BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

Objective To explore the application value of three mainstream large language models in the diagnosis, differential diagnosis, and treatment decision support of the primary diseases related to pediatric liver transplantation. Methods Seventy-nine cases of pediatric liver transplantation-related diseases diagnosed through pathological or clinical follow-up data were collected from Renji Hospital, Shanghai Jiao Tong University School of Medicine or published high-quality case reports. These cases covered 25 types of primary diseases such as cholestatic liver disease, metabolic diseases, and tumors. Standardized prompts were used to input the case information into the DeepSeek-R1, ChatGPT-4o and Grok-3 models, and the accuracy of their preliminary diagnosis and differential diagnosis based on basic clinical data was evaluated. The final diagnosis accuracy and the response time after supplementary examination were also assessed, as well as the completeness and rationality of their analysis of disease treatment principles. Results In the initial diagnosis and differential diagnosis stage, the comprehensive accuracy of DeepSeek-R1 was the highest [72.1%, 95% confidence interval (CI) 61.4% - 80.8%], and there was a statistically significant difference in the comprehensive accuracy of the three models for initial diagnosis (P = 0.008). After adding further examination information, the final diagnosis accuracy of the three models increased, with DeepSeek-R1 at 88.6% (95% CI 79.7% - 93.9%), ChatGPT-4o at 87.3% (95% CI 78.2% - 93.0%), and Grok-3 at 78.5% (95% CI 68.2% - 86.1%). There was no statistically significant difference among the three models (P = 0.05). The scores given by experts for the treatment principles showed good consistency (Kappa = 0.769). In addition, the response time of ChatGPT-4o is shorter than that of the other two models [(24 ± 7) s]. Conclusions Large language models demonstrate good efficacy in the diagnosis and treatment decision-making process of various pediatric liver diseases, have a good application prospect for auxiliary diagnosis and decision support, and are expected to help improve the accuracy and efficiency of clinical diagnosis and treatment of pediatric liver transplantation-related primary diseases.

ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Objective To explore the independent risk factors for long-term adverse prognosis after percutaneous renal artery angioplasty in patients with transplant renal artery stenosis(TRAS).Methods We retrospectively collected medical records and surgery details of TRAS patients who underwent renal artery angioplasty at the Department of Peripheral Vascular Diseases,The First Affiliated Hospital of Xi'an Jiaotong University,from January 2017 to June 2021.All patients were followed up for 3 years post-operation.Multivariate Cox regression analyses were performed to find the independent predictive factors for long-term adverse prognosis after renal artery angioplasty in the TRAS patients.Results A total of 45 TRAS patients who underwent percutaneous renal artery angioplasty were included in this study.During the five-year follow-up period,10 patients(22.2％)experienced long-term adverse events.These consisted of 3 patients(6.7％)who died from any cause,1 patient(2.2％)who developed transplant renal artery dissection,6 patients(13.3％)who had restenosis of the transplant renal artery,and 1 patient(2.2％)who lost the transplant kidney and received dialysis again.Multivariate Cox regression analysis showed that male gender(HR=4.915,95％CI:1.036-23.328,P=0.045)and balloon angioplasty alone(HR=8.594,95％CI:2.191-33.710,P=0.002)were independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.Conclusion Male gender and balloon angioplasty alone are independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.

Objective To investigate the anatomical structure and surface location of the Lieque(LU7)acupoint.Methods Firstly,the anatomical localization descriptions of the Lieque(LU7)acupoint from classical medical literature were reviewed and summarized.A total of 21 participants were recruited from Shandong Provincial Hospital Affiliated to Shandong First Medical University from January to March 2025.A Cartesian coordinate system was established over the Lieque(LU7)region on the right forearm.Following standardized manual pressure stimulation,the coordinates of the participant′s reported acupoint sensations were recorded.Based on surface pressure mapping result,10 participants were arbitrarily selected for acupuncture intervention.Upon elicitation of acupoint sensation,the ultrasound imaging was used for real-time visualization of anatomical spatial relationships between the needle tip and distal radial osseous landmarks.Five red latex-perfused adult upper limb specimens were selected for microdissection of the Lieque(LU7)regions pre-localized via ultrasonography,achieving definitive structural characterization of its anatomical strata.Another 10 participants were arbitrarily selected to find the physical structure of the Lieque(LU7)acupoint using ultrasound,and the similarities and differences of acupoint sensation responses were verified using acupuncture needle insertions into both the demarcated zone and peripheral tissues.Results The descriptions of the localization of the Lieque(LU7)acupoint in ancient books can be summarized as"one and a half cun above the wrist side"longitudinally,and"at the intersection head,between two tendons and two bones in the hollow"transversely.During surface pressure application,the sites of the participant′s elicited acupoint sensation were anatomically concentrated in the proximal depression adjacent to the radiopalmar ridge,specifically at the transitional interface between the extensor pollicis brevis tendon and scaphoid bone.During acupuncture-induced acupoint sensation,ultrasound imaging demonstrated that the location of the needle tip was located within the proximal depression adjacent to the radiopalmar ridge,accompanied by arterial hemodynamic perfusion signals into adjacent osseous interfaces.Microdissection findings revealed perforating branches of the radial artery traversing the cortical bone interface within the Lieque(LU7)acupoint region.Acupuncture stimulation at the proximal depression adjacent to the radiopalmar ridge elicited consistent acupoint sensations in all 10 participants,and the acupoint sensations differed from those of other surrounding tissues.Conclusion The anatomical structure of Lieque(LU7)acupoint is located within the proximal depression adjacent to the radiopalmar ridge,characterized by the presence of"hilus of bone"structure.

Objective This study aims to explore the correlation between the grade of testicular tissue damage and clinical features which is used to evaluate the viability of testicular tissue after the orchidopexy for testicular torsion.Methods We conducted a retrospective,multicenter analysis of pathological specimens obtained from patients who under-went unilateral orchiectomy due to testicular torsion.Tissue viability was reassessed by the Mikuz grading scale.The corre-lations among tissue viability,duration of torsion symptoms,the angle of torsion,preoperative Doppler ultrasound image and intraoperative testicular resuscitation methods were analyzed.Results Eighty-five pathological specimens were en-rolled from 4 medical centers.The age range was 18 years(IQR 14-33),with a median torsion angle of 480°(IQR 180°-1080°).The interval from the torsion onset to surgical intervention was 18 hours(IQR 9-84).In the subgroup analysis of different torsion durations,the distribution of Grade I injuries was as follows.The subgroup within 12 hours ac-counted for 37.5％.The subgroup between 12 to 24 hours accounted for 14.28％.And the subgroup between 24 to 48 hours ac-counted for 6.45％.The subgroup exceeding 48 hours only accounted for 3.13％.Four patients received orchiectomy due to pre-operative ultrasound image indicating necrosis,correlating with Mikuz grade 3 tissue damage.The decision was made based on the failure of color recovery of affected testis in 57 cases,revealing 12.28％with grade 1 and 35.89％with grade Ⅱ damage.Twenty-four cases were identified as an Arda score of 3,with 4.16％showing grade 1 and 20.83％showing grade Ⅱ Mikuz damage.The method of Arda's grading could be used to determine the vitality of testicular tissue more accurately compared to the post-resusci-tation color observation method(P=0.032).Conclusion Pathological reassessment provides a precise determination of tis-sue viability in the affected testis.In some instances,the testicular tissue damage can be found potentially reversible.

Objective:To investigate the effects of toosendanin(TSN)on the proliferation,apoptosis,migration and invasion of esophageal squamous cell carcinoma(ESCC)KYSE150 cells,and to elucidate its underlying molecular mechanisms.Methods:CCK-8 assay,colony formation assay,and EdU assay were used to assess the effects of varying TSN concentrations(0.062 5,0.125,and 0.25 μmol/L)on KYSE150 cell proliferation.The impacts of TSN on the apoptosis,migration,and invasion of KYSE150 cells were evaluated using flow cytometry,wound healing assay,and Transwell chamber assay,respectively.The expression of hypoxia-inducible factor 1 alpha(HIF1A)in esophageal cancer tissues was analyzed using the GEPIA database.qPCR was used to detect the expression level of HIF1A mRNA in human esophageal epithelial Het-1A and KYSE150 cells,and in TSN-treated KYSE150 cells.Western blot(WB)was performed to detect the effects of TSN on the upstream signaling pathway AKT/mTOR of HIF1A and the expression of downstream proteins related to cell migration,invasion,and apoptosis.Results:TSN of varying concentrations significantly inhibited proliferation,migration,and invasion of KYSE150 cells and promoted apoptosis in a dose-dependent manner(P<0.05 or P<0.01).HIF1A mRNA was highly expressed in KYSE150 cells,and its expression was significantly downregulated after TSN treatment(P<0.05 or P<0.01).TSN markedly downregulated the expression of HIF1A and key upstream signaling proteins p-AKT and p-mTOR.In addition,TSN significantly suppressed the expression of downstream proteins associated with cell migration,invasion,and apoptosis,including N-cadherin,vimentin,Bcl-2,and caspase-3,while upregulating the expression of E-cadherin(P<0.05 or P<0.01).Conclusion:TSN inhibits the proliferation,migration,and invasion,and induces apoptosis in ESCC KYSE150 cells by down-regulating HIF1A expression through suppression of the AKT/mTOR signaling pathway.