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.

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.

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.

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.

Objective To explore the effect of vascular stress changes on endothelial function recovery and vascular restenosis inhibition in dynamic degradation process of the degradable stent. Methods The material parameters of the hyper-elastic vascular constitutive relationship was fitted, and the stress distribution on the intima of the blood vessel before stent implantation and during dynamic degradation was calculated by numerical simulation. In vitro culture experiments were carried out, and the stretch ratios of the silicon chambers were 0%, 5%, 10% and 15%, respectively, to simulate the mechanical environment at different degradation stages, and to explore the effects of different stretch ratios on growth state of the endothelial cells （ECs）. Results After the stent was completely degraded, the circumferential intimal stress and strain of the vessel were restored to 0.137 MPa and 5.5%, which were close to the physiological parameters (0.122 MPa, 4.8%) before stent implantation. In vitro experiments showed that the survival rate of ECs was the highest under the condition of 0.1 MPa circumferential stress and 5% strain, and adhesion growth could be achieved. Conclusions With the occurrence of stent degradation process, the circumferential stress and strain of the intima were restored to a range close to physiological parameters, which promoted the growth of ECs. The recovery of intimal function could effectively inhibit the process of vascular restenosis. The results can provide the theoretical basis and experimental platform for studying coronary intervention for the treatment of vascular restenosis.

Objective To explore the effects of ring finger protein 43 (RNF43) on fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods Synovial tissues from patients with RA treated by knee arthroplasty were used to isolate FLSs by type 2 collagenase.RNF43 lentivirus overexpressing plasmid was constructed and transfected in to RA-FLS.After successful transfection,RNA and super natant of RA-FLS were extracted.QRT-polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect the mRNA and protein expression levels of matrix metalloproteinase (MMP)-1,MMP-3 and MMP-13.Data were analyzed with Student's t test.Results Transfection efficiency could meet the test requirements when the multiplicity of infection was 40 and was in conjunction with appropriate concentration of polybrene.The mRNA of RNF43 increased for 26158-fold than the control group.In vitro,compared with the control group,RNF43 could significantly inhibit the mRNA of MMP-1,MMP-3 and MMP-13 and MMP-13 [(0.19±0.06),t=28.314,P＜0.05;(0.28±0.07),t=23.413,P＜0.05;(0.21±0.09),t=18.365,P＜0.05]and the protein of MMP-1,MMP-3 and MMP-13 and MMP-13 [(31.0±9.4) pg/ml,(17.1±2.1) pg/ml,t=3.198,P=0.029],MMP-3 [(38.7±8.1) pg/ml,(24.9±3.5) pg/ml,t=3.514,P=0.015],MMP-13 [(35.9±5.4) pg/ml,(20.6±2.9) pg/ml,t=5.632,P=0.001].Conclusion The results of study suggest that RNF43 could inhibit the secretion of MMPs in RA-FLS by suppressing the activity of Wnt signal pathway.

Objective To develop an innovative device for endothelial cell culture in vitro, namely, to develop a vascular endothelial cell culture device based on hemodynamic environment, so as to introduce the development and experimental study of endothelial cell culture device in vitro. Methods A device of dynamic culture system for endothelial cells in vitro on the basis of the existing research was designed with the theory and method of hemodynamics. The shear stress, positive stress and tensile stress existed at the same time in the flow environment. The development and experimental research of the device were described in detail from 5 aspects, such as the development background, structure and composition, design principle, theoretical basis and experimental research. Results The device could accurately simulate the hemodynamic environment of endothelial cells at normal level, with precise control of shear stress in 0-12 Pa range, positive stress in 0-15.96 kPa range, and tensile stress in 0-0.5 MPa range. Conclusions The device can provide a hemodynamic environment which is closer to the physiological conditions of human body, as well as a more ideal experimental environment and means for further exploring the mechanism of vascular intimal injury.