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.

Objective To explore the clinical efficacy of omacycline(OMC)in the treatment of diabetes mellitus complicated with community-acquired bacterial pneumonia(CABP).Methods Clinical data of T2DM patients with CABP admitted to The First Hospital of Jiaxing from August 2022 to July 2023 were divided into OMC group and non-OMC(NOMC)group according to wheter they received OMC treatment or not.The absorption of pulmonary lesions after treatment,changes in inflammatory indicators[white blood cell count(WBC),C-reactive protein(C-reactive protein,CRP),and anterior calcitonin(procalcitonin,PCT)],comprehensive index[hospitalization days,total hospitalization costs,blood glucose standard within 3 d and glucocorticoid use]and the occurrence of adverse reactions were analyzed and compared.Results A total of 100 diabetes mellitus patients with CABP were included in this study,including 36 cases in OMC group and 64 cases in NOMC group.The absorption of pulmonary inflammation in the OMC group was significantly higher than that in the NOMC group(P<0.05).Before treatment,there was no statistical difference in WBC,CRP and PCT between the two groups(P>0.05).After treatment,WBC,CRP,and PCT in both groups were significantly lower than those before treatment(P<0.05).Furthermore,WBC,CRP,PCT levels,hospital stay,total hospitalization costs and glucocorticoid use rate were significantly lower in the OMC group than in the NOMC group(P<0.05).The blood glucose compliance rate within 3 d in the OMC group was significantly higher than that in the NOMC group(P<0.05).None of the patients had serious complications during the treatment period.Conclusion OMC treatment of T2DM complicated with CABP is helpful for early disease control and rehabilitation,and reduces the treatment burden.

Objective:To explore the effects of the immune responses mediated by topological structures of three-dimensional bioprinted scaffolds on hair follicle cycle in mice.Methods:The study was an experimental research. The alginate-gelatin composite hydrogels were printed into scaffolds using a three-dimensional bioprinter and named T45 scaffolds, T60 scaffolds, and T90 scaffolds according to the 3 topological structures of the scaffolds (the rotation angles of the printhead during printing were 45°, 60°, and 90°, respectively), and the morphology of the three scaffolds was observed after cross-linking by naked eyes. Nine 8-week-old female C57BL/6J mice were divided into T45 group, T60 group, and T90 group, according to the random number table, with three mice in each group, and the T45, T60, and T90 scaffolds were subcutaneously implanted on the back of mice, respectively. On post implantation day (PID) 7, the hair growth in the dorsal depilated area of mice was observed, the thickness of the fiber capsule around the scaffolds was observed by hematoxylin-eosin staining, and the expression levels of CD68, bone morphogenetic protein-2 (BMP-2), and tumor necrosis factor (TNF) protein in the tissue surrounding the scaffolds were observed by immunofluorescence staining. The samples of the above experiments were all 3.Results:The topological structures of the three scaffolds were all clear with high fidelity after cross-linking. On PID 7, the hair growth was obvious in the dorsal depilated area of mice in T45 group and T90 group, while hair growth was slow in the scaffold implantation area of mice in T60 group, which was significantly different from that of the unimplanted area. On PID 7, compared with (18±4) μm in T90 group, the thickness of both the fiber capsule around the scaffolds ((39±4) and (55±8) μm) of mice in T45 group and T60 group was significantly increased ( P<0.05); the thickness of the fiber capsule around the scaffolds of mice in T60 group was also significantly increased compared with that in T45 group ( P<0.05). On PID 7, the expression level of CD68 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05). The expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05), and the expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T45 group was significantly higher than that in T90 group ( P<0.05). The expression level of TNF protein in the tissue surrounding the scaffolds of mice in T60 group was significantly lower than the levels in T45 group and T90 group (with both P values <0.05). Conclusions:Three-dimensional bioprinted scaffolds with different topological structures mediate different degrees of immune responses after being implanted in mice. A moderate immune response promotes hair growth in depilated area of mice, while an excessive immune response results inhibits the hair follicle entering into the anagen phase.

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.

To analyze the current quality of treatment for hospitalized cancer patients in Beijing, identify major issues in treatment practices, and propose improvements.

Objective To compare the effect of extreme learning machine(ELM)vs logistic regression analysis on prediction of the risk to PICC-related central line associated bloodstream infections(PICC-CLABSI)in cancer patients.Methods Clinical data of 1,146 patients who received PICC,from January 2019 to March 2023,in the Department of Oncology of a ⅢA hospital were analysed.A total of 786 patients who received PICC between January 2019 and December 2021 were assigned to the modelling group,and the rest of 360 patients who received PICC between January 2022 and March 2023 were assigned to the validation group.The risk prediction model was established based on the data of modelling group analysed by Chi-square test,and then by the binary logistic regression to determine the statistically significant variables.Based on the analyses of the two models,a nomogram was plotted to evaluate the fitting and predictive effectiveness.Performance of the two models were evaluated using Hosmer-Lemeshow test as well as the area under the curve(AUC)of receiver operating characteristic(ROC).Risk factors identified by the logistic regression and the PICC-CLABSI risks were used as input and output parameters respectively,to establish an ELM prediction model.The two models were compared in terms of predictive effectiveness using the data of the validation group.Results History of diabetes mellitus,frequency of chemotherapy(≥3 times),maintenance cycle(>7 days),maintenance site(out of hospital),white blood cell count(<3.5×109/L),and albumin(<40g/L)were risk factors for PICC-CLABSI in cancer patients.The logistic regression model demonstrated a good predictability by Hosmer-Lemeshow test(χ 2=5.201,P=0.736),with an AUC-ROC of 0.860(95%CI:0.799～0.922),sensitivity at 0.893,specificity at 0.704 and accuracy at 72.8%.The ELM prediction model exhibited a determination coefficient of 0.823 and mean squared error of 0.051,with a fitting rate at 74.5%,hence it indicated a good predictive power.The ELM model showed a superior predictive power than the logistic regression model.Conclusion The ELM model and logistic regression model,based on logistic regression analysis,offers higher prediction accuracy.It provides valuable guidance to healthcare providers in identification of high risks of PICC-CLABSI for cancer patients.

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.