[摘 要] 目的：明确线粒体DNA（mtDNA）部分缺失对结肠上皮细胞NCM460的影响。方法：通过溴化乙锭（EB）诱导建立mtDNA部分缺失细胞模型（mtDNA-reduced）及恢复模型（reverted），采用CCK-8、活性氧（ROS）及线粒体膜电位检测评估线粒体功能，通过葡萄糖、乳酸及糖酵解关键酶活性检测评估代谢表型，通过Transwell实验及WB法检测细胞侵袭及上皮-间质转化（EMT），通过polyHEMA包被培养检测失巢凋亡抵抗能力；检测PI3K/Akt/mTOR信号通路及程序性死亡配体1（PD-L1）表达，并通过PI3K抑制剂LY294002验证。结果：GEPIA数据库分析显示mtDNA编码基因在结直肠癌中低表达（P < 0.05）；组织芯片显示COX1蛋白在正常结肠组织高表达，在癌组织中低表达（P < 0.05）。mtDNA-reduced NCM460细胞线粒体功能受损（生长速率下降、ROS生成减少、线粒体膜电位降低，P < 0.05），呈现Warburg效应（葡萄糖摄取增加、乳酸分泌增多、糖酵解关键酶活性增强，P < 0.05），侵袭能力增强（P < 0.05）且发生EMT，并抵抗失巢凋亡（P < 0.05）。该细胞PI3K/Akt/mTOR通路激活且PD-L1表达上调；经LY294002处理后，葡萄糖含量有降低趋势（P > 0.05）、细胞活性下降（P < 0.05），PD-L1表达下调（P < 0.05）。结论：结肠上皮细胞NCM460中mtDNA部分缺失可诱导其恶性转化及免疫逃逸。

AIM:To evaluate the clinical efficacy of three types of spectacle lenses with different peripheral microstructure designs in controlling myopia progression among children.METHODS: Retrospective case analysis was conducted. Children diagnosed with myopia aged 6 to 12 y who were received initial spectacle fitting and completed 1-year follow-up at the Optometry Clinic of Suining Central Hospital between January 2023 and August 2024 were enrolled. Only right eye data of all subjects were included for analysis. Based on the type of spectacle lenses independently selected by the children and their parents/guardians, they were divided into four groups: diffusion optics technology(DOT), cylindrical annular refractive element(CARE), highly aspherical lenslets(HAL), and single-vision lenses(SVL). Changes in axial length(AL)and spherical equivalent(SE)from baseline were observed after 1-year lens wear in four groups. Variations between three peripheral microstructure-designed spectacles and single-vision spectacles were compared. The effects of different lens designs on spherical power, astigmatism, corneal curvature, corneal astigmatism, anterior chamber depth, lens thickness, and vitreous cavity depth were analyzed.RESULTS:In this retrospective study, a total of 118 eyes from 118 myopic children were included. There were 28 eyes in 28 children in DOT group [16 males and 12 females, age 10(9, 12)y]. CARE group contained 26 eyes in 26 children, [12 males and 14 females, age 11(9, 12)y]. HAL group had 26 eyes in 26 children [16 males and 10 females, age 10(9, 11)y]. SVL group included 38 eyes in 38 children [20 males and 18 females, age 11(9, 12)y]. There were no significant differences in age, gender, baseline AL, or SE among the four groups(all P>0.05). After 1-year wearing, no increase and slight regression were observed in AL and SE in the DOT group, with no significant differences compared with baseline(all P>0.05). AL and SE increased to varying degrees in the CARE, HAL and SVL groups(all P<0.01). Significant inter-group differences were found in the changes of AL and SE(F=22.820, 30.949, both P<0.001). The mean changes in AL and SE for the DOT group(-0.034±0.180 mm, 0.040±0.243 D)were significantly smaller than those in the CARE group(0.225±0.174 mm, -0.375±0.308 D)and the HAL group(0.147±0.130 mm, -0.255±0.256 D). The changes of AL and SE in the three groups were significantly lower than those in the SVL group(0.355±0.240 mm, -0.891±0.592 D)(all P<0.05).CONCLUSION: In children, short-term wear of spectacles with peripheral microstructural design demonstrates better myopia control efficacy compared to single-vision spectacles. DOT lenses show superior short-term efficacy compared with CARE and HAL lenses.

Natural product-based drug combinations (NPDCs) present distinctive advantages in treating complex diseases. While high-throughput screening (HTS) and conventional computational methods have partially accelerated synergistic drug combination discovery, their applications remain constrained by experimental data fragmentation, high costs, and extensive combinatorial space. Recent developments in artificial intelligence (AI), encompassing traditional machine learning and deep learning algorithms, have been extensively applied in NPDC identification. Through the integration of multi-source heterogeneous data and autonomous feature extraction, prediction accuracy has markedly improved, offering a robust technical approach for novel NPDC discovery. This review comprehensively examines recent advances in AI-driven NPDC prediction, presents relevant data resources and algorithmic frameworks, and evaluates current limitations and future prospects. AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
Artificial Intelligence ; Biological Products/chemistry* ; Humans ; Drug Combinations ; Drug Discovery/methods* ; Machine Learning ; Algorithms

Objective To explore the predictive value of fat attenuation index(FAI)and fibrous plaque index(FPI)for the prognosis of patients with acute coronary syndrome(ACS).Methods A retrospective cohort study was conducted on 334 ACS patients undergoing percutaneous coronary intervention(PCI)in the First Affiliated Hospital of Army Military Medical University and Yongchuan Hospital of Chongqing Medical University from March 2021 to July 2023.All patients received coronary computed tomography angiography(CCTA)to measure FAI and FPI.According to the occurrence of major adverse cardiovascular events(MACE)with 1 year of follow-up,they were divided into MACE group(n=108)and non-MACE group(n=226).The baseline data,CCTA data and results of laboratory tests were collected and compared between the 2 groups.Multivariate logistic regression analysis was used to analyze the relationship of FAI and FPI with the prognosis of ACS patients,and ROC curve was drawn to evaluate its predictive efficiency.Results Among the 334 ACS patients,108(32.34%)experienced MACE.When compared with the non-MACE group,the MACE group exhibited significantly larger proportions of diabetes(72.22%vs 31.86%)and left main coronary artery disease(18.52%vs 7.08%),but lower success rate of operation(79.63%vs 93.81%,P<0.05).Radiologic results showed that the proportion of severe stenosis(20.37%vs 10.62%),FAI(-80.12±6.41 HU vs-72.34±7.09 HU)and FPI(0.58±0.41 vs 0.26±0.12)were obviously increased in the MACE group than the non-MACE group(P<0.05).Laboratory tests indicated that there were statistical differences between the 2 groups in high-density lipoprotein-cholesterol(HDL-C,1.20±0.15 vs 1.09±0.16 mmol/L),miR-126(0.91±0.12 vs 0.96±0.15)and SST2(38.45±5.67 vs 34.30±4.89 ng/mL,P<0.05).Multivariate Logistic regression analysis revealed that FAI(OR=1.200,95%CI:1.136～1.268),FPI(OR=63.157,95%CI:14.126～282.374),moderate stenosis(OR=1.332,95%CI:1.024～1.859),severe stenosis(OR=1.480,95%CI:1.074～2.039),miR-126(OR=0.007,95%CI:0.001～0.077),and sST2(OR=1.192,95%CI:1.113～1.277)were independent predictors of MACE(P<0.05).ROC curve analysis displayed that stenosis degree(AUC=0.622,95%CI:0.561～0.683,P=0.001),FAI(AUC=0.790,95%CI:0.741～0.839,P=0.001)and FPI(AUC=0.700,95%CI:0.638～0.761,P=0.001),miR-126(AUC=0.646,95%CI:0.584～0.707,P=0.001),sST2(AUC=0.700,95%CI:0.638～0.761,P=0.001)had certain predictive values for ACS prognosis.Conclusion Coronary FAI and FPI can be used as independent prognostic indicators of ACS patients,and their numerical changes are closely related to plaque stability and inflammatory state.

OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R2=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

Objective: To improve the efficiency and standardization of preoperative anemia diagnosis and treatment by establishing a systematic intelligent management platform for preoperative anemia. Methods: A multidisciplinary collaborative model was adopted to develop a preoperative anemia management system that integrates intelligent early warning, standardized treatment pathways, and quality control. The system utilizes natural language processing technology to automatically capture laboratory data and establish evidence-based medical decision support functions. A pre-post study design was employed to compare changes in preoperative anemia screening rates, preoperative anemia intervention rates, reasonable use of iron supplements, and perioperative red blood cell transfusion rates before and after system implementation. Results: After system implementation, the standardization of anemia diagnosis and treatment significantly improved: 1) Screening effectiveness: The anemia screening rate increased to 50.00% (an increase of 27.24%); 2) Intervention effectiveness: The anemia treatment rate rose to 56.30% (an increase of 14.02%); 3) Treatment standardization: The reasonable use rate of iron supplements increased to 55.33% (an increase of 21.02%); the red blood cell transfusion rate decreased to 18.29% (a decrease of 4.07%), and the amount of red blood cell transfusions was reduced by 291 units. Conclusion: This system achieves full-process management of preoperative anemia through information technology, significantly enhancing the standardization of diagnosis and treatment as well as intervention effectiveness, providing an effective solution for perioperative anemia management.

By systematically combing ancient and modern literature， this paper examined Tribuli Fructus and Astragali Complanati Semen（ACS） used in the famous classical formulas from the aspects of name， origin， production area， harvesting and processing， clinical efficacy， so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology， and there were nicknames such as Baijili， Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas， and there were nicknames such as Baijili， Shayuan Jili and Tongjili. Because both of them had the name of Baijili， confusion began to appear in the Song dynasty. In ancient and modern times， the main origin of Tribuli Fructus were Tribulus terrestris， and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu， but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part， harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times， and the plump， firm texture， grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing， while modern commonly used is purified， fried and salt-processed. The ancient records of Tribuli Fructus were spicy， bitter， and warm in nature， with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders， improving vision， promoting muscle growth， and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today， the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed， traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter， followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior， while modern standards prioritize plump， uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying， while modern practice commonly employs purification methods. In terms of medicinal properties， the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus， its effects were thus regarded as equivalent to those of Tribuli Fructus， serving as the medicine for treating wind disorders， additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang， solidify sperm and reduce urine， nourish the liver and brighten the eye， etc. Based on the textual research results， it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials， we should pay attention to the specific reference object of Baijili， T. terrestris and A. complanatus should be identified and selected， and the processing method should be in accordance with the requirements of the formulas.

Epidural spinal cord stimulation (eSCS) represents an emerging neuromodulation technology that ameliorates motor dysfunction in patients with spinal cord injury, Parkinson's disease, and stroke by activating sensory afferent fibers, enhancing spinal cord neural network integration, optimizing brain-spinal cord information transmission, and inducing neural plasticity. This article reviews the mechanism, electrode implantation, and stimulation parameter of eSCS, and application of eSCS in spinal cord injury, Parkinson's disease, and stroke, aiming to provide valuable insight for its clinical implementation.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.