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 explore the mechanism through which Banxia Baizhu Tianmatang ameliorates cognitive impairment in epileptic rats induced by lithium chloride-pilocarpine by regulating the neuroinflammatory reaction mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes. MethodsSixty male SD rats were randomly allocated into blank， model， carbamazepine （0.125 g·kg^-1·d^-1）， Banxia Baizhu Tianmatang （1.04 g·kg^-1·d^-1）， and carbamazepine （0.125 g·kg^-1·d^-1） + Banxia Baizhu Tianmatang （1.04 g·kg^-1·d^-1） groups （n=12）. After the modeling of epilepsy， rats were administrated with corresponding agents by gavage for 12 weeks. At the 6th and 12th week of the intervention， the rats’ hyper-excited behavior was evaluated by the stylus experiment， and at the 12^th week of intervention， the cognitive function was evaluated by Barnes maze. At the same time， the seizure frequency and severity grade （Racine score） were recorded. The serum and hippocampus tissue samples were collected after anesthesia for the following tests. Nissl staining was used to evaluate the degree of neuronal damage in the hippocampal CA1 area. The content of malondialdehyde （MDA） in the hippocampus was determined by the thiobarbituric acid （TBA） method. Serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemical method was adopted to detect the expression of apoptosis-associated speck-like protein containing a card （ASC） in the hippocampus. Western blot was employed to quantitatively analyze the protein levels of NLRP3， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， and brain-derived neurotrophic factor （BDNF） in the hippocampus. ResultsThe model group showed increased stylus scores at the 6th and 12^th week after modeling， a decreased Barnes maze strategy score at the 12^th week， a prolonged incubation period （P<0.05）， elevated serum levels of inflammatory factors （P<0.05）， decreased neurons with scattered arrangement and large gaps in the hippocampus， increased content of MDA in the hippocampus （P<0.05）， an increased positive expression of ASC， and up-regulated protein levels of Caspase-1， NLRP3， and BDNF （P<0.05）. Compared with the model group， the intervention with Banxia Baizhu Tianmatang for 12 weeks was accompanied by a decreased stylus score， epileptic seizures with a decreased score， a decreased number， and shortened duration， an increased Barnes maze strategy score， shortened escape latency （P<0.01）， declined serum levels of inflammatory factors （P<0.05）， regular morphology of hippocampal neurons， reduced MDA content in the hippocampus （P<0.05）， a decreased positive expression of ASC， and down-regulated protein levels of Caspase-1， NLRP3， and BDNF （P<0.05， P<0.01）. In addition， compared with the carbamazepine group， Banxia Baizhu Tianmatang + carbamazepine showed improved performance in controlling the seizure， improved the cognitive behavior score and morphology of hippocampal neurons， alleviated the oxidative stress products， lowered the levels of inflammatory factors， reduced the positive expression of ASC in the hippocampus， and down-regulated the expression of Caspase-1， NLRP3 and BDNF， with no significant differences. ConclusionBanxia Baizhu Tianmatang may reduce neuroinflammation， control epileptic seizures， and ameliorate cognitive impairment by inhibiting the expression of NLRP3 inflammasomes.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective:To elucidate the prognostic differences and risk factors associated with different patterns of recurrence and metastasis following pancreatic cancer (PC) resection.Methods:This is a retrospective case series study. Clinicopathological data and follow-up information were retrospectively collected from 210 patients who underwent surgery for PC at the Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, between January 2014 and December 2023. There were 114 males and 96 females; the age was (64.5±10.3) years (range: 29 to 89 years). Survival functions based on different times to recurrence and metastasis and different patterns of recurrence and metastasis were estimated using the Kaplan-Meier method, and survival differences among groups were compared using the Log-rank test. Identifying the optimal cutoff for time to postoperative recurrence/metastasis predicting overall survival (OS) in pancreatic cancer patients via the minimum p-value approach. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS following pancreatectomy.Results:A total of 210 patients met the inclusion and exclusion criteria. Among them, 71 patients remained free of recurrence and metastasis, while 139 developed recurrence and metastasis. The patterns included local recurrence ( n=34), liver metastasis ( n=39), lung metastasis ( n=11), peritoneal metastasis ( n=13), multiple sites metastasis ( n=38), bone metastasis ( n=3), and kidney metastasis ( n=1). OS was significantly shorter in the group with postoperative recurrence and metastasis compared to the group without recurrence/metastasis (23.07 months vs.not reached, P<0.01). The optimal cut-off time distinguishing early from late recurrence and metastasis was 13 months. There was a significant difference in post-recurrence survival between patients with early and late recurrence and metastasis (16.03 months vs. 52.40 months, P=0.009). The Kaplan-Meier survival curve showed that different postoperative recurrence and metastasis patterns had different impacts on OS, with lung metastasis showing the best prognosis compared to local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastasis ( P<0.01). Multivariate Cox analysis revealed that Eastern Cooperative Oncology Group (ECOG) score 1, postoperative carcinoembryonic antigen (CEA) ≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for postoperative recurrence and metastasis (all P<0.05). Conclusions:Considerable prognostic heterogeneity exists in postoperative PC patients depending on the site and pattern of recurrence or metastasis. Specifically, lung metastasis portends a significantly more favorable prognosis than liver metastasis, peritoneal metastasis, local recurrence, or multiple sites metastases. ECOG score 1, postoperative CEA≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for OS in postoperative PC patients.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Aim To verify the mechanism of action of Carthami Flos-Lycopodii Herba in treating KOA carti-lage inflammation based on network pharmacology and in vitro and in vivo experiments.Methods The effec-tive ingredients of Carthami Flos-Lycopodii Herba were screened through the database,the core targets of"drug disease"were analyzed,and pathway enrichment analy-sis and molecular docking verification were conducted.Experimental verification:Primary chondrocytes were extracted from mice and divided into the control group,IL-1β group,treatment group,and treatment+TLR4 agonist group.CCK-8 method was used to screen the optimal intervention concentration of Carthami Flos-Ly-copodii Herba.ELISA was used to detect the content of inflammatory factors in chondrocytes.Western blot was employed to detect the protein expression related to cellular pathways.Subsequently,a KOA mouse model was constructed using the DMM method.After admin-istration,the knee joint injury of mice was evaluated u-sing safranin O-green staining.ELISA was used to de-tect the levels of inflammatory factors in serum.West-ern blot was employed to detect collagen Ⅱ,MMP13,Aggrecan,and apoptosis related protein expression in cartilage tissue.TUNEL staining was used to detect the apoptosis rate of cells.Results A total of 26 active ingredients of Carthami Flos-Lycopodii Herba were screened,as well as 123 potential targets for treating KOA.The enrichment analysis results indicated that it mainly involved mechanisms such as Toll like receptors and cell apoptosis.The experimental results showed that Carthami Flos-Lycopodii Herba alleviated the in-flammatory response of chondrocytes and affected the expression of pathway related proteins.Compared with KOA mice,safflower stretched muscle grass could im-prove cartilage damage and reduce the concentration of serum inflammatory factors,regulate the expression of collagen Ⅱ,MMP13,Aggrecan,and apoptosis related proteins in cartilage tissue,and reduce the fluorescence intensity of TUNEL staining in the tissue.Conclusions Carthami Flos-Lycopodii Herba can improve KOA cartilage inflammation,and its mechanism may be relat-ed to the TLR4/MyD88/NF-κB signaling pathway.

An electrochemical sensor based on a chitosan-carbon nanotube(CS-CNT)composite-modified glassy carbon electrode(GCE)was developed in this work for highly sensitive detection of sunset yellow(SY)in food.The CS-CNT composite dispersion was prepared via an ultrasonic dispersion method.Combined with quantum chemical calculations,the adsorption mechanism of SY molecules onto the electrode surface,facilitated by π-π conjugation and electrostatic interactions,was elucidated.The optimized experimental conditions were determined as follows:12 μL of CS-CNT dispersion modification volume,accumulation time of 300 s,and a phosphate buffer solution at pH 7.0 as supporting electrolyte solution.Experimental results demonstrated that CS significantly enhanced the dispersion of CNT,increasing the effective surface area of the modified electrode by 2.22 times(reaching 0.1587 cm2)compared to the bare GCE.The sensor exhibited a linear detection range of 3.0×10-7 mol/L to 1.0×10-5 mol/L,with a detection limit(S/N=3)of 5.0×10-10 mol/L.Satisfactory spiked recoveries ranging from 96.9%to 101.1%were achieved,along with good preparation reproducibility(relative standard deviation,RSD=4.96%).Interference tests indicated high selectivity of the sensor against citric acid,glucose,and common metal ions.The reliability of the sensor was validated through the detection of SY in actual beverage samples.This electrode design simplified operational procedures,avoiding cross-contamination between measurements,and provided an efficient solution for the on-site monitoring of food additives.

Objective:This study identifies independent predictive indicators to distinguish autoimmune gastritis from Helicobacter pylori ( H. pylori)-induced atrophic gastritis and validates their diagnostic performance to compare laboratory indicators of autoimmune gastritis and H. pylori-induced atrophic gastritis. Methods:A retrospective comparison of laboratory examination indicators was conducted for chronic atrophic gastritis patients with involvement of the gastric fundus and corpus, who were followed up at the Department of Gastroenterology, Xijing Hospital, from January 2014 to September 2024. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff points and corresponding diagnostic thresholds. In addition, multivariate logistic regression analysis was conducted to identify independent predictive indicators for autoimmune gastritis, with further assessment in a validation cohort.Results:A total of 139 patients with autoimmune gastritis and 209 patients with H. pylori-induced atrophic gastritis were included. Pepsinogen (PG) Ⅰ levels and the PG Ⅰ/PG Ⅱ ratio in patients with autoimmune gastritis were significantly lower than in those with H. pylori-induced atrophic gastritis [11.0 (4.8, 22.5) vs. 41.8 (32.2, 59.9) μg/L, U=722.00, P<0.001; 1.24 (0.75, 3.54) vs. 5.76 (4.31, 7.12), U=817.00, P<0.001], while gastrin levels were significantly higher [375 (84, 738) vs. 49 (35, 81) ng/L, U=378.00, P<0.001]. PG Ⅰ was identified as an independent predictive variable, with an area under the ROC curve of 0.847 (95% CI 0.791-0.904), sensitivity of 77.6%, specificity of 91.8%, positive predictive value of 80.5%, and negative predictive value of 90.5%. Conclusions:Significant differences in laboratory indicators were observed between autoimmune gastritis and H. pylori-induced atrophic gastritis in chronic atrophic gastritis involving gastric fundus and corpus. Besides, PG Ⅰ demonstrated good diagnostic performance in identifying autoimmune gastritis and can effectively differentiate between different types of atrophic gastritis.

Objective:To investigate the clinical efficacy of pancreatic cancer surgery with arterial resection.Methods:The clinicopathological and follow-up data of 135 patients undergoing pancreatectomies with arterial resection in Pancreas Center, the First Affiliated Hospital of Nanjing Medical University from Sep 2013 to Dec 2023 were retrospectively analyzed.Results:There were 77 males and 58 females, with age [ M( IQR)] of 63 (14) years old. Among the 135 patients, 122 (90.4%) were distal pancreatectomies, 8 (5.9%) were pancreaticoduodenectomies, 4 (3.0%) were total pancreatectomies and 1 (0.7%) was resection for local recurrence after distal pancreatectomy. There were 120 (88.9%) celiac axis resections, 11 (8.1%) hepatic artery resections, 1 (0.7%) superior mesenteric artery resection and 3 (2.2%) other artery resections. Simultaneous portal vein-superior mesenteric vein or organ resection accounted for 26.7% (36/135) and 29.6% (40/135),respectively. The median blood loss was 300 (300) ml and the median operation time was 275 (105) minutes. The 90-day mortality rate was 7.4% (10/135). The overall morbidity rate was 70.4% (95/135) while the major morbidity rate was 18.5% (25/135). Postoperative hemorrhage occurred in 8.9% (12/135), clinically relevant postoperative pancreatic fistula in 57.0% (77/135), bile leak in 0.74% (1/135), delayed gastric emptying in 9.6% (13/135), liver failure in 3.7% (5/135) and transient liver enzyme elevation in 44.4% (60/135). All of the 135 cases were confirmed as pancreatic cancer histologically, including 54.6% (71/130) moderately differentiated, 45.4% (59/130) poorly differentiated and no for well differentiated. The median tumor size was 4.5 (2.3) cm. The median number of harvested lymph nodes was 14 (13) and the percentage of N0, N1 and N2 according to AJCC 8th staging system was 27.1% (36/133), 52.6% (70/133) and 20.3% (27/133), respectively. The R 0 resection was achieved in 40 of 123 cases (32.5%), whose margins of specimens were assessed circumferentially based on the 1mm rule. The median overall survival time (MST) after surgery was 22.5 months, and the median progress-free survival time was 16.1 months. The overall survival rate at 1-, 2- and 5-year was 71.5%, 45.1% and 11.3%, respectively. The MST of patients who received no adjuvant therapy, chemotherapy after surgery was 8.4 months, 25.3 months, respectively. Conclusions:Pancreatectomy with arterial resection is generally safe and feasible. Survival outcome improves significantly when combined with adjuvant chemotherapy.

Objective:This study aims to analyze historical trends and predict future trends of disability-adjusted life years (DALYs) attributable to high BMI for osteoarthritis (OA) in China. OA is a common chronic degenerative joint disease, with high body mass index (BMI) being a significant risk factor. in China.Methods:Based on the Global Burden of Disease (GBD) 2021 database, we analyzed trends in high-BMI-attributable OA. The ASR of hogh-BMI-attributable OA DALYs increased from DALYs in China from 1990 to 2021. A Bayesian age-period-cohort (BAPC) model was used to predict trends from 2022 to 2046. Age-standardized rates (ASR) and estimated annual percentage changes (EAPC) were calculated to assess trend changes of trends. A Bayesian age-period-cohort (BAPC) model was used to predict trends from 2022 to 2046. Chi-square tests were used to compare differences in high BMI attribution proportions between regions and years.Results:From 1990 to 2021, China′s OA DALYs increased from 1.829 to 5.327 million, with the proportion attributable to high BMI rising from 13.47% to 21.86% ( χ2=60 527.25, P<0.001). The ASR of high-BMI-attributable to OA increased from 27.4 (-2.2, 81.5) per 100,000 to 53.0 (-4.7, 150.7) per 100 000, with an EAPC of 2.48% [95% (uncertainty interval, UI): 2.35, 2.62]. In 2021, females showed significantly higher ASR (69.2 per 100 000) than males (36.1 per 100 000). Knee OA (ASR: 50.5/100 000) demonstrated substantially higher burden than hip OA (ASR: 2.5/100 000). Age effect analysis showed DALYs peaked at ages 80~90; period effect indicated accelerated growth after 2005; cohort effect showed a U-shaped trend with the 1990 birth cohort having the highest relative risk (approximately 3.0). Projections indicated that up to 2046, total OA DALYs will reach approximately 2.39 million with an ASR of about 71, showing more significant growth among females (ASR reaching 100). Conclusion:High-BMI-attributable to OA DALYs in China shows a significant upward trend, and is expected to continue. This trend is more pronounced among females and elderly populations than males, highlighting the urgency of implementing preventive measures for high-risk groups, particularly in weight management.