention and control of severe dis-eases.METHODS The clinical data of the 2 patients with leptospirosis were retrospectively analyzed after the super typhoon'Yagi'on Sep.6,2024.The cases of leptospirosis that were reported at home and abroad in recent 5 years were retrieved.The epidemiological characteristics,clinical manifestations and treatment outcomes of the cases were observed.RESULTS The 2 patients began to have symptoms on the nineth day after the typhoon,both cases presented with the manifestation such as fever,pain and fatigue,shortness of breach and cough,jaundice and anu-ria,with the blood culture negative;the definite diagnosis was mased by blood metagenomic capture method(MetaCAP).The poultry was considered as the infection source,and the illness condition progressed to sepsis and MODS.Case 1 was complicated with empsyxis,jaundice hemorrhage and renal failure and finally died.Case 2 was also detected with leptospira from cerebrospinal fluid and was complicated with renal failure and meningoencephal-itis but was cured.Among 17 cases of leptospirosis from the literatures,the male and peasants were dominant,the infected water was the major infection factor(at least 7 cases);fever,pain and fatigue,shortness of breath and cough as well as hemoptysis were the major symptoms.There were at least 12 cases with the decline of plate-lets counts,10 cases complicated with empsyxis,11 cases complicated with shock and MODS and 10 cases treated with invasive mechanical ventilation.The misdiagnosis rate was up to 76.47％,and the mortality rate was 29.41％.CONCLUSIONS The leptospirosis is a severe disease,early precise antimicrobial treatment and timely or-gan function support are the crucial to the improvement of prognosis.The health care workers should attach great importance to inquiry for diagnosis,maintain vigilant to the disease for the people with fever of unknown ori-gin,shortness of breath,pain and fatigue by combining the epidemiological history,and make an early definite di-agnosis based on novel molecular diagnosis technique so as to avoid the progression to sepsis and MODS.