ObjectiveTo investigate the effects of hypoxia-treated mesenchymal stem cell （MSCs） exosomes （Exo） and their loading with curcumin on microglial inflammatory responses， and to explore the enhancing effect of hypoxia treatment on the function of MSCs Exo. MethodsThe supernatants of human umbilical cord （hUC）-MSCs cultured under normal and hypoxic conditions were collected， and Exo were isolated using ultracentrifugation. After identification by transmission electron microscopy and Western blot， curcumin was loaded using the co-incubation method. The lipopolysaccharide （LPS）-induced microglial inflammation model was treated with dimethyl sulfoxide （DMSO）， curcumin， normoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin， respectively. The expression of the M1-type marker inducible nitric oxide synthase （iNOS） in BV2 cells was detected by immunofluorescence （IF）. Western blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the expression and secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in the cells and their culture supernatants. ResultsNormoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin exhibited a "saucer-like" shape with a diameter ranging from 30~150 nm， and the expression of exosomal markers CD9， CD81， and TSG101 were positive. After treating the BV2 cell inflammation model， IF results showed that， compared with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression of iNOS. Moreover， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， the expression level of iNOS significantly decreased after treatment with hypoxic Exo loaded with curcumin. The results of Western blot and ELISA indicated that， in comparison with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression and secretion of the inflammatory cytokines TNF-α， IL-1β， and IL-6. Additionally， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， both the expression and secretion of TNF-α， IL-1β， and IL-6 significantly decreased after treatment with hypoxic Exo loaded with curcumin. ConclusionHypoxia preconditioning can enhance the ability of hUC-MSCs-Exo in the inhibition of microglial polarization and inflammatory factors’ secretion. Additionally， using Hypoxia-MSCs-Exo as a drug-delivery carrier of curcumin can improve its solubility and stability， facilitating its absorption by cells and exerting the therapeutic effect of combination therapy.

Objective:To determine the best scoring system for assessing the severity of perioperative aortic dissection.Methods:All data were obtained from the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ) database in the United States. The predictive value of the Acute Physiology Score Ⅲ(APS Ⅲ), Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score Ⅱ(SAPS Ⅱ), and Charlson Comorbidity Index (CCI) scoring systems were evaluated using the receiver operating characteristic ( ROC) curve. The area under the curve ( AUC) was used to determine the best predictive score, and the ideal cutoff value of the score was calculated based on the Youden index. Patients were divided into high and low groups according to the cutoff value. The Kaplan- Meier curve was used to show the impact on the survival rate of patients with aortic dissection. Results:ROC curve analysis showed that APS Ⅲ( AUC: 0.803, 95% CI: 0.721-0.885) was superior to SAPS Ⅱ( AUC: 0.767, 95% CI: 0.654-0.880), OASIS( AUC: 0.760, 95% CI: 0.635-0.885), SOFA( AUC: 0.753, 95% CI: 0.649-0.857), and CCI( AUC: 0.670, 95% CI: 0.524-0.817) in assessing in-hospital mortality. Based on the ROC curve and the Youden index calculation, the ideal cutoff value of the APS Ⅲ score was 57.5. Kaplan- Meier survival analysis showed that patients in the high group of APS Ⅲ had a shorter 28-day survival time. Patients in the high group of APS Ⅲ had a higher incidence of postoperative complications, and correlation analysis showed that patients in the high group of APS Ⅲ had a longer hospital stay. Conclusion:The APS Ⅲ scoring system is more valuable in predicting the 28-day mortality and prognosis of patients with aortic dissection.

Objective:To determine the best scoring system for assessing the severity of perioperative aortic dissection.Methods:All data were obtained from the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ) database in the United States. The predictive value of the Acute Physiology Score Ⅲ(APS Ⅲ), Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score Ⅱ(SAPS Ⅱ), and Charlson Comorbidity Index (CCI) scoring systems were evaluated using the receiver operating characteristic ( ROC) curve. The area under the curve ( AUC) was used to determine the best predictive score, and the ideal cutoff value of the score was calculated based on the Youden index. Patients were divided into high and low groups according to the cutoff value. The Kaplan- Meier curve was used to show the impact on the survival rate of patients with aortic dissection. Results:ROC curve analysis showed that APS Ⅲ( AUC: 0.803, 95% CI: 0.721-0.885) was superior to SAPS Ⅱ( AUC: 0.767, 95% CI: 0.654-0.880), OASIS( AUC: 0.760, 95% CI: 0.635-0.885), SOFA( AUC: 0.753, 95% CI: 0.649-0.857), and CCI( AUC: 0.670, 95% CI: 0.524-0.817) in assessing in-hospital mortality. Based on the ROC curve and the Youden index calculation, the ideal cutoff value of the APS Ⅲ score was 57.5. Kaplan- Meier survival analysis showed that patients in the high group of APS Ⅲ had a shorter 28-day survival time. Patients in the high group of APS Ⅲ had a higher incidence of postoperative complications, and correlation analysis showed that patients in the high group of APS Ⅲ had a longer hospital stay. Conclusion:The APS Ⅲ scoring system is more valuable in predicting the 28-day mortality and prognosis of patients with aortic dissection.

Abstract: Objective　To construct a mouse model of Schistosoma japonicum liver disease induced by direct injection of Schistosoma japonicum eggs through the portal vein and evaluate its effectiveness, in order to provide a new animal model for schistosomiasis liver disease research. Methods　Fifteen 8-week-old C57BL/6 male mice were randomly divided into control group and egg injection group, with 5 in the control group and 10 in the egg injection group. On day -14, 5 000 live eggs were injected into the abdominal cavity of mice, and on day 0, the mice were anesthetized and the abdominal cavity was opened. 5 000 live eggs were injected through the portal vein, and the control group was injected with equal volume of phosphate buffer (PBS). 5 mice in the egg group were killed on day 10 and 30, respectively. The control group mice were killed on day 10, and their serum and liver tissue were collected. Hematoxylin eosin staining (HE) and Masson staining were performed, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver hydroxyproline (HYP) content were detected using a microplate spectrophotometer. Liver fibrosis-related genes, Th1 and Th2 type immune response-related genes were analyzed by real-time fluorescence quantitative PCR (qPCR). Liver injury, egg granuloma and fibrosis, and adaptive immune response were detected to evaluate the effect of portal vein injection of eggs while inducing mouse model of schistosomiasis liver disease. Results　The results showed that significant egg granulomas appeared in the liver of mice after injection of eggs into the portal vein for 10 and 30 days. There was no statistically significant difference in the area of egg granulomas between the 10-day group and the 30-day group (t=0.975, P=0.332). Masson staining and liver hydroxyproline content detection showed significant fibrosis in the liver. The qPCR results showed that, compared with the control group, the expression levels of fibrosis marker genes, such as α⁃Sma (alpha smooth muscle actin), Col1a1 (collagen type Ⅰ alpha 1), and Tgfb1 (transforming growth factor beta 1), were significantly increased (t=6.380, 7.533, 5.314; P=0.002, 0.001, 0.007), and then decreased on the 30th day, with no statistical difference compared to the control group (t=0.940, 1.529, 1.746; P=0.778, 0.543, 0.457). At the same time, the expression levels of Th1 type immune response-related genes, such as tumor necrosis factor alpha (Tnf), interferon gamma (Ifng), and Th2 type immune response-related genes, such as interleukin-5 (Il5), interleukin-13 (Il13), significantly increased 10 days after eggs injection (t=6.163, 4.589, 5.651, 5.367; P=0.003, 0.018, 0.020, 0.009). In addition, there was no significant change in the levels of AST and ALT in the serum of each group of mice (t=0.982, 3.450; P=0.771, 0.074. t=1.164, 0.564; P=0.697, 0.917). Conclusions　A mouse model of schistosomiasis liver disease induced by portal vein injection of worm eggs was constructed. The study provides a new modeling method for studying the mechanism of liver fibrosis in schistosomiasis..

Objective:To investigate the effect and mechanism of miR-195 regulating FOXK1 gene and PI3K/Akt pathway on stomach adenocarcinoma proliferation, invasion and migration ability.Methods:Public database samples were employed to analyze the expression differences and prognostic significance of miR-195 in stomach adenocarcinoma. After overexpression of mir-195-5p in two cell lines, MGC803 and AGS, altered cell proliferation, invasion, and migration abilities were detected by Alamar Blue, Wound healing, and Transwell assays. The potential target genes and binding sites of miR-195 were predicted by the starBase. Western blot was used to detect the expression levels of foxk1 and phosphorylation sites in the PI3K/Akt pathway of target genes after overexpression of mir-195-5p. A Dual-luciferase reporter assay was used to verify the relationship between mir-195-5p and foxk1. Statistical analyses were performed with IBM SPSS 22 software and R 4.0.3.Results:Our results showed a significant over-expression of miR-195 in the tumor tissues, compared with the paired normal tissues ( P<0.001) , which could inhibit the proliferation and invasion of stomach carcinoma cells and significantly correlated with survival ( P=0.011) . Moreover, our study indicated that miR-195 depressed the expression of FOXK1 and significantly reduced the activation of the PI3K/Akt pathway, which had a negative effect on the proliferation and invasion of stomach carcinoma cells. The phosphorylated Akt (s473 site) expression in the PI3K/Akt pathway was significantly decreased after overexpression of miR-195. Conclusion:Overall, our studies clarify the important function of the miR-195 in the diagnosis and therapy of patients with stomach carcinoma and reveal the FOXK1 and PI3K/Akt pathway regulation by the miR-195, which are of important clinical significance in the differential diagnosis.

A 62-year-old female osteoporosis patient received alendronate sodium 70 mg orally once a week (taking the drug 30 minutes before breakfast with plenty of water and keeping upright during and after taking drug for a while). After taking the drug for 3 times, the patient developed retrosternal pain on swallowing with occasional acid aversion and epigastric dull pain. Gastroscopy showed multiple shallow ulcers, with yellow and white fur on the surface, in the esophagus 20 cm to 37 cm from the incisors. Esophagitis was considered, which might be related to alendronate sodium. Alendronate was stopped, and the treatments of acid suppression, mucosal repair, proper rehydration, and total liquid intake were given. Two days later, the stabbing pain behind the sternum was relieved; 7 days later, the pain was obviously relieved and symptoms of the acid aversion and epigastric dull pain disappeared; 1 month later, the retrosternal pain on swallowing disappeared.

A 62-year-old female osteoporosis patient received alendronate sodium 70 mg orally once a week (taking the drug 30 minutes before breakfast with plenty of water and keeping upright during and after taking drug for a while). After taking the drug for 3 times, the patient developed retrosternal pain on swallowing with occasional acid aversion and epigastric dull pain. Gastroscopy showed multiple shallow ulcers, with yellow and white fur on the surface, in the esophagus 20 cm to 37 cm from the incisors. Esophagitis was considered, which might be related to alendronate sodium. Alendronate was stopped, and the treatments of acid suppression, mucosal repair, proper rehydration, and total liquid intake were given. Two days later, the stabbing pain behind the sternum was relieved; 7 days later, the pain was obviously relieved and symptoms of the acid aversion and epigastric dull pain disappeared; 1 month later, the retrosternal pain on swallowing disappeared.

Objective:To compare the clinical efficacy between puncture assisted by a "TINAVI" orthopaedic robot versus freehand puncture in vertebroplaty for osteoporotic vertebral compression fracture(OVCF) of the upper thoracic vertebra.Methods:A retrospective study was conducted of the 19 patients (20 vertebral bodies) with OVCF of the upper thoracic vertebra who had been treated at Department of Spine Surgery, Honghui Hospital from January 2018 to March 2019 by robotic vertebroplasty (robot group) and of another 21 counterpart patients (21 vertebral bodies) who had been treated by conventional vertebroplasty from January 2016 to December 2017 (freehand group). Puncture was conducted by a "TINAVI" orthopaedic robot in the robotic vertebroplasty but freehand in the conventional vertebroplasty. The robot group had 5 males and 14 females, aged from 62 to 88 years; the freehand group had 6 males and 15 females, aged from 64 to 83 years. The 2 groups were compared in terms of operation time, bone cement volume, postoperative complications (cement leakage, infection and embolism), visual analogue scale (VAS), Oswestry disability index (ODI), anterior height (AH) and kyphosis angulation (KA) of the injured vertebra at day 1 and last follow-up after surgery.Results:The 2 groups were comparable because there were no significant differences between them in the preoperative general data ( P>0.05). Vertebroplasty via unilateral puncture approach was completed uneventfully in the 19 patients (20 vertebral bodies) in the robot group and in the 21 patients (21 vertebral bodies) in the freehand group. The 40 patients were followed up for 6 to 12 months (mean, 8.3 month). The operation time [(37.9±8.2) min], bone cement volume [(2.3±0.9) mL] and rate of cement leakage (10.0%, 2/20) in the robot group were all significantly less or lower than those in the freehand group [(46.2±9.4) min, (4.2±1.3) mL and 42.9% (9/21)] ( P<0.05). No infection or embolism was observed in either group. There were no significant differences between the 2 groups in VAS, ODI, AH or KA of the injured vertebra at day 1 or last follow-up after surgery ( P>0.05). Conclusion:In vertebroplaty for OVCF of the upper thoracic vertebra, compared with conventional freehand puncture, puncture assisted by a "TINAVI" orthopaedic robot can lead to satisfactory clinical efficacy because it reduces operation time, volume of bone cement injection, and thus incidence of bone cement leakage.

ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P＜0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII ＞758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of ＞50% and a mean survival time of 55.584 months (95% confidence interval［CI］: 53550-57.617), while the high SII group had a cumulative survival rate of ＜50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P＜005). The univariate analysis showed that SII ＞758.92 (hazard ratio ［HR］=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses