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.

ObjectiveTo investigate the association of the single nucleotide polymorphism （SNP） of the insulin-like growth factor binding protein-3 （IGFBP3） gene at rs10225396 （A>G） locus with the susceptibility to hepatocellular carcinoma， as well as its potential molecular regulatory mechanisms， and to provide novel genetic biomarkers and a theoretical basis for early screening and precise targeted therapy for hepatocellular carcinoma. MethodsA total of 192 patients with hepatocellular carcinoma who were admitted to The Affiliated Hospital of Yanbian University and Yanbian Cancer Hospital from January 2009 to August 2016 were enrolled as experimental group， and 190 healthy individuals who underwent physical examination in Physical Examination Center of Yanbian Hospital during the same period of time were enrolled as control group. Peripheral blood samples were collected from all subjects， and after DNA was extracted from whole blood， the DNA samples meeting quality standards were sent to Beijing Genomics Institute Research Center Co.， Ltd.， for Mass ARRAY mass spectrometry， while genotyping was completed. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. A binary Logistic regression model was used to analyze the association of the SNP of the IGFBP3 gene at rs10225396 locus with the susceptibility to hepatocellular carcinoma， and odds ratio （OR） and 95% confidence interval （CI） were calculated to assess the risk of developing hepatocellular carcinoma in individuals carrying different genotypes. ResultsThere were two alleles （G and A） at the rs10225396 locus of the IGFBP3 gene， yielding the three genotypes of AA， AG， and GG， and its genotype distribution was consistent with the Hardy-Weinberg equilibrium （χ²=0.072， P=0.789）. The stratified genetic analysis showed that carriers of the IGFBP3 rs10225396 AA genotype had a significant increased risk of hepatocellular carcinoma among individuals of age <63 years， male sex， smoking history， drinking history， and the Chinese Korean population （all P<0.001）. The binary Logistic regression analysis showed that after adjustment for related risk factors in the codominant model， the population with genotype AG and GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）， and in the dominant model， the population with genotype AG+GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）. ConclusionThrough a genotyping analysis of hepatocellular carcinoma patients and healthy individuals in Yanbian Korean Autonomous Prefecture of Jilin Province， China， this study shows that genotype AA at rs10225396 locus of the IGFBP3 gene is significantly associated with the susceptibility to hepatocellular carcinoma， and this genotype can significantly increase the risk of developing hepatocellular carcinoma with the presence of specific risk factors， which provides a potential genetic marker for early screening and precise treatment of hepatocellular carcinoma.

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

OBJECTIVE: To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism. METHODS: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively. RESULTS: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis. CONCLUSION AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism* ; Animals ; Diabetic Nephropathies/metabolism* ; Saponins/therapeutic use* ; Triterpenes/therapeutic use* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Male ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endoribonucleases/metabolism* ; Endoplasmic Reticulum Chaperone BiP ; Rats ; Diabetes Mellitus, Experimental/complications* ; Endoplasmic Reticulum/metabolism* ; Multienzyme Complexes

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

PURPOSE: Early mortality in major trauma has decreased, but MODS remains a leading cause of poor outcomes, driven by trauma-induced cytokine storms that exacerbate injuries and organ damage. METHODS: This prospective cohort study included 79 major trauma patients (ISS >15) treated in the National Center for Trauma Medicine, Peking University People's Hospital, from September 1, 2021, to July 31, 2023. Patients (1) with ISS >15 (according to AIS 2015), (2) aged 15-80 years, (3) admitted within 6 h of injury, (4) having no prior treatment before admission, were included. Exclusion criteria were (1) GCS score <9 or AIS score ≥3 for TBI, (2) confirmed infection, infectious disease, or high infection risk, (3) pregnancy, (4) severe primary diseases affecting survival, (5) recent use of immunosuppressive or cytotoxic drugs within the past 6 months, (6) psychiatric patients, (7) participation in other clinical trials within the past 30 days, (8) patients with incomplete data or missing blood samples. Admission serum inflammatory cytokines and pathophysiological data were analyzed to develop machine learning models predicting MODS within 7 days. LR, DR, RF, SVM, NB, and XGBoost were evaluated based on the area under the AUROC. The SHAP method was used to interpret results. RESULTS: This study enrolled 79 patients with major trauma, and the median (Q₁, Q₃) age was 51 (35, 59) years (52 males, 65.8%). The inflammatory cytokine data were collected for all participants. Among these patients, 35 (44.3%) developed MODS, and 44 (55.7%) did not. Additionally, 2 patients (2.5%) from the MODS group succumbed. The logistic regression model showed strong performance in predicting MODS. Ten key cytokines, IL-18, Eotaxin, MCP-4, IP-10, CXCL12, MIP-3α, MCP-1, IL-1RA, Cystatin C, and MRP8/14 were identified as critical to the trauma-induced cytokine storm and MODS development. Early elevation of these cytokines achieved high predictive accuracy, with an AUROC of 0.887 (95% CI 0.813-0.976). CONCLUSION Trauma-induced cytokine storms are strongly associated with MODS. Early identification of inflammatory cytokine changes enables better prediction and timely interventions to improve outcomes.
Humans ; Prospective Studies ; Middle Aged ; Male ; Female ; Adult ; Aged ; Cytokine Release Syndrome/etiology* ; Adolescent ; Young Adult ; Aged, 80 and over ; Wounds and Injuries/complications* ; Cytokines/blood* ; Multiple Organ Failure/diagnosis* ; Machine Learning

To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

OBJECTIVE: To explore the application value of joint detection of serum neutrophil-to-lymphocyte ratio (NLR), prostate-specific antigen (PSA) and MMP26 in differentiating prostate cancer (PCa) from benign prostatic hyperplasia (BPH). METHODS: A total of 61 PCa patients (PCa group) and 63 BPH patients (BPH group) who were treated in The Affiliated Huaian Hospital of Xuzhou Medical University from May 2022 to May 2024 were retrospectively included. The relevant clinical data of all subjects were collected with the serum NLR, PSA and MMP26 levels being detected. Multivariate logistic regression analysis was used to analyze the influencing factors in differentiating PCa from BPH. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum NLR, PSA and MMP26 in differentiating PCa from BPH. RESULTS: The levels of TC and LDL-C in the PCa group were higher than those in the BPH group. And the level of HDL-C in the PCa group was lower than that in the BPH group (P<0.05). The serum levels of NLR, PSA and MMP26 in the PCa group were higher than those in the BPH group (P<0.05). The results of multivariate logistic regression analysis showed that NLR, PSA and MMP26 were risk factors for the diagnosis of PCa in patients (P<0.05). The ROC results showed that the area under the curve (AUC) of NLR, PSA MMP26 and joint diagnosis in the identification of PCa was 0.804, 0.800, 0.809 and 0.905, respectively. The comparison results of AUC showed that the joint diagnosis was superior to the single diagnosis (Z=2.262, 2.177, 2.002, P<0.05). CONCLUSION The joint detection of serum NLR, PSA and MMP26 has significant application value in the differentiation of PCa and BPH, which is expected to become an effective tool for early screening and diagnosis of PCa.
Humans ; Male ; Prostatic Hyperplasia/blood* ; Prostate-Specific Antigen/blood* ; Diagnosis, Differential ; Prostatic Neoplasms/blood* ; Retrospective Studies ; Neutrophils ; Lymphocytes ; ROC Curve ; Aged ; Middle Aged