The concept of holism is the core idea of traditional Chinese medicine （TCM）. Various organs and tissues coordinate with each other to maintain the body's life activities， with a close and mutual influence between the spleen， stomach， and the central nervous system （brain）. The gut-brain axis plays an important bridging role between the digestive system and the central nervous system， achieving bidirectional information exchange between the brain and the gastrointestinal tract through complex neuroendocrine and immune mechanisms. The theory of cross-organ interaction involves the mutual influence， coordination， and integration between different organs and systems； multimodality， on the other hand， utilizes multiple sensory modalities， such as vision， hearing， and touch， to convey information. By combining TCM theory with the gut-brain axis theory， a cross-organ multimodal characterization system is established to explore its mechanism and application value in refractory diseases such as functional gastrointestinal disorders， precancerous gastrointestinal diseases， Alzheimer's disease， Parkinson's syndrome， type 2 diabetes， and depression.

Lung cancer （LC） is a significant global public health issue， with both its incidence and mortality rates ranking among the highest worldwide. The age-standardized incidence and mortality rates are increasing annually， posing a serious threat to the life and health of LC patients. Radical surgical resection is the primary treatment for malignant lung tumors. However， postoperative multidimensional functional impairments， including respiratory， mucosal， and psychological functions， are common. These impairments not only reduce patients' quality of life and affect their treatment tolerance and duration， but also negatively correlate with prognosis， facilitating disease recurrence and metastasis. At present， postoperative functional dysfunction after LC surgery remains a key clinical challenge that urgently needs to be addressed. There is a lack of standardized and regulated postoperative rehabilitation treatment management and traditional Chinese medicine （TCM） differentiation and treatment strategies for LC. Focusing on the core underlying pathogenesis of "Qi sinking" after LC surgery， and guided by the classical TCM theory of "lungs governing Qi"， this study， based on the core concept of the "five perspectives on treatment" theory， innovatively proposes the respiratory dysfunction as the core pathogenesis of "Qi sinking in the chest" during the rapid rehabilitation phase， mucosal dysfunction as the core pathogenesis of "Yin deficiency and Qi sinking" during the postoperative adjuvant treatment phase， and the psychological dysfunction as the core pathogenesis of "Qi sinking with emotional constraint" during the consolidation phase. Accordingly， stage-specific dynamic functional protection strategies are constructed. In the rapid rehabilitation phase， the strategy emphasizes tonifying Qi and uplifting sinking Qi， with differentiation and treatment based on the principle of ''descending before ascending''. In the adjuvant treatment phase， the approach focuses on nourishing Yin and uplifting Qi， with prescription combinations that integrate unblocking and tonification. In the consolidation phase， the strategy aims to resolve constraint and uplift Qi， with clinical treatment emphasizing a combination of dynamic and static methods. At each stage of functional rehabilitation， clinical differentiation and treatment should support healthy Qi and eliminate pathogenic factors simultaneously. This study is the first to propose the concept of postoperative functional protection in TCM， offering a new approach for TCM differentiation and treatment in the full-cycle， stage-based， and dynamic protection of postoperative function in LC patients. It is expected to contribute to the construction and development of an integrated TCM-Western medicine comprehensive program for cancer prevention and treatment in China.

OBJECTIVE: To discuss the elbow skin fold extension line in Kirschner wire internal fixation of extended supracondylar humeral fractures in children. METHODS: The clinical data of 58 children with extended supracondylar fractures of the humerus who met the selection criteria between August 2021 and July 2024 were retrospectively analyzed. In 28 cases, needle placement of medial epicondyle of humerus was performed with the assistance of the elbow skin fold extension line (study group), and 30 cases were assisted by routine touch of the medial epicondyle of the humerus (control group). There was no significant difference in baseline data such as gender, age, side, cause of injury, Gartland type, Kirschner wire configuration, and time from injury to operation between the two groups ( P>0.05). The closed reduction rate, total operation time, time of medial humeral condyle pin placement, fluoroscopy times during medial pin placement, rate of one-time determination of medial entry point, ulnar nerve injury incidence, and fracture healing time were recorded and compared between the two groups. At the same time, the closed reduction rate of patients with the time from injury to operation ≤24 hours and >24 hours was compared. The elbow function was evaluated by Mayo elbow function score. RESULTS: The closed reduction rate of the study group was significantly higher than that of the control group ( P<0.05). Among all patients, the closed reduction rate of patients with the time from injury to operation ≤24 hours [73.3% (22/30)] was significantly higher than that of patients >24 hours [42.9% (12/28)] ( χ ²=5.545, P=0.019). The total operation time, medial needle placement time, and fluoroscopy times in the study group were significantly less than those in the control group, and the one-time determination rate of medial needle entry point in the study group was significantly higher than that in the control group ( P<0.05). There were 4 cases of ulnar nerve injury in the control group, and no ulnar nerve injury in the study group, but there was no significant difference in the incidence of ulnar nerve injury between the two groups ( P>0.05). All patients were followed up 6-12 months (mean, 8 months). There was no bone nonunion in both groups, and the fracture healing time of the study group was significantly shorter than that of the control group ( P<0.05). Volkmann ischemic contracture, heterotopic ossification, myositis ossificans, and premature epiphyseal closure were not observed after operation. No complications such as loosening or fracture of Kirschner wire occurred. At last follow-up, the Mayo elbow joint function score was used to evaluate function, and there was no significant difference between the two groups ( P>0.05). CONCLUSION In the treatment of extended supracondylar fractures of the humerus in children, the elbow skin fold extension line can help to quickly locate the medial epicondyle of the humerus, quickly insert Kirschner wire, and reduce the operation time and trauma.
Humans ; Humeral Fractures/surgery* ; Bone Wires ; Male ; Female ; Fracture Fixation, Internal/instrumentation* ; Retrospective Studies ; Child ; Elbow Joint/physiopathology* ; Child, Preschool ; Treatment Outcome ; Fracture Healing ; Ulnar Nerve/injuries* ; Adolescent ; Range of Motion, Articular

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT). METHODS: Four pairs of WT and adjacent tissues were collected for high-throughput circRNA sequencing to identify the differentially expressed circular RNAs. RT-qPCR was used to verify the expression levels of the top 6 candidate circRNAs in the clinical samples. hsa_circ_0001900 was selected for analysis of its correlation with clinicopathological features and prognosis in 34 patients with WT. Sanger sequencing and RNase R digestion experiments were used to verify the cycling site and structural stability of hsa_circ_0001900 molecule. RESULTS: A total of 23 978 circular RNA molecules were identified in WT tissues by high-throughput circular RNA sequencing, and among them 614 were differentially expressed in WT. hsa_circ_0001900 showed the highest expression level among the differentially expressed circRNAs, which was consistent with the findings in clinical tumor samples and the sequencing results. Correlation analysis showed that hsa_circ_0001900 expression level was positively correlated with WT volume, and the children with high hsa_circ_0001900 expression had a lowered recurrence-free survival rate. The results of Sanger sequencing verified the circular splice site sequence of the molecule, and Rnase R digestion assay confirmed its stable covalent structure. CONCLUSIONS This study presents a comprehensive expression profile of circular RNAs in WT, and the expression level of hsa_circ_0001900 is related to the size of WT and the patients' prognosis, suggesting its possible role as a key driving gene in WT progression.
Humans ; RNA, Circular ; Wilms Tumor/pathology* ; Prognosis ; High-Throughput Nucleotide Sequencing ; Kidney Neoplasms/genetics* ; Sequence Analysis, RNA ; Male ; Female

Objective To investigate the expression of Thymosinβ10(TMSB10)in gastric cancer and its molecular mechanism in promoting the progression of gastric cancer.Methods We collected pathological sections of 70 patients with gastric cancer in our hospital,detected expression of TMSB10 in gastric adenocarcinoma by immunohistochemistry,and analyzed its prognostic effect.In order to study the mechanism of action,the effects of TMSB10 on the proliferation and glycolysis of gastric cancer cells and its related mechanism were observed by trans-fection technique,CCK8 test,EDU assay,Transwell assay,scratch test,glycolysis assay and Western blot.Results Immunohistochemistry showed that TMSB10 was highly expressed in gastric cancer,while the expression level of TMSB10 was correlated with tumor size(P=0.032),TNM stage(P=0.002)and distant metastasis.In the mechanism study,we found that overexpression of TMSB10 promoted the proliferation,invasion,migration and glycolytic phenotype of gastric cancer cells through in vitro CCK-8 test,EDU assay,Transwel assay and glycolysis assay,and vice versa.Western blot results showed that overexpression of TMSB10 may regulate the occurrence of gastric cancer through up-regulation of the AMPK/mTOR signaling pathway.Conclusions TMSB10 promotes the proliferation,invasion,migration and glycolysis gastric cancer through the AMPK/mTOR signaling pathway.

Objective:Study on the correlation between the active components of Salviea Miltiorrhizae Radix et Rhizoma screened by high-throughput sequencing and the regulation of lncRNA-mRNA in human lung adenocarcinoma A549 cells.Methods:A549 cells were cultured, and the IC 50 dose of cryptotanshinone and tanshinone ⅡA was confirmed according to the cell proliferation experiment. A549 cells were randomly divided into blank control group, cryptotanshinone group, and tanshinone IIA group using a random number table method. After 24 hours of intervention, the cell cycle was detected by flow cytometry. High-throughput sequencing technique was used to detect the expressions of lncRNA and mRNA in A549 cells in intervention group and non-intervention group. By analyzing the expression profiles of differential genes related to cryptotanshinone and tanshinone ⅡA, the obtained differential genes were analyzed by GO and KEGG. Results:The cell cycle results showed that the proportion of G0/G1 phase cells in cryptotanshinone and Tanshinone ⅡA was increased ( P<0.01), the proportion of S phase cells was decreased ( P<0.01), and the proportion of G2/M phase cells in cryptotanshinone was decreased ( P<0.01). The results of high-throughput screening showed that cryptotanshinone could up-regulate 4 698 lncRNA, down-regulate 1 557 lncRNA, up-regulate 4 810 mRNA and down-regulate 5 644 mRNA. Tanshinone ⅡA could up-regulate 1 348 lncRNA, down-regulate 1 299 lncRNA, up-regulate 4646 mRNA and down-regulate 4 741 mRNA. The function and pathway enrichment analysis of differential lncRNA and mRNA showed that the differentially expressed genes of cryptotanshinone and tanshinone ⅡA were mainly related to cell cycle, autophagy, AMPK signaling pathway, FoxO signaling pathway and EGFR signaling pathway. GAS5 may be one of the targets for the inhibitory effects of cryptotanshinone and tanshinone ⅡA. Conclusion:Cryptotanshinone and tanshinone ⅡA have certain inhibitory effects on A549 cells, and there are differentially expressed genes of lncRNA-mRNA, which are closely related to cell cycle and signal pathway.

AIM:To investigate the effect of doublecortin-like kinase 1(DCLK1)on the biological properties of gastric cancer stem cells,and to explore its possible mechanism.METHODS:Serum-free suspension culture of gastric cancer stem cells and targeted inhibition of DCLK1 activity in gastric cancer stem cells with DCLK1 inhibitor DCLK1-IN-1 were performed.The expression levels of DCLK1,stemness-related proteins(SOX2 and OCT4),proliferation-related pro-teins(cyclin D1 and c-MYC),drug resistance-related proteins(ABCG2 and TOP2A),epithelial-mesenchymal transition-related proteins(E-cadherin,vimentin and Snail),and PI3K/AKT/mTOR signaling pathway-related proteins in gastric cancer stem cells were examined by Western blot.The effects of DCLK1 on viability and drug resistance of gastric cancer stem cells were determined by CCK-8 assay,and the effects of DCLK1 on self-renewal of gastric cancer stem cells were de-termined by methylcellulose spheroid-forming assay.Wound-healing and Transwell assays were performed to assess the ef-fect of DCLK1 on the migration and invasion of gastric cancer stem cells.RESULTS:The expression levels of DCLK1 and stemness-related proteins SOX2 and OCT4 in gastric cancer stem cells were significantly higher than those in parental cells(P＜0.01).The proliferation,drug resistance,migration and invasion of gastric cancer stem cells in DCLK1 inhibi-tion group were significantly lower than those in Sphere cell group(P＜0.01).The expression levels of proliferation-related proteins(c-MYC and cyclin D1)and drug resistance-related proteins(TOP2A and ABCG2)were down-regulated,the ex-pression of epithelial marker E-cadherin was up-regulated,the expression of mesenchymal markers vimentin and Snail was down-regulated,and the expression levels of PI3K/AKT/mTOR signaling pathway-related proteins and their phosphoryla-tion levels were reduced in DCLK1 inhibition group(P＜0.05).CONCLUSION:DCLK1 is highly expressed in gastric cancer stem cells,which may be involved in the proliferation,drug resistance and invasion of gastric cancer stem cells by regulating PI3K/AKT/mTOR signaling pathway.It suggests that DCLK1 can be used as a potential target for gastric cancer stem cells.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

Objective To explore the impact of high glucose(HG)intervention on immune escape of pancreatic cancer cells and its molecular mechanisms.Methods PANC-1 cells were treated with different concentrations of glucose(0,7.5,15,30 mmol/L)for 24 h to establish high glucose intervention PANC-1 cells.miR-429 mimics and its negative control(mimics NC)were transfected into PANC-1 cells,which were divided into control group,HG group,HG+mimics NC group,HG+mimics group,HG+mimics+oe-NC group,and HG+mimics+oe-ZEB1 group.Flow cytometry was utilized to measure the expression level of cell surface molecule PD-L1;qRT-PCR was used to detect the expression levels of miR-429 and ZEB1 mRNA in cells;Western blot was used to detect the ex-pression level of ZEB1 protein in cells.The above-mentioned PANC-1 cells from each group were co-cultured with CD8+T cells to establish a co-culture system,and CCK-8 was used to assess cell proliferation activity;apoptosis levels of cells were measured using flow cytometry;lactate dehydrogenase(LDH)release assay was used to detect the killing effect of CD8+T cells on PANC-1 cells;dual-luciferase reporter system was used to validate the target-regulatory relationship between mi R-429 and ZEB1.Results HG could promote the expression of cell surface mole-cules PD-L1 and ZEB1 in PANC-1 cells(P＜0.05),inhibit the expression of miR-429,and exhibit concentration dependence.Overexpression of miR-429 could significantly suppress the expression of cell surface molecule PD-L1 induced by HG in PANC-1 cells,while overexpression of ZEB1 could reverse the inhibitory effect of miR-429 over-expression on the expression of cell surface molecule PD-L1 induced by HG.After establishing a co-culture system with CD8+T cells,compared with the control group,the proliferation activity of PANC-1 cells in the HG group sig-nificantly increased,and the apoptosis rate and cytotoxicity significantly decreased(P＜0.05).Compared with the HG+mimics NC group,the proliferation activity of PANC-1 cells in the HG+mimics group significantly decreased,and the apoptosis level and cytotoxicity significantly increased(P＜0.05).Compared with the HG+mimics group,the proliferation activity of PANC-1 cells in the HG+mimics+oe-ZEB1 group significantly increased,and the apop-tosis rate and cytotoxicity significantly decreased(P＜0.05).Dual luciferase reporter gene assay confirmed that miR-429 negatively regulated ZEB1.Conclusion High glucose promotes immune escape of PANC-1 cells by down-regulating the expression level of miR-429,negatively regulating the expression of ZEB1 mRNA,and increasing the expression level of cell surface molecule PD-L1 in PANC-1 cells.