Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Objective To investigate the feasibility, safety, and clinical value of endoscopic-assisted skin-sparing mastectomy combined with immediate implant-based breast reconstruction performed as day surgery for breast cancer, aiming to provide a reference for major hospitals seeking to implement a day surgery model for breast cancer treatment. Methods We retrospectively analyzed the patients who underwent endoscopic-assisted skin-sparing mastectomy combined with immediate implant-based breast reconstruction for breast cancer at West China Hospital of Sichuan University from June 2021 to December 2022, and they were divided into a day surgery group and a conventional inpatient group based on their admission model. The operative indicators, Breast-Q scores, preoperative waiting time, length of hospital stay, hospitalization costs and complications of the two groups were analyzed. Results Except for intraoperative bleeding (P=0.007), the difference between the two groups in comparison of the rest of the operative indicators was not statistically significant (all P>0.05); there was no significant difference between the two groups in preoperative and postoperative Breast-Q scores (all P>0.05); the preoperative waiting time and length of stay in hospital of the day surgery group were 4.0 (3.0, 11.0) days and 1.0 (1.0, 1.0) days, respectively, which were significantly shorter than that of the conventional inpatient group; the postoperative pain score in the day surgery group [1.0 (1.0, 1.0) points] was lower than that in the conventional inpatient group [3.0 (3.0, 3.0) points], with a statistically significant difference between the two groups (P<0.001). Additionally, the total hospitalization costs for the day surgery group and conventional inpatient group were 50 656.5 (48 145.3, 62 597.3) RMB and 53 689.3 (50 469.1, 64 826.5) RMB, respectively.The total hospitalization cost in the day surgery group was significantly lower than that in the conventional inpatient group, with a statistically significant difference between the two groups (P=0.001). There was no statistically significant difference in complications between the two groups (all P>0.05). Conclusion Endoscopic-assisted skin-sparing mastectomy combined with immediate implant-based breast reconstruction in day surgery is feasible and safe. Without increasing postoperative complications, it effectively reduces hospitalization costs and shortens medical care time, demonstrating significant clinical value.

OBJECTIVE To systematically review medication-related risk factors for falls in older adults， to provide references for ensuring medication safety among older adults. METHODS A systematic search was conducted in PubMed， Embase， Web of Science， and CNKI for relevant literature published from database inception to November 1， 2025. Relevant studies on medication-related falls in older adults， both domestic and international， were included. Drug factors influencing falls in older adults were summarized and analyzed. RESULTS A total of 22 studies were included. Four major classes of fall-risk-increasing drugs were identified： psychotropic medications [12 studies， odds ratio （OR） range 1.500-5.790]， cardiovascular system drugs （5 studies， OR range 1.236-4.784）， analgesics （3 studies， OR range 1.500-4.490）， and hypoglycemic agents （3 studies， OR range 2.070-2.751）. Additionally， anticholinergic burden （1 study， OR was 2.610） and polypharmacy （7 studies， OR range 2.902-25.897 for the use of ≥4 medications） were identified as significant risk factors for falls. CONCLUSIONS Falls in older adults are significantly associated with psychotropic medications， cardiovascular system drugs， analgesics， and hypoglycemic agents， among which psychotropic medications pose the highest risk. Anticholinergic burden and polypharmacy are also important risk factors. In clinical practice， interventions should be implemented through deprescribing and risk monitoring to effectively reduce the risk of falls in older adults.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.

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: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Methods: Fifty patients who underwent UBE-TLIF and 50 patients who underwent W-TLIF, each with >2 years of follow-up, were retrospectively analyzed. Outcomes included operative parameters, time to postoperative mobilization, paravertebral muscle atrophy and fat infiltration rates, clinical scores (Visual Analog Scale [VAS], Oswestry Disability Index [ODI], Japanese Orthopaedic Association [JOA]), modified Macnab criteria, fusion rates, and complications. Results: Compared with W-TLIF, the UBE-TLIF group had significantly less intraoperative blood loss, shorter operative times, and lower postoperative drainage volumes (p <0.05). The UBE-TLIF group showed faster postoperative recovery and shorter hospital stays. At 6 months, 1 year, and 2 years, W-TLIF patients had higher multifidus and erector spinae atrophy, and greater paravertebral muscle fat infiltration (p <0.05). The UBE-TLIF group also had lower VAS and ODI scores at 1 year and 2 years (p <0.05) and fewer surgical complications (6% vs. 10%). Fusion rates (94% vs. 92%) and modified Macnab outcomes (88% vs. 86%) were comparable (p >0.05). Conclusions UBE-TLIF is associated with reduced intraoperative trauma, quicker recovery, and fewer complications. In the long-term, it better preserves paravertebral muscle integrity and provides superior pain and functional outcomes.

Objective: To address systemic challenges in the blood system, such as supply-demand imbalance, inefficient allocation, and inappropriate clinical use, while bridging gaps in current theories regarding the integration of social mobilization, institutional practice, and policy coordination. It sought to construct a system dynamics model spanning from macro to micro levels to analyze the blood management system holistically. Methods: Key variables were identified by a systematic literature search in both Chinese and English databases. An improved Delphi method was then employed to conduct expert consultations across different fields, leading to the selection and determination of core variable sets for each sub-model. Furthermore, by defining their logical relationships, a system dynamics model was constructed to systematically analyze the operation mechanism of the blood management system. Results: Four core sub-models were developed: 1) A macro "Dynamic Balance" model quantifying regional supply-demand equilibrium and inventory control; 2) a mobilization "Three-Layer Funnel" model analyzing how socio-cultural factors, service channels, and policy incentives influence donation behavior; 3) an institutional "Dual-Cycle Regulation" model revealing hospital blood usage is driven by both disease burden (demand cycle) and management practices (regulation cycle); and 4) an individual "Three-Layer Filter" model standardizing clinical transfusion decisions based on necessity, risk-benefit, and context. These were integrated into a "Multi-Layer Linkage and Feedback" model, elucidating bidirectional interactions among five levels: policy environment, regional supply, blood station mobilization, hospital application, and clinical decision-making. Conclusion: This study constructed a system dynamics model for blood management. By defining key variables and their logical relationships, it systematically analyzes the system′s operational mechanism. The integrated framework connects multiple levels—regional supply, voluntary donation, hospital blood use, and clinical decision-making—revealing their intrinsic linkages. Future efforts should employ systems thinking to synergistically enhance supply-side mobilization, demand-side management, systemic regulation, and decision standardization to build a safe, efficient, and sustainable blood security system.

Objective: To analyze the association between intraoperative blood transfusion and adverse perinatal outcomes(a composite of maternal death, hepatic encephalopathy, etc) in patients with acute fatty liver of pregnancy (AFLP), identify independent risk factors for these outcomes, and develop and validate a risk prediction model for early identification of high-risk patients. Methods: Clinical data of 56 AFLP patients admitted to our hospital from January 2008 to January 2025 were retrospectively analyzed. The chi-square test was used to compare the incidence of adverse perinatal outcomes between the transfusion group and the non-transfusion group. Univariate and multivariate Firth-penalized logistic regression analyses were performed to identify independent predictors of adverse outcomes. Based on the identified independent risk factors, a combined prediction model was developed. Internal validation was performed using the Bootstrap method (1 000 resamplings) to assess the model′s generalizability. Model performance was evaluated using receiver operating characteristic(ROC) curves and calibration curves. Finally, a nomogram for predicting adverse perinatal outcomes in AFLP was constructed. Results: Overall, 57.1%(32/56) of the patients received blood product transfusion during the termination of pregnancy. Multivariate Firth-penalized logistic regression analysis showed that, given the limited sample size, intraoperative blood transfusion had no independent statistical effect on adverse outcomes (OR=0.812, 95%CI:0.133-3.698, P=0.797). Mediation analysis also revealed no significant indirect effect. The independent risk factors were decreased preoperative fibrinogen (OR=14.062, 95%CI:2.389-126.656, P=0.003), pregnancy with infection (OR= 4.536, 95%CI:1.143-22.107, P=0.031), and cesarean section (OR=8.691, 95%CI:1.321-90.081, P=0.023). The combined prediction model achieved an AUC of 0.881 (95% CI:0.793-0.969, P<0.001), indicating good discrimination. At the optimal cut-off value, the sensitivity was 65.6%, specificity 95.8%, positive predictive value 95.5%, and negative predictive value 67.6%. Internal validation by the Bootstrap method showed that the predictive model had good discrimination and no obvious overfitting. The calibration curve demonstrated that the model′s predicted risk was consistent with the actual observed risk. Based on this, an AFLP perinatal adverse outcome nomogram model was constructed. Conclusion: Under the limited sample size of this study, no independent statistical effect of intraoperative blood product infusion on adverse perinatal outcomes in AFLP patients was detected. A multivariate Firth-penalized logistic regression model incorporating decreased preoperative fibrinogen, pregnancy with infection, and cesarean delivery demonstrated good discrimination and calibration. The derived nomogram may serve as an exploratory tool for early risk stratification and proactive intervention.