AIM:To evaluate the efficacy of intravitreal ranibizumab injection(IVR)combined with subthreshold micropulse(STMP)in the treatment of diabetic macular edema(DME).METHODS: Retrospective study. A total of 98 DME patients(98 eyes)admitted to our hospital from March 2022 to March 2023 were enrolled and divided into two groups based on treatment methods: the control group(49 eyes)received STMP yellow laser therapy alone, while the study group(49 eyes)underwent combined IVR and STMP yellow laser therapy. Comparisons were made between the two groups regarding best corrected visual acuity(BCVA), retinal neovascularization(RNV)leakage area, parafoveal macular thickness(PMT), foveal macular thickness(FMT), central retinal thickness(CRT), and foveal avascular zone(FAZ)area, quality of life was assessed using the Chinese-version low vision quality of life questionnaire(CLVQOL), and complication rates were recorded. Additionally, serum levels of nitric oxide synthase(NOS)and vascular endothelial growth factor(VEGF)were measured before and after treatment in both groups.RESULTS: At 3 mo after treatment, both groups showed improved BCVA compared to baseline, with reduced RNV leakage area, PMT, FMT, CRT, FAZ, and serum levels of VEGF, while serum NOS levels and all CLVQOL domain scores were higher than pre-treatment(all P<0.05). Furthermore, the study group demonstrated superior outcomes in all these parameters compared to the control group(all P<0.05), and no ocular or systemic complications occurred in any patient.CONCLUSION: IVR combined with STMP yellow laser for DME improves visual acuity, reduces RNV leakage area, PMT, FMT, CRT, and FAZ, modulates serum NOS and VEGF levels, enhances quality of life, and demonstrates good safety.

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

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Drug development encompasses multiple processes, wherein protein subcellular localization is essential. It promotes target identification, treatment development, and the design of drug delivery systems. In this research, a deep learning framework called LocPro is presented for predicting protein subcellular localization. Specifically, LocPro is unique in (a) combining protein representations from the pre-trained large language model (LLM) ESM2 and the expert-driven tool PROFEAT, (b) implementing a hybrid deep neural network architecture that integrates convolutional neural network (CNN), fully connected (FC) layer, and bidirectional long short-term memory (BiLSTM) blocks, and (c) developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels. Additionally, a dataset was curated and divided using a homology-based strategy for training and validation. Comparative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction. The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization. All in all, LocPro serves as a valuable complement to existing protein localization prediction tools. The web server is freely accessible at https://idrblab.org/LocPro/.

Health consumption upgrading is an important way to benefit residents'livelihood,protect health and promote the construction of healthy China.It analyzes the practical foundation and development dilemma of China's health consumption upgrading in the new period through literature and logical analysis,and puts forward strategies to alleviate the dilemma.It concludes that in the new period,China's health consumption upgrading has the practical foundation of significant effect of health poverty alleviation policies,continuous upgrading of national health consumption concepts,and continuous emergence of health science and technology innovations,but also faces the development dilemmas of unstable health market order,insufficient supply of health products,insufficient application of health science and technology,and lack of deep cultivation of health literacy.Accordingly,the following strategies are proposed to alleviate the difficulties:strengthen top-level design to create a new"environment"for health consumption;promote diversified participation to meet the new"demand"for health consumption;strengthen technology-driven to build a new"industry"for health consumption;and cultivate health literacy.Cultivating health literacy and cultivating new"potential"for healthy consumption.

Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4％),121 cases were middle-onset group(31.8％),and 60 cases were late-onset group(15.8％).There were 26.6％of patients in the early-onset group in-itially diagnosed as depression,23.1％in the middle-onset group,and 11.7％in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.

OBJECTIVE To explore the ameliorative effect and mechanism of emodin on infectious preterm rats. METHODS The infectious preterm rat model was established and divided into model group， emodin group （60 mg/kg， i.g.）， IKK activation group （2 μg pcDNA3.1-IKK recombinant plasmid via tail vein）， emodin+IKK activation group （i.g. 60 mg/kg emodin+2 μg pcDNA3.1-IKK recombinant plasmid via tail vein）， with 14 rats in each group. Another 14 pregnant female rats were set up as control group. Each group received corresponding intervention for 7 days. The muscle tension of the uterine muscle strip， and the indicator levels of serum inflammation [interleukin 1β （IL-1β）， IL-6， tumor necrosis factor α（TNF-α）] and oxidative stress [superoxide dismutase （SOD）， malondialdehyde （MDA）， catalase （CAT）] were detected； the pathological morphological changes of uterine tissue in rats were observed； the protein expressions of NOD-like receptor protein 3 （NLRP3）， cleaved-caspase-1 and IKK/IκB/NF-κB signaling pathway were detected. RESULTS Compared with control group， a large number of inflammatory cells infiltrated into the smooth muscle layer of uterus in model group with irregular cell distribution； the uterine muscle strip muscle tone， serum levels of IL-1β， IL-6， TNF-α and MDA， protein expressions of NLRP3， cleaved-caspase-1， IKK， IκB and NF-κB p65 in uterine tissue were significantly increased in model group， and the serum levels of SOD and CAT were significantly decreased （P＜0.05）. Compared with the model group， the infiltration of inflammatory cells in the uterine smooth muscle layer was reduced in the emodin group， and all quantitative indexes were significantly improved （P＜0.05）； the infiltration of inflammatory cells in the uterine smooth muscle layer was increased in IKK activation group， and all quantitative indexes further deteriorated （P＜0.05）. Activation of IKK could significantly reduce the improvement effect of emodin on the above indexes in infectious preterm rats （P＜0.05）. CONCLUSIONS Emodin can relieve inflammation and oxidative stress in infectious preterm rats by inhibiting the IKK/IκB/NF-κB signaling pathway， thus improving uterine smooth muscle contraction.

This article aims to explore the significant influence of the Communist Party of China(CPC)on traditional Chinese medicine(TCM).The article reviews the historical development of TCM in modern times and the impact of the CPC,combined with the achievements of the TCM department of comprehensive hospitals,to explore the approach of building pioneer branches with distinctive TCM national cultural characteristics,and to consider how to inherit and innovate the development of TCM cultural essence.The article emphasizes the significant contribution of the CPC to the modernization of TCM and the cause of human health.Through this research,it will contribute to a better understanding of the important role of the CPC in the protec-tion and inheritance of TCM culture and explore cultivation programs for party branches with TCM characteristics to better inherit,innovate and develop traditional Chinese medicine.