This paper summarizes Professor WANG Yaoxian's experience in treating diabetic kidney disease （DKD） from the perspective of spleen and stomach based on the "internal heat leading to concretions" theory. It is considered that internal heat leading to concretions constitutes the core pathogenesis of DKD， with the spleen and stomach serving as the source of internal heat； therefore， treatment should be based on regulating the spleen and stomach. In the early stage of DKD， dysfunction of the spleen and stomach leads to the initial generation of internal heat. Common syndrome patterns include gastrointestinal heat accumulation and constrained heat in the liver and stomach， for which modified Gegen Qinlian Decoction （葛根芩连汤） can be used to clear heat bind while modified Dachaihu Decoction （大柴胡汤） is used to clear stomach and soothe liver， respectively. In the middle stage of DKD， weakness of the spleen and stomach results in the initial formation of concretions and conglomerations. Common patterns include spleen deficiency with prevalence of dampness and deficiency of both the spleen and kidney. Treatment emphasizes strengthening the spleen and resolving dampness， raising yang and boosting the stomach with modified Shengyang Yiwei Decoction （升阳益胃汤）， or supplementing spleen and boosting kidney， dissipating bind and dispe-ring concretions with modified Shenqi Dihuang Decoction （参芪地黄汤）， respectively. In the late stage of DKD， it is characterized by spleen and stomach depletion， and rampant accumulation of turbidity and toxin， and the common syndrome patterns are damp-turbidity obstruction in the middle jiao （焦） and spleen-kidney yang deficiency. Treatment aims to remove turbidity and harmonize the stomach， or to warm the kidney and strengthen the spleen while elimina-ting turbidity， using modified Dahuang Gancao Decoction（大黄甘草汤） and Jupi Zhuru Decoction （橘皮竹茹汤） or modified Baoyuan Decoction （保元汤） and Lizhong Decoction （理中汤）， respectively. In clinical practice， appropriate formulas and medications are flexibly selected according to specific syndromes.

Gastric cancer （GC） has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present， the treatment plans are optimized mainly in terms of surgery， radiotherapy， and intervention， while the endpoints of clinical trials， such as patients' overall survival， progression-free survival， and disease-free survival， are still unsatisfactory. Therefore， effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s， Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then， the abnormal metabolic network inside tumor cells has gradually entered into researchers' view， and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years， traditional Chinese medicine （TCM） is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore， linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically， while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer （PLGC） in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor （HIF）-1α， cancer-Myc （c-Myc）， apolipoprotein E （APOE） and pyruvate kinase M2 （PKM2） were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized， with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.

Gastric cancer （GC） has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present， the treatment plans are optimized mainly in terms of surgery， radiotherapy， and intervention， while the endpoints of clinical trials， such as patients' overall survival， progression-free survival， and disease-free survival， are still unsatisfactory. Therefore， effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s， Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then， the abnormal metabolic network inside tumor cells has gradually entered into researchers' view， and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years， traditional Chinese medicine （TCM） is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore， linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically， while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer （PLGC） in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor （HIF）-1α， cancer-Myc （c-Myc）， apolipoprotein E （APOE） and pyruvate kinase M2 （PKM2） were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized， with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.

Repeated transcranial magnetic stimulation (rTMS) is one of the commonly used brain stimulation techniques. In order to investigate the effects of rTMS on the excitability of different types of neurons, this study is conducted to investigate the effects of rTMS on the cognitive function of mice and the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons from the perspective of electrophysiology. In this study, mice were randomly divided into glutaminergic control group, glutaminergic magnetic stimulation group, gamma-aminobutyric acid energy control group, and gamma-aminobutyric acid magnetic stimulation group. The four groups of mice were injected with adeno-associated virus to label two types of neurons and were implanted optical fiber. The stimulation groups received 14 days of stimulation and the control groups received 14 days of pseudo-stimulation. The fluorescence intensity of calcium ions in mice was recorded by optical fiber system. Behavioral experiments were conducted to explore the changes of cognitive function in mice. The patch-clamp system was used to detect the changes of neuronal action potential characteristics. The results showed that rTMS significantly improved the cognitive function of mice, increased the amplitude of calcium fluorescence of glutamergic neurons and gamma-aminobutyric neurons in the hippocampus, and enhanced the action potential related indexes of glutamergic neurons and gamma-aminobutyric neurons. The results suggest that rTMS can improve the cognitive ability of mice by enhancing the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons.
Animals ; Mice ; Hippocampus/cytology* ; Transcranial Magnetic Stimulation ; Neurons/physiology* ; Male ; Cognition/physiology* ; gamma-Aminobutyric Acid/metabolism* ; Action Potentials/physiology*

OBJECTIVES: Lymph node metastasis in papillary thyroid cancer (PTC) is closely associated with tumor recurrence and patient survival. However, current technologies have limited sensitivity in detecting occult cervical lymph node metastases. Identifying accurate molecular markers for predicting PTC metastasis holds significant clinical value. This study aims to analyze WNT10A expression in PTC and its clinical significance, and to explore the role of WNT10A gene knockdown in PTC cell proliferation, invasion, and metastasis. METHODS: The expression of WNT10A in thyroid carcinoma was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and University of Alabama at Birminghara Cancer data analysis Portal (UALCAN) databases. Real-time RT-PCR was used to measure WNT10A mRNA levels in tumor and adjacent normal tissues from 32 PTC patients. Immunohistochemistry was conducted on 158 PTC specimens to assess WNT10A protein expression and its correlation with clinicopathological features. In vitro experiments were performed using K1 and TPC-1 cell lines. Cell proliferation was assessed using the Celigo system and methyl thiazolyl tetrazolium (MTT) assays; apoptosis was measured via flow cytometry; invasion and metastasis were evaluated using scratch and Transwell assays. A xenograft model was established in nude mice to observe tumor growth, and tumor weight and volume were compared between cell lines. Differentially expressed genes regulated by WNT10A were identified via mRNA sequencing, followed by Gene Ontology (GO) and ingenuity pathway analysis (IPA). Real-time PCR and Western blotting were used to validate the effects of WNT10A on key downstream mRNA and protein in the Tec kinase signaling pathway. RESULTS: WNT10A mRNA expression was significantly higher in thyroid cancer tissues compared to adjacent normal tissues according to GEPIA and UALCAN (both P<0.01). The real-time RT-PCR result showed that WNT10A mRNA expression in PTC tissues was high than that in adjacent tissues (P<0.01). Immunohistochemistry revealed significantly higher WNT10A protein expression in PTC tissues compared to adjacent tissues (P<0.01), and its expression correlated with multifocality, extrathyroidal invasion, and lymph node metastasis. WNT10A knockdown significantly inhibited proliferation, altered cell cycle distribution, and increased apoptosis in K1 and TPC-1 cells (all P<0.01). WNT10A silencing also reduced migration and invasion abilities in both cell lines. In vivo, WNT10A knockdown in TPC-1 cells suppressed tumor formation in nude mice. GO analysis and IPA suggested that the Tec kinase signaling pathway was a key downstream target of WNT10A. RT-PCR and Western blotting confirmed that WNT10A knockdown downregulated the expression of key genes (STAT3, MAPK8, TNFRSF21, and AKT2) in this pathway. CONCLUSIONS WNT10A is highly expressed in PTC and is associated with tumor proliferation, invasion, and metastasis. Its tumor-promoting effects may be mediated through suppression of the Tec kinase signaling pathway.
Humans ; Cell Proliferation ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/metabolism* ; Animals ; Wnt Proteins/metabolism* ; Neoplasm Invasiveness ; Mice ; Cell Line, Tumor ; Female ; Male ; Mice, Nude ; Apoptosis ; Lymphatic Metastasis ; Middle Aged ; Cell Movement ; Adult

OBJECTIVES: Increasing detection of low-risk papillary thyroid carcinoma (PTC) is associated with overdiagnosis and overtreatment. N6-methyladenosine (m⁶A)-mediated microRNA (miRNA) dysregulation plays a critical role in tumor metastasis and progression. However, the functional role of m⁶A-miRNAs in PTC remains unclear. This study aims to elucidate the regulatory mechanism of m⁶A-miR-139-5p expression in PTC, determine its association with PTC metastasis, and evaluate its potential as a diagnostic biomarker for PTC metastasis, thereby providing experimental evidence for precision diagnosis and therapy. METHODS: Expression profiles of m⁶A-miRNAs were compared between the The Cancer Genome Atlas (TCGA) and GSE130512 cohorts to identify metastasis-associated candidates. Clinical specimens from 13 metastasis and 18 non-metastasis PTC patients were analyzed to assess m⁶A-miR-139-5p expression and its correlation with metastasis. Functional experiments were conducted to investigate the effect of fat mass and obesity-associated protein (FTO) on pri-miR-139 methylation and processing, clarifying its regulatory role in miR-139-5p expression. In TPC-1 cells, MTT assays were performed to evaluate whether miR-139-5p overexpression could counteract FTO-mediated cell proliferation. Transwell invasion assays were used to determine the impact of miR-139-5p on PTC cell invasion, exploring whether it functions through the ZEB1/E-cadherin axis. RESULTS: By comparing TCGA and GSE130512 cohorts, it was found that circulating m⁶A-miR-139-5p could serve as a biological indicator for detecting PTC metastasis. Detection of 13 metastatic and 18 non-metastatic clinical specimens showed that FTO inhibited the processing of pri-miR-139 by reducing its methylation level, leading to the dysregulation of miR-139-5p in PTC (P<0.05). In TPC-1 cells, MTT assay showed that overexpression of miR-139-5p could partially reverse FTO overexpression-mediated cell proliferation (P<0.05). In addition, miR-139-5p inhibited the invasive ability of PTC cells by targeting the ZEB1/E-cadherin axis, while FTO overexpression could partially weaken this inhibitory effect. CONCLUSIONS Circulating miR-139-5p can be a potential marker for evaluating PTC metastasis. FTO affects the expression and function of miR-139-5p by regulating m⁶A modification of pri-miR-139, but its clinical value needs further verification.
Humans ; MicroRNAs/metabolism* ; Thyroid Cancer, Papillary/metabolism* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism* ; Thyroid Neoplasms/metabolism* ; Cell Line, Tumor ; Neoplasm Metastasis ; Adenosine/genetics* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Cadherins/metabolism* ; Cell Proliferation ; Zinc Finger E-box-Binding Homeobox 1/genetics*

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Objective To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule,ophiopogonin,on enhancing the immune response of a subunit vaccine with the receptor-binding domain(RBD)of coronavirus spike protein as the antigen.Methods CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D'(OPD')on bone marrow-derived dendritic cells(BMDCs).Female Balb/c mice were randomly divided into RBD,RBD/OPD',RBD/Alum,and control groups.The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse,and immunization was carried out according to the intramuscular injection immunization procedure on days 0,21,and 42.The titers of specific IgG and its subtype antibodies were detected by ELISA.The cytokine levels in the supernatant of splenocytes were detected using ELISA.The number of splenocytes secreting IFN-γ was detected by ELISpot.Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs.The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry.The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.Results When the concentration of OPD'was less than 5 μg/mL,the survival rate of BMDCs was 100%.After a single intramuscular injection in mice,except for a slight decrease in body weight,the other biochemical indicators were within corresponding normal ranges.After intramuscular injection immunization of the vaccine,the titers of serum-specific IgG,IgG1,and IgG2a in the RBD/OPD'group were significantly higher than those in the RBD group(P<0.05).Compared with the RBD group,the RBD/OPD'group induced a high-level Th1 cell immune response of IL-1β,TNF-α,and IFN-γ(P<0.01)and had more lymphocytes secreting IFN-γ(P<0.001).Laser confocal microscopy displayed that BMDCs took up more antigens after OPD'treatment,which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate(P<0.01).Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD'group than the RBD group,suggesting that OPD'may activate the PPAR signaling pathway to exert its adjuvant effect.Conclusion OPD'effectively enhances the immune response of the RBD subunit vaccine,and its action mechanism may be related to the activation of the PPAR signaling pathway.

Objective To analyze the focus and shortcomings of provincial-level digitalization policies for Traditional Chinese Medicine(TCM),and to provide references for improving relevant policies.Methods A three-dimensional analytical framework—comprising"digitalization policy coverage-economic level-TCM development level"was constructed to quantitatively analyze provincial TCM digitalization policy documents issued over the past five years.Results A total of 750 policy items were extracted.Among them,digital applications accounted for the largest proportion(58.13%),while digital governance(26.53%)and digital infrastructure(15.33%)were relatively less emphasized.Two-dimensional analysis revealed that 48.4%of provinces had both low economic levels and low digital policy coverage,while 45.2%had both low TCM development levels and low policy coverage.Multiple linear regression result showed a positive association between digitalization policies coverage and TCM development level,with no significant correlation to economic level.Conclusion Most provincial TCM digitalization policies prioritize application while neglecting governance and infrastructure.There is a need to strengthen talent development and standard system construction,The extent of policy coverage is closely related to the level of TCM development,indicating the need to enhance top-level policy design,Provincial policies vary in focus and can be categorized into three types:industry-driven,technology-driven,and demand-driven.

Professor Song Airen is a famous contemporary traditional Chinese medicine(TCM)scientist and educator,and also a master of typhoid fever and warm disease,who is passionate about TCM education.He advocates that TCM teaching should be taught with rules and regulations as well as principles and flexibility,keep pace with the times,and"respect classics and respect practical learning".He opposes unrealistic empty talk,the dispute between cold and warm diseases;advocate the integration of cold and warm diseases;carry forward the treatment of summer heat syndrome.He also advocates expelling evil and protecting the healthy qi;the key to exogenous seasonal diseases lies in Yangming and Shaoyin meridian syndromes;the six meridians and Wei Qi Ying Xue are involved together and should be treated according to the syndromes;treating various diseases requires the spleen and stomach to work together,and the five internal organs to work together.Professor Song Airen attaches importance to tonifying the kidney and replenishing yin;takes both the heart and kidney into consideration;prioritizes the analysis of symptoms and root causes,with a focus on distinguishing between deficiency and excess,and a foundation in balancing yin and yang.