OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic liver disease closely related to metabolic dysfunction. Its global prevalence is increasing year by year and shows a trend toward younger onset. It is closely associated with cardiovascular and cerebrovascular diseases， chronic kidney disease， and extrahepatic malignant tumors， and has become a major public health problem affecting the health of the Chinese population. At present， the treatment of MAFLD mainly focuses on lifestyle intervention. When metabolic cardiovascular risk factors and liver injury are present， pharmacological intervention is required. However， there is still no specific drug therapy for MAFLD. In recent years， many studies have found that the pathogenesis of MAFLD involves interactions among multiple factors， including insulin resistance， oxidative stress， endoplasmic reticulum stress， programmed cell death， immune dysregulation， inflammasomes， gut microbiota imbalance， and bile acid metabolism. Traditional Chinese medicine （TCM） has advantages in integrated regulation with multiple components and multiple targets， and shows significant efficacy in the treatment of MAFLD. Active components of Chinese medicinal herbs and Chinese medicine compound formulas exert definite therapeutic effects by regulating multiple signaling pathways to improve lipid metabolism disorders， inhibit inflammatory responses， and regulate the gut microbiota， thereby effectively improving clinical symptoms and delaying the occurrence and development of MAFLD. Therefore， strengthening research on the mechanisms of action of TCM in MAFLD is of crucial importance and significance for its treatment. This article summarizes the mechanisms by which Chinese medicine monomers and compound formulas intervene in MAFLD through the regulation of related signaling pathways， based on the retrieval and analysis of relevant literature from multiple databases， with the aim of providing theoretical support and a reference basis for the clinical application of TCM in the treatment of MAFLD.

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.

The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

BACKGROUND:Currently,exercise therapy is an effective non-pharmacological treatment for low back pain,and exercise therapy can maintain lumbar spine stabilization through mechanical-chemical coupling between bones and muscles,but there is no clear description of the research progress and optimal treatment protocols for exercise therapy to relieve chronic non-specific lower back pain through mechanical-chemical coupling. OBJECTIVE:To review the research progress related to the influence of paravertebral muscles on lumbar spine stabilization during exercise therapy through mechanical-chemical coupling,which in turn relieves chronic non-specific lower back pain,as well as the current optimal treatment protocols of exercise therapy for chronic non-specific lower back pain. METHODS:Literature searches were performed in WanFang database,CNKI,VIP,Web of Science,and PubMed database,with search terms of"chronic non-specific low back pain,lumbar spine stabilization,paravertebral muscles,exercise therapy"in Chinese and English.Relevant literature published from database inception to January 2024 was searched and 93 articles were included for final summarization. RESULTS AND CONCLUSION:Exercise therapy can act on the paravertebral muscles and bones through appropriate mechanical stimulation and produce corresponding changes.Exercise therapy is an important intervention for chronic non-specific lower back pain as it improves the quality of the paravertebral muscles,primarily through mechanical-chemical coupling,and thus maintains lumbar spine stabilization for better relief of chronic non-specific lower back pain.However,there are no clear reports on the exact effective protocols for exercise therapy to treat chronic non-specific lower back pain through lumbar spine stabilization.The development of an individualized exercise program is particularly important for the treatment and prognosis of chronic non-specific low back pain.Muscle mass and bone mass of the same individual are closely related,and imaging assessment of paravertebral muscle mass and quantity is important for disease detection and intervention.

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

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.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

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*

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.