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.

This article reports one case of adult COVID-19-associated acute necrotizing encephalopathy(ANEC).The patient developed disturbance of consciousness and seizure on the 12th day after SARS-CoV-2 infection.Imaging showed significant swelling and signal changes in the bilateral thalamus,brainstem,cerebral hemisphere and cerebellar hemisphere,which were consistent with the characteristic images of Acute necrotizing encephalitis(ANE).Although methylprednisolone shock therapy and high-dose human immunoglobulin therapy were given early,the patient died.ANEC often starts quickly and progresses rapidly,unconsciousness and seizure are the main manifestations.Imaging features of thalamic and subtentorial symmetry and multifocal lesions are specific for diagnosis,but the treatment and prognosis still face challenges and need further study.

Objective To explore the risk factors for suicidal ideation among the relatives and friends of suicide victims through psychological support hotline.Methods Calls from the relatives and friends of suicide victims to the Beijing psychological support hotline between 2009 and 2023 were included.Their current suicidal ideation was assessed by asking whether they had suicidal thoughts in the past two weeks.Demographic information of the callers was collected and the severity of their depression was assessed using the depression diagnostic screening scale.Interviews were conducted to evaluate distress,sense of hope,history of suicide attempts,and suicide risk factors.Logistic regression analysis was used to explore the risk factors for suicidal ideation among callers.Results A total of 360 cases were included in this study.There were 50.3%(181 cases)of the callers reporting suicidal ideation within 2 weeks before the call.Years of education(OR=0.86,95%CI:0.79-0.94)and high levels of hope(OR=0.19,95%CI:0.11-0.32)were protective factors against suicidal ideation in callers.History of suicide attempts(OR=2.01,95%CI:1.20-3.36),high levels of distress(OR=3.28,95%CI:1.92-5.61),and high levels of depression(OR=1.73,95%CI:1.05-2.84)were independent risk factors for suicidal ideation in callers.Conclusions History of suicide attempts,high levels of distress and high levels of depression among the relatives and friends of suicide victims calling the psychological support hotline are risk factors for their own suicidal ideation.

Objective·To measure and analyze age-related changes in cortical bone thickness and alveolar bone height and width in the posterior teeth of the maxilla.Methods·Cone-beam CT(CBCT)data of the implant patients in the Department of Stomatology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were collected from January 2019 to December 2022.There were 40 cases in the youth group(18?30 years)and 40 cases in the elderly group(≥60 years),with a male-to-female ratio of 1∶1.The i-Dixel software was used to measure the thickness of buccal and palatal cortical bone,and the width and height of alveolar bone in three regions of the posterior teeth of the maxilla on the side with regular dentition(part Ⅰ:between the first and the second premolar of maxillary;part Ⅱ:between the second premolar and the first molar of maxillary;part Ⅲ:between the first and the second molar of maxillary),and the differences between different groups were compared.Results·In part Ⅲ,the buccal cortical bone thickness of the elderly men[(1.49±0.29)mm]was significantly greater than that of the young men[(1.11±0.34)mm](P＜0.001).In part Ⅰ and Ⅱ,the thickness of palatal cortical bone in the elderly women[part Ⅰ:(1.27±0.30)mm;part Ⅱ:(1.28±0.27)mm]was significantly smaller than that in the young women[part Ⅰ:(1.70±0.32)mm;part Ⅱ:(1.58±0.61)mm](P＜0.05).The width of alveolar bone showed a trend of being smaller in the elderly group than in the young group in all three regions,but there were significant differences only between the elderly males[part Ⅱ:(8.61±1.15)mm;part Ⅲ:(11.06±2.40)mm]and the young males[part Ⅱ:(10.29±1.69)mm;part Ⅲ:(13.39±1.59)mm]in the part Ⅱ and Ⅲ(P＜0.05).The alveolar bone height in part Ⅰ andⅡ was significantly greater in elderly men and women than that in the young men and women,respectively(P＜0.05).In the elderly group,the thickness of buccal cortical bone in men was significantly greater than that in women in part Ⅰ and Ⅲ(P＜0.05).Conclusion·The thickness of palatal cortical bone in female maxillary posterior teeth significantly decreases with age;the width of alveolar bone in maxillary posterior region shows a narrowing trend with age,especially in elderly men;the height of alveolar bone in the maxillary posterior region of the elderly increases significantly.

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.