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 investigate the clinical efficacy of minimally invasive mitral valvuloplasty (MVP) in the treatment of infective endocarditis (IE) with mitral regurgitation (MR). Methods A retrospective analysis was conducted on the clinical data of patients who underwent MVP for IE with MR at the Department of Cardiovascular Surgery in Zhongshan Hospital, Fudan University from 2016 to 2020. Patients were divided into two groups based on the surgical incision: those with a right mini-thoracotomy were classified as a minimally invasive surgery (MIS) group, and those with a median sternotomy (MS) were classified as an MS group. All patients had isolated mitral valve involvement. Perioperative data were analyzed, and mid- to long-term outcomes were compared between the two groups. Results A total of 86 patients were included, with 40 in the MIS group [22 males and 18 females, with a mean age of (39.78±15.36) years ranging from 14 to 75 years] and 46 in the MS group [27 males and 19 females, with a mean age of (49.94±16.13) years ranging from 14 to 71 years]. The patients in the MIS group were relatively younger (P=0.004) with better preoperative cardiac function (P=0.004). There was no statistical difference in preoperative fever, gender, or comorbidities between the two groups (P>0.05). The MIS group had shorter postoperative ventilation times, less postoperative 24-hour drainage, less blood transfusion, and shorter total hospital stays compared to the MS group (P＜0.05). There was no statistical difference in cardiopulmonary bypass times or ICU stays between the two groups (P>0.05). The perioperative complication rates and mortality rates were not significantly different between the two groups (P>0.05). Follow-up was conducted for 11-92 months, with a mean duration of (49±19) months and an overall follow-up rate of 91.9%. During the follow-up, 3 patients in each group required reoperation for mitral valve issues, with no statistical difference in incidence (7.5% vs. 6.5%, P=0.691). There were no warfarin-related complications, recurrences, or deaths in either group during follow-up. Multivariate regression analysis identified age, preoperative cardiac function, and surgeon experience as influencing factors for the choice of surgical approach. Conclusion Minimally invasive MVP for IE with MR is relatively safe in the perioperative period and shows significant efficacy, with clear mid- to long-term outcomes. It is recommended for younger patients with better preoperative cardiac function and when performed by surgeons with extensive experience in mitral valvuloplasty.

Background Against the backdrop of global warming, extreme high-temperature weather events are becoming more frequent and pose a substantial threat to human health. Urumqi is located in a typical arid climate zone, but the health effects of heatwaves in this region remain insufficiently understood. Objective To evaluate the association between heatwave events and non-accidental mortality among residents in Urumqi, quantify the attributable mortality burden, identify vulnerable populations, and provide scientific evidence to support the development of targeted regional intervention strategies. Methods Data on non-accidental mortality, meteorological variables, and air pollutants in Urumqi from 2018 to 2024 were collected. A heatwave was defined as three or more consecutive days with daily mean temperature exceeding the 90th percentile of the study period. Under a time-stratified case-crossover design, a generalized additive model incorporating a cross-basis function within the distributed lag nonlinear model framework was applied to simultaneously assess the single-day (lag0-lag7) and cumulative (lag01-lag07) lag effects and exposure-response relationship of heatwave exposure with non-accidental mortality. Heatwave-attributable excess deaths was further estimated. Results The exposure-response relationship between daily mean temperature exposure and non-accidental mortality in Urumqi exhibited a J-shaped curve. Using 25 ℃ as the reference temperature, mortality risk increased when temperature exceeded 27.4 ℃. The cumulative relative mortality risk over lag07 following heatwave exposure was 1.100 (95%CI: 1.059, 1.142), with the highest effect observed at lag06 (RR=1.151, 95%CI: 1.095, 1.209). Subgroup analyses showed that females (lag06, RR=1.169, 95%CI: 1.082, 1.262) and residents aged ≥65 years (lag06, RR=1.156, 95%CI: 1.092, 1.224) had higher mortality risks than males (lag06, RR=1.140, 95%CI: 1.069, 1.216) and residents aged <65 years group (lag06, RR=1.141, 95%CI: 1.035, 1.257), respectively. The increased risk appeared earlier among females, beginning at lag02, compared with lag03 among males. Heatwave-attributable excess deaths showed an overall upward trend, peaking at 248 (95%CI: 152, 341) deaths in 2023 and 229 (95%CI: 141, 314) deaths in 2024. Conclusion Heatwave events are significantly associated with an increased risk of non-accidental mortality among residents in Urumqi, primarily through cumulative lag effects under consecutive days of exposure. Females and residents aged ≥65 years are identified as vulnerable populations. The estimated excess deaths attributable to heatwaves show an overall upward trend.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Objective: To explore the association between sleep quality and dry eye symptoms in adolescents,so as to provide the evidence for reducing the prevalence of dry eye symptoms. Methods: The study population was adolescents aged 12-24 years from the Psychology and Behavior Investigation of Chinese Residents (PBICR) survey, which was conducted from 20 June to 31 August 2022. A stratified random sampling and quota sampling method was used to select 6 456 adolescents within mainland China. The Ocular Surface Disease Index (OSDI) and Brief version of the Pittsburgh Sleep Quality Index (B-PSQI) were used to assess dry eye symptoms and sleep quality. Multiple Logistic regression model was used to explore the relationship between sleep quality and dry eye symptoms in adolescents. The influence of gender on the association was explored by using interaction terms. Results: A total of 2 815 adolescents reported having dry eye symptoms, with a prevalence of 43.6%. Logistic regression analysis results showed an increased risk of exacerbation of dry eye symptoms in adolescents with poor sleep quality. The OR (95% CI ) for mild, moderate, and severe dry eye symptoms groups were 1.39(1.16-1.67), 1.52(1.28-1.81), and 2.35(2.02-2.72), respectively, compared with the ocularly normal group ( P <0.05). There was a significant interaction between sleep quality and gender on dry eye symptoms in adolescents ( P <0.01). Conclusions Sleep quality is associated with dry eye symptoms in adolescents, and those with poor sleep quality have a higher risk of dry eye symptoms. The effect of sleep quality on dry eye symptoms is greater in boys.

Objective: Patients with severe symptomatic aortic stenosis are assessed for coronary artery disease (CAD) prior to transcatheter aortic valve implantation (TAVI) with treatment implications. Invasive coronary angiography (ICA) is the recommended modality but is associated with peri-procedural complications. Integrating machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) into existing TAVI-planning CT protocol may aid exclusion of significant CAD and thus avoiding ICA in selected patients. Materials and Methods: A single-center, retrospective study was conducted, 41 TAVI candidates with both TAVI-planning CT and ICA performed were analyzed. CT datasets were evaluated by a ML-based CT-FFR software. Beta-blocker and nitroglycerin were not administered in these patients. The primary outcome was to identify significant CAD. The diagnostic performance of CT-FFR was compared against ICA. Results: On per-patient level, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were 89%, 94%, 80%, 97% and 93%, respectively. On per-vessel level, the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 75%, 94%, 67%, 96% and 92%, respectively. The area under the receiver operative characteristics curve per individual coronary vessels yielded overall 0.90 (95% confidence interval 85%–95%). ICA may be avoided in up to 80% of patients if CT-FFR results were negative. Conclusion ML-based CT-FFR can provide accurate screening capabilities for significant CAD thus avoiding ICA. Its integration to existing TAVI-planning CT is feasible with the potential of improving the safety and efficiency of pre-TAVI CAD assessment.