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.

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 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 investigate the efficacy of alveolar lavage combined with montelukast in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and its effect on oxidative stress and inflammatory factors in patients.Methods:A prospective study was conducted involving 90 patients with AECOPD who were admitted to the Intensive Care Unit of Shan County Central Hospital from December 2021 to December 2022. The patients were randomly divided into a control group and an observation group, with 45 patients in each group, using the random number table method. The control group received conventional treatment, while the observation group was additionally treated with alveolar lavage combined with montelukast. Symptom score, Acute Physiology and Chronic Health Evaluation II score, overall response rate, serum levels of oxidative stress markers (malondialdehyde, 4-hydroxynonenal, and superoxide dismutase), and serum levels of inflammatory factors (C-reactive protein, tumor necrosis factor-α, interleukin-6, and procalcitonin) were compared between the two groups before and after treatment.Results:After treatment, the symptom scores for both groups decreased significantly compared with their respective scores before treatment ( t = 6.68, 11.32, both P < 0.05). After treatment, the symptom score in the observation group was significantly lower than that in the control group [(8.69 ± 0.84) points vs. (15.39 ± 1.18) points, t = 8.75, P < 0.05]. After treatment, the Acute Physiology and Chronic Health Evaluation II score in the observation group was significantly lower than that in the control group ( t = 9.19, P < 0.05). The overall response rate in the observation group was significantly higher than that in the control group [93.33% (42/45) vs. 75.56% (34/45), t = 4.56, P < 0.05]. After treatment, serum levels of 4-hydroxynonenal and malondialdehyde in the observation group were significantly lower than those in the control group ( t = 4.20, 5.15, both P < 0.05), while serum level of superoxide dismutase in the observation group was significantly higher than that in the control group ( t = 5.23, P < 0.05). After treatment, serum levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and procalcitonin in the observation group were significantly lower than those in the control group ( t = 6.86, 5.60, 8.75, 4.89, all P < 0.05). Conclusion:Alveolar lavage combined with montelukast can reduce clinical symptoms in patients with AECOPD, promote recovery, enhances clinical efficacy, decreases oxidative stress responses, increases the body's antioxidant capacity, lowers the expression of inflammatory factors, and reduces inflammatory responses.

Objective:To investigate the clinical characteristics and structural and functional cardiac changes in heart failure with preserved ejection fraction(HFpEF)complicated with atrial fibrillation(AF)in elderly patients.Methods:As a cross-sectional study, 835 patients with HFpEF aged ≥60 years admitted to the Department of Geriatric Cardiovascular Medicine of the First Hospital of Lanzhou University between April 2009 and December 2020 were divided into an HFpEF+ AF group(267 cases)and an HFpEF group(568 cases)according to whether they had AF in addition to HFpEF, and their cardiac structure and function were evaluated.The optimal cutoff point of the ratio of the peak early diastolic velocity(E)to the maximum early diastolic velocity(e')of the mitral annulus(E/e')was analysed using the receiver operating characteristic(ROC)curve.The HFpEF+ AF group was divided into two subgroups, E/e'>11 and E/e'≤11, and differences in their clinical presentation, cardiac structural and function, and the relationship between the left and right heart were compared.Results:Compared with the HFpEF group, the left atrial volume index(LAVi)was larger[(60.0±23.3)ml/m 2vs.(43.9±19.0)ml/m 2, t=10.130, P<0.01]and the left ventricular ejection fraction(EF), mitral annular septal systolic velocity(s' S)and E/e' were smaller than in the HFpEF+ AF group(all P<0.01), whereas the right ventricular diameter(RVD), right atrial diameter(RAD)and area(RAA), tricuspid regurgitation velocity(TRv), and pulmonary arterial systolic pressure(PASP)in the HFpEF+ AF group were all greater than those in the HFpEF group(all P<0.05).In the E/e'>11 subgroup of HFpEF+ AF, the prevalence of hypertension, coronary heart disease and diabetes were higher, AF courses were shorter, and the decline of s' was more severe(all P<0.05).Furthermore, E/e' was independently correlated with LAVi, as was LAVi with PASP( t=2.114, 1.963, P=0.034, 0.042).The above-mentioned features were similar to those in the HFpEF group.The E/e'≤11 subgroup had a higher proportion of women, longer duration of AF than the E/e'>11 subgroup(median: 5 years vs.1 year, P=0.003), more noticeable enlargement of the right ventricle and right atrium, higher TRv and PASP( P<0.05). Conclusions:In elderly patients with HFpEF complicated with AF, the left atrial volume is increased further, and left ventricular systolic function and right heart morphology show serious deterioration, suggesting there might be two phenotypes of HFpEF+ AF with different pathophysiological mechanisms.

Objective:To explore the value of quantitative susceptibility mapping (QSM) in evaluating renal injury in patients with early diabetic nephropathy (DN).Methods:From October 2019 to December 2020, 32 patients with early DN were prospectively enrolled in the Third Affiliated Hospital of Soochow University. According to the estimated glomerular filtration rate (eGFR), they were divided into three groups: DN1 (eGFR≥90 ml·min -1·1.73 m -2, 11 cases), DN2 (60-<90 ml·min -1·1.73 m -2, 11 cases) and DN3 (30-<60 ml·min -1·1.73 m -2, 10 cases). At the same time, 32 normal volunteers were recruited as the control group. Both kidneys were scanned by QSM to measure the susceptibility of renal cortex and medulla. Paired samples t-test was used to compare the differences of the susceptibility between left and right kidneys and between cortex and medulla. One-way analysis of variance was performed to compare the differences of corresponding susceptibility values among different groups, and LSD- t was used for the pairwise comparison. Pearson correlation test was performed between the susceptibility value of the medulla and eGFR. The ROC curve was used to analyze the diagnostic efficacy of QSM parameters in the diagnosis of DN and different degrees of severity of DN. Results:The susceptibility values of bilateral renal medulla in normal volunteers and patients with DN were lower than those of renal cortex (all P<0.001). There was no significant difference in the susceptibility value between left and right renal cortex (all P>0.05). There was significant difference in the susceptibility value between left and right medulla (all P<0.05). There was no significant difference in the susceptibility value of bilateral renal cortex among the control group and the DN1－DN3 groups (both P>0.05). The susceptibility values of left renal medulla in control group, DN1, DN2 and DN3 groups were (-4.46±1.16)×10 -2, (-5.96±0.97)×10 -2, (-7.97±1.25)×10 -2, (-9.58±1.45)×10 -2 ppm, of right renal medulla were (-3.70±0.65)×10 -2, (-5.06±1.28)×10 -2, (-7.33±1.46)×10 -2, (-9.09±2.22)×10 -2 ppm, respectively. The overall difference of the susceptibility value of bilateral renal medulla was statistically significant (both P<0.05), and there were significant differences between each two groups (all P<0.05). The linear positive correlation were found between the susceptibility values of renal medulla and the corresponding eGFR (left kidney r=0.732, P<0.001; right kidney r=0.684, P<0.001). The areas under the ROC curve (AUC) of left and right renal medulla susceptibility value in diagnosis of normal and DN were 0.931 and 0.943, of DN1 and DN (2 and 3) were 0.952 and 0.883, of DN (1 and 2) and DN3 were 0.888 and 0.831, respectively. Conclusion:The susceptibility value of QSM quantitative parameter has a certain value in the staging and differential diagnosis of early DN, among which the susceptibility value of renal medulla has higher diagnostic efficiency.

Objective:To investigate the clinical efficacy of hemoperfusion in the treatment of severe organophosphorus poisoning and its effect on diaphragm function.Methods:Eighty-five patients with severe organophosphorus poisoning who received treatment in Affiliated Huxi Hospital of Jining Medical University (Shanxian Central Hospital), China between January 2018 and January 2020 were included in this study. They were randomly divided into treatment ( n = 43)and control ( n = 42) groups. The control group was given conventional treatment including gastric lavage, catharsis, and application of reactivators and anticholinergic drugs. The treatment group was subjected to three times of hemoperfusion, with an interval of 24 hours between two hemoperfusion interventions based on the conventional treatment used in the control group. Before and after three times of hemoperfusion, serum levels of cholinesterase (CHE), interleukin-6 (IL-6), arterial partial pressure of oxygen (PaO 2), and arterial partial pressure of carbon dioxide (PaCO 2) were measured. The Acute Physiology and Chronic Health Evaluation (APACHE) II score and oxygenation index (OI) in each group were calculated. Right diaphragmatic activity, diaphragmatic thickness at the end of inspiration (DTei) and diaphragmatic thickness at the end of expiration were measured by bedside ultrasound. The diaphragmatic thickening rate (DTF) and diaphragmatic rapid shallow breathing index (D-RSBI) were calculated. Serum CHE and IL-6 levels, OI, diaphragmatic activity, DTF and D-RSBI were compared between the treatment and control groups. The incidence of intermediate syndrome, tracheal intubation rate, 28-day mortality rate, and hospital stay were compared between the two groups. Results:Before hemoperfusion, there were no significant differences in serum levels of CHE and IL-6, OI, right diaphragmatic activity, DTF, and D-RSBI between the treatment and control groups (all P > 0.05). After three times of hemoperfusion, serum IL-6 level and D-RSBI in the treatment group were (37.9 ± 6.2) ng/L and (0.77 ± 0.20) times /min/mm, which were significantly lower than those in the control group [(45.9 ± 5.3) ng/L, (0.90 ± 0.16) times/min/mm ( t = -6.295, -3.382, P < 0.001, P = 0.001)]. Serum CHE level, OI, DE and DTF in the treatment group were (2.29 ± 0.52) kU/L, (264.5 ± 24.3) mmHg, (16.5 ± 1.9) mm, (27.2 ± 4.7) %, respectively, which were significantly higher than those in the control group [(1.96 ± 0.39) kU/L, (252.6 ± 27.2) mmHg, (14.3 ± 1.6) mm, (23.5 ± 4.1) %, t = 3.258, 2.141, 5.598, 3.877, all P < 0.05]. The incidence of intermediate syndrome, tracheal intubation rate, hospital stay in the treatment group were [4.7% (2/43)], [2.3% (1/43)] and [(11.8 ± 1.8) days], respectively, which were significantly lower than those in the control group [23.8% (10/42), 19.0% (8/42) and (12.9 ± 1.8) days, χ2 = 6.432, P = 0.011; χ2 = 6.276, P = 0.012; t = -2.932, P = 0.004]. There was no significant difference in 28-day mortality rate between the two groups ( P > 0.05). Conclusion:Hemoperfusion can improve diaphragmatic function, reduce inflammatory reaction and shorten hospital stay in patients with severe organophosphorus poisoning.

Objective:To explore the clinical value of nasal high flow oxygen therapy in patients with acute exacerbation of chronic obstructive pulmonary disease.Methods:From June 2017 to June 2018, 61 patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) admitted to the Huxi Hospital (Shanxian Central Hospital) Affiliated to Jining Medical College were taken as the clinical research objects. The patients were divided into control group and treatment group by using the random number table method with 31 patients in control group and 30 patients in treatment group. They all treated with anti-infection, anti-inflammation, expectoration, spasmolysis, asthma relief, anticoagulation and nutritional support. The control group was given conventional low flow oxygen therapy, while the treatment group was given nasal high flow oxygen therapy. The changes of partial pressure of oxygen (PaO 2), partial pressure of carbon dioxide (PaCO 2), pulmonary artery systolic pressure (PSAP), right ventricular pressure maximum rise rate (dp/dt) and the application rate of non-invasive and invasive mechanical ventilation within 7 d were observed before and 12, 24, 48 and 72 h after treatment. Results:Before treatment, PaO 2, PaCO 2, PSAP and dp/dt of patients in the two groups showed no statistical difference, indicating comparability between groups. Compared with the control group, the PaO 2 in the treatment group decreased at all time points after treatment [(54.37 ± 5.39) mmHg (1 mmHg=0.133 kPa) vs. (57.77 ± 6.06) mmHg, (61.87 ± 5.20) mmHg vs. (65.03 ± 4.91) mmHg, (66.93 ± 6.59) mmHg vs. (72.58 ± 7.13) mmHg, (70.20 ± 8.18) mmHg vs. (75.55 ± 7.37) mmHg, P<0.05]. PaCO 2 decreased [(57.97 ± 6.18) mmHg vs. (61.84 ± 6.20) mmHg, (51.27 ± 4.53) mmHg vs. (55.77 ± 5.87) mmHg, (48.57 ± 5.37) mmHg vs. (51.55 ± 4.62) mmHg, (44.70 ± 5.40) mmHg vs. (47.68 ± 5.86) mmHg, P<0.05]. PSAP all decreased [(50.80 ± 6.94) mmHg vs. (54.55 ± 6.58) mmHg, (48.70 ± 6.22) mmHg vs. (52.55 ± 6.91) mmHg, (45.33 ± 7.51) mmHg vs. (49.19 ± 6.40) mmHg, (41.23 ± 9.22) mmHg vs. (45.94 ± 7.35) mmHg, P<0.05]. Dp/dt all increased [(403.77 ± 109.43) mmHg/s vs. (345.39 ± 112.50) mmHg/s, (429.83 ± 102.56) mmHg/s vs. (369.77 ± 110.55) mmHg/s, (483.43 ± 105.20) mmHg/s vs. (426.48 ± 107.27) mmHg/s, (532.43 ± 107.01) mmHg/s vs. (473.74 ± 105.00) mmHg/s. P<0.05]. The application rate of non-invasive/invasive mechanical ventilation in the treatment group was lower than that in the control group within treated for 7 d ( P<0.05). Conclusions:Transnasal high-flow oxygen therapy has a better clinical effect on patients with chronic obstructive pulmonary disease and is helpful to improve the right heart function.