The occurrence of diabetes mellitus （DM） is closely related to insulin resistance and islet β cell dysfunction. Modern studies have found that macrophages are widely present in the liver，fat，skeletal muscle，islets， and other tissues and organs. Macrophage M1/M2 polarization plays an important role in the occurrence and development of diabetes mellitus and its related complications by intervening in inflammatory response，improving insulin resistance，and promoting tissue repair. Most of the traditional Chinese medicines that regulate the activation and polarization of macrophages are Qi-replenishing and Yin-nourishing，heat-clearing， and detoxicating medicinal，which are consistent with the etiology and pathogenesis of diabetes and its related complications. Therefore，by summarizing the mechanisms between macrophage activation，polarization， and insulin resistance in various tissues，this paper reviewed traditional Chinese medicine and its effective components and compounds in improving diabetes mellitus and its related complications through multi-channel regulation of macrophage polarization and regulation of M1/M2 ratio，providing references for the future treatment of DM and its related complications with traditional Chinese medicine.

As a representative prescription of stagnated blood syndrome,Didang Decoction has the effect of breaking blood,removing blood stasis and purging heat.According to the pathogenesis characteristics of"blood stasis and heat accumulation",Didang Decoction has been widely used in the treatment of diabetes and its complications,cerebrovascular diseases,gynecology and andrology and other diseases.This article summarized the effects of factors such as drug compatibility,processing methods and decocting time on the chemical components of Didang Decoction,and concluded its pharmacological effects from the aspects of improving insulin resistance,antioxidation,regulating cell death,anti-inflammatory,anti-tumor,anti fibrosis,anticoagulation,reducing toxicity of Gelsemium elegans,regulating blood lipid metabolism,and improving microcirculation,providing references for the research and clinical application of Didang Decoction.

As a representative prescription of stagnated blood syndrome,Didang Decoction has the effect of breaking blood,removing blood stasis and purging heat.According to the pathogenesis characteristics of"blood stasis and heat accumulation",Didang Decoction has been widely used in the treatment of diabetes and its complications,cerebrovascular diseases,gynecology and andrology and other diseases.This article summarized the effects of factors such as drug compatibility,processing methods and decocting time on the chemical components of Didang Decoction,and concluded its pharmacological effects from the aspects of improving insulin resistance,antioxidation,regulating cell death,anti-inflammatory,anti-tumor,anti fibrosis,anticoagulation,reducing toxicity of Gelsemium elegans,regulating blood lipid metabolism,and improving microcirculation,providing references for the research and clinical application of Didang Decoction.

OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

The theory of "linkage between spleen and small intestine" has been put forward by doctors as early as the Ming dynasty. In traditional Chinese medicine， the spleen and small intestine cooperate and work together physiologically， and they are also closely related and interact with each other pathologically. The spleen governs transportation and transformation， which involves the function of the small intestine in transforming water and grain. The small intestine， governing the receiving and transformation of substances， depends on the normal transportation of the spleen. At the same time， it provides guarantee for the spleen to transform Qi and generate blood as well as ascend lucidity and descend turbidity. The dysfunction of spleen in transportation is closely related to the dysfunction of small intestine. The stability of intestinal microecology necessitates the normal functioning of the spleen. When the original balance of intestinal flora is disturbed， the spleen functioning will be affected. This study explored the pathogenesis and treatment of diabetes based on the physiological functions of the spleen and small intestine and the Western medicine targets of "nutrients-intestinal flora". According to modern medicine， nutrients are essential to maintain the normal physiological activities of the human body. Proper intake of nutrients can affect the absorption and metabolism of the human body for nutrients by regulating the composition and function of intestinal flora， so as to prevent the occurrence of diabetes. The imbalance of intestinal flora which harbors rich microorganisms may lead to the disturbance of energy metabolism and the dysfunction of the immune system， eventually leading to diabetes. As a metabolic disease， diabetes is closely related to the imbalance of intestinal flora and nutrient intake. Based on the theory of "linkage between spleen and small intestine"， this paper discusses the relationship between spleen and small intestine. Furthermore， this paper discusses the correlation between "spleen-small intestine" and "nutrients-intestinal flora" by reviewing the latest progress in modern medicine and clinical research， aiming to provide a theoretical basis and new ideas for the clinical prevention and treatment of type 2 diabetes mellitus.

Objective To explore the effects of Xin Jia Congrong Tusizi decoction on mitochondrial biosynthesis and mitochondrial function in ovarian granulosa cells.Methods We prepared the functional injury model of human ovarian granulosa cells KGN induced by triptolide.We divided the cells into control group,model group,Tiao jing Cuyun Pill group,Xin Jia Congrong Tusizi decoction group,SIRT1 inhibitor group and SIRT1 inhibitor+Xin Jia Congrong Tusizi decoction group.After 6 h incubation with triptolide to cause functional impairment of granulosa cells,SIRT1 inhibitor,blank serum and medicated serum were added for 48 h.Cell viability and apoptosis rate were assessed using CCK-8 and flow cytometry.Anti-Müllerian(AMH),follicle-stimulating hormone(FSH)and inhibin B(INHB)were detected by ELISA.ATP enzyme and MMP were used to detect by biochemical kit and JC-1 method.apoptosis rate and MMP were assessed using flow cytometry.The morphology,structure,quantity and activity changes of mitochondria were observed by electron microscope and fluorescence microscope.Western blot and PCR were used to detect the protein and mRNA expressions of SIRT1,p-SIRT1,PGC-1α,NRF1 and TFAM.Results Chinese patent medicine TiaojingCuyun Pill and bushen Yangxue Huoxue therapy compound Xin Jia Congrong Tusizi decoction augmented the activity of granulosa cells(P<0.05),decreased the apoptosis rate(P<0.05),increased ATP enzyme and MMP(P<0.05),improved mitochondrial morphological and structural damage,added the mtDNA level,the number and activity of mitochondria(P<0.01)and up-regulated and the protein and mRNA expressions of SIRT1,PGC-1α,NRF1,TFAM(P<0.05).Conclusion Xin Jia Congrong Tusizi decoction protected ovarian granulosa cells damage caused by triptolide.Its mechanism may related to improve mitochondrial dysfunction by regulating SIRT1/PGC-1α signaling pathway in order to promote the biosynthesis of new mitochondria.

Objective To investigate the effect of miR-2110 on the biological behaviors,such as cell proliferation,apoptosis,and metastasis,of lung adenocarcinoma(LUAD)cells by means of cell and animal experiments.Methods Bioinformatics websites,including ENCORI,TargetScan,miRTarBase,and Tarbase,were used to analyze the changes in the expression of miR-2110 in LUAD samples and to predict miR-2110 target.LUAD tissue samples and cells were collected and the changes in the expression of miR-2110 were verified through PCR technology.CCK-8 assay,clonogenic assay,Transwell assay,and flow cytometry were conducted to analyze alterations in the functions of LUAD cells.In addition,10 BALB/c female nude mice aged 6 to 8 weeks were randomly divided into 2 groups,and the effect of miR-2110 on LUAD was investigated by in vivo experiments.Results miR-2110 was significantly decreased in LUAD tissues and cells compared with the normal lung tissues.miR-2110 overexpression inhibited the proliferation and metastasis of LUAD cells and promoted the apoptosis of tumor cells(P＜0.05).Bioinformatics prediction and dual luciferase reporter gene assay results confirmed that miR-2110 could target and bind to CDT1.In addition,overexpression of CDT1 gene reversed the proliferation,metastasis,and apoptosis of miR-2110 compared with the miR-2110 overexpression group(P＜0.05).Nude mice in vivo experiments showed that miR-2110 overexpression significantly decreased the expression of Ki67,a tumor proliferation index,and vimentin and MMP9,two metastasis indices,compared with the control group.Conclusion miR-2110 can inhibit proliferation and metastasis of LUAD by targeting CDT1,providing a new rationale for the treatment of LUAD.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Objective To establish a quantitative polymerase chain reaction(PCR)method for the analysis of human-derived SRY DNA in mouse tissues,and to study the tissue distribution of human umbilical cord mesenchymal stem cells(HUCMSCs)in immunodeficient NOG mice after a single intravenous injection.Methods We established a quantitative PCR method for the analysis of human SRY DNA in mouse tissues,and validated the standard curve,linear range,accuracy,precision,and stability.Thirty-six NOG mice(18 male,18 female)were administered 3.5×107 HUCMSCs/kg by single intravenous injection.Six mice were then anesthetized and dissected after blood collection(EDTA anticoagulation)at 6,12,24,and 72 h,and at 1 and 2 weeks,respectively.DNA was extracted from lung,kidney,heart,liver,brain,spinal cord,stomach,small intestine,fat,skin,spleen,testis,uterus,and ovary tissues,and the distribution of HUCMSCs in each tissue was determined by the validated quantitative PCR method for detecting the human-derived SRY gene in mouse tissues.In addition,18 NOG mice(9 male,9 female)were divided into control(n = 6)and treatment groups(n = 12)injected intravenously with 0.9%sodium chloride and 3.5×107 cells/kg,respectively.Acute toxic reactions were observed during the administration period,and four animals were dissected at 72 h and at 2 and 4 weeks after administration to observe the gross organs.Mitochondrial protein expression was detected in paraffin sections of lung tissues by immunohistochemistry to analyze the colonization of HUCMSCs in lung tissues.Results The established RT-qPCR method for human-derived SRY DNA in mouse tissues met the validation criteria for each index.After a single intravenous injection in NOG mice,HUCMSCs were mainly distributed in the lungs and blood within 1 week after administration,with higher concentrations in lung tissues than in blood.The concentrations of HUCMSCs in lung tissue and blood remained relatively stable within 6～24 h and 6～72 h,respectively,and then decreased over time.The distribution of HUCMSCs in other tissues was not measured at all sampling points.The colonization result showed that HUCMSCs were detected in lungs 72 h after intravenous injection,but not at 2 and 4 weeks.No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs.Conclusions The above method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible.HUCMSCs were mainly distributed in lung and blood in NOG mice within 1 week after a single intravenous injection,and mainly colonized lung tissue at 72 h.A single intravenous administration of HUCMSCs has a good safety profile.

Hypovarianism diseases mainly include diminished ovarian reserve， premature ovarian insufficiency， and premature ovarian failure， which decreased female reproductive capacity due to various causes. Mitochondrial dysfunction in ovarian cells can interfere with the pathway of mitochondrial energy supply to germ cells and affect follicular development and egg quality. Therefore， the role of mitochondrial homeostasis in the pathogenesis of such diseases has gradually received attention. Traditional Chinese medicine （TCM） believes that the pathogenesis of hypovarianism diseases is deficiency of kidney Qi， essence and blood as well as stasis caused by deficiency. Accordingly， tonifying kidney and nourishing and activating blood is established as the fundamental treatment. In TCM， Chinese herbal compounds for tonifying kidney， replenishing essence， and nourishing and activating blood were mostly used， which can improve the secretion of ovarian hormones and ovulatory function to enhance female reproductive capacity. These compounds have definite clinical efficacy and unique advantage of treating different diseases with same method. The effect of Chinese herbal compounds for tonifying kidney and nourishing and activating blood on "Qi and blood" is closely related to mitochondrial function， and thus more and more studies have been conducted to explore the experimental mechanism of these Chinese herbal compounds in regulating mitochondrial homeostasis and protecting ovarian function. On this basis， the paper summarized and elaborated the experimental studies on the dynamic regulation of mitochondrial homeostasis in the treatment of hypovarianism diseases by Chinese herbal compounds for tonifying kidney， replenishing essence and nourishing and activating blood. Moreover， the paper reviewed the related mechanism of regulating mitochondrial homeostasis in ovarian cells， promoting follicular development， and delaying ovarian aging by Chinese herbal compounds for tonifying kidney and nourishing and activating blood through improving mitochondrial function， resisting mitochondrial oxidative stress damage as well as regulating mitochondrial quality and quantity in multi-effect and multi-target way， in order to provide a new perspective for further research on improving female fertility with Chinese medicine.