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.

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

Bacteria have posed a threat to human health,and the emergence of super bacteria has made it more difficult to cure bacterial infections in clinical practice.Currently,vaccines are one of the effective means of preventing bacterial infections.With the rapid development of cutting-edge technologies in recent years in such disciplines as biology,medicine,and materials science,various innovative strategies have been provided for vaccine research and preparation.This article summarizes the status quo and prospects of innovative vaccines for treating bacterial infections in recent years,including subunit vaccines,mRNA vaccines and attenuated live vaccine in the hopes of providing data for subsequent development and research of bacterial vaccines.

Background and purpose:Leptomeningeal metastasis is a form of central nervous system metastasis of melanoma.High mobility group A2(HMGA2)has been proven to play an important role in the occurrence and development of various tumors,but its biological functions in leptomeningeal metastatic melanoma cells remain unclear.On the basis of building mouse models of central nervous system metastasis of melanoma,this study investigated the differences in cell migration and cell proliferation among leptomeningeal metastatic melanoma cells,primary site melanoma cells and brain parenchymal metastatic melanoma cells,and further clarified the effects of differentially expressed gene HMGA2 on cell migration and proliferation of leptomeningeal metastatic melanoma cells.Methods:B16 mouse melanoma cells(B16-parental cells,B16-Par)stably expressing tdTomato and luciferase were generated by lentiviral infection.Subsequently,B16 specific brain parenchymal metastatic cells(B16-brain metastatic cells,B16-BrM)and B16 specific leptomeningeal metastatic cells(B16-leptomeningeal metastatic cells,B16-LM)were collected after adaptive screening of metastatic sites in vivo.The differences in migration and proliferation among B16-Par,B16-BrM and B16-LM were assessed by wound healing assay and cell counting kit-8(CCK-8).RNA sequencing(RNA-seq)was used to analyze differential gene expression in B16-Par,B16-BrM and B16-LM,and HMGA2 gene specifically upregulated in B16-LM was screened out.The results were verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Gene ontology(GO)analysis was performed for genes which were upregulated in B16-LM specifically.siRNA was used to interfere with the expression of HMGA2 gene in B16-LM,and the knock-down effect was verified by RTFQ-PCR and Western blot.The effects of knocking down HMGA2 on cell migration and proliferation were detected by wound healing assay and CCK-8 assay.Using GSE174401 data in Gene Expression Omnibus(GEO),the specificity of HMGA2 gene expression in leptomeningeal metastatic melanoma cells from patients was verified.Results:Compared with Par cells,tumor cells screened by the brain environment were more likely to colonize the central nervous system.B16-LM had stronger migration and proliferation abilities,and upregulated the expression of HMGA2 gene.GO analysis revealed that HMGA2 was associated with many biological processes such as angiogenesis and cell proliferation.When the expression of HMGA2 gene was knocked down,the migration and proliferation of B16-LM could be inhibited.HMGA2 was upregulated in leptomeningeal metastatic melanoma cells from patients.Conclusion:Leptomeningeal metastatic melanoma cells had relatively unique cellular characteristics,which promoted cell migration and proliferation by upregulating HMGA2 gene expression.

BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as"biness,"which is closely related to"biness"caused by blood stasis and blood vessels blocking collaterals in the theory of"blood stasis"in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the"blood stasis"theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE:Based on the"blood stasis"theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were"ferroptosis,iron,iron overload,osteoarthritis,blood stasis"and the English search terms were"ferroptosis,iron,iron overload,osteoarthritis,TCM."In the end,76 articles were included for further review. RESULTS AND CONCLUSION:First of all,we explored the potential of the"blood stasis"theory in treating knee osteoarthritis,and found that"blood stasis"is a crucial part in the progress of knee osteoarthritis,indicating that the"blood stasis"theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,"blood stasis"and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of"blood stasis"theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the"blood stasis"theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between"blood stasis"theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of"blood stasis"theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.

ObjectiveUsing the Delphi method and analytic hierarchy process （AHP） to screen diagnostic items for qi stagnation syndrome and determine their weights， providing a reference for the development of a diagnostic scale of qi stagnation syndrome. MethodsLiterature related to qi stagnation syndrome were screened from databases including CNKI， Wanfang， VIP， SinoMed （from inception to October 31， 2020）. Through systematic review of literature and expert discussions， the information on the four examinations of traditional Chinese medicine were organized and an item pool was constructed. The Delphi method was used to screen the item indicators， while the AHP was employed to determine their weights. Statistical methods such as mean value， full score ratio， rank sum， unimportant percentage， and coefficient of variation were used for item screening， with the weights calculated by AHP serving as the item weights. ResultsA total of 235 articles and books were included for analysis， resulting in an item pool of 16 items. After three rounds of expert consultation， a total of 84 valid questionnaires were collected， with a total expert enthusiasm coefficient of 99% and authority coefficient of 0.86， 0.84， 0.83， respectively， and the coordination coefficients were 0.45， 0.49， and 0.29， respectively. Through the statistics analysis， 8 diagnosis items were screened out， including distension （stuffi-ness） or distending pain or scurrying pain， wiry pulse， depressed emotions， frequent sighing， deep and wiry pulse， irritability， pale red tongue， and thin white coating. The AHP showed that the order of weights of the first-level indicators from high to low was clinical symptoms， pulse manifestation， and tongue manifestation； the order of weights of the second-level indicators from high to low was distension （stuffiness） or distending pain or scurrying pain， wiry pulse， depressed emotions， frequent sighing， deep and wiry pulse， irritability， pale red tongue， and thin white coating. ConclusionBy applying the Delphi method and AHP to analyze and evaluate the diagnostic items for qi stagnation syndrome， key diagnostic items were screened and their weights determined， laying the foundation for the development of a diagnostic scale for qi stagnation syndrome.

Objective To develop and validate a predictive model for in-hospital mortality in elderly patients with severe acute pancreatitis (SAP). Methods A total of 368 elderly SAP hospitalized patients were selected as study objects, and were divided into mortality group (96 patients, 26.09%) and survival group (272 patients, 73.91%) based on their survival status during hospitalization. Multivariable Logistic regression analysis was performed to identify influencing factors associated with in-hospital mortality in SAP patients, and a predictive model was constructed based on these factors. Receiver operating characteristic (ROC) curves were plotted, and the predictive performance of the model was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity. Results Univariate analysis revealed that the mortality group had a higher proportion of patients aged over 60 years, with renal insufficiency, coronary heart disease, and undergoing laparoscopic surgery. Additionally, the mortality group had significantly higher levels of red blood cell distribution width, fasting blood glucose, interleukin-6, procalcitonin, neutrophil-to-lymphocyte ratio (NLR), lactate, modified CT severity index (MCTSI) score, and bedside index for severity in acute pancreatitis (BISAP) score compared to the survival group (P < 0.05). Multivariable Logistic regression analysis identified age, renal insufficiency, MCTSI score, fasting blood glucose, and NLR as independent influencing factors of in-hospital mortality in elderly SAP patients (P < 0.05). A regression equation was constructed based on these factors: C-index=-1.569+0.258×(age)+0.334×(renal insufficiency)+0.672×(MCTSI score)+0.281×(fasting blood glucose)+0.410×(NLR). The ROC curve analysis showed that the AUC of the model for predicting in-hospital mortality in elderly SAP patients was 0.877 (95%CI, 0.840 to 0.915), with an accuracy of 84.23%, sensitivity of 75.00%, and specificity of 87.50%. Conclusion Age, renal insufficiency, MCTSI score, fasting blood glucose, and NLR are independent predictors of in-hospital mortality in elderly SAP patients. The predictive model constructed based on these factors can assist in identifying high-risk patients and predicting all-cause mortality risk in SAP.

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

Objective:To evaluate the effect of pre-injection of young rat plasma on cognitive dysfunction after cerebral ischemia-reperfusion (I/R) in aged rats and the role of phosphatidylinositol 3-kinase/serine threonine protein kinase (PI3K/Akt) signaling pathway.Methods:Seventy-two SPF-grade healthy male Sprague-Dawley rats, aged 18 months, weighing 600-650 g, were divided into 4 groups ( n=18 each) by the random number table method: control group (group C), cerebral I/R group (group IR), pre-injection of young rat plasma group (group P) and PI3K inhibitor LY294002 group (group LY). In group P and group LY, young rat plasma 100 μl/time was injected via the tail vein. In group C and group IR, the equal volume of normal saline was injected via the the tail vein, 2 times a week for 4 weeks. Then the model of cerebral I/R injury was developed under sevoflurane anesthesia in IR, P and LY groups. LY294002 0.3 mg/kg was injected through the tail vein at 1 h before anesthesia in LY group. The neurological deficit score (Longa score) was performed at 24 h after reperfusion, and then 6 rats were randomly sacrificed, and brain tissues were obtained to determine the cerebral infarct volume. Spontaneous mobility and anxiety-like behavior were assessed by the open field test at day 29 of reperfusion, and cognitive function was assessed by the novel object recognition test at day 30 of reperfusion. At the end of the behavioral test, rats were sacrificed, hippocampal tissues were isolated for determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), postsynaptic dense protein-95 (PSD-95) and synaptic vesicle protein (SYN) (by Western blot), and the dendritic length and dendritic spine density of neurons in the hippocampal CA1 region. Results:There was no significant difference in motor speed, distance traveled, and time of staying at the center of the open field among the four groups ( P>0.05). Compared with group C, the Longa score and cerebral infarct volume were significantly increased, the percentage of novel object exploration and discrimination index were decreased, the expression of p-PI3K, p-Akt, PSD-95 and SYN in hippocampal tissues was down-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were decreased in IR, P and LY groups ( P<0.05). Compared with group IR, Longa score and cerebral infarct volume were significantly decreased, the percentage of novel object exploration and discrimination index were increased, the expression of p-PI3K, p-Akt, PSD-95 and SYN in hippocampal tissues was up-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were increased in group P ( P<0.05), and no significant change was found in the parameters mentioned above in group LY ( P>0.05). Compared with group P, Longa score and cerebral infarct volume were significantly increased, the percentage of novel object exploration and discrimination index were decreased, the expression of p-PI3K, p-Akt, PSD-95 and SYN in hippocampal tissues was down-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were decreased in group LY ( P<0.05). Conclusions:Pre-injection of young rat plasma can attenuate cognitive dysfunction after cerebral I/R in aged rats, and the mechanism is related to activation of hippocampal PI3K/Akt signaling pathway and improvement in synaptic plasticity.

Objective:To evaluate the effects of hemoclips on preventing delayed bleeding for early gastric cancer (EGC) after endoscopic submucosal dissection (ESD).Methods:Clinical data of 459 patients who underwent ESD for EGC in Beijing Friendship Hospital from June 2013 to August 2020 were collected retrospectively. Patients were divided into group A (hemoclip group, n=162) and group B (non-hemoclip group, n=297) according to whether preventive hemostatic clip treatment was performed after resection. Delayed bleeding within 2 weeks after ESD was observed. Univariate analysis and subgroup analysis were conducted for the delayed bleeding incidence and clinicopathological features. Results:Delayed bleeding incidences of group A and group B were 3.1% (5/162) and 8.1% (24/297) with significant difference between the two groups ( χ2=4.418, P=0.036). Subgroup analysis showed that there were significant differences in the delayed bleeding incidence between the two groups when the diameter of the tumor >20 mm [3.5% (2/57) VS 15.3% (13/85), χ2=5.016, P=0.025], the tumor located in the lower part of the stomach [1.0% (1/97) VS 10.4% (20/192), χ2=8.425, P=0.004], and the depth of tumor invasion was M/SM1 [3.2% (5/157) VS 8.1% (23/285), χ2=4.072, P=0.044]. There were no significant differences in the delayed bleeding incidence between group A and group B when the diameter of the tumor ≤20 mm, the tumor located in the upper/medial part of the stomach and the depth of tumor invasion was SM2 ( P>0.05). Conclusion:Hemoclips can prevent delayed bleeding after ESD for EGC, which is mainly observed in a tumor of diameter >20 mm, located in the lower part of the stomach and M/SM1 tumor invasion. It has little effect on the prevention when the tumor diameter ≤20 mm and located in the upper/medial part of the stomach.