Dental stem cells (DSCs), a distinct subset of mesenchymal stem cells (MSCs), are isolated from dental tissues, such as dental pulp, exfoliated deciduous teeth, periodontal ligament, and apical papilla. They have emerged as a promising source of stem cell therapy for tissue regeneration and autoimmune disorders. The main types of DSCs include dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAP). Each type exhibits distinct advantages: easy access via minimally invasive procedures, multi-lineage differentiation potential, and excellent ethical acceptability. DSCs have demonstrated outstanding clinical efficacy in oral and maxillofacial regeneration, and their long-term safety has been verified. In oral tissue regeneration, DSCs are highly effective in oral tissue regeneration for critical applications such as the restoration of dental pulp vitality and periodontal tissue repair. A defining advantage of DSCs lies in their ability to integrate with host tissues and promote physiological regeneration, which render them a better option for oral tissue regenerative therapies. Beyond oral applications, DSCs also exhibit promising potential in the treatment of systemic diseases, including type Ⅱ diabetes and autoimmune diseases due to their immunomodulatory effects. Moreover, extracellular vesicles (EVs) derived from DSCs act as critical mediators for DSCs' paracrine functions. Possessing regulatory properties similar to their parental cells, EVs are extensively utilized in research targeting tissue repair, immunomodulation, and regenerative therapy-offering a "cell-free" strategy to mitigate the limitations associated with cell-based therapies. Despite these advancements, standardizing large-scale manufacturing, maintaining strict quality control, and clarifying the molecular mechanisms underlying the interaction of DSCs and their EVs with recipient tissues remain major obstacles to the clinical translation of these treatments into broad clinical use. Addressing these barriers will be critical to enhancing their clinical applicability and therapeutic efficacy. In conclusion, DSCs and their EVs represent a transformative approach in regenerative medicine, and increasing clinical evidence supports their application in oral and systemic diseases. Continuous innovation remains essential to unlocking the widespread clinical potential of DSCs.
Humans ; Dental Pulp/cytology* ; Translational Research, Biomedical ; Mesenchymal Stem Cells/cytology* ; Periodontal Ligament/cytology* ; Stem Cells/cytology* ; Regeneration ; Tooth, Deciduous/cytology* ; Cell Differentiation ; Tissue Engineering/methods* ; Regenerative Medicine

Peri-implant diseases are characterized by the resorption of hard tissue and the inflammation of soft tissue. Epigenetics refers to alterations in the expression of genes that are not encoded in the DNA sequence, influencing diverse physiological activities, including immune response, inflammation, and bone metabolism. Epigenetic modifications can lead to tissue-specific gene expression variations among individuals and may initiate or exacerbate inflammation and disease predisposition. However, the impact of these factors on peri-implantitis remains inconclusive. To address this gap, we conducted a comprehensive review to investigate the associations between epigenetic mechanisms and peri-implantitis, specifically focusing on DNA methylation and microRNAs (miRNAs or miRs). We searched for relevant literature on PubMed, Web of Science, Scopus, and Google Scholar with keywords including "epigenetics," "peri-implantitis," "DNA methylation," and "microRNA." DNA methylation and miRNAs present a dynamic epigenetic mechanism operating around implants. Epigenetic modifications of genes related to inflammation and osteogenesis provide a new perspective for understanding how local and environmental factors influence the pathogenesis of peri-implantitis. In addition, we assessed the potential application of DNA methylation and miRNAs in the prevention, diagnosis, and treatment of peri-implantitis, aiming to provide a foundation for future studies to explore potential therapeutic targets and develop more effective management strategies for this condition. These findings also have broader implications for understanding the pathogenesis of other inflammation-related oral diseases like periodontitis.
Peri-Implantitis/genetics* ; Humans ; Epigenesis, Genetic ; DNA Methylation ; MicroRNAs/genetics*

Immune checkpoint inhibitors （ICIs） have shown good efficacy in tumor treatment and have changed the landscape of tumor treatment. However， some patients treated with ICIs have not only failed to achieve the desired therapeutic effect， but also developed an atypical response pattern of abnormally accelerated tumor growth， namely hyperprogressive disease （HPD）. The pathogenesis of HPD is still unclear and it is difficult to diagnose， which poses a challenge for clinical identification and treatment decisions. Exploring the underlying mechanism of HPD is important to improve the effect of immunotherapy. Based on the theory of "Yang deficiency and toxic knot"， this paper discussed the mechanism of HPD in immunotherapy from the perspective of "spleen and kidney Yang deficiency and hefty toxic pathogens". It was concluded that the inactivation of p53 oncogene and immunosuppressive microenvironment were the manifestations of the deficiency of healthy qi in the body and declined yang in the spleen and kidney， serving as an important basis for the occurrence of HPD. Adverse reactions caused by ICIs belong to the category of "drug toxicity". The occurrence and development of murine double minute 2 （MDM2）/murine double minute 4 （MDM4） activation， epidermal growth factor receptor （EGFR） mutation， and tumor inflammatory microenvironment are the manifestations of the hyperactivity of pathogenic Qi， conflict of cancer toxicity and drug toxicity， and being hefty by virtue of deficiency， which can promote the abnormal proliferation of tumor cells， and they are the core pathogenic elements of HPD and are closely related to disease prognosis. In terms of treatment， under the guidance of the theory of "five views on differentiation and treatment" （time-space view， core view， symptom view， precision view， and disease-before-onset view）， which was summarized according to the clinical practice of this research team， this paper， taking the prevention and treatment of HPD as the entry point， formulated traditional Chinese medicine （TCM） compounds to reinforce healthy Qi and warm Yang and realize the dynamic management of the whole spatiotemporal cycle， and removed toxins and resisted cancer to realize the all-round systemic intervention of the specimen. Additionally， targets were enriched in the macro-clinical manifestations and microscopic pathological changes of HPD to improve the targeting of drug selection and the precision of prevention and treatment， giving full play to the unique therapeutic advantages of TCM， and providing new ideas for the clinical application of TCM in the prevention and treatment of HPD.

Objective To investigate the clinical effect of lithium disilicate glass ceramic cantilever resin-bonded fixed partial dentures(CRBFPDs)on single anterior tooth loss to provide a reference for the selection of restoration methods for single anterior tooth loss.Methods This study was reviewed and approved by the Ethics Committee,and informed consent was obtained from the patients.Forty-two patients with less than two anterior teeth with monomaxillary loss were included in this study.After 6 months,1 year,2 years,and 3 years,the aesthetic and functional effects of the restorations and the periodontal health status were evaluated,and the visual analog scale(VAS)was used to assess pa-tient satisfaction.Results During the observation period,the connector fractured in one case within 3 months.One case had debonded within 2 years.The aesthetic restoration effect of all lithium disilicate glass ceramic CRBFPDs was categorized as Class A.The periodontal health was good,there was no clinical absorption in the soft and hard tissues of the abutment or subbridge,periodontal status according to the evaluation indices was classified as class A,and the total satisfaction rate of the patient was 100%.Conclusion For single anterior tooth loss patients,lithium disilicate glass ceramic cantilever resin-bonded fixed partial denture can achieve the restoration effect of less invasion,better adhesion,aesthetics,comfort and good biocompatibility.With high patient satisfaction,it can be considered an ideal restoration method for replacing a single anterior tooth.

Dysbiosis can cause microenvironmental dysregulation, which can further lead to local or systemic diseases, such as caries, inflammatory bowel disease, obesity, and diabetes. Dysbiosis is primarily manifested as the disturbance of metabolic processes and products. Arginine plays an important role in various metabolic processes and homeostasis of the microbial flora and the host. This study aims to explore the potential therapeutic value of arginine and its metabolism and homeostasis regulation in diseases associated with oral-intestinal dysbiosis. Host and microbial homeostasis can be restored by regulating the composition or function of host microbiota, and arginine has been found to exhibit significant clinical potential in restoring host microbiota composition and function. For example, arginine can reduce the risk of caries by regulating the relative abundance of Streptococcus mutans and Streptococcus sanguineus. Additionally, arginine metabolism may play a therapeutic role in inflammatory bowel disease and obesity by regulating the relative abundance of Firmicutes and Bacteroidetes. In addition, supplementation of arginine and its metabolite polyamine has clinical prospects in the treatment of diabetic patients with ketoacidosis. Although studies have demonstrated the therapeutic role of arginine in oral, intestinal, and metabolism-related diseases, the specific mechanism is yet to be explored. In addition, further research is required to determine the optimal clinical dosage of arginine that can maintain microbiota homeostasis without causing any side effects.

Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.

As an important concept in Chinese medicine theory， "qi sinking" is the inheritance and extension of the thought core of sinking of qi in whole body. This article explored the concept of sinking of pectoral qi， center qi， and kidney qi in the theory of qi sinking， and believed that sinking of pectoral qi， stagnation and sinking of center qi， deficiency and sinking of kidney qi were the core pathogenesis of postoperative injury in malignant tumours. Anchored to the method of reinforcing healthy qi and lifting the sunken， this article recommended to identify pattern and treat by guiding supplement and lifting the sunken. For lung gold impairment， heart yang depletion， and pectoral qi sinking， the treatment is to warm and supplement heart and lung， lift pectoral qi， and restore the respiratory function by modified Shengxian Decoction （升陷汤） plus Guizhi Decoction （桂枝汤）； for spleen depletion and pathways blockage， liver failing to act freely， and center qi stagnation and sinking， the treatment is to warm and supplement center qi， raise yang and lift the sunken， and restore the digestive function by modified Buzhong Yiqi Decoction （补中益气汤）； for source exhausted and essence deficiency， liver qi hiding， and kidney qi deficiency to inward invasion， the treatment is to nourish the kidney and astringe the liver， consolidate the original qi and lift qi， improve the pelvic floor dysfunction， and protect the kidney function by modified Liuwei Dihuang Pill （六味地黄丸） plus Shengma Chaihu Decoction （升麻柴胡汤）. Modification need base on different disease patterns and stages， and new ideas for postoperative traditional Chinese medicine treatment and rehabilitation of malignant tumours were provided.

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*

Objective:To investigate the clinical efficacy and related adverse reactions of ixazomib-based chemotherapy regimens in the treatment of relapsed/refractory multiple myeloma (RRMM).Methods:Twenty-one patients with RRMM who received ≥2 courses of ixazomib-based chemotherapy regimens in Heze Municipal Hospital and Zoucheng People's Hospital of Shandong Province from October 2018 to February 2020 were collected. Among them, 15 patients had previously received the bortezomib-based regimens, 10 patients had received the lenalidomide-based regimens, and 6 patients had received the treatment regimens containing the above two drugs. The patients were treated by a two-drug or three-drug regimen: 4 mg ixazomib was taken orally on day 1, 8 and 15 in combination with other drugs (dexamethasone, cyclophosphamide or lenalidomide). The therapeutic efficacy and safety were evaluated after the 2nd and the 4th treatment cycles.Results:The overall response rate (ORR) of 21 patients with RRMM after 2 treatment cycles was 38.09% (8/21), including 6 cases of partial remission (PR) and 2 cases of very good partial remission (VGPR). After 4 cycles, ORR was 57.14% (12/21), including 7 cases of PR, 4 cases of VGPR, and 1 case of complete remission (CR). The incidence of grade 3-4 adverse reactions of the ixazomib-based chemotherapy regimens was 23.81% (5/21). Hematological adverse reactions included neutropenia, thrombocytopenia and anemia, and other common adverse reactions included the digestive tract reactions, fatigue, hypokalemia, etc., and the peripheral nerve adverse reactions were all grade 2 or below grade 2.Conclusion:The ixazomib-based chemotherapy regimens are effective and safe in treating RRMM.

Objective To compare the protective effects of pharmacological batch RC28-E1 and pilot batch RC28-E2 on retinal vascular endothelial cells (RF/6A) under the stimulation of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF).Methods RF/6A cells were divided into normal control group,VEGF + FGF group and RC28-E1 groups with different concentrations.The optimal concentration of RC28-E1 was determined by cell counting kit-8 (CCK-8) method.Cells were divided into normal control group,VEGF+FGF group,RC28-E1 group,RC28-E2 group,conbercept group and FGF trap group,and cultured with serum-free culture medium,serum-free culture medium containing VEGF+FGF,serum-free culture medium containing VEGF+FGF+RC28-E1,serum-free culture medium containing VEGF+FGF+RC28-E2,and serum-free culture medium containing VEGF+FGF+ conbercept,serum-free medium containing VEGF+FGF+FGF trap,respectively.Cell proliferation rate was measured by CCK-8 method,cell migration ability was detected by Transwell test,and tube formation ability was detected by Matrigel assay.Results The cell proliferation rate of 0.080 mg/ml RC28-E1 group was significantly lower than that of VEGF+FGF group (P＜0.05).The cell proliferation rate of RC28-E1 group,RC28-E2 group and FGF trap group were significantly lower than that of VEGF+FGF group (P＜0.05).The number of migrated cells in RC28-E1 group,RC28-E2 group,conbercept group and FGF trap group were significantly lower than that in VEGF+FGF group (P=0.000).The numbers of meshes formed by retinal vascular endothelial cells in RC28-E1 group,RC28-E2 group,conbercept group and FGF trap group were significantly lower than that in VEGF+FGF group (P =0.003,0.001,0.009,0.018).The number of tube formation in FGF trap group was significantly higher than those in RC28-E1 group,RC28-E2 group,conbercept group and normal control group (P =0.014,0.000,0.008,0.014).Conclusions Under the stimulation of VEGF + FGF,the inhibitory effect of RC28-E on the proliferation of retinal vascular endothelial cells is greater than that of conbercept,and its inhibitory effect on the tube formation is superior to that of FGF trap.There is no significant difference in the effects of different batches of recombinant decoy receptor innovative drugs on retinal vascular endothelial cells.