Exosome-mediated regulatory mechanisms in skeletal muscle: a narrative review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Skeletal muscle plays a paramount role in physical activity, metabolism, and energy balance, while its homeostasis is being challenged by multiple unfavorable factors such as injury, aging, or obesity. Exosomes, a subset of extracellular vesicles, are now recognized as essential mediators of intercellular communication, holding great clinical potential in the treatment of skeletal muscle diseases. Herein, we outline the recent research progress in exosomal isolation, characterization, and mechanism of action, and emphatically discuss current advances in exosomes derived from multiple organs and tissues, and engineered exosomes regarding the regulation of physiological and pathological development of skeletal muscle. These remarkable advances expand our understanding of myogenesis and muscle diseases. Meanwhile, the engineered exosome, as an endogenous nanocarrier combined with advanced design methodologies of biomolecules, will help to open up innovative therapeutic perspectives for the treatment of muscle diseases.

Effect of total flavonoids of Rosa rugosa on PI3K/AKT pathway and endoplasmic reticulum stress apoptosis in rats with cerebral ischemia-reperfusion injury / 中国药理学通报

Aim To investigate the effects of total flavonoids from Rosa rugosa (TFR) on cerebral ischemia reperfusion injury (CIRI) in rats, and to investigate whether TFR inhibited neuronal apoptosis by regulating phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and endoplasmic reticulum stress (ERS) pathways. Methods SD rats were randomly divided into sham operation group, model group, low-dose group (50 mg · kg

Magnetic controlled capsule endoscope (MCCE)'s diagnostic performance for H. pylori infection status based on the Kyoto classification of gastritis.

BACKGROUND: Previous studies have shown that the Kyoto classification of gastritis can accurately predict H. pylori infection status on conventional gastroscopy. The aim of this study was to test whether the Kyoto classification of gastritis applies well to magnetic controlled capsule endoscopy (MCCE). METHODS: We consecutively recruited 227 participants who underwent both MCCE and urea breath tests (UBTs). Two physicians who were blinded to the UBT results independently made the diagnosis of H. pylori infection status according to 10 findings listed in the Kyoto classification of gastritis after reviewing MCCE images. We also developed 2 predictive models to assess H. pylori infection status by combining these 10 findings. RESULTS: The MCCE's overall diagnostic accuracy for H. pylori infection status was 80.2%. The sensitivity, specificity and diagnostic odds ratio (DOR) for current infection were 89.4%, 90.1% and 77.1, respectively. Major specific findings were mucosal swelling and spotty redness for current infection, regular arrangement of collecting venules (RAC), streak redness, fundic gland polyp (FGP) for noninfection, and map-like redness for past-infection. In the two prediction models, the area under the curve (AUC) values for predicting noninfection and current infection were 84.7 and 84.9, respectively. CONCLUSIONS: The Kyoto classification of gastritis applied well to MCCE. H. pylori infection status could be accurately assessed on MCCE according to the Kyoto classification of gastritis.

Preliminary study on differentially expressed proteins in a mouse model of secondary alveolar echinococcosis based on data independent acquisition proteomics / 中国血吸虫病防治杂志

Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of alveolar echinococcosis using high-resolution mass spectrometry with data independent acquisition (DIA), and to identify the key proteins contributing to the pathogenesis of alveolar echinococcosis. Methods Protoscoleces were isolated from Microtus fuscus with alveolar echinococcosis and the experimental model of alveolar echinococcosis was established in female Kunming mice aged 6 to 8 weeks by infection with Echinococcus multilocularis protoscoleces. Mice were divided into the experimental and control groups, and animals in the experimental group was injected with approximately 3 000 protoscoleces, while mice in the control group were injected with the same volume of physiological saline. Mouse liver specimens were sampled from both groups one year post-infection and subjected to pathological examinations. In addition, the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the experimental group and the normal liver specimens (the normal group) were sampled from mice in the control group for DIA proteomics analysis, and the differentially expressed proteins were subjected to bioinformatics analysis. Results A total of 1 020 differentially expressed proteins were identified between the lesion group and the normal group, including 671 up-regulated proteins and 349 down-regulated proteins, and 495 differentially expressed proteins were identified between the peri-lesion group and the normal group, including 327 up-regulated proteins and 168 down-regulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these differentially expressed proteins were involved in peroxisome, peroxisome proliferator-activated receptor (PPAR) and fatty acid degradation pathways, and the peroxisome and PPAR signaling pathways were found to correlate with liver injury. Several differentially expressed proteins that may contribute to the pathogenesis of alveolar echinococcosis were identified in these two pathways, including fatty acid binding protein 1 (Fabp1), Acyl-CoA synthetase long chain family member 1 (Acsl1), Acyl-CoA oxidase 1 (Acox1), Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and Acetyl-Coenzyme A acyltransferase 1B (Acaa1b), which were down-regulated in mice in the experimental group. Conclusion A large number of differentially expressed proteins are identified in the liver of the mouse model of alveolar echinococcosis, and Fabp1, Acsl1, Acox1, Ehhadh and Acaa1b may contribute to the pathogenesis of alveolar echinococcosis.

Preliminary study on differentially expressed proteins in a mouse model of secondary cystic echinococcosis based on data independent acquisition proteomics / 中国血吸虫病防治杂志

Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of cystic echinococcosis (CE), so as to provide insights into the research and development of therapeutic drugs targeting CE. Methods Female Kunming mice at ages of 6 to 8 weeks were randomly assigned into the CE group and the control group. Mice in the CE group were intraperitoneally infected with 2 000 Echinococcus multilocularis protoscoleces, while mice in the control group were injected with the same volume of physiological saline. All mice in both groups were sacrificed after breeding for 350 d, and the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the CE group and the normal liver specimens (the normal group) were sampled from mice in the control group for data independent acquisition (DIA) proteomics analysis, and the differentially expressed proteins were subjected to Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results A total of 26 differentially expressed proteins were identified between the lesion group and the normal group and between the peri-lesion group and the normal group, including 8 up-regulated proteins and 18 down-regulated proteins. GO term enrichment analysis showed that these differentially expressed proteins were predominantly enriched in endoplasmic reticulum membrane (biological components), oxidoreductase activity (molecular function) and oxoacid metabolic process and monocarboxylic acid metabolic process (biological processes). KEGG pathway enrichment analysis revealed that the differentially expressed protein Acyl-CoA oxidase 1 (Acox1), which contributed to primary bile acid biosynthesis during the fatty acid oxidation, was involved in peroxisome signaling pathway, and the differentially expressed protein fatty acid binding protein 1 (Fabp1), which contributed to fatty acid transport, was involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Conclusion Differentially expressed proteins are identified in the liver specimens between mouse models of CE and normal mice, and some differentially expressed proteins may serve as potential drug targets for CE.

Association between outdoor activity, screen time and the performance of 20 meter shuttle run test among children and adolescents / 中国学校卫生

Objective@#To analyze the relationship between outdoor activity, screen time and 20 meter shuttle run test (20 m SRT) score among children and adolescents in Baoan District, Shenzhen, so as to provide scientific basis for the management and promotion of physical health of children and adolescents.@*Methods@#Stratified cluster sampling was used to select students from 14 schools in 6 communities in Baoan District of Shenzhen, from April to May 2019. A self designed questionnaire was used to investigate demographic characteristics, outdoor activity duration and screen time of primary and middle school students. A total of 3 192 primary and secondary school students in grade 1-12 were selected from each school. Weight, height and 20 m SRT were measured.@*Results@#About 985(30.9%) out of 3 192 primary and middle school students were estimated excellent on 20 m SRT test, with boys being higher than that of girls (34.7% vs 26.3%) ( χ 2=26.43, P <0.01). Logistic regression analysis showed that compared with the group with outdoor activity <2 h/d, the excellent and good performers on 20 m SRT with outdoor activity time ≥2 h/d was higher( OR=1.38, 95%CI =1.12-1.70). Compared with students with screen time ≥2 h/d, the excellent and good performers on 20 m SRT with screen time <2 h/d was higher( OR=1.42, 95%CI=1.17-1.71). Compared with students with outdoor activity time < 2 h/d and screen time ≥ 2 h/d, students with outdoor activity time ≥2 h/d and video time < 2 h/d had a higher proportion of excellent score on 20 m SRT( OR=1.97, 95%CI =1.46-2.67).@*Conclusion@#Increasing outdoor activity and reducing screen time are helpful to improve the performance score of 20 m SRT among primary and secondary school students.

Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology / 亚洲男科学杂志(英文版)

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

Modified strict sperm morphology threshold aids in the clinical selection of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) / 亚洲男科学杂志(英文版)

For infertility treatment, the selection of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is decided by multiplying indicators (including fallopian tube factors, semen count, and semen motility), except for sperm morphology. In this study, we conducted a retrospective analysis, from implantation to birth, over a period of 5 years. A total of 1873 couples with primary or secondary fallopian tube factors and an increased defective sperm morphology rate (DSMR) were divided into different groups to receive IVF or ICSI cycles. By comparing the outcomes, we found that the F1 group (DSMR <96%, IVF group 1) had higher cleavage rate, biochemical pregnancy rate, clinical pregnancy rate, and live birth rate than the F3 group (DSMR >98%, IVF group 3; P < 0.05). In contrast, there was no significant difference in the ICSI subgroups. Furthermore, a comparison of the outcomes between IVF and ICSI showed that the S3 group (DSMR >98%, ICSI group 3) had higher cleavage rate (P < 0.001), biochemical pregnancy rate (P < 0.05), clinical pregnancy rate (P < 0.05) and live birth rate (P < 0.05) than the F3 group. However, the ICSI subgroup had a lower two pronuclei fertilization rate than the IVF subgroup (P < 0.05). Our data suggest that the sperm morphology should also be considered when selecting IVF or ICSI combined with other semen parameters before the first assisted reproductive technologies (ART) cycle, especially for males with severe sperm defects.

Analysis of influencing factors of medical cost ratio of breast cancer cases treated with chemotherapy and molecular targeted therapy / 中华医院管理杂志

Objective:To understand the medical cost ratio and its influencing factors of breast cancer chemotherapy and molecular targeted therapy in a hospital, for reference for reasonable control of medical cost.Methods:The first page data of all breast cancer chemotherapy and molecular targeted therapy cases in a tertiary hospital from January to June 2021 were selected to extract the data of age, hospitalization expenses, hospitalization time, complications or complications. The influence of each index on the distribution of medical expense ratio was analyzed by single factor analysis and chi-square test was used for comparison between groups.Results:A total of 3 109 cases of chemotherapy and molecular targeted therapy for breast malignant tumors were included, of which very low-rate, low-rate, high-rate and very high-rate accounted for 7.04%(219 cases), 58.32%(1 813 cases), 30.81%(958 cases) and 3.83%(119 cases) respectively. In addition to the way of admission, there were significant differences in the distribution of medical cost rates under different ages, time consumption index, complications or concomitants, admission departments, treatment methods and medical insurance types( P<0.01). Conclusions:There were many factors affecting the medical cost rate of breast malignant tumors. Relevant departments should expand the pilot scope of DRG payment, promote the multi-disciplinary diagnosis and treatment mode of tumors, refine the DRG grouping scheme, to provide standardized and homogeneous diagnosis and treatment services for tumor patients, and reasonably control the excessive growth of medical costs.

Using magnetic-controlled capsule endoscopy for small intestine screening in physical examination population / 中华健康管理学杂志

Objective:To investigate the application value of magnetic-controlled capsule endoscopy (MCE) for small intestine disease screening in physical examination population.Methods:Physical examination data of 1 230 individuals who received MCE examination from January to December 2019 in institute of Health Management were collected and retrospectively analyzed, and then divided into the gastrointestinal symptoms group and the group without gastrointestinal symptoms. Statistical analysis included the completion rate of MCE, the detection rate for small intestine disease in two groups, the relation between the gastrointestinal symptoms and small intestine diseases.Results:The mean age of the subjects was (54.4±17.3) years. The success rate of completion was 99.43%, and the detection rate of intestine diseases was 30.09%(368/1 230). Different genders and symptoms had no effect on the passage time of MCE through the small intestines, but the passage time of MCE through the small intestines in the age group younger than 50 years old [(242.9±88.7) min] was significantly less than in the age group greater than or equal to 50 years old [(336.4±112.1) min]( P<0.05). The detection rate of a duodenal bulbal ulcer and duodenitis was 1.73% (11/635) and 6.14% (39/635) respectively, in the symptomatic group, which were significantly higher than in the asymptomatic group 0.17%(1/595)及2.02%(20/595)( P<0.05). However, there was no significant difference in the detection rate of positive lesions between the two groups. Conclusion:There is a certain incidence of small intestinal diseases in people undergoing physical examinations. Magnetic-controlled capsule endoscopy can effectively complete the screening and diagnosis of small intestinal diseases while completing stomach examination, which is an effective tool for early diagnosis and prevention of small intestinal diseases in people undergoing physical examinations.

Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl4, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl4-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl4-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

circZNF124 regulates the proliferation, migration and invasion of colorectal cancer SW620 cells by targeting miR-4262 / 中国临床药理学与治疗学

AIM: To explore the effect and mechanism of circZNF124 on the proliferation, migration and invasion of colorectal cancer SW620 cells. METHODS: The expression levels of circZNF124 and miR-4262 in colorectal cancer tissues were measured by qRT-PCR method. Human colorectal cancer cells SW620 were cultured in vitro, and were randomly grouped into si-NC group, si-circZNF124 group, miR-NC group, miR-4262 group, si-circZNF124 j anti-miR-NC group, si-circZNF124 j antimiR-4262 groups. CCK-8 method, plate clone formation test, scratch test and Transwell test respectively were used to detect cell proliferation, clone formation, migration and invasion of SW620 cells. The dual luciferase reporter experiment analyzed the targeted binding of circZNF124 to miR-4262. Western blot was used to detect the expression of E-cadherin and N-cadherin protein. RESULTS: The expression of circZNF124 in colorectal cancer tissue was increased by about 3.75 times compared with that in the adjacent tissue (P i 0.05), and the expression of miR-4262 was decreased by about 0.73 times compared with the adjacent tissue (P i 0.05). Compared with the si-NC group, the cell viability, scratch healing rate and the protein level of N-cadherin in the si-circZNF124 group were decreased (P i 0.05), the number of cell clone formation and the number of invasive cells were decreased (P i 0.05), while the protein level of E-cadherin was increased (P i 0.05). circZNF124 could negatively regulate the expression of miR-4262. Compared with the miR-NC group, the cell viability, scratch healing rate and the protein level of N-cadherin in the miR-4262 group were reduced (P i 0.05), the number of cell clones and the number of invasive cells were reduced (P i 0.05), while the protein level of E-cadherin was increased (P i 0.05). Inhibition of miR-4262 expression reversed the effect of interfering circZNF124 expression on the proliferation, migration and invasion of SW620 cells.CONCLUSION: Interference with the expression of circZNF124 can attenuate the proliferation, migration and invasion of colorectal cancer cells by targeting miR-4262.

A Carboxyl-Functionalized Covalent Organic Framework Synthesized in a Deep Eutectic Solvent for Dye Adsorption.

Instead of using organic solvents, a deep eutectic solvent (DES) composed of tetrabutylammonium bromide and imidazole (Bu4 NBr/Im) was employed as a solvent for the first time to synthesize covalent organic frameworks (COFs). Due to the low vapor pressure of the Bu4 NBr/Im-based DES, a new carboxyl-functionalized COF (TpPa-COOH) was synthesized under environmental pressure. The as-synthesized TpPa-COOH has open channels, and the DES can be removed completely from the pores. The dye adsorption performance of TpPa-COOH was examined for three organic dyes with similar molecular sizes: one anionic dye (eosin B, EB) and two cationic dyes (methylene blue, MB and safranine T, ST). TpPa-COOH showed an excellent selective adsorption effect on MB and ST. The electronegative keto form in TpPa-COOH might help to form electrostatic and π-π interactions between the π-stacking frameworks of TpPa-COOH and the positive plane MB and ST molecules. The adsorption isotherms of MB and ST on TpPa-COOH were further investigated in detail, and the equilibrium adsorption was well modeled by using a Langmuir isotherm model. Together with hydrogen bonding, TpPa-COOH showed higher adsorption capacity for ST than for MB (1135 vs. 410 mg g-1 ). These results could provide a guidance for the green synthesis of adsorbents in removing organic dyes from wastewater.

Establishment of A Mixed Chimeric Mouse Model of Allogeneic Bone Marrow Transplantation and Its Influencing Factors / 中国实验血液学杂志

OBJECTIVE@#To establish a mouse mixed chimerism (MC) model of nonmyeloablative allogeneic bone marrow transplantation(allo-BMT) and explore its affecting factors.@*METHODS@#The MC model was established by nonmyeloablative allo-BMT followed by high-dose post-transplant cyclophosphamide (PTCY). 123 mice in the experiments was retrospectively analyzed, and the factors related with the chimerism were explored with the univariate and multivariate logistic regression analysis. A multivariate linear regression was performed by R project to obtain a mathematical model for predicting the chimeric level with relevant affecting factors.@*RESULTS@#The model presented mixed chimerism on day 14 after transplantation, and was characterized by a donor lymphocyte infusion (DLI) which significantly promoted donor engraftment on day 15, but transfplantation of PBS in control group was failed. Among 123 mice, 47 (38.21%) mice were MC, while 76 (61.79%) mice were non-MC in 123 mice, respectively; univariate analysis showed that the baseline body weight of mice (P=0.001, 17.84±1.19 g vs 18.50±0.94 g), total body irradiation(TBI，P=0.048) and the using of cyclophosphamide (P=0.16) were affected the chimeric state of mice, while the number of infusing cells and the time of detection showed no significant effects. Multivariate regression analysis showed that under certain conditions, the body weight of mice on day 0 was an independent factor affecting chimeric levels (OR=0.493, 95% CI 0.307-0.791, P=0.003). Through R project multiple linear regression, the math model was achieved, which was chimerism=6.09-12×weight(g)+80.03×TBI(Gy)-4.4×cell-counts (× 10@*CONCLUSION@#The experiment presents a method for establishing a mixed chimeric mice model after non-myeloablative bone marrow transplantation and constructs a mathematical model with relevant factors affected chimerism status.

Using magnetic-controlled capsule endoscopy for small in testine screening in physical examination population / 中华健康管理学杂志

Objective:To investigate the application value of magnetic-controlled capsule endoscopy (MCE) for small intestine disease screening in physical examination population.Methods:Physical examination data of 1 230 individuals who received MCE examination from January to December 2019 in Health Research institutes were collected and retrospectively analyzed, and then divided into the gastrointestinal symptoms group and the group without gastrointestinal symptoms. Statistical analysis in cluded the completion rate of MCE, the detection rate for small intestine disease in two groups, the relation between the gastrointestinal symptom and small intestine diseases.Results:The mean age of the subjects was (54.4±17.3) years. The success rate of completion was 99.43%, and the detection rate of intestine diseases was 30.09%(368/1 230). Different genders and symptoms had no effect on the passage time of MCE through the small intestines, but the passage time of MCE through the small intestine in the age group younger than 50 years old [(242.9±88.7) min] was significantly less than in the age group greater than or equal to 50 years old [(336.4±112.1) min]( P<0.05). The detection rate of a duodenal bulbal ulcer and duodenitis was 1.73% (11/635) and 6.14% (39/635), respectively, in the symptomatic group, which were significantly higher than in the asymptomatic group 0.17%(1/595)及2.02%(20/595)( P<0.05). However, there was no significant difference in the detection rate of positive lesions between the two groups. Conclusion:There is a certain incidence of small intestinal diseases in people undergoing physical examinations. Magnetic-controlled capsule endoscopy can effectively complete the screening and diagnosis of small intestinal diseases while completing stomach examination, which is an effective tool for early diagnosis and prevention of small intestinal diseases in people undergoing physical examinations.

Clinical analysis of golimumab in the treatment of severe/refractory cardiovascular involvement in Behcet syndrome / 北京大学学报(医学版)

OBJECTIVE@#To explore the effectiveness and safety of golimumab in the treatment of severe/refractory cardiovascular Behcet syndrome (BS).@*METHODS@#We retrospectively analyzed the clinical data of nine patients diagnosed with severe/refractory cardiovascular BS and treated with golimumab from February 2018 to July 2020 in Peking Union Medical College Hospital. We analyzed levels of erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hsCRP), imaging findings, and the doses of glucocorticoids and immunosuppressive agents during the period of combined treatment with golimumab.@*RESULTS@#Nine patients were enrolled, including 8 males and 1 female, with a mean age and median course of (37.0±8.6) years and 120 (60, 132) months, respectively. Seven patients presented with severe aortic regurgitation combined with other cardiovascular involvement secondary to BS. Two patients presented with large vessel involvement, including multiple aneurysms and vein thrombosis. Prior to golimumab treatment, seven patients were treated with glucocorticoids and multiple immunosuppres-sants [with a median number of 3 (1, 3) types] while still experienced disease progression or elevated inflammation biomarkers during postoperative period. Eight patients with disease progression, uncontrolled inflammation and history of severe postoperative complications required effective and fast control of inflammation during perioperative period. One patient had adverse reaction with tocilizumab and switched to golimumab during perioperative period. The patients were treated with golimumab 50 mg every 4 weeks, along with concomitant treatment of glucocorticoid and immunosuppressants. After a median follow-up of (16.3±5.6) months, all the patients achieved clinical improvement. Vascular lesions were radiologically stable and no vascular progressive or newly-onset of vascular lesions was observed. The eight patients who experienced cardiac or vascular operations showed no evidence of postoperative complications. The ESR and hsCRP levels decreased significantly [16.5 (6.8, 52.5) mm/h vs. 4 (2, 7) mm/h, and 21.24 (0.93, 32.51) mg/L vs. 0.58 (0.37, 1.79) mg/L (P < 0.05), respectively]. The dose of prednisone was tapered from 35 (15, 60) mg/d to 10.0 (10.0, 12.5) mg/d. No prominent adverse reactions were observed.@*CONCLUSION@#Our study suggests that golimumab is effective in the treatment of severe/refractory cardiovascular BS. Combination immunosuppression therapy with golimumab contributes to control of inflammation, reduction of postoperative complications and tapering the dose of glucocorticoids or immunosuppressants.

A new non-invasive liver disease model to judge the prognosis of patients with acute upper gastrointestinal hemorrhage due to cirrhosis / 中国医师杂志

Objective@#To evaluate the accuracy of the new non-invasive liver disease model platelet-albumin-bilirubin index (PALBI) in the diagnosis of patients with acute upper gastrointestinal hemorrhage (AUGIB) due to cirrhosis.@*Methods@#277 patients with AUGIB due to cirrhosis were analyzed retrospectively. The data of platelet, total bilirubin, albumin, creatinine, international standardized ratio and etiology of cirrhosis were collected. Univariate and multivariate logistic regression analysis was used to identify independent risk factors for death in patients with cirrhosis complicated by AUGIB. Analysis of variance was used to compare the differences between the model for end-stage liver disease (MELD) and PALBI grades. Pearson correlation analysis was used to assess the association between MELD and PALBI. The operating characteristic curve (ROC) was used to compare the predictive power of both for short-term and long-term mortality in patients with cirrhosis complicated by AUGIB.@*Results@#The short-term and long-term mortality rates of patients with cirrhosis complicated by AUGIB were 13.7% and 23.5%, respectively. The average hospital stay was (9.1±3.9)days. The high MELD score and high PALBI index were confirmed as independent risk factors of death by single factor and multiple factors [odds ratio (OR)=1.17, 4.43; P<0.05]; the Pearson correlation analysis showed there was a positive correlation between MELD score and PALBI index (r=0.735, P<0.05). The PALBI score was scored in MELD-a patients, further subdivided into PALBI-1a and PALBI-1b. There were statistical difference in the 1-year mortality rate between the two groups (7.0% vs 17.8%, χ2=4.033, P<0.05). The ROC curve was used to compare the predictive power of MELD and PALBI for short-term mortality. The area under curve (AUC) of PALBI was 0.767 (95% CI: 0.712-0.815), while the AUC of the MELD score was 0.651 (95% CI: 0.591-0.707), with statistically significant difference (Z=2.328, P<0.05). The predictive power of PALBI and MELD for long-term mortality were 0.731(95% CI: 0.674-0.782), 0.754 (95% CI: 0.699-0.804), but the difference was not statistically significant (Z=0.828, P>0.05).@*Conclusions@#PALBI has a better predictive effect on patients with cirrhosis complicated by AUGIB than MELD scores. PALBI can achieve a more precise prognosis classification for patients with MELD-a, and maintain a good prediction ability on the short-term (within 30 days of hospitalization and discharge) and long-term (within 1 year after discharge) mortality of patients. As a new liver disease model, PALBI can be used as an effective non-invasive means to judge the prognosis of patients with liver cirrhosis complicated by AUGIB .

Effect of Panax Notoginseng Saponins on Breast Cancer Cell Line 4T1 in Tumor-bearing Mice Through MEKK1/SEK1/JNK1/AP-1 Pathway / 中国实验方剂学杂志

Objective:To explore the potential mechanisms of Panax Notoginseng Saponins （PNS） on growth inhibition of breast cancer cell line 4T1 in tumor-bearing mice by investigating the mitogen-activated protein kinase kinase kinase 1 （MEKK1）/stress activated protein kinase （SAPK）/extracellular regulated protein kinases （Erk） Kinase （SEK1）/c-Jun N-terminal kinase 1 （JNK1）/activator protein-1 （AP-1） signaling pathways. Method:The 4T1 breast cancer mice model was established. Forty-eight mice with successful modeled and randomly divided into the low， medium and high-dose PNS groups （10， 20， 40 mg·kg-1） and the model control group （12 mice in each group）. The PNS groups received intraperitoneal injection with dosage of 10 mL·kg-1， while the controlled group was given the same dosage of saline. After administration with PNS for 28 days， tumor tissues were isolated， weighed， sliced and homogenized. Tumor cell apoptosis was detected by TdT mediated-dUTP nick end labeling （TUNEL） staining. The mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by Real-time polymerase chain reaction（Real-time PCR）. The protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by immunofluorescence staining and Western blot. Result:Compared with model group， the tumor weights of medium-dose and high-dose PNS groups were decreased significantly （P<0.05）. TUNEL staining showed that the number of apoptotic tumor cells increased with the rise of dosage of PNS （P<0.05）. The medium-dose and high-dose PNS groups showed a significant increase in the mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 as well as the protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissues （P<0.05）， with statistically significant differences （P<0.05）. Conclusion:PNS could inhibit the tumor growth of breast cancer cell line 4T1 in tumor-bearing mice， which may be related to the activation of MEKK1/SEK1/JNK1/AP-1 signaling pathways.