ObjectiveFrom the perspective of cardiovascular-kidney-metabolic （CKM） syndrome， this study aims to construct and validate a diagnostic machine learning model integrating traditional Chinese and Western medicine for severe coronary artery stenosis in patients with CKM， thereby providing clinical decision-making support for patients with borderline lesions. MethodsBased on a retrospective study design， a total of 535 hospitalized patients from two independent campuses of Jiangsu Province Hospital of Traditional Chinese Medicine： the main campus （from January 2024 to August 2024） and Zidong branch （from September 2024 to December 2024） were screened. Data from the main campus were randomly divided into the training dataset （376 cases） and the internal validation dataset （95 cases） at a 4∶1 ratio， while data from Zidong branch served as the external validation dataset （64 cases）. Risk factors were analyzed and screened through literature review， expert interviews， and the least absolute shrinkage and selection operator （LASSO） algorithm. Nine machine learning algorithms were utilized to construct diagnostic models. Comparative analyses of common evaluation metrics， calibration curves， and decision curves were conducted to select the model through internal and external validation. The Shapley additive explanations （SHAP） method and two cases were utilized to help understand the operational logic of the best model. Finally， the best model was applied to patients with borderline lesions to calculate diagnostic efficacy. ResultsNine risk factors were screened by LASSO regression， such as phlegm， hematoma， stagnation， deficiency， hypertension duration， gender， arterial stiffness index （ASI）， uric acid to high-density lipoprotein cholesterol ratio （UHR）， and glycosylated hemoglobin （HbA1c）. After comparison from multiple dimensions， the light gradient boosting machine （LightGBM） was the best model， achieving area under the curve （AUC） of 0.918 （95% confidence interval （CI）： 0.890-0.945） in the training dataset， 0.885 （95%CI： 0.820-0.951） in the internal validation dataset， and 0.897 （95%CI： 0.818-0.975） in the external validation dataset. Calibration curves indicated good consistency in the predicted probabilities， while decision curve analysis showed clinical benefit when threshold probabilities were less than 90%. SHAP importance rankings were stagnation， deficiency， hematoma， HbA1c， gender， phlegm， hypertension duration， ASI， and UHR. When applied to the patients with borderline lesions， the diagnostic model achieved an AUC of 0.783 （95%CI： 0.637-0.930）， with 73% of patients with actual severe stenosis getting benefit. ConclusionGuided by clinical value， the diagnostic model integrating traditional Chinese and Western medicine established in this study demonstrates favorable performance， providing a basis for clinical diagnosis， treatment， and decision-making in patients with CKM.

ObjectiveFrom the perspective of cardiovascular-kidney-metabolic （CKM） syndrome， this study aims to construct and validate a diagnostic machine learning model integrating traditional Chinese and Western medicine for severe coronary artery stenosis in patients with CKM， thereby providing clinical decision-making support for patients with borderline lesions. MethodsBased on a retrospective study design， a total of 535 hospitalized patients from two independent campuses of Jiangsu Province Hospital of Traditional Chinese Medicine： the main campus （from January 2024 to August 2024） and Zidong branch （from September 2024 to December 2024） were screened. Data from the main campus were randomly divided into the training dataset （376 cases） and the internal validation dataset （95 cases） at a 4∶1 ratio， while data from Zidong branch served as the external validation dataset （64 cases）. Risk factors were analyzed and screened through literature review， expert interviews， and the least absolute shrinkage and selection operator （LASSO） algorithm. Nine machine learning algorithms were utilized to construct diagnostic models. Comparative analyses of common evaluation metrics， calibration curves， and decision curves were conducted to select the model through internal and external validation. The Shapley additive explanations （SHAP） method and two cases were utilized to help understand the operational logic of the best model. Finally， the best model was applied to patients with borderline lesions to calculate diagnostic efficacy. ResultsNine risk factors were screened by LASSO regression， such as phlegm， hematoma， stagnation， deficiency， hypertension duration， gender， arterial stiffness index （ASI）， uric acid to high-density lipoprotein cholesterol ratio （UHR）， and glycosylated hemoglobin （HbA1c）. After comparison from multiple dimensions， the light gradient boosting machine （LightGBM） was the best model， achieving area under the curve （AUC） of 0.918 （95% confidence interval （CI）： 0.890-0.945） in the training dataset， 0.885 （95%CI： 0.820-0.951） in the internal validation dataset， and 0.897 （95%CI： 0.818-0.975） in the external validation dataset. Calibration curves indicated good consistency in the predicted probabilities， while decision curve analysis showed clinical benefit when threshold probabilities were less than 90%. SHAP importance rankings were stagnation， deficiency， hematoma， HbA1c， gender， phlegm， hypertension duration， ASI， and UHR. When applied to the patients with borderline lesions， the diagnostic model achieved an AUC of 0.783 （95%CI： 0.637-0.930）， with 73% of patients with actual severe stenosis getting benefit. ConclusionGuided by clinical value， the diagnostic model integrating traditional Chinese and Western medicine established in this study demonstrates favorable performance， providing a basis for clinical diagnosis， treatment， and decision-making in patients with CKM.

[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Ribosomal protein(RP)is an important part of ribosome,which is very important for the assembly and function of ribosome.Recent studies have shown that RP is closely related to the processes of growth,senescence,apoptosis,invasion and drug resistance of tumor cells.The drug resistance of tumors is one of the main reasons for the low cure rate of tumors.RP can affect the drug resistance of tumor cells through a variety of mechanisms,such as changes in signal pathway,epithelial-mesenchymal transformation,cancer stem cells and tumor microenvironment,resulting in a poor prognosis of cancer patients.Ribosome tar-geting therapy is a promising method for the treatment of cancer patients.This review summarizes the mecha-nism of RP and many kinds of cancer drug resistance,provides new ideas for elucidating the mechanism of tumor drug resistance,and then provides new strategies for clinical prevention and reduction of tumor drug re-sistance.

ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 （STAT1）/interferon regulatory factor 3 （IRF3） signaling pathway in a pneumonia model induced by lipopolysaccharide （LPS） and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group， and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling， the rats were randomly divided into the model group， dexamethasone group （0.5 mg·kg^-1）， and Yifei Jianpi prescription high-dose （12 mg·kg^-1）， medium-dose （6 mg·kg^-1）， and low-dose （3 mg·kg^-1） groups， with 10 rats in each group. Treatment was administered once daily， and the normal control and model groups received the same volume of normal saline. After 14 days， flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of immunoglobulin G （IgG）， immunoglobulin A （IgA）， immunoglobulin M （IgM）， and the content of tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in alveolar lavage fluid （BALF）. Hematoxylin-eosin （HE） staining was used to observe lung tissue pathology and score the damage. Thymus weight， spleen weight， and wet-to-dry weight ratio （W/D） were recorded. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT1， IRF3， IL-6， and interferon-alpha （IFN-α） in lung tissues， while Western blot was performed to assess the protein expression of STAT1， IRF3， IL-6， and IFN-α. ResultsCompared with the normal control group， the model group showed significantly increased proportion of B lymphocytes in peripheral blood， decreased proportions of NK cells and CD4⁺/CD8⁺ （P<0.05， P<0.01）， decreased serum levels of IgG and IgA， significantly increased IgM levels （P<0.01）， significantly elevated content of TNF-α， IL-6， and IL-8 in BALF， and significantly decreased IL-10 levels （P<0.01）. Lung tissue damage was evident， with significant increases in thymus and spleen weights and a higher W/D ratio （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly upregulated （P<0.05，P<0.01）. Compared with the model group， the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood， increased proportions of NK cells and CD4⁺/CD8⁺ ratios （P<0.05， P<0.01）， significantly increased serum levels of IgG and IgA， significantly decreased IgM levels （P<0.05， P<0.01）， significantly reduced levels of TNF-α， IL-6， and IL-8 in BALF， and significantly increased IL-10 levels （P<0.01）. Lung tissue damage was alleviated， thymus and spleen weights were significantly reduced， and the W/D ratio was markedly decreased （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly downregulated （P<0.05， P<0.01）. ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.

Objective:To evaluate the effects of exercise interventions on fatigue, quality of life and physical function in head and neck cancer patients receiving radiotherapy, chemotherapy and simultaneous radiochemotherapy.Methods:Embase, Web of Science, PubMed, Cochrane Library, Wanfang Database and CNKI, databases were searched with the timeframe from the establishment of the database to April 2024. Two researchers independently screened the literature, extracted information, assessed the quality of literature using the Physiotherapy Evidence Database (PEDro) scale, and statistically analyzed using RevMan 5.4 software. The main outcome indexes included cancer-related fatigue, 6 min walking distance (6MWD), body mass index (BMI) and fat-free mass.Results:A total of 12 articles involving 710 patients were included. PEDro scale scores were ranged from 5 to 8. Meta-analysis showed that exercise interventions relieved cancer-related fatigue [standard mean difference (SMD)=-0.90, 95% CI=-1.33 to -0.48, P<0.001], prolonged 6MWD (SMD=0.84, 95% CI=0.05 to 1.62, P=0.040), improved body composition, reduced BMI (SMD=-0.36, 95% CI=-0.66 to -0.70, P=0.020), and had no statistical significance for the increase of fat-free mass (SMD=0.32, 95% CI=-0.11 to 0.74, P=0.130). Subgroup analyses showed that taking aerobic combined with resistance training (SMD=-1.12, 95% CI=-1.46 to -0.79, I2=0%) and stretching (SMD=-0.90, 95% CI=-1.56 to -0.25, I2=75%) were more effective in relieving fatigue, aerobic combined with resistance training interventions (SMD=1.23, 95% CI= 0.28 to 2.18, I2=89%) was the most effective in extending the 6MWD. Patients receiving radiochemotherapy (SMD=-1.34, 95%CI=-1.67 to -1.01, I2=47%) and chemotherapy (SMD=-1.12, 95% CI=-1.80 to -0.45) showed more significant improvement in relieving cancer-related fatigue after exercise interventions. Those receiving radiochemotherapy (SMD=1.14, 95% CI=0.81 to 1.48, I2=0%) and chemotherapy (SMD=2.62, 95% CI=1.98 to 3.25) showed even better results in prolonging 6MWD after exercise interventions. Conclusion:Exercise intervention has a significant improvement effect on alleviating cancer-related fatigue, prolonging 6MWD, improving the quality of life and reducing BMI in head and neck cancer patients.

[Objective]To introduce Director CAO Yuxia's experience in treating congenital preauricular fistula infection and abscess with SHI's thick fire needle based on the thought of"treating fire depression with effusion".[Methods]By following the clinical works and case collation,the basic pathomechanism of congenital preauricular fistula infection and abscess was elaborated,and the innovative use of SHI's thick fire needle based on the therapeutic principle of"treating fire depression with effusion"to implement the"burnt needle robbing and stabbing"method was analyzed,and Director CAO's clinical experience in treating this disease by using SHI's thick fire needle and robbing stabbing method based on the therapeutic principle of"treating fire depression with effusion"was summarized,and a medical case was presented to support it.[Results]Director CAO believes that the disease was caused by the accumulation of heat and the decay into pus.The treatment should be based on the theory of"treating fire depression with effusion".For the first time,she proposes and adopts one of the new nine needles,SHI's thick fire needle,to quickly stab and eliminate pus,which can obtain the effect of"discharging heat,expelling pus,eliminating pathogens and stopping pain".In the medical case cited,the patient was suffered from this disease,combining the tongue and pulse with symptoms,he was identified as the syndrome of the accumulation of fire-heat toxin.Therefore,the key treatment principle was to eliminate pathogens and expel pus,relieve heat and resolve toxin,and after once fire needle treatment,good effect was obtained.[Conclusion]Director CAO treats congenital preauricular fistula infection and abscess,focusing on the"treating fire depression with effusion"principle,taking the fire and heat nature of fire needle and exerting the effect of"opening the way to eliminate pathogens,and expelling heat with heat",and achieves better clinical efficacy.The experience can provide ideas for the treatment of fire-heat and toxicity-containing diseases,which is worthy of clinical reference.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To explore the genetic basis for a girl with primary microcephaly and growth retardation.Methods:A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).Results:DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. Conclusion:Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.