Objective To investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). Methods Genome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and IEU OpenGWAS, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. Results IVW analysis results showed that Actinobacteria [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222, 0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. Conclusion Actinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.

ObjectiveTo address the challenges of unstructured classical Chinese expressions， nested entity relationships， and limited annotated data in famous traditional Chinese medicine（TCM） case records， this study proposes a joint relation extraction framework that integrates data augmentation and entity mapping， aiming to support the construction of TCM diagnostic knowledge graphs and clinical pattern mining. MethodsWe developed an annotation structure for entities and their relationships in TCM case texts and applied a data augmentation strategy by incorporating multiple ancient texts to expand the relation extraction dataset. A cascade binary tagging framework for relation triple extraction（CasRel） model for TCM semantics was designed， integrating a pre-trained bidirectional encoder representations from transformers（BERT） layer for classical TCM texts to enhance semantic representation， and using a head entity-relation-tail entity mapping mechanism to address entity nesting and relation overlapping issues. ResultsExperimental results showed that the CasRel model， combining data augmentation and entity mapping， outperformed the pipeline-based Bert-Radical-Lexicon（BRL）-bidirectional long short-term memory（BiLSTM）-Attention model. The overall precision， recall， and F₁-score across 12 relation types reached 65.73%， 64.03%， and 64.87%， which represent improvements of 14.26%， 7.98%， and 11.21% compared to the BRL-BiLSTM-Attention model， respectively. Notably， the F₁-score for tongue syndrome relations increased by 22.68%（69.32%）， and the prescription-syndrome relations performed the best with the F₁-score of 70.10%. ConclusionThe proposed framework significantly improves the semantic representation and complex dependencies in TCM texts， offering a reusable technical framework for structured mining of TCM case records. The constructed knowledge graph can support clinical syndrome differentiation， prescription optimization， and drug compatibility， providing a methodological reference for TCM artificial intelligence research.

In the tumor microenvironment, a bidirectional feedback regulation exists between aberrant angiogenesis and antitumor immunity, which provides a basis for the synergistic effects of antiangiogenic therapy and immunotherapy. The underlying mechanisms include relief of immunosuppression mediated by proangiogenic factors, induction of vascular normalization to reshape the immune microenvironment, and formation of a positive immune-vascular feedback loop. Based on these mechanisms, the combination of antiangiogenic therapy and immunotherapy has demonstrated synergistic efficacy in advanced non-small cell lung cancer (NSCLC) and is gradually being moved forward to the neoadjuvant setting. However, in the perioperative treatment of resectable lung cancer, this regimen still faces challenges, including primary resistance, a brief window of vascular normalization, and an unclear understanding of spatial interaction mechanisms. This review systematically elucidates the synergistic mechanisms of antiangiogenic agents combined with immunotherapy in NSCLC and the latest advances of this combination strategy in the neoadjuvant therapy setting, aiming to provide a reference for clinical practice.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

Alopecia areata （AA） is a common hair loss disorder， and the core pathogenesis is the internal gene-ration of turbid toxin caused by qi movement disorder in the liver， spleen， and kidney. Turbid toxin serves as both a pivotal etiological trigger and a pathological driver of disease exacerbation. Clinically， AA can be classified into four principal patterns， including liver constraint with spleen deficiency， internal accumulation of damp-heat， liver-kidney depletion， and qi-blood depletion. Therapeutic strategies prioritize clearing and resolving turbid toxin while regulating the qi movement of the liver， spleen， and kidney. Accordingly， different formulas were applied. Self-formulated Shugan Jianpi Huazhuo Formula （疏肝健脾化浊方） is suggested to drain dampness， resolve turbidity， and unblock qi movement. Self-formulated Sanjiao Fenxiao Jiedu Formula （三焦分消解毒方） can be used to clear heat， drain dampness and resolve toxin. Self-formulated Zishen Yanggan Toudu Decoction （滋肾养肝透毒汤） can clear and vent latent toxins， while Self-formulated Guiqi Shengfa Didu Formula （归芪生发涤毒方） is employed to tonify qi and blood， purge toxins， and regenerate vitality. By differentiating and treating AA based on the functional patterns of the liver， spleen， and kidney， this approach expands the application scope of the turbid toxin theory and provides valuable insights for treatment of AA.

With the increasing attention paid by the state to traditional medicine and the need for the inheritance and innovative development of Tibetan medicine in the new era， the research and development of new Tibetan medicines has attracted the attention of the industry. This article analyzes the characteristics of prescriptions， dosage forms， preparation methods， and processing of the 34 Tibetan medicine formulas included in the Catalogue of Ancient Famous Classical Formulas（Second Batch）， discusses the problems and challenges in the research and development of ancient famous classical formulas of Tibetan medicine， and puts forward opinions and suggestions in order to promote the research and development of new Tibetan medicine. The main issues that may be encountered in the research and development of 34 Tibetan medicine formulas are as follows：①Some medicinal material resources are scarce， and planting/breeding technologies are not yet mature. Among the 34 formulas， there are not only ingredients derived from endangered protected animals， but also national second-class protected plants and rare high-altitude wild species. ②The quality control level of Tibetan medicinal materials urgently needs to be strengthened and improved. After review， among the 102 medicinal materials in the 34 Tibetan medicine formulas， there are 2 varieties that currently have no national or local medicinal material standards/decoction piece processing specifications. Excluding those without quality standards， the proportion of varieties without any quantitative testing items is 49%. ③There are a large number of mineral medicines in Tibetan medicine formulas， making quality control difficult. The proportion of formulas containing mineral medicines among the 34 formulas is 35%， and most of them have not yet established a targeted quality standard system. ④Some Tibetan medicinal materials in the 34 formulas have unclear origins， with issues such as different substances with the same name and the same substance with different names. ⑤The 34 formulas contain medicinal materials labeled as toxic or slightly toxic in the current quality standards. It is recommended to accelerate the verification of key information of Tibetan medicine， and on this basis， to intensify research on planting and breeding， quality control in response to the above issues. It is also suggested to encourage the rational use of new technologies and processes that are suitable for the characteristics of preparations to develop new drugs from ancient famous classical formulas of Tibetan medicine， and promote the inheritance and innovative development of Tibetan medicine.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy worldwide, accounting for more than 90% of all oral cancers, and is characterized by high invasiveness and poor long-term prognosis. Its etiology is multifactorial, involving tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Oral leukoplakia and erythroplakia are the main precancerous lesions lesions, with oral leukoplakia being the most common. Both OSCC and premalignant lesions are closely associated with aberrant activation of multiple signaling pathways. Post-translational modifications (such as ubiquitination and deubiquitination) play key roles in regulating these pathways by controlling protein stability and activity. Growing evidence indicates that dysregulated ubiquitination/deubiquitination can mediate OSCC initiation and progression via aberrant activation of signaling pathways. The ubiquitination/deubiquitination process mainly involves E3 ligases (E3s) that catalyze substrate ubiquitination, deubiquitinating enzymes (DUBs) that remove ubiquitin chains, and the 26S proteasome complex that degrades ubiquitinated substrates. Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumor-related proteins, thereby driving OSCC initiation and progression. Therefore, understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components. Here, we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway, Wnt/β-catenin pathway, Hippo pathway, and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways, along with potential drug targets. PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70% of OSCC cases. It is modulated by E3s (e.g., FBXW7 and NEDD4) and DUBs (e.g., USP7 and USP10): FBXW7 and USP10 inhibit signaling, while NEDD4 and USP7 potentiate it. Aberrant activation of the Wnt/β‑catenin pathway leads to β‑catenin nuclear translocation and induction of cell proliferation. This pathway is modulated by E3s (e.g., c-Cbl and RNF43) and DUBs (e.g., USP9X and USP20): c-Cbl and RNF43 inhibit signaling, while USP9X and USP20 potentiate it. Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis. This pathway is modulated by E3s (e.g., CRL4^DCAF1 and SIAH2) and DUBs (e.g., USP1 and USP21): CRL4^DCAF1 and SIAH2 inhibit signaling, while USP1 and USP21 potentiate it. Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance. This pathway is modulated by E3s (e.g., TRAF6 and LUBAC) and DUBs (e.g., A20 and CYLD): A20 and CYLD inhibit signaling, while TRAF6 and LUBAC potentiate it. Targeting these E3s and DUBs provides directions for OSCC drug research. Small-molecule inhibitors such as YCH2823 (a USP7 inhibitor), GSK2643943A (a USP20 inhibitor), and HOIPIN-8 (a LUBAC inhibitor) have shown promising antitumor activity in preclinical models; PROTAC molecules, by binding to surface sites of target proteins and recruiting E3s, achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors, for example, PU7-1-mediated USP7 degradation, offering new strategies to overcome traditional drug limitations. Currently, NX-1607 (a Cbl-b inhibitor) has entered phase I clinical trials, with preliminary results confirming its safety and antitumor activity. Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.