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/.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective To explore the effect of multimodal exercise combined with enteral nutrition dur-ing radiotherapy in the patients with esophageal cancer complicating diabetes.Methods A total of 52 patients with esophageal cancer complicating diabetes in Zhejiang Provincial Tumor Hospital from January to Decem-ber 2021 were selected as the study subjects and divided into the control group(n=27)and intervention group(n=25)by using the random number table method.The control group implemented the routine exercise scheme,while the intervention group was given the multimodal exercise intervention on the basis of routine exercise.The blood glucose metabolism indicators,related biochemical indicators during radiotherapy and the incidence rate of adverse events during exercise were compared between the two groups.Results The levels of fasting blood glucose,random blood glucose and blood glucose before sleep in the intervention group during radiotherapy were(7.79±1.61)mmol/L,(9.47±1.77)mmol/L and(9.97±3.02)mmol/L,which were lower than(11.84±3.47)mmol/L,(14.18±5.42)mmol/L and(14.62±3.83)mmol/L in the control group with statistically significant differences(P<0.05).During the radiotherapy period,the levels of albumin,total protein and prealbumin in the intervention group were(37.96±2.13)g/L,(68.13±5.02)g/L and(232.89±41.11)g/L,which were lower than(36.05±2.89)g/L,(64.96±5.95)g/L and(207.76±47.59)g/L in the control group with statistically significant differences(P<0.05).The incidence rates of adverse e-vents such as falls,hypoglycemia and accidental extubation during multimodal exercise in the intervention group were lower than those in the control group,and the differences were statistically significant(P<0.05).Conclusion The multimodal exercise could significantly improve the nutritional status during radiotherapy in the patients with esophageal cancer complicating diabetes,stabilize the blood glucose level of the patients,and has good feasibility and safety.

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.

[Abstract] [Objective] To compare and analyze the efficacy of platelet transfusion in patients with different doses, and to analyze the risk factors for platelet transfusion refractoriness. [Methods] A total of 5 827 patients who received platelet transfusion in the PLA General Hospital from May 2023 to May 2024 were selected as the research subjects, among which 4 780 patients were transfused with 1 therapeutic dose of platelets, and 1 047 patients were transfused with 0.5 therapeutic dose of platelets, and the efficacy of platelet transfusion was compared between the two groups. The effects of gender, disease type, white blood cell count before transfusion, fever, number of platelet transfusions, and platelet antibodies on platelet transfusion refractoriness were analyzed using univariate analysis, and the independent risk factors affecting platelet transfusion refractoriness were further analyzed by multivariate logistic regression. [Results] Among 4 780 patients, 3553 (74.3%) were effective and 1 227 (25.7%) were ineffective. Among 1 047 patients, 0.5 platelet infusion was effective in 755 cases (72.1%) and ineffective in 292 cases (27.9%). There was no significant difference in the effective rate of platelet transfusion between the two groups (P>0.05). Univariate analysis showed that the therapeutic effect of platelet transfusion was related to age, the number of platelet transfusion, disease type, platelet antibodies and white blood cell count before transfusion (P<0.05), while age, gender, fever and blood type were not related to the therapeutic effect of platelet transfusion (P>0.05). The results of multi-factor analysis showed that age, white blood cell count >50×10⁹/L, platelet transfusion times, disease type and platelet antibody were independent risk factors for ineffective transfusion (P<0.05). [Conclusion] There is no significant difference in the efficacy of platelet infusion with 0.5 therapeutic dose or 1 therapeutic dose. In addition, age, white blood cell count >50×10⁹/L, the number of platelet transfusion, disease type and platelet antibodies were the factors affecting the ineffective platelet transfusion in group 2.