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 explore the relationship between the changes of quadriceps femoris and ICU acquired weakness(ICU-AW)in children.Method:A prospective collection of pediatric patients treated in the intensive care unit of Shenzhen children's hospital from October 2022 to March 2023.The thickness and cross-sectional area of rectus femoris and the thickness of vastus intermedius were measured by ultrasound on the 1st,4th and 7th day after ICU.The first day served as the baseline to calculate the atrophy rate for each muscle.On the 7th day,the Medical Re-search committee muscle strength score(MRC score)and critical physical function test score(PFIT-s score)were performed.According to the MRC score＜48,patients were divided into ICU-AW group and non-ICU-AW group to analyze the relationship between ICU-AW and the changes of quadriceps femoris.Result:A total of 21 critically ill children were included,including 11 males and 10 females.The incidence of ICU-AW in children was 41.2％(4 cases were not evaluated because of delirium).Within 7 days after en-tering ICU,the atrophy rate of cross-sectional area of rectus femoris was the highest,reaching-8.00％±15.10％.Both groups showed the greatest rate of change in the vastus intermedius thickness over 7 days,with the ICU-AW group mainly showing an increase in thickness(19.51％±16.51％over 4 days,14.14％±28.13％over 7 days),while the non-ICU-AW group primarily showed atrophy(-16.07％±17.46％over 4 days,-15.55％±30.04％over 7 days).The ICU-AW group had an average increase in rectus femoris thickness of 4.51％±8.38％within 7 days of ICU admission,while the non-ICU-AW group had an average atrophy rate of-8.19％±11.79％.There was no correlation between muscular atrophy rate and PFIT-s score(all P＞0.05),but there was a moderate negative correlation between rectus femoris thickness atrophy rate and femoral intermediate muscle thickness atrophy rate and MRC score within 4 days,respectively(ritual color 0.541 million 0.657 million 0.004),and moderate negative correlation between MRC score and thickness atrophy rate of rectus femoris and vastus medius within 7 days.There was no significant correlation between the atrophy rate of cross-section-al area of rectus femoris and MRC score.Conclusion:Compared with the non-ICU-AW group,the muscle thickness in the ICU-AW group is mainly thickened rather than atrophied,which can be identified by ultrasound on the 4th day after ICU.The specific diagnostic threshold is worthy of further study.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.

Objective:To investigate the control status of out-of-hospital blood glucose and blood lipids in patients with acute myocardial infarction (AMI) complicated with diabetes mellitus and its correlation with prognosis.Methods:The clinical data of 406 patients with AMI complicated with diabetes mellitus from January 2017 to December 2022 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The demographic and out-of-hospital clinical information of patients were recorded, and the control level of out-of-hospital risk factors and the occurrence of major adverse cardiovascular event (MACCE) were also recorded. The patients were grouped according to the levels of glycosylated hemoglobin (HbA 1c) and low-density lipoprotein cholesterol (LDL-C). HbA 1c<6.0% was the low HbA 1c group, HbA 1c 6.0% to 7.0% was the medium HbA 1c group, and HbA 1c>7.0% was the high HbA 1c group; LDL-C<1.4 mmol/L was low LDL-C group, LDL-C 1.4 to 1.8 mmol/L was medium LDL-C group, and LDL-C>1.8 mmol/L was high LDL-C group. Multivariate Cox regression analysis was used to analyze the independent risk factors for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus. Results:The HbA 1c data of 249 patients were recorded in detail, and only 51.0% (127/249) of patients with HbA 1c≤7%. There were statistical differences in the history of cerebral infarction, out-of-hospital fasting blood glucose, out-of-hospital total cholesterol (TC) and out-of-hospital LDL-C among the low HbA 1c group (24 cases), medium HbA 1c group (103 cases) and high HbA 1c group (122 cases) ( P<0.05). The incidences of out-of-hospital MACCE in low HbA 1c group, medium HbA 1c group and high HbA 1c group were 20.8%(5/24), 12.6%(13/103) and 32.0%(39/122), respectively. The incidence of out-of-hospital MACCE in high HbA 1c group was significantly higher than that in medium HbA 1c group, and there was statistical difference ( P<0.05); there was no statistical difference between low HbA 1c group and high HbA 1c group ( P>0.05). Among the 406 patients, 53.4%(217/406) had LDL-C≤1.8 mmol/L, and only 20.0%(81/406) had LDL-C<1.4 mmol/L. There were statistical differences in hyperlipidemia, out-of-hospital HbA 1c, out-of-hospital fasting blood glucose, out-of-hospital alanine aminotransferase (ALT), out-of-hospital TC and out-of-hospital triglyceride (TG) among low LDL-C group (81 cases), medium LDL-C group (136 cases) and high LDL-C group (189 cases) ( P<0.05). The incidences of MACCE in low LDL-C group, medium LDL-C group and high LDL-C group were 18.5% (15/81), 25.7% (35/136) and 36.5% (69/189), respectively. The incidence of MACCE in high LDL-C group was significantly higher than that in low LDL-C group, and there was statistical difference ( P<0.05); there was no statistical difference between low LDL-C group and medium LDL-C group ( P>0.05). In the different HbA 1c groups, multivariate Cox regression analysis result showed that HbA 1c>7% and high out-of-hospital fasting blood glucose were independent risk factors for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus ( OR = 2.575 and 1.064, 95% CI 1.345 to 4.927 and 1.005 to 1.128, P<0.01 and <0.05). In different LDL-C groups, multivariate Cox regression analysis result showed that high out-of-hospital HbA 1c was an independent risk factor for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus ( OR = 1.303, 95% CI 1.144 to 1.485, P<0.01). Conclusions:The control rates of out-of-hospital blood glucose and blood lipids are low in patients with AMI complicated with diabetes mellitus, and HbA 1c level can independently predict the risk of out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus.

Objective:To investigate the correlation of neutrophil-to-albumin ratio (NAR) and glucose-to-lymphocyte ratio (GLR) with in-hospital death in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 657 patients with AMI from January 2017 to December 2022 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. Using receiver operating characteristic (ROC) curve to determine the optimal cutoff values of GLR and NAR (6.02 and 0.25) for predicting in-hospital mortality in patients with AMI, the patients were divided into high GLR group (GLR≥6.02, 768 cases) and low GLR group (GLR<6.02, 1 889 cases), high NAR group (NAR≥0.25, 547 cases) and low NAR group (NAR<0.25, 2 110 cases) according the optimal cutoff values. The baseline characteristics and occurrence of in-hospital major adverse cardiovascular events (MACE) were recorded. Multivariate Logistic regression was used to analyze the independent risk factors for in-hospital death in patients with AMI.Results:Among the 2 657 patients with AMI, 265 patients had in-hospital MACE (10.0%), and 50 patients (1.9%) died. The age, proportion of Killip≥ 2 grade, proportion of diabetes, proportion of myocardial infarction, proportion of cerebral infarction history, proportion of ST-elevation myocardial infarction (STEMI), thrombolysis in myocardial infarction clinical trial score (TIMI score), global registry of acute coronary event score (GRACE score), fibrinogen, fasting blood glucose, glycated hemoglobin, high-density lipoprotein cholesterol (HDL-C), cardiac troponin I (cTnI) peak, N-terminal B-type natriuretic peptide (NT-proBNP), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), NAR, GLR, neutrophil count, left ventricular end-diastolic diameter (LVEDD) in high GLR group were significantly higher than those in low GLR group, the proportion of males, body mass index (BMI), proportion of smoking history, proportion of non-ST elevation myocardial infarction (NSTEMI), albumin, estimated glomerular filtration rate (eGFR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), lymphocyte count, monocyte count and left ventricular ejection fraction (LVEF) were significantly lower than those in low GLR group, and there were statistical differences ( P<0.01 or <0.05). The proportion of Killip≥2 grade, proportion of STEMI, TIMI score, GRACE score, fibrinogen, fasting blood glucose, TC, LDL-C, cTnI peak, hs-CRP, IL-6, NAR, GLR, white blood cell count, neutrophil count and monocyte count in high NAR group were significantly higher than those in low NAR group, the age, proportion of myocardial infarction history, proportion of NSTEMI, albumin, lymphocyte count, left atrial diameter (LAD) and LVEF were significantly lower than those in low NAR group, and there were statistical differences ( P<0.01 or <0.05). The incidences of in-hospital MACE, death, ventricular fibrillation or pulseless ventricular tachycardia, atrial fibrillation, cardiac arrest and bleeding in high GLR group were significant higher than those in low GLR group: 15.2% (117/768) vs. 7.8% (148/1 889), 4.6% (35/768) vs. 0.8% (15/1 889), 5.3% (41/768) vs. 2.9% (54/1 889), 6.9% (53/768) vs. 4.0% (75/1 889), 4.7% (36/768) vs. 1.4% (26/1 889) and 2.3% (18/768) vs. 0.7% (13/1 889), and there were statistical differences ( P<0.01); there was no statistical difference in the incidence of heart rupture between two groups ( P>0.05). The incidence of in-hospital MACE, death, ventricular fibrillation or pulseless ventricular tachycardia, cardiac arrest, cardiac rupture and bleeding in high NAR group were significantly higher than those in low NAR group: 16.6% (91/547) vs. 8.2% (174/2 110), 5.9% (32/547) vs. 0.9% (18/2 110), 8.0% (44/547) vs. 2.4% (51/2 110), 5.9% (32/547) vs. 1.4% (30/2 110), 1.6% (9/547) vs. 0.4% (9/2 110) and 2.4% (13/547) vs. 0.9% (18/2 110), and there were statistical differences ( P<0.01); there was no statistical difference in the incidence of atrial fibrillation between two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the Killip 3 and 4 grades, high NAR, high GRACE score, high fasting glucose and low LVEF were independent risk factors for in-hospital death in patients with AMI ( OR = 3.827, 4.660, 3.779, 1.020, 1.095 and 0.962; 95% CI 1.158 to 12.649, 1.184 to 18.344, 1.856 to 7.649, 1.009 to 1.032, 1.027 to 1.167 and 0.932 to 0.993; P<0.05 or <0.01). Conclusions:The NAR can independently predict the risk of in-hospital death in patients with AMI.

Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.

Objective To observe the value of preoperative magnetization transfer imaging(MTI)for predicting postoperative pancreatic fistula(POPF)after distal pancreatectomy(DP).Methods A total of 65 patients with pancreatic tumor who underwent DP and preoperative MR scanning were retrospectively enrolled and divided into clinically relevant POPF(CR-POPF)group(n=14,with grade B or C fistula),biochemical fistula group(n=31,postoperative drain fluid amylase level exceeding 3 times the upper limit of normal)and non-fistula group(n=20,postoperative drain fluid amylase level not exceeding 3 times the upper limit of normal)based on postoperative records.Clinical data and magnetization transfer ratio(MTR)of pancreatic tissue at the surgical margin were compared among 3 groups.The predictive value of MTR for CR-POPF was evaluated according to the area under the curve(AUC)of receiver operating characteristic(ROC)curve.Results Patients' age,intraoperative blood loss and the proportion of pancreatic ductal adenocarcinoma in both CR-POPF group and biochemical fistula group were lower than those in non-fistula group(all adjusted P＜0.05),while no significant difference was found between the former two groups(all adjusted P＞0.05).MTR of pancreatic tissue at the surgical margin in CR-POPF group was lower than that in both biochemical fistula group and non-fistula group(both P＜0.05),whereas no statistical difference was detected between the latter two groups(P＞0.05).The AUC of MTR for predicting CR-POPF after DP was 0.727.Conclusion Preoperative MTI could be used to predict POPF after DP.

Objective:To explore the relationship between the changes of quadriceps femoris and ICU acquired weakness(ICU-AW)in children.Method:A prospective collection of pediatric patients treated in the intensive care unit of Shenzhen children's hospital from October 2022 to March 2023.The thickness and cross-sectional area of rectus femoris and the thickness of vastus intermedius were measured by ultrasound on the 1st,4th and 7th day after ICU.The first day served as the baseline to calculate the atrophy rate for each muscle.On the 7th day,the Medical Re-search committee muscle strength score(MRC score)and critical physical function test score(PFIT-s score)were performed.According to the MRC score＜48,patients were divided into ICU-AW group and non-ICU-AW group to analyze the relationship between ICU-AW and the changes of quadriceps femoris.Result:A total of 21 critically ill children were included,including 11 males and 10 females.The incidence of ICU-AW in children was 41.2％(4 cases were not evaluated because of delirium).Within 7 days after en-tering ICU,the atrophy rate of cross-sectional area of rectus femoris was the highest,reaching-8.00％±15.10％.Both groups showed the greatest rate of change in the vastus intermedius thickness over 7 days,with the ICU-AW group mainly showing an increase in thickness(19.51％±16.51％over 4 days,14.14％±28.13％over 7 days),while the non-ICU-AW group primarily showed atrophy(-16.07％±17.46％over 4 days,-15.55％±30.04％over 7 days).The ICU-AW group had an average increase in rectus femoris thickness of 4.51％±8.38％within 7 days of ICU admission,while the non-ICU-AW group had an average atrophy rate of-8.19％±11.79％.There was no correlation between muscular atrophy rate and PFIT-s score(all P＞0.05),but there was a moderate negative correlation between rectus femoris thickness atrophy rate and femoral intermediate muscle thickness atrophy rate and MRC score within 4 days,respectively(ritual color 0.541 million 0.657 million 0.004),and moderate negative correlation between MRC score and thickness atrophy rate of rectus femoris and vastus medius within 7 days.There was no significant correlation between the atrophy rate of cross-section-al area of rectus femoris and MRC score.Conclusion:Compared with the non-ICU-AW group,the muscle thickness in the ICU-AW group is mainly thickened rather than atrophied,which can be identified by ultrasound on the 4th day after ICU.The specific diagnostic threshold is worthy of further study.