Objective To analyze the overall characteristics, research hotspots, and development trends of immune cell-related studies in radiotherapy for rectal cancer. Methods A systematic search was conducted by using Web of Science Core Collection to retrieve articles related to radiation therapy and immune cells in rectal cancer published from 1991 to 2024. Advanced bibliometric tools, such as VOSviewer and CiteSpace, were utilized to facilitate analysis and describe publication trends, geographic contributions, institutional affiliations, journal prominence, author collaboration, and prominent keywords. Results The annual number of relevant publications has increased steadily, showing remarkable growth over the past five years. Studies focusing on adaptive immune cells (T and B cells) account for the largest proportion of works and form the most extensive collaboration networks, reflecting the central role of T cell–mediated antitumor immunity in radiotherapy. Meanwhile, innate immune cells, including myeloid-derived suppressor cells, macrophages, monocytes, and neutrophils, are increasingly investigated for their regulatory roles in shaping the tumor immune microenvironment and influencing therapeutic responses. Among countries, China and the United States have contributed the highest number of publications and demonstrated strong academic influence. While several stable research groups have been formed, intergroup collaboration remains limited. Keyword analysis revealed that radiotherapy-induced immune modulation, tumor immune microenvironment remodeling, and treatment response have emerged as major research hotspots. Conclusion Research on immune cells in rectal cancer radiotherapy has progressed rapidly in recent years. The emphasis of this field has gradually shifted from single-treatment approaches to mechanistic studies investigating the interaction between radiotherapy and the tumor immune microenvironment. The field still demonstrates considerable potential for future research and clinical translational applications.

Objective To develop a predictive model of acute hematologic toxicity (HT) based on preradiotherapy CT radiomic features combined with clinical and dosimetric characteristics for patients with cervical cancer undergoing definitive radiotherapy. Methods Data from 82 patients with cervical cancer who received definitive radiotherapy were retrospectively analyzed. The patients were divided into training and test sets at an 8:2 ratio, with grade ≥2 HT as the study endpoint. Clinical characteristics and dosimetric parameters of pelvic regions were collected, and 1 046 radiomic features were extracted from the overall pelvic structure using PyRadiomics. Radiomic features were processed using Z-score normalization, Spearman correlation analysis (>0.9), and LASSO regression for feature selection. A radiomics model was constructed using K-nearest neighbor machine learning with fivefold cross-validation. For 56 clinical and dosimetric features, independent predictors were identified through univariate and multivariate analyses to establish a clinical-dose model. A hybrid model was further constructed by combining the two sets of features. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), decision curve analysis, and calibration curves. Results Forty patients (48.8%) developed grade ≥2 HT. Univariate and multivariate analyses showed that V20 of the lumbosacral spine was significantly associated with grade ≥2 HT (P<0.05). The AUC values for the radiomics, clinical-dose, and hybrid models were 0.802, 0.750, and 0.861 in the training set, respectively, and 0.703, 0.633, and 0.781 in the test set, respectively. Conclusion Preradiotherapy CT radiomic features combined with dosimetric characteristics can predict the occurrence of acute hematologic toxicity in patients with cervical cancer, potentially facilitating early clinical intervention.

L-valine is an important branched-chain amino acid widely used in the food, pharmaceutical, and feed industries. Microbial fermentation has become the primary production method for L-valine. However, current industrial production still faces issues such as inefficient carbon flux utilization, imbalance in cofactor supply and demand, and suboptimal fermentation processes, which limit the efficient synthesis of L-valine. To further enhance the production performance of L-valine, In this study, metabolic engineering was conducted for a previously constructed Escherichia coli strain with a high yield of L-valine to optimize carbon flux distribution and balance cofactor consumption. Dual-phase oxygen-controlled fermentation was carried out to enhance L-valine production. Firstly, to address the pyruvate loss, we knocked out multiple competing pathway genes (ldhA, poxB, pflB, frdA, and pta), which resulted in a 48% increase in flask yield of the constructed strain VL-04. Next, we optimized the cofactor supply and demand balance by replacing ilvE with bcd (NADH-preferential) from Bacillus subtilis to construct the strain VL-06, which achieved a flask yield of 22.80 g/L, a further improvement of 25.8%. Subsequently, the fermentation conditions of VL-06 were optimized in a 5 L bioreactor with dual-phase oxygen-controlled fermentation. After optimization, the L-valine production reached 86.44 g/L in 26 h, with a glucose-to-acid conversion rate of 44.08% and a production intensity of 3.32 g/(L·h). This study not only shortens the time for L-valine production but also improves the economic efficiency, providing insights for similar fermentation processes employing dual-phase oxygen control.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Valine/biosynthesis* ; Fermentation ; Bacillus subtilis/genetics*

Peripheral nerve injury (PNI) encompasses damage to nerves located outside the central nervous system, adversely affecting both motor and sensory functions. Although peripheral nerves possess an intrinsic capacity for self-repair, severe injuries frequently result in significant tissue loss and erroneous axonal junctions, thereby impeding complete recovery and potentially causing neuropathic pain. Various therapeutic strategies, including surgical interventions, biomaterials, and pharmacological agents, have been developed to enhance nerve repair processes. While preclinical studies in animal models have demonstrated the efficacy of certain pharmacological agents in promoting nerve regeneration and mitigating inflammation, only a limited number of these agents have been translated into clinical practice to expedite nerve regeneration. Chinese herb medicine (CHM) possesses a longstanding history in the treatment of various ailments and demonstrates potential efficacy in addressing PNI through its distinctive, cost-effective, and multifaceted methodologies. This review critically examines the advancements in the application of CHM for PNI treatment and nerve regeneration. In particular, we have summarized the most commonly employed and rigorously investigated CHM prescriptions, individual herbs, and natural products, elucidating their respective functions and underlying mechanisms in the context of PNI treatment. Furthermore, we have deliberated on the prospective development of CHM in both clinical practice and fundamental research.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Peripheral Nerve Injuries/drug therapy* ; Animals ; Nerve Regeneration/drug effects* ; Medicine, Chinese Traditional

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Protein structure determines function, and structural information is critical for predicting protein thermostability. This study proposes a novel method for protein thermostability prediction by integrating graph embedding features and network topological features. By constructing residue interaction networks (RINs) to characterize protein structures, we calculated network topological features and utilize deep neural networks (DNN) to mine inherent characteristics. Using DeepWalk and Node2vec algorithms, we obtained node embeddings and extracted graph embedding features through a TopN strategy combined with bidirectional long short-term memory (BiLSTM) networks. Additionally, we introduced the Doc2vec algorithm to replace the Word2vec module in graph embedding algorithms, generating graph embedding feature vector encodings. By employing an attention mechanism to fuse graph embedding features with network topological features, we constructed a high-precision prediction model, achieving 87.85% prediction accuracy on a bacterial protein dataset. Furthermore, we analyzed the differences in the contributions of network topological features in the model and the differences among various graph embedding methods, and found that the combination of DeepWalk features with Doc2vec and all topological features was crucial for the identification of thermostable proteins. This study provides a practical and effective new method for protein thermostability prediction, and at the same time offers theoretical guidance for exploring protein diversity, discovering new thermostable proteins, and the intelligent modification of mesophilic proteins.
Neural Networks, Computer ; Algorithms ; Protein Stability ; Proteins/chemistry* ; Protein Conformation ; Temperature

Objective Based on the national drug sampling inspection program,this study aims to comprehensively and systematically evaluate the quality of Xuanmai Ganjie preparations,analyze existing quality issues,and provide references and suggestions for quality control of this variety.Methods A total of 237 batches of Xuanmai Ganjie preparations were tested using legal standards,and methods were established for detecting adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels,and determining the content of platycodin D in Xuanmai Ganjie preparations.These methods were applied to the quality control and evaluation of Xuanmai Ganjie preparations.Results Through statutory inspection,one batch of Xuanmai Ganjie granules was found non-compliant.Specific batches were identified to contain the following irregularities:adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels exceeding proposed limits,and platycodin D content below the established threshold.Conclusion The overall quality of Xuanmai Ganjie granules was average,while the overall quality of Xuanmai Ganjie capsules and lozenges was relatively good.Manufacturing enterprises should strengthen their sense of primary responsibility and enhance control over the entire drug production process.

Objective: To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata (Willd.) Ohwi root (P. lobata, Ge Gen) and Hovenia dulcis Thunb. (H. dulcis, Zhi Ju Zi) against ethanol-induced liver damage in vitro, using a human hepatoma cell line G2 (HepG2) cell model. Methods: HepG2 cells were cultured in medium containing 4% ethanol to establish a model of alcoholic liver damage. The cells were then treated with the combined extract obtained via cryogenic extraction. Biochemical assays and Western blot analyses were performed to assess the levels of oxidative stress markers, antioxidant enzymes, and inflammatory cytokines. In addition, activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was examined to elucidate the mechanisms underlying the effects of the extract. Results: Treatment with the extract contributed to a significant reduction in the release of nitric oxide and reactive oxygen species in the ethanol-treated HepG2 cells; promoted the elevated expression of superoxide dismutase, catalase, and glutathione, indicating enhanced antioxidant defenses; and showed strong free radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radicals. In addition, by activating the PI3K/AKT pathway, treatment promoted increases in the expression of nuclear factor erythroid 2-related factor 2 and its downstream targets, subsequently inhibiting apoptosis. Moreover. inflammatory responses were mitigated, as indicated by reductions in the expression of tumor necrosis factor-alpha and interleukin-6, and we detected reduction in the levels of alanine aminotransferase and aspartate aminotransferase, thereby indicating hepatoprotective effects. Conclusion The combined P. lobata root and H. dulcis extract was established to have notable antioxidative and anti-inflammatory properties, effectively alleviating ethanol-induced liver damage in vitro. These findings highlight the potential applicability of this extract as a candidate for treating alcoholic liver disease.

Objective Based on the national drug sampling inspection program,this study aims to comprehensively and systematically evaluate the quality of Xuanmai Ganjie preparations,analyze existing quality issues,and provide references and suggestions for quality control of this variety.Methods A total of 237 batches of Xuanmai Ganjie preparations were tested using legal standards,and methods were established for detecting adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels,and determining the content of platycodin D in Xuanmai Ganjie preparations.These methods were applied to the quality control and evaluation of Xuanmai Ganjie preparations.Results Through statutory inspection,one batch of Xuanmai Ganjie granules was found non-compliant.Specific batches were identified to contain the following irregularities:adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels exceeding proposed limits,and platycodin D content below the established threshold.Conclusion The overall quality of Xuanmai Ganjie granules was average,while the overall quality of Xuanmai Ganjie capsules and lozenges was relatively good.Manufacturing enterprises should strengthen their sense of primary responsibility and enhance control over the entire drug production process.

ObjectiveExosomes are microvesicles which could be secreted by all cell types with diameters between 30 and 150 nm. It was widely distributed in body fluids including blood, urine, and breast milk. Exosomes are considered as potential biomarkers and drug carriers by reason of containing nucleic acids, lipids, proteins and other bioactive molecules. Milk-derived exosomes have been widely used as drug delivery carriers to treat targeted diseases with a lower cost, higher biocompatibility and lower immunogenicity. Until now, there is no research about the milk-derived exosomes phosphorylation to reveal the difference of protein phosphorylation in different species of milk. To investigate the pathways and proteins with specific functions, phosphorylated proteomic analysis of milk-derived exosomes from different species is performed, and provide new ideas for exploring diversified treatments of disease. MethodsWhey and exosomes derived from bovine, porcine and caprine milk were performed for proteomics and phosphoproteomics analysis. The relationship between milk exosome proteins from different species and signaling pathways were analyzed using bioinformatics tools. ResultsA total of 4 191 global proteins, 1 640 phosphoproteins and 4 064 phosphosites were identified from 3 species of milk-derived exosomes, and the exosome proteins and phosphoproteins from different species were significantly higher than those of whey. Meanwhile, some special pathways were enriched like Fcγ-mediated phagocytosis from bovine exosomes, pathways related with neural and immune system from caprine exosomes, positive and negative regulation of multiple activities from porcine exosomes. ConclusionIn this study, the proteomic and phosphoproteomic analyses of exosomes and whey from bovine, porcine and caprine milk were carried out to reveal the difference of composition and related signaling pathways of milk exosome from different species. These results provided powerful support for the application of exosomes from different milk sources in the field of disease treatment.