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.

Dietary interventions such as fasting are gaining increasing attention for their synergistic effects in anti-tumor therapy, yet the precise underlying mechanisms remain incompletely understood. Recent research has unveiled a novel mode of cell death named “mitoxyperilysis”, providing a fresh perspective on the molecular mechanisms by which fasting may interfere with tumor treatment. This form of death is primarily triggered by the synergy between metabolic dysfunction and innate immune activation. Its mechanism involves the mTORC2 signaling pathway mediating prolonged abnormal contact between damaged mitochondria and the plasma membrane. This leads to massive local release of reactive oxygen species (ROS), which further induces lipid peroxidation of the plasma membrane, ultimately resulting in the physical rupture and death of the cell. The most significant distinction between mitoxyperilysis and classical cell death pathways lies in its independence from caspases and GSDMD. This comment aims to systematically elucidate the process, molecular mechanisms, and differences from other classical cell death pathways of mitoxyperilysis, while also exploring its potential for clinical translation in oncological diseases. Targeting induction of mitoxyperilysis may enhance the efficacy of existing anti-tumor drugs and overcome chemotherapy resistance. However, intervention protocols require further optimization to achieve an optimal balance between safety and therapeutic effectiveness in clinical application.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

Depression is a common mental disorder that falls under the category of "stagnation syndrome" in traditional Chinese medicine （TCM）. Its complex pathogenesis poses challenges for the development of novel therapeutic agents. Currently， clinically used antidepressants are often accompanied by significant side effects， and statistics show that about one-third of patients do not respond to these medications. TCM demonstrates advantages in the treatment of depression through multi-target， multi-pathway and multi-mechanistic approaches. Pinelliae Rhizoma， a phlegm-resolving herb， exhibits effects such as drying dampness and resolving phlegm， as well as eliminating stuffiness and reducing masses. The characteristics of harmonizing Yin and Yang and resolving stagnation in the middle energizer align precisely with the pathogenesis of depression syndrome， demonstrating therapeutic efficacy in affected patients. Literature studies have found that the active ingredients of Pinelliae Rhizoma， such as cavidine， baicalein， β-sitosterol， as well as Pinelliae Rhizoma herb pairs， such as Pinelliae Rhizoma-Magnoliae Officinalis Cortex， Pinelliae Rhizoma-husked sorghum， Pinelliae Rhizoma-Prunellae Spica， exhibit significant antidepressant effects. Furthermore， TCM formulas containing Pinelliae Rhizoma as the principal therapeutic agent， such as Banxia Xiexin Tang， Banxia Houpo Tang， and Wendan Tang， as well as formulas incorporating Pinelliae Rhizoma like compound Xiaochaihu Tang， Chaihu Jia Longgu Muli Tang， and Erchen Tang， have also demonstrated favorable antidepressant efficacy. The antidepressant mechanism of these agents may involve modulation of 5-hydroxytryptamine （5-HT） and dopamine （DA） levels， up-regulation of brain-derived neurotrophic factor （BDNF） expression， regulation of the hypothalamus-pituitary-adrenal （HPA） axis， reduction of oxidative stress， modulation of nuclear transcription factor-κB （NF-κB） signaling pathway， and inhibition of microglia-mediated inflammatory responses. This review summarized the antidepressant mechanisms and clinical applications of the active components， herb pairs， and TCM formulas containing Pinelliae Rhizoma， aiming to provide a reference for modern research on the use of Pinelliae Rhizoma in antidepressant therapy.

Objective To analyze the relationship of protein intake level with high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in patients with diabetic kidney disease (DKD) and its influence on prognosis. Methods A total of 325 patients with DKD admitted from June 2021 to June 2024 were included and classified into a low protein group and a high protein group. The levels of hs-CRP, IL-6, and TNF-α were compared between the two groups of patients before follow-up and after 1 year of follow-up. The correlation was analyzed by linear mixed model. The incidence of endpoint events during follow-up and disease progression-free survival time were compared between the two groups. Results The inflammatory indicators exhibited no statistical differences between the two groups before follow-up (P>0.05). After 1 year of follow-up, the levels of hs-CRP, IL-6, and TNF-α in the two groups were higher than those before follow-up, and the levels in the high protein group were higher than those in the low protein group (P<0.05). Linear mixed model analysis suggested that the protein intake level, time, and the interaction term of protein intake level × time were correlated with the changes of hs-CRP, IL-6 and TNF-α levels (P<0.05). The incidence rate of endpoint events in the high-protein group during follow-up was 24.84% (40/161), which was significantly higher than 12.80% (21/164) in the low-protein group (χ²=7.724, P=0.005). The disease progression-free survival time was longer in the low-protein group than that in the high-protein group (Log Rank χ²=9.007, P=0.003). Conclusion The level of protein intake in patients with diabetic kidney disease is closely related to inflammatory response and prognosis.

AIM: To investigate the differences in morphological structure and retinal blood perfusion between the affected eye and the contralateral healthy eye using optical coherence tomography angiography(OCTA)in patients with idiopathic macular epiretinal membrane(IMEM)before and after surgery, and to evaluate the association of these parameters with functional and anatomical outcomes to inform prognostic assessment. METHODS:A prospective study was conducted at Zhejiang Provincial People's Hospital between January 2023 and December 2024. Consecutive patients diagnosed with unilateral IMEM were enrolled; the fellow eye served as an internal control. All participants underwent standardized ophthalmic evaluations, including optical coherence tomography(OCT), OCTA, and color fundus photography. Key quantitative parameters assessed included best-corrected visual acuity(BCVA), central macular thickness(CMT), foveal avascular zone(FAZ)area, vessel density in the inner capillary plexus(ICP), superficial capillary plexus(SCP), deep capillary plexus(DCP), and choroidal capillary perfusion area(CCPA). Measurements were obtained preoperatively and at 1 and 3 mo postoperatively. Correlation analyses were performed between the above parameters and postoperative BCVA and CMT.RESULTS: This study enrolled 30 patients(60 eyes)diagnosed with IMEM, comprising 14 males and 16 females, with a mean age of 65.4±10.8 y.At baseline, IMEM-affected eyes demonstrated significantly reduced BCVA, DCP density, and FAZ area, alongside significantly increased CMT and CCPA, compared with contralateral controls. Following vitrectomy with membrane peeling, CMT decreased significantly at both 1 and 3 mo(both P<0.05)postoperatively; DCP density and BCVA showed significant improvement(both P<0.05). No significant change in FAZ area was observed postoperatively(P>0.05). At 3 mo postoperatively, BCVA of the affected eye was negatively correlated with CMT(r=-0.549, P=0.022). At 1 mo postoperatively, CMT was negatively correlated with preoperative DCP and FAZ, positively correlated with preoperative CMT, and positively correlated with ICP and SCP at 1 mo postoperatively, and negatively correlated with FAZ at 1 mo postoperatively(all P<0.05). Furthermore, CMT at 3 mo postoperatively was negatively correlated with preoperative DCP(r=-0.498,P=0.042).CONCLUSION:In patients with IMEM, the affected eyes exhibit significantly reduced DCP density and FAZ area, alongside increased CMT and CCPA. Following vitrectomy with membrane peeling, CMT decreased progressively, DCP density demonstrated partial restoration, and vision improved gradually. Preoperatively, smaller CMT larger DCP, and FAZ were associated with more favorable surgical outcomes; postoperatively, smaller ICP and SCP densities—combined with a larger FAZ—also correlated with better functional recovery.

Background Nitrosamines (NAms), emerging as disinfection by-products in drinking water, are highly carcinogenic. Given the significant NAms contamination reported in various regions of China, evaluating the contamination levels and health risks of NAms in terminal direct drinking water is of great urgency. Objective To investigate the concentration levels of NAms in piped direct drinking water at primary and secondary schools in Shanghai, and to assess the potential health risks posed to different age groups through this exposure pathway. Methods A total of 198 water samples were collected from 66 primary and secondary schools across five districts in Shanghai from May to June 2023. The mass concentrations of eight major NAms were quantified using solid-phase extraction coupled with gas chromatography-mass spectrometry (GC-MS). A carcinogenic health risk model was employed to evaluate the lifetime cancer risks associated with NAms exposure via direct drinking water for various age groups. Results Among the 198 samples, NAms were detected in 196 samples, with concentrationsranging from below the limit of detection (LOD) to 106.06 ng·L⁻¹. The average concentration of total NAms was 21.30 ng·L⁻¹, with N-nitrosodimethylamine (NDMA) exhibiting the highest detection rate at 98.5%. Significant differences in NAms concentrations were observed among water treatment systems utilizing ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) as core processes (P<0.05). The lifetime cancer risks for different age groups ranged from 1.38×10⁻⁶ to 1.11×10⁻⁵, with NDMA contributing the most to the overall risk (82.1%). The carcinogenic risk for adults (1.08×10⁻⁵) was higher than that for children and adolescents (1.38×10⁻⁶ to 2.61×10⁻⁶). Among children and adolescents under 18 years of age, the risk decreased as age increased. Conclusion Trace levels of NAms, primarily NDMA, are detected in the piped direct drinking water at primary and secondary schools in Shanghai, with concentrations vary significantly depending on the water treatment process. The carcinogenic risks of NAms exposure via direct drinking water for all age groups are below the acceptable level (1×10⁻⁴) recommended by the U.S. Environmental Protection Agency (EPA).

Objective: To investigate the correlation between color parameters (L^*, a^*, b^*, Eab^*) and the contents of reducing sugars, total polysaccharides, total oligosaccharides, as well as four saccharides (fructose, glucose, sucrose, and kestose) during the nine cycles of steaming and sun-drying processing of Polygonatum kingianum, and to preliminarily explore the optimal processing duration.
Methods: The color changes were objectively evaluated using a colorimeter. The anthrone-sulfuric acid method was employed to determine total polysaccharides and oligosaccharides. The 3,5-dinitrosalicylic acid (DNS) colorimetric method was used to measure total reducing sugar content. High-performance liquid chromatography coupled with charged aerosol detection (HPLC-CAD) was applied for quantitative analysis of fructose, glucose, sucrose, and kestose. Multivariate statistical analysis was conducted to assess samples from different processing stages.
Results: Significant variations in color and component contents were observed across processing stages. The herbal pieces progressively darkened with increased processing cycles: brightness (L^*) and total color difference (Eab^*) initially decreased then stabilized, while a^* (red-green) and b^* (yellow-blue) values first increased then declined. Total polysaccharides and oligosaccharides showed overall decreasing trends, whereas reducing sugars initially increased before stabilizing. Fructose and glucose levels rose continuously, while sucrose and kestose decreased progressively, becoming undetectable after five cycles.
Conclusion: The chromatic alteration and saccharide composition of P. kingianum showed significant correlation with processing duration. Both total color difference (Eab^*) and reducing sugar content stabilized after four processing cycles (12 hours), suggesting that four cycles of steaming and sun-drying may represent the optimal processing duration.

Objective To explore a method for rapid and differential diagnosis of rejection after kidney transplantation through urine hyperspectral imaging technology. Methods Hyperspectral data information from urine samples of 118 recipients after kidney transplantation was collected, and a deep learning model was constructed to diagnose and classify the types of rejection. Results A deep learning diagnostic model based on the 34-layer residual network (ResNet-34) was constructed, and 118 patients were included and divided into the training set and the test set. Based on the pathological results of the transplanted kidney puncture, the urine samples of the patients were classified into five groups: the non-rejection group, the T-cell-mediated rejection group, the antibody-mediated rejection group, the mixed rejection group and the nephropathy recurrence group. The results showed that the diagnostic sensitivities of the model for the above five groups were 0.960, 0.980, 0.930, 0.940 and 0.943 respectively, and the diagnostic specificities were 0.983, 0.993, 0.997, 0.989 and 0.989 respectively. The overall diagnostic accuracy rate reached 95.7%. Conclusions The study provides a non-invasive, rapid and accurate auxiliary diagnostic method for the differential diagnosis of rejection after kidney transplantation.