Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Objective:To analyze the risk factors for postoperative cardiovascular events (PCE) after renal transplantation and their impact on transplant kidney function.Methods:The clinical data of 120 patients who underwent kidney transplant at Xuanwu Hospital, Capital Medical University from March 2020 to March 2022 were retrospectively analyzed. Among them, 23 cases occurred PCE (PCE group), and 97 cases did not occur PCE (non-PCE group). The relevant preoperative and postoperative data were recorded. Multivariate Logistic regression was used to analyze the independent risk factors of PCE in kidney transplant patients.Results:The incidence rate of PCE in kidney transplant patients was 19.17% (23/120). There were no statistical differences in the gender composition, preoperative dyslipidemia rate, preoperative hypertension rate and immunosuppressant use between two groups ( P>0.05); the age, preoperative body mass index>30 kg/m 2 rate, preoperative dialysis time>12 months rate, preoperative diabetes rate, preoperative cardiovascular disease rate, preoperative diabetic nephropathy rate, cadaver kidney transplant rate, postoperative dyslipidemia rate, postoperative serum creatinine >200 μmol/L rate, postoperative new-onset diabetes rate, postoperative delayed failure rate and postoperative acute reaction rate in PCE group were significantly higher than those in non-PCE group, and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis showed that age, preoperative diabetes, preoperative cardiovascular disease, preoperative diabetic nephropathy, postoperative serum creatinine >200 μmol/L and postoperative acute reaction were independent risk factors of PCE in kidney transplant patients ( OR = 2.40, 3.42, 3.85, 1.98, 2.62 and 2.11; 95% CI 1.67 to 3.58, 1.61 to 7.05, 2.61 to 5.55, 1.05 to 3.85, 1.25 to 4.52 and 1.20 to 4.78; P<0.01 or <0.05). There was no statistically significant difference in serum creatinine 3 months after surgery between two groups ( P>0.05); the serum creatinine 6 and 12 months after surgery in PCE group was significantly higher than that in non-PCE group: (139.58 ± 31.54) μmol/L vs. (105.36 ± 21.05) μmol/L and (198.32 ± 40.12) μmol/L vs. (107.63 ± 24.64) μmol/L, and there were statistical differences ( P<0.01). Conclusions:The incidence of PCE in kidney transplant patients is higher, and there are many risk factors for PCE. If relevant measures are taken to correct or remove risk factors, it may reduce the incidence of PCE and prolong survival time in kidney transplant patients.

Objective:To investigate the relationship between body mass index (BMI) and gestational hypertension using two-sample Mendelian randomization analysis.Methods:The summary level data for BMI and gestational hypertension were obtained from the genome-wide association study (the deadline for data inclusion was October 31, 2023). All data were analyzed by inverse variance weighting, MR-Egger regression, weighted median, simple model and weighted model methods. Cochrane Q test was used to evaluate heterogeneity, MR-Egger regression intercept test and funnel plot were used to assess horizontal pleiotropy. Results:Inverse variance weighting result under fixed effects and random effects models showed that the risk of gestational hypertension increased with the increase of BMI ( OR = 1.62 and 1.62, 95% CI 1.39 to 1.88 and 1.39 to 1.88, P<0.01). Sensitivity analysis results including MR-Egger regression, weighted median and weighted model methods showed that BMI increased the risk of gestational hypertension ( OR = 1.51, 1.56 and 1.71; 95% CI 1.01 to 2.26, 1.23 to 1.99 and 1.09 to 2.69; P<0.05 or <0.01). Although Cochrane Q test result showed evidence of heterogeneity ( P = 0.04), inverse variance weighting under a random model suggested that BMI increased the risk of gestational hypertension. Horizontal pleiotropy was not observed in the above analysis ( P = 0.73). Conclusions:Obesity may increase the risk of gestational hypertension. Pregnant women should pay attention to weight control to decrease the risk of gestational hypertension.

ObjectiveTo evaluate some properties of scutellarin-phospholipid complex nanoemulsion（SCU-PC-NE）， such as release， cell uptake and tissue distribution， and to investigate its effect on ameliorating lipopolysaccharide（LPS）-induced vascular endothelial injury. MethodSCU-PC-NE was prepared by weighting SCU-PC， ethyl oleate， Kolliphor HS15， 1，2-propylene glycol（50， 400， 514.3， 85.7 mg）， respectively. And the appearance of SCU-PC-NE was observed by transmission electron microscope， the average paticle size and Zeta potential were measured by nanopotential particle size analyzer. The cumulative release of SCU-PC-NE in vitro was measured by dynamic dialysis， thiazolyl blue（MTT） colorimetric assay was used to investigate the effect of SCU-PC-NE on the viability of human umbilical vein endothelial cells（HUVECs）， the inverted fluorescence microscope and flow cytometry were used to investigate cell uptake of HUVECs by SCU-PC-NE in vitro using coumarin 6 as a fluorescent probe， the tissue distribution of DiR/SCU-PC-NE labeled by near infrared fluorescent dyes was obeserved by small animal in vivo imaging system. The inflammation injury model was established by co-incubation with LPS（1 mg·L^-1） and HUVECs， the effect of SCU-PC-NE on the levels of interleukin（IL）-1β and IL-6 were determined by enzyme-linked immunosorbent assay（ELISA）， 18 Kunming male mice were randomly divided into blank group， model group， blank preparation group（equivalent to high dose group）， SCU group and SCU-PC-NE low and high dose groups（5， 10 mg·kg^-1）， 3 mice in each group， and the drug administration groups were administered once in the tail vein at the corresponding dose every 48 h， equal volume of normal saline was given to the blank group and the model group， and the drug was administered for 4 consecutive times. Except for the blank group， the endothelial inflammatory injury was induced by intraperitoneal injection of LPS（10 mg·kg^-1） at 12 h before the last administration in each group. Hematoxylin-eosin（HE） staining was used to investigate the effect of SCU-PC-NE on the histopathological changes in the thoracic aorta of mice. ResultThe appearance of SCU-PC-NE displayed pale yellow milky light， mostly spherical with rounded appearance and relatively uniform particle size distribution， with the average particle size of 35.31 nm， Zeta potential of 7.23 mV， and the encapsulation efficiency of 75.24%. The cumulative release in vitro showed that SCU-PC-NE exhibited sustained release properties compared with SCU. The cell viability of SCU-PC-NE was >90% at a concentration range of 1.05-8.4 mg·L^-1. The results of cellular uptake experiments showed that the cellular uptake ability of SCU-PC-NE was significantly enhanced when compared with the SCU group（P<0.01）. Compared with normal mice， the results of tissue distribution showed that the fluorescence intensity of DiR/SCU-PC-NE was significantly enhanced in the spleen， kidney， brain and thoracic aorta of mice at different time points after intraperitoneal injection of LPS（P<0.05， P<0.01）， especially in thoracic aorta. ELISA results showed that the levels of IL-1β and IL-6 in the model group were significantly increased when compared with the blank group（P<0.05， P<0.01）， and compare with the model group， all administration groups significantly down-regulated IL-1β level， with the strongest effect in the SCU-PC-NE high-dose group（P<0.01）， and all administration groups significantly down-regulated IL-6 level， with the strongest effect in the SCU-PC-NE low-dose group（P<0.05）. Compare with the blank group， the results of HE staining showed that the endothelial cells were damaged， the elastic fibers were broken and arranged loosely in the model group， although similar vascular injury could be observed in the blank preparation group， SCU group and SCU-PC-NE low-dose group， the vascular endothelial damage was significantly reduced in the high-dose group of SCU-PC-NE， which had a better effect than that in the SCU group. ConclusionSCU-PC-NE can promote the uptake of drugs by endothelial cells and effectively enriched in the site of vascular endothelial injury caused by LPS， suggesting that it has a protective effect on vascular endothelial injury and is a good carrier of SCU.

Objective To investigate the correlation between serum basic helix-loop-helix transcription fac-tor family member E40(BHLHE40)levels and subclinical atherosclerosis(SAS)in patients with type 2 dia-betes mellitus(T2DM).Methods A total of 145 T2DM patients admitted to the Department of General Prac-tice of Suzhou Municipal Hospital from January 2021 to January 2023 were selected as the study objects.Pa-tients were divided into SAS group(n=80)and non-SAS group(n=65)according to whether SAS occurred.Serum BHLHE40 level and clinical data of the two groups were compared.The correlation between serum BHLHE40 level and carotid intima media thickness(CIMT)was analyzed by Pearson correlation.The risk factors of SAS in T2DM patients were analyzed by multi-factor Logistic regression.The value of serum BHL-HE40 level in the diagnosis of SAS in T2DM patients was analyzed by receiver operating characteristic(ROC)curve.Results The age,duration of diabetes,low-density lipoprotein cholesterol(LDL-C),CIMT and serum BHLHE40 levels in SAS group were significantly higher than those in non-SAS group,with statistical differ-ence(P＜0.001).Correlation analysis showed that serum BHLHE40 level was positively correlated with CI-MT(r=0.671,P＜0.001).Multivariate Logistic regression analysis showed that duration of diabetes,age,CIMT,LDL-C and serum BHLHE40 level were all risk factors for SAS in T2DM patients(P＜0.05).ROC curve analysis indicated that the area under the curve(AUC)of serum BHLHE40 for the diagnosis of SAS in T2DM patients was 0.742,the sensitivity was 75.0％,and the specificity was 73.9％.Conclusion Serum BHLHE40 expression level is closely related to the occurrence of SAS in T2DM patients,and is of great diag-nostic value for the occurrence of SAS in T2DM patients.

Objective To explore the correlation between serum levels of miR-193a-3p,activated transcription factor 5(ATF5),clinicopathological characteristics and chemotherapy efficacy in patients with triple negative breast cancer(TNBC).Methods A total of 120 patients with TNBC admitted to our hospital were collected as the research group.In the same period,120 cases with benign breast disease in our hospital were selected as the control group.Serum levels of miR-193a-3p and ATF5 were detected,and the relationship between them and clinicopathological characteristics were detected in two groups.According to the therapeutic effect,TNBC patients were divided into the treatment ineffective group(n=50)and the treatment effective group(n=70).The expression levels of miR-193a-3p and ATF5 were compared between the two groups,and factors affecting the chemotherapy efficacy of TNBC patients were analyzed.Results Compared with before chemotherapy,the serum miR-193a-3p level increased and ATF5 level decreased in TNBC patients after chemotherapy(P＜0.05).Compared with the control group,the serum miR-193a-3p level of TNBC patients decreased in the research group before chemotherapy,and ATF5 level increased(P＜0.05).The expression level of miR-193a-3p was lower and the expression level of ATF5 was higher in patients with tumor diameter≥3 cm,lymph node metastasis,low histological grade,clinical stage Ⅲ and Ki-67＞30%(P＜0.05).In TNBC patients,compared with the treatment effective group,patients in the treatment ineffective group showed a decreased serum miR-193a-3p level and an increased ATF5 level(P＜0.05).Lower level of miR-193a-3p,higher level of ATF5,lymph node metastasis,tumor diameter≥3 cm,low histological grade,and TNM stage Ⅲ were risk factors affecting the efficacy of chemotherapy in TNBC patients(P＜0.05).Conclusion Low level of miR-193a-3p and high level of ATF5 in the serum of TNBC patients are risk factors for chemotherapy efficacy.

Objective To explore the efficacy and safety of low-dose tirofiban in stent-assisted coil embolization(SAC)for ruptured intracranial aneurysms.Methods From April 2011 to September 2020,335 patients of ruptured intracranial aneurysms with subarachnoid hemorrhage(SAH)admitted in the First People's Hospital of Changzhou were retrospectively analyzed.All cases underwent stent-assisted coil embolization within 24-48 h and antiplatelet medications.The patients were divided into dual antibody group(89 cases)and tirofiban group(246 cases).Baseline and clinical data of all patients were collected for comparison between groups,including age,sex,hypertension,diabetes mellitus,Hunt-Hess grade at admission,modified Fisher scale score at admission,aneurysm diameter(＞5 mm,≤5 mm),aneurysm location(anterior circulation,posterior circulation),postoperative acute hydrocephalus or intraventricular hemorrhage,postoperative complete embolization rate of ruptured aneurysm.All patients with ruptured intracranial aneurysm with SAH were confirmed by emergency cerebral CT scan after admission.The Raymond grading criteria were used to evaluate the embolization effect after operation:grade Ⅰ refers to no development(complete embolization),grade Ⅱ refers to only aneurysm neck development(incomplete embolization),and grade Ⅲ refers to aneurysm body development,in which Raymond grading Ⅰ orⅡ indicates effective embolization.Tirofiban group:4.2 μg/kg tirofiban was intravenously injected after the coil was placed in the aneurysm lumen and the stent was released,followed by maintenance dose 0.07 μg/(kg·min)for 6-8 h,and aspirin 100 mg and clopidogrel 75 mg were given as sequential dual antiplatelet therapy 2 hours before the tirofiban infusion was stopped.Dual antiplatelet group:a loading dose of aspirin 300 mg and clopidogrel 300 mg was given at least 2 hours before stent implantation,and then transferred to aspirin 100 mg and clopidogrel 75 mg given on the second day after operation.All patients received aspirin(100mg/d)for 6 months and clopidogrel(75 mg/d)for 3 months after operation.The efficacy indicators,safety indicators,adverse events and other complications of the two groups were collected and compared.The efficacy indicators were the incidence of thrombotic events during operation and within 72 hours after operation.The safety indicators were the incidence of intraoperative and early postoperative intracranial hemorrhage(within 48 hours after operation),the incidence of late postoperative intracranial hemorrhage(over 48 hours after operation),and the incidence of intracranial hemorrhage related to external ventricular drainage(symptomatic and asymptomatic).The adverse event was the occurrence of drug-related thrombocytopenia.Other complications were delayed ischemic events.The modified Rankin scale(mRS)score was used to evaluate the clinical prognosis of patients at 180 days after operation.mRS score ≤2 was defined as good prognosis,mRS score＞2 was defined as poor prognosis,of which 6 was defined as death.Results(1)There were no significant differences in baseline and clinical data between the tirofiban group and the dual antibody group(all P＞0.05).(2)There was no significant difference in the proportion of patients with good outcome(75.2％[185/246]vs.74.2％[66/89],P=0.845)and death(10.2％[25/246]vs.12.4％[11/89],P=0.566)at 180 days after operation between the tirofiban group and the dual antiplatelet group.(3)There was no significant difference in the incidence of intraoperative(0.8％[2/246]vs.4.5％[4/89],P=0.075)and postoperative thrombotic events(11.0％[27/246]vs.13.5％[12/89],P=0.527)between the tirofiban group and the dual antiplatelet group.(4)Results about safety comparison between this two antiplatelet regimens showed that the incidence of early postoperative intracranial hemorrhage were lower in the tirofiban group than that in the dual antiplatelet group(2.8％[7/246]vs.10.1％[9/89],P=0.014).There were no significant differences in the symptomatic external ventricular drainage related intracranial hemorrhage(0 vs.2/15,P=0.050),incidences of intraoperative intracranial hemorrhage(1.6％vs.3.4％,P=0.580),late postoperative intracranial hemorrhage(3.3％vs.4.5％,P=0.836),and drug-related thrombocytopenia(0.4％vs.1.1％,P=0.461)between the two groups.Conclusion Low-dose tirofiban infusion in SAC for ruptured aneurysms may prevent perioperative thromboembolic events without high risk of intracranial hemorrhage.

Objective:To observe the occurrence of perioperative adverse events of carotid endarterectomy in patients with carotid artery stenosis, and analyze the influencing factors of perioperative adverse events.Methods:The clinical data of 120 carotid artery stenosis patients underwent carotid endarterectomy from October 2021 to October 2022 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. Among them, 42 patients experienced perioperative adverse events (adverse events group), and 78 patients did not experience perioperative adverse events (non-adverse events group). The baseline data, imaging findings, laboratory indexes, surgical indexes and postoperative complications were recorded. Multivariate Logistic regression was used to analyze the independent risk factors of perioperative adverse events of carotid endarterectomy in patients with carotid artery stenosis.Results:The rates of history of cerebrovascular disease, severe stenosis or occlusion of anterior cerebral artery, patch repair and plaque ulceration in adverse events group were significantly higher than those in non-adverse events group: 35.71% (15/42) vs. 15.38% (12/78), 52.38% (22/42) vs. 26.92% (21/78), 50.00% (21/42) vs. 20.51% (16/78) and 61.90% (26/42) vs. 24.36% (19/78), and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that the severe stenosis or occlusion of anterior cerebral artery, patch repair and plaque ulceration were the independent risk factors of perioperative adverse events of carotid endarterectomy in patients with carotid artery stenosis ( OR = 2.874, 2.632 and 3.214; 95% CI 1.421 to 3.654, 1.748 to 3.287 and 2.101 to 4.697; P<0.05 or <0.01). Conclusions:The severe stenosis or occlusion of anterior cerebral artery, patch repair and plaque ulceration are the independent risk factors of perioperative adverse events of carotid endarterectomy in patients with carotid artery stenosis. Identifying and taking effective measures to prevent the perioperative adverse events can effectively reduce disability and mortality rates.