ObjectiveTo observe the effect of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on high-fat diet-induced apolipoprotein E gene knockout （ApoE^-/-） mice， and explore its mechanism of treating atherosclerosis by regulating intestinal flora. MethodThirty-two 8-week-old male ApoE^-/- mice were randomly divided into model group， rosuvastatin group （10 mg·kg^-1）， high-， low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis （75， 25 mg·kg^-1）， with 8 mice in each group. Eight C57BL/6 mice were used as blank group. After 8 weeks of continuous administration， blood was taken to determine the blood lipid level. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of related indexes in serum of mice. Hematoxylin-eosin （HE） staining was used to observe the formation of aortic plaque in mice. Cecal contents were collected and 16S rRNA amplicon sequencing was used to detect intestinal flora. ResultCompared with the blank group， the plaque area of the model group was significantly increased with inflammatory infiltration， the contents of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， inflammatory factors and inducible nitric oxide synthase （iNOS） were increased， while the content of high-density lipoprotein cholesterol （HDL-C） was decreased. Compared with the model group， rosuvastatin group and high- and low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could improve the deposition of aortic plaque， reduce the contents of TG， TC， LDL-C， inflammatory factors and iNOS， and increase the content of HDL-C. Compared with the blank group， the relative abundances of Firmicutes and Proteobacteria in the model group increased， while the relative abundance of Bacteroidetes decreased. Alpha and Beta diversity analysis showed that samples of each group could be significantly isolated， and the total number and abundance of intestinal flora species in the model group were low. Compared with the model group， ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could increase the relative abundance of beneficial bacteria and decrease the relative abundance of pathogenic bacteria. ConclusionEthyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis was mainly composed of flavonoids， which can treat atherosclerosis by regulating the intestinal flora and improve the pathological changes in the aorta of ApoE^-/- mice induced by high-fat diet. The mechanism may be related to its ability to reduce the level of inflammatory factors， improve antioxidant capacity and repair the disorder of intestinal flora structure.

Objective: To compare the effects of three treatment options: emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery, on the pathological characteris- tics of surgically-resected specimens from patients with completely obstructive colorectal cancer. Methods: This was a retrospective cohort study analyzing clinicopathological data of patients with complete obstructive colorectal cancer who were admitted to the General Surgery Department of Beijing Chaoyang Hospital, Capital Medical University, between May 2012 and August 2020. The inclusion criteria were diagnosed with complete colorectal obstruction, pathologically confirmed as adenocarcinoma, resectable on imaging assessment, and without distant metastasis, combined with the patients' clinical manifestations and imaging examination findings. Patients with multiple colorectal cancers, refusal to undergo surgery, and concurrent peritonitis or intestinal perforation before stenting of the intestinal obstruction were excluded. Eighty-nine patients with completely obstructive colorectal cancer were enrolled in the study and were divided into emergency surgery group (n=30), stent-surgery group (n=34), and stent-neoadjuvant chemotherapy- surgery group (n=25) according to the treatment strategy. Differences in the pathological features (namely perineural infiltration, lymphovascular infiltration, tumor deposits, specimen intravascular necrosis, inflammatory infiltration, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cell ratio) and biomolecular markers (namely cluster of differentiation (CD)34, Ki67, Bcl-2, matrix metalloproteinase-9, and hypoxia-inducible factor alpha) were recorded. Pathological evaluation was based on the presence or absence of qualitative evaluation of pathological features, such as peripheral nerve infiltration, vascular infiltration, and cancer nodules within the specimens. The evaluation criteria for the pathological features of the specimens were as follows: Semi-quantitative graded evaluation based on the proportion of tissue necrosis, inflammatory infiltrates, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cells in the field of view within the specimen were classified as: grade 0: not seen within the specimen; grade 1: 0-25%; grade 2: 25%-50%; grade 3: 50%-75%; and grade 4: 75%-100%. The intensity of cellular immunity was classified as none (0 points), weak (1 point), moderate (2 points), and strong (3 points). The two evaluation scores were then multiplied to obtain a total score of 0-12. The immunohistochemical results were also evaluated comprehensively, and the results were defined as: negative (grade 0): 0 points; weakly positive (grade 1): 1-3 points; moderately positive (grade 2): 4-6 points; strongly positive (grade 3): 7-9 points; and very strong positive (grade 4): 10-12 points. Normally-distributed values were expressed as mean±standard deviation, and one-way analysis of variance was used to analyze the differences between the groups. Non-normally-distributed values were expressed as median (interquartile range: Q1, Q3). A nonparametric test (Kruskal-Wallis H test) was used for comparisons between groups. Results: The differences were not statistically significant when comparing the baseline data for age, gender, tumor site, American Society of Anesthesiologists score, tumor T-stage, N-stage, and degree of differentiation among the three groups (all P>0.05). The differences were not statistically significant when comparing the pathological characteristics of the resected tumor specimens, such as foreign body giant cells, inflammatory infiltration, and mucus lake formation among the three groups (all P>0.05). The rates of vascular infiltration were 56.6% (17/30), 41.2% (15/34), and 20.0% (5/25) in the emergency surgery, stent-surgery, and stent- neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences between the groups (χ²=7.142, P=0.028). Additionally, the rate of vascular infiltration was significantly lower in the stent-neoadjuvant chemotherapy-surgery group than that in the emergency surgery group (P=0.038). Peripheral nerve infiltration rates were 55.3% (16/30), 41.2% (14/34), and 16.0% (4/25), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (χ²=7.735, P=0.021). The infiltration peripheral nerve rates in the stent-neoadjuvant chemotherapy-surgery group were significantly lower than those in the emergency surgery group (P=0.032). The necrosis grade was 2 (1, 2), 2 (1, 3), and 2 (2, 3) in the emergency surgery, stent- surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=10.090, P=0.006). Post hoc comparison revealed that the necrosis grade was higher in the stent-surgery and stent-neoadjuvant chemotherapy-surgery groups compared with the emergency surgery group (both P<0.05). The abscess grade was 2 (1, 2), 3 (1, 3), and 2 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=6.584, P=0.037). Post hoc comparison revealed that the abscess grade in the emergency surgery group was significantly lower than that in the stent-surgery group (P=0.037). The fibrosis grade was 2 (1, 3), 3 (2, 3), and 3 (2, 3), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=11.078, P=0.004). Post hoc analysis revealed that the fibrosis degree was higher in both the stent-surgery group and the stent- neoadjuvant chemotherapy-surgery group compared with the emergency surgery group (both, P<0.05). The tumor cell ratio grades were 4 (3, 4), 4 (3, 4), and 3 (2, 4), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=8.594, P=0.014). Post hoc analysis showed that the tumor cell ratio in the stent-neoadjuvant chemotherapy-surgery group was significantly lower than that in the emergency surgery group (P=0.012). The CD34 grades were 2 (2, 3), 3 (2, 4), and 3 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, and the difference was statistically significant (H=9.786, P=0.007). Post hoc analysis showed that the CD34 grades in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups were 2 (2, 3), 3 (2, 4), and 3 (2,3), respectively. Post hoc analysis revealed that the CD34 concentration was higher in the stent-surgery group than that in the emergency surgery group (P=0.005). Conclusion: Stenting may increase the risk of distant metastases in obstructive colorectal cancer. The stent-neoadjuvant chemotherapy-surgery treatment model promotes tumor cell necrosis and fibrosis and reduces the proportion of tumor cells, vascular infiltration, and peripheral nerve infiltration, which may help decrease local tumor infiltration and distant metastasis in completely obstructive colorectal cancer after stent placement.
Humans ; Neoadjuvant Therapy/methods* ; Abscess ; Retrospective Studies ; Intestinal Obstruction/etiology* ; Stents ; Colorectal Neoplasms/therapy* ; Necrosis

OBJECTIVE: To investigate the role of tacrolimus-binding protein 38 (FKBP38) in follicle development and the mechanism by which Fkbp38 gene deletion causes premature ovarian insufficiency (POI). METHODS: The Cre-loxp system was used to construct oocyte-specific Fkbp38 knockout transgenic mice. The genotype of the transgenic mice was identified using PCR, and the expression of FKBP38 in the oocytes was verified. The numbers of primordial follicles, primary follicles, secondary follicles and antral follicles in Fkbp38 knockout mice and non-transgenic littermate control mice were counted with HE staining under a microscope for analyzing the effect of Fkbp38 deletion on follicular development. The fertility and serum sex hormone levels of the mice were determined by reproduction experiments and ELISA to assess ovarian function. Ovarian granulosa cell apoptosis of the mice was assessed using TUNEL assay. The activity of the downstream target protein of phosphorylated ribosomal S6 (PS6) of mTOR signaling pathway was detected, and the expressions of BCL-2 and BAX proteins were determined using immunofluorescence assay for assessing oocyte development in the mice. RESULTS: The oocyte-specific Fkbp38 knockout transgenic mouse model was successfully constructed, which showed decreased fertility, disordered sex hormone levels, and significantly reduced primordial follicles, primary follicles and secondary follicles in the ovary (P < 0.05), demonstrating POI-like changes. Compared with the control mice, oocyte-specific Fkbp38 knockout caused activation of the mTOR signaling pathway, significantly increased apoptosis of the granulosa cells, and obviously increased the BAX/BCL- 2 ratio by increasing BAX expression and reducing BCL-2 expression in the oocytes (P < 0.05). CONCLUSION FKBP38 plays an important role in follicle development, and Fkbp38 gene deletion in mice causes POI possibly by activating the mTOR signaling pathway and inducing granulosa cell apoptosis.
Female ; Humans ; Mice ; Animals ; Primary Ovarian Insufficiency/genetics* ; Apoptosis ; Signal Transduction ; Proto-Oncogene Proteins c-bcl-2 ; Granulosa Cells ; Mice, Transgenic ; Mice, Knockout ; TOR Serine-Threonine Kinases

Extracellular matrix (ECM) is a major component of the cellular microenvironment.ECM not only provides physical support for cells, hut also participates in various biological processes.In recent years, hundreds of cancer-related ECM (C-ECM) genes have been identified, and some of them can he used as biomarkers.However, rich information about C-ECM genes is scattered among thousands of publications, and there is no systematic summary of their role in tumorigenesis.Here, we present the CECMAtlas (http://biokb.ncpsb.org.cn/CECMAtlas/), a database which collects 225 C-ECM genes and the information of biological processes that they participate in through literature mining and manual curation.This database will contribute to the study of the mechanism of tumorigenesis and possible clinical application.

Objective: To evaluate the relationship between plasma osteoprotegerin (OPG) level and coronary artery calcification in patients with hypertension and the relationship between OPG and angiotensin Ⅱ (AngⅡ). Methods: A total of 348 patients with hypertension were enrolled in this study. Coronary calcification was determined by 64-row coronary CT. Patients with hypertension were divided into coronary calcification group and non-coronary calcification group according to their coronary calcification score. We compared the clinical and laboratory indications of the two groups. The odds ratio (OR) value of risk factors for coronary calcification and the correlation coefficient between OPG and AngⅡ levels were calculated. Results: The OPG and AngⅡ levels in patients with coronary calcification were higher than those in patients without coronary calcification (P<0.001). Multivariate logistic regression analysis showed that OPG level (OR 3.728, 95% CI 1.314-7.714) and AngⅡ level (OR 2.385, 95% CI 1.281-4.836) were both independent risk factors for coronary calcification (P<0.001). Moreover, OPG and AngⅡ levels were both correlated with the severity of coronary artery calcification. In patients with coronary calcification, OPG level was positively correlated with AngⅡ level (r=0.509, P<0.001), while in patients without coronary calcification, OPG level was not correlated with AngⅡ level (P>0.05). Conclusion: OPG is an independent risk factor for coronary artery calcification in patients with hypertension and is related to the severity of coronary artery calcification. In hypertensive patients with coronary artery calcification, OPG and AngⅡ levels are positively correlated.

Objective:To investigate the effect and mechanism of Sanhuang Yinchi decoction (SHYCD) in preventing carbon tetrachloride (CCl₄)-induced acute liver injury by regulating high mobility group box1(HMGB1) signaling pathway. Method:A total of 48 KM mice were randomly divided into blank control group, model group, low, middle and high-dose SHYCD groups and positive control group. The model of acute liver injury induced by CCl₄ in mice was established. The low, middle and high-dose SHYCD groups were intragastrically administered with drugs (16, 32, 48 g·kg^-1·d^-1) respectively, and the positive control group was given cell growth stimulating hormone (20 mg·kg^-1·d^-1) through intraperitoneal injection. Pathological changes of mouse liver tissue sections were observed by hematoxylin-eosin staining (HE); relevant enzyme kits were used to determine liver function indexes in mice serum-alanine aminotransferase (AST) and aspartate aminotransferase (ALT); the expression level of interleukin-6 (IL-6) in mouse serum was determined by enzyme-linked immunosorbent assay (ELISA); Western blot was used to detect the expressions of high mobility group box-1(HMGB1), cysteine aspartic acid protease(Caspase-3), apoptosis-related molecules B cell lymphoma(Bcl-2), Bcl-2 associated x protein(Bax), and Toll-like receptor 4 (TLR4). Result:Compared with the normal group, the model group significantly increased serum AST, ALT (P<0.05) and IL-6 levels (P<0.05) and expressions of HMGB1, TLR4 and Caspase-3 (P<0.05), and down-regulated Bcl-2/Bax ratio (P<0.05) in liver tissue; compared with the model group, SHYCD can effectively alleviate the pathological damage of liver in mice, reduce serum AST and ALT levels and expressions of IL-6, HMGB1, TLR4 and Caspase-3 protein in liver homogenate (P< 0.05), and increased the ratio of Bcl-2/Bax (P<0.05) in a dose-dependent manner. Conclusion:SHYCD can prevent liver injury by regulating HMGB1/TLR4/NF-κB signaling pathway, reducing cellular inflammatory response and inhibiting apoptosis, so as to prevent acute liver injury in mice. This indicates that HMGB1 may become a new target to prevent acute liver injury.

Objective: To investigate the protective effect of compound Longmaining isoprenaline hydrochloride-induced myocardial infarction model and its effect on Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor-kappa B (NF-κB) signaling pathway.Method: Forty-eight male SD rats were randomly divided into 6 groups:normal group,model group,compound salvia miltiorrhiza drop pill group (0.072 9 g·kg^-1),and low,medium and high-dose compound Longmaining decoction groups (0.36,0.71,1.43 g·kg^-1).The acute myocardial infarction model was induced through subcutaneous injection with isoproterenol.The pathological changes of myocardial tissue were examined by hematoxylin-eosin (HE) staining.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemotaxis protein-1(MCP-1) and nitrogen (NO) in serum were measured by enzyme linked immunosorbent assay (ELISA).The expression levels of inhibitors of NF-κB kinase subunit-β(IKKβ),NF-κB inhibitor α(IκBα),TLR4,MyD88 and NF-κB p65 were measured by immunohistochemical staining and Western blot.Result: Compared with normal group,the myocardial injury in model group was obvious.The levels of IL-1β,IL-6,TNF-α,MCP-1 and NO in serum increased significantly (P<0.05),the expression level of IκBα decreased significantly (P<0.05),and the expression levels of IKKβ,TLR4,MyD88 and NF-κB p65 increased significantly in myocardial tissue (P<0.05).Compared with model group,low,medium and high-dose compound Longmaining groups could significantly alleviate the degree of myocardial injury in rats,significantly decrease IL-1β,IL-6,TNF-α,MCP-1 and NO levels in the serum (P<0.05),significantly increase the expression level of IκBα(P<0.05),and decreased the expression levels of IKKβ,TLR4,MyD88 and NF-κB p65(P<0.05).Conclusion: Compound Longmaining plays a protective effect on acute myocardial infarction by regulatingthe expressions of TLR4/MyD88/NF-κB p65 signaling pathway and relevant inflammatory factors.

Objective To evaluate the effect of SvO2-guided early goal directed fluid therapy on hemodynamic and oxygen dynamics in septic shock pig model. Methods Twelve Bama miniature pigs (male, 21-24 kg) were equally randomized into 2 groups, group C and group G. Septic shock was induced by intravenous infusion endotoxin. Group C received hemodynamic support aiming central venous pressure at 8 to 12 mmHg, urinary output 0.5 mL/kg per hour, and mean arterial pressure greater than 65 mmHg. Group G maintained SvO2 greater than 0.65 in addition to the above indicators. The interventions lasted 6 h and at T0-T8 (0, 60, 120, 180, 240, 300, 360, 420 and 480 min) recorded temperature, hemodynamic and oxygen dynamics indexes for each group, and recorded 6 hours for accumulated liquid volume, vascular active drug, and changes of urine. Results There were no significant differences in mean arterial blood pressure (MAP), heart rate (HR) and systemic vascular resistance index (SVRI) at each time point between group G and group C ( P>0.05). Values of CI and CVP were increased at T4-T8 in group G (P<0.05). Values of MPAP and PVRI were decreased at T8 in group G (P<0.05). Values of SvO2 were increased at T3-T8, O2ER were decreased at T3-T8 (P<0.05), DO2 were increased at T4-T8 (P<0.05), Lac were decreased at T5-T8, andΔp(CO2) was decreased at T8 in group G (P<0.05). There were no significant differences in values of VO2 at T1-T8 between two groups (P>0.05). The amount of intravenous infusion and urine volume were more and the amount of norepinephrine was less in animals of group G (P<0.05). The dosage of dobutamine was more in animals of group G, and which was not used in animals of group C. Conclusion SvO2 guided fluid therapy is more effective than conventional treatment to stabilize hemodynamics and oxygen kinetics, which is characterized by the increased cardiac output, increased oxygen supply, normal oxygen uptake rate and good tissue perfusion.

Objective To explore the expression of macrophage migration inhibitory factor(MIF)in rat hearts with experimental autoimmune myocarditis(EAM)and the possible mechanism of resveratrol's therapeutic effect.Methods Experimental myocarditis model was established by using porcine myocardial immunoglobulin. Twenty-four male 6-week-old Lewis rats were randomly divided into control group(Con),EAM model group(MC) and resveratrol treatment group(MC+ Res).All the rats were detected and compared in the cardiac function according to echocardiographic analysis,and the expression of MIF was detected by Western blot.The degree of myocardial injury was detected by HE staining and the degree of macrophage infiltration in the myocardium was detected by immunohistochemistry.Results In control group,there was no significant inflammatory infiltration or myocardial injury in the myocardium.Heavy local infiltration of macrophages,and dissolved and fractured myocardial fibers were observed in model group.Resveratrol significantly decreased macrophage density and myocardial injury in the heart(P＜ 0.05).Compared with those in control group,LVEDs were significantly increased(P＜0.01)while LVEF and LVFS were markedly decreased in model group(P＜0.01).Compared with model group,LVEDs were significantly decreased(P＜0.05)while LVEF and LVFS were markedly increased in resveratrol group(P＜0.05).The protein expression of MIF was markedly increased in rats of model group(P＜0.01),but was decreased in resveratrol group compared with model groups(P＜ 0.05).Conclusion Increased expression of MIF may be involved in the pathogenesis of EAM.The therapeutic effect of resveratrol on EAM may be associated with down-regulated MIF expression and decreased macrophage infiltration.

Rational nutritional support shall be based on nutritional screening and nutritional assessment.This study is aimed to explore nutritional risk screening and its influencing factors of hospitalized patients in central urban area.It is helpful for the early detection of problems in nutritional supports,nutrition management and the implementation of intervention measures,which will contribute a lot to improving the patient's poor clinical outcome.A total of three tertiary medical institutions were enrolled in this study.From October 2015 to June 2016,1202 hospitalized patients aged ≥18 years were enrolled in Nutrition Risk Screening 2002 (NRS2002) for nutritional risk screening,including 8 cases who refused to participate,5 cases of same-day surgery and 5 cases of coma.A single-factor chi-square test was performed on 312 patients with nutritional risk and 872 hospitalized patients without nutritional risk.Logistic regression analysis was performed with univariate analysis (P＜0.05),to investigate the incidence of nutritional risk and influencing factors.The incidence of nutritional risk was 26.35％ in the inpatients,25.90％ in male and 26.84％ in female,respectively.The single-factor analysis showed that the age ≥60,sleeping disorder,fasting,intraoperative bleeding,the surgery in recent month,digestive diseases,metabolic diseases and endocrine system diseases had significant effects on nutritional risk (P＜0.05).Having considered the above-mentioned factors as independent variables and nutritional risk (Y=1,N=0)as dependent variable,logistic regression analysis revealed that the age ≥60,fasting,sleeping disorders,the surgery in recent month and digestive diseases are hazardous factors for nutritional risk.Nutritional risk exists in hospitalized patients in central urban areas.Nutritional risk screening should be conducted for inpatients.Nutritional intervention programs should be formulated in consideration of those influencing factors,which enable to reduce the nutritional risk and to promote the rehabilitation of inpatients.