The immunomodulatory， repair， and regeneration-promoting functions of mesenchymal stem cells make them one of the potential treatment methods for liver diseases. At present， viral and non-viral delivery methods have been developed to genetically modify mesenchymal stem cells， and gene modification can promote the survival， homing， and cytokine secretion of mesenchymal stem cells， thereby enhancing the ability of mesenchymal stem cells to treat liver diseases. This article mainly summarizes the research advances in gene-modified mesenchymal stem cells in the treatment of liver diseases， in order to provide new insights and strategies for the clinical treatment of liver diseases.

OBJECTIVE To study the improvement effects and mechanism of proanthocyanidins （PACs） on steroid-induced osteonecrosis of the femoral head （SONFH） in rabbits based on the receptor-interacting protein kinase 1 （RIPK1）/RIPK3/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS SONFH model in rabbits was induced by injecting Escherichia coli endotoxin+methylprednisolone. The successfully modeled rabbits were randomly divided into Model group （normal saline）， low-dose PACs group （PACs-L group， 11 mg/kg）， high-dose PACs group （PACs-H group， 22 mg/kg）， high-dose PACs+ RIPK1 activator （rRIPK1） group （PACs-H+rRIPK1 group， 22 mg/kg PACs+4 μg/kg rRIPK1）， along with a control group （normal saline）， with 6 rabbits in each group. Each administration group was given relevant medicine once a day intragastrically/via injection， for 4 consecutive weeks. After the last administration， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rabbit serum were measured. The changes in the microstructure of rabbit femurs， including bone mineral density （BMD）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular separation （Tb. Sp） were examined. The histopathological features of rabbit femoral tissues were observed， and the apoptotic status of cells within the rabbit femoral tissues was detected. The mRNA expressions of vascular endothelial growth factor （VEGF） and bone morphogenetic protein 2 （BMP2） in rabbit femoral tissues were determined. The expressions of RIPK1/RIPK3/MLKL signaling pathway-related proteins in femoral tissues were detected. RESULTS Compared with the Control group， serum contents of TNF-α and IL-6， Tb.Sp， empty bone cavity rate， cell apoptosis rate， phosphorylation levels of RIPK1， RIPK3 and MLKL in femoral tissue were significantly increased in the Model group （P＜0.05）. BMD， Tb.Th， Tb.N， as well as the mRNA expression of VEGF and BMP2， along with protein expression of caspase-8， in the femoral tissues were all decreased （P＜0.05）. The bone cells in the femoral tissue were unevenly distributed， and the trabeculae were arranged sparsely. Compared with the Model group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in all dosage groups of PACs showed significant improvements. Compared with the PACs-H group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in the PACs-H+rRIPK1 group showed significant reversal. CONCLUSIONS PACs can ameliorate SONFH in rabbits， and its mechanism of action may be related to the inhibition of the activation of the RIPK1/RIPK3/MLKL signaling pathway， suppression of apoptosis in femoral tissue cells， and promotion of angiogenesis.

Liver fibrosis is pathological in most chronic liver diseases. Exosomes secreted by mesenchymal stem cells (MSCs) can regulate liver fibrosis through mechanisms such as inhibition of inflammatory response and proliferation of activated hepatic stellate cells, regulation of immune cells and metabolism. Therefore, MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease, expanding new ideas for the treatment of chronic liver disease. Recent researches on MSC-derived exosomes in the treatment of liver fibrosis are reviewed in this article.

OBJECTIVE To systematically evaluate the clinical efficacy of dapagliflozin in the treatment of heart failure with diabetes mellitus type 2. METHODS The clinical trials of dapagliflozin in the treatment of heart failure with diabetes mellitus type 2 were searched in Embase, PubMed, Web of Science, Cochrane Library, VIP, CNKI and Wanfang databases from the establishment of the database to March 18, 2022. The RevMan 5.3 software was used for meta-analysis, and the TSA 0.9 software was used for sequential analysis. RESULTS The 31 RCT studies meeting the criteria were finally included, involving 2 906 patients. Meta-analysis showed that compared with the control group, the experimental group significantly improved LVEF[MD=4.43, 95% CI(3.35, 5.50), P<0.000 01], total effective rate[MD=4.19, 95%CI(2.52, 6.99), P<0.000 01], and reduced NT-proBNP[MD=–451.84, 95%CI(–608.09, –295.60), P<0.000 01], LVEDD[MD=–2.74, 95%CI(–3.67, –1.82), P<0.000 01, Hb1ac[MD=–0.88, 95%CI(–1.19, –0.57), P<0.000 01], FPG[MD=–1.10, 95%CI(–1.45, –0.75), P<0.000 01], 2hPG[MD=–2.52, 95%CI(–3.37, –1.66), P<0.000 01] and the incidence of adverse reactions[MD=0.63, 95%CI(0.47, 0.83), P=0.001]. Sequential analysis showed that the effect of dapagliflozin on LVEF in patients with heart failure with type 2 diabetes was accurate, and the possibility of excluding false positive was possible. CONCLUSION The treatment of heart failure with diabetes mellitus type 2 with good efficacy and safety is achieved by dapagliflozin, but it still needs to be included in more high-quality RCT studies for further demonstration.

Digital intraoral scanning is a hot topic in the field of oral digital technology.In recent years,digital intra-oral scanning has gradually become the mainstream technology in orthodontics,prosthodontics,and implant dentistry.The precision of digital intraoral scanning and the accuracy and stitching of data collection are the keys to the success of the impression.However,the operators are less familiar with the intraoral scanning characteristics,imaging process-ing,operator scanning method,oral tissue specificity of the scanned object,and restoration design.Thus far,no unified standard and consensus on digital intraoral scanning technology has been achieved at home or abroad.To deal with the problems encountered in oral scanning and improve the quality of digital scanning,we collected common expert opin-ions and sought to expound the causes of scanning errors and countermeasures by summarizing the existing evidence.We also describe the scanning strategies under different oral impression requirements.The expert consensus is that due to various factors affecting the accuracy of digital intraoral scanning and the reproducibility of scanned images,adopting the correct scanning trajectory can shorten clinical operation time and improve scanning accuracy.The scanning trajec-tories mainly include the E-shaped,segmented,and S-shaped methods.When performing fixed denture restoration,it is recommended to first scan the abutment and adjacent teeth.When performing fixed denture restoration,it is recommend-ed to scan the abutment and adjacent teeth first.Then the cavity in the abutment area is excavated.Lastly,the cavity gap was scanned after completing the abutment preparation.This method not only meets clinical needs but also achieves the most reliable accuracy.When performing full denture restoration in edentulous jaws,setting markers on the mucosal tissue at the bottom of the alveolar ridge,simultaneously capturing images of the vestibular area,using different types of scanning paths such as Z-shaped,S-shaped,buccal-palatal and palatal-buccal pathways,segmented scanning of dental arches,and other strategies can reduce scanning errors and improve image stitching and overlap.For implant restora-tion,when a single crown restoration is supported by implants and a small span upper structure restoration,it is recom-mended to first pre-scan the required dental arch.Then the cavity in the abutment area is excavated.Lastly,scanning the cavity gap after installing the implant scanning rod.When repairing a bone level implant crown,an improved indi-rect scanning method can be used.The scanning process includes three steps:First,the temporary restoration,adjacent teeth,and gingival tissue in the mouth are scanned;second,the entire dental arch is scanned after installing a standard scanning rod on the implant;and third,the temporary restoration outside the mouth is scanned to obtain the three-di-mensional shape of the gingival contour of the implant neck,thereby increasing the stability of soft tissue scanning around the implant and improving scanning restoration.For dental implant fixed bridge repair with missing teeth,the mobility of the mucosa increases the difficulty of scanning,making it difficult for scanners to distinguish scanning rods of the same shape and size,which can easily cause image stacking errors.Higher accuracy of digital implant impres-sions can be achieved by changing the geometric shape of the scanning rods to change the optical curvature radius.The consensus confirms that as the range of scanned dental arches and the number of data concatenations increases,the scanning accuracy decreases accordingly,especially when performing full mouth implant restoration impressions.The difficulty of image stitching processing can easily be increased by the presence of unstable and uneven mucosal mor-phology inside the mouth and the lack of relatively obvious and fixed reference objects,which results in insufficient ac-curacy.When designing restorations of this type,it is advisable to carefully choose digital intraoral scanning methods to obtain model data.It is not recommended to use digital impressions when there are more than five missing teeth.

Liver fibrosis is pathological in most chronic liver diseases.Exosomes secreted by mes-enchymal stem cells(MSCs)can regulate liver fibro-sis through mechanisms such as inhibition of in-flammatory response and proliferation of activated hepatic stellate cells,regulation of immune cells and metabolism.Therefore,MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease,expanding new ideas for the treatment of chronic liver disease.Recent researches on MSC-de-rived exosomes in the treatment of liver fibrosis are reviewed in this article.

Liver fibrosis is pathological in most chronic liver diseases.Exosomes secreted by mes-enchymal stem cells(MSCs)can regulate liver fibro-sis through mechanisms such as inhibition of in-flammatory response and proliferation of activated hepatic stellate cells,regulation of immune cells and metabolism.Therefore,MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease,expanding new ideas for the treatment of chronic liver disease.Recent researches on MSC-de-rived exosomes in the treatment of liver fibrosis are reviewed in this article.

Liver fibrosis is pathological in most chronic liver diseases.Exosomes secreted by mes-enchymal stem cells(MSCs)can regulate liver fibro-sis through mechanisms such as inhibition of in-flammatory response and proliferation of activated hepatic stellate cells,regulation of immune cells and metabolism.Therefore,MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease,expanding new ideas for the treatment of chronic liver disease.Recent researches on MSC-de-rived exosomes in the treatment of liver fibrosis are reviewed in this article.

Liver fibrosis is pathological in most chronic liver diseases.Exosomes secreted by mes-enchymal stem cells(MSCs)can regulate liver fibro-sis through mechanisms such as inhibition of in-flammatory response and proliferation of activated hepatic stellate cells,regulation of immune cells and metabolism.Therefore,MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease,expanding new ideas for the treatment of chronic liver disease.Recent researches on MSC-de-rived exosomes in the treatment of liver fibrosis are reviewed in this article.

Liver fibrosis is pathological in most chronic liver diseases.Exosomes secreted by mes-enchymal stem cells(MSCs)can regulate liver fibro-sis through mechanisms such as inhibition of in-flammatory response and proliferation of activated hepatic stellate cells,regulation of immune cells and metabolism.Therefore,MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease,expanding new ideas for the treatment of chronic liver disease.Recent researches on MSC-de-rived exosomes in the treatment of liver fibrosis are reviewed in this article.