The aim of the experimental study is to investigate shortterm toxicity of an initial domestic Methotrexate microspheres(MTX-ms)by hepatic arterial infusion in rats,provide some experimental bases for clinic interventional treatment of liver carcinoma with this new chemoembolization agent.Compareing with control group and MTX group, MTX-ms of largedoses could result in temporal rise of GPT and AKP,deterioration or necroses of animal's liver at different degrees,12 days later a number of microspheres could still be found in the small arteries of the necrotizing area.No pathological changes related to microsphere could be found in other main organs(heart,spleen,lung and kidney).Results suggested that chemoembolization effect of MTX-ms is relatively strong;for effectively oc- cluding blood flow of hepatic arteries on the level of small arteries.Meanwhile MTX-ms oc- clud blood supply of liver carcinoma,they may also cause damages of normal liver tissue. Clinically more attention ought to be paid to the dosage of MTX1 microspheres and thus avoid the overflow of more microspheres to the normal liver tissue causing damage.

Tumor tissue is a complex of tumor cells, stromal cells, and extracellular matrix, and they constitute a disordered and aggressive microenvironment, which plays an indispensable role in the occurrence and development of tumors. In breast cancer, cancer-associated fibroblasts (CAF) not only promote the occurrence, proliferation, invasion, metastasis, and drug resistance of tumor, but also participate in events including angiogenesis, lymph angiogenesis, extracellular matrix remodeling, and reconstruction of the microenvironment, which are known to induce cancer. Therefore, a new strategy for tumor therapy is provided by targeting CAF. This article reviews the research progress of CAF in breast cancer.

OBJECTIVETo investigate the effect of Src kinase inhibitor PP2 on hypoxia/reoxygenation (H/R) injury in rat astrocytes in vitro.

METHODSIn vitro cultured rat astrocytes were exposed to hypoxia for 8 h followed by reoxygenation for 24 h with or without pretreatment with PP2 (10 µmol/L) for 24 h before H/R injury. MTT assay and flow cytometry were used to detect the viability and apoptosis of the exposed astrocytes, respectively, and the protein expressions of Src, Bax, and Bcl-2 in the cells were determined using Western blotting.

RESULTSPP2 pretreatment significantly increased the viability and decreased the apoptosis rate of rat astrocytes exposed to H/R injury (P<0.01). Western blotting showed that H/R injury caused increased expression of Src kinase, which was lowered by PP2 pretreatment. The ratio of Bax/bcl-2 in the astrocytes increased after H/R injury, and was significantly decreased by PP2 pretreatment (P<0.01).

CONCLUSIONPP2 protects rat astrocytes from H/R injury possibly by inhibiting the expression of Src kinase and activating the anti-apoptotic mechanisms in the cells.

Animals ; Apoptosis ; Astrocytes ; pathology ; Cell Hypoxia ; Cells, Cultured ; Flow Cytometry ; Pyrimidines ; pharmacology ; Rats ; src-Family Kinases ; antagonists & inhibitors

Background：Global Handwashing Day (GHD) is a handwashing promotion campaign organized by the Global Public-Private Partnership of Handwashing with Soap. In China, it has been promoted by the Chinese public health authorities, international organizations and multinational corporations through various channels including social media such as Sina Weibo, the leading Chinese microblogging site similar to Twitter. The objective of this study is to qualitatively assess Chinese social media users’ reactions to a health promotion campaign using Global Handwashing Day (GHD) 2012 as an example.Methods：We conducted a qualitative content analysis of 552 Weibo posts generated on GHD 2012 by Weibo users with 1000 or more followers with the Chinese keyword for “handwashing.” We categorized the Weibo posts into groups by keywords that frequently appeared in the data set. These groups were either exact reposts of an original post, or they conveyed similar information.Results：We observed the interconnections between traditional media and social media in handwashing promotion. Social media were found to serve as amplifiers of contents provided by traditional media. We observed the contextualization of global hygiene messages in a unique national social media market in China.Discussion：Our study showed that social media and traditional media are two interconnected arms of the GHD campaign in China. Our analysis demonstrated that public health campaigns in China can be evaluated using social media data. The themes and topics identified in this study will help public health practitioners evaluate future social media handwashing promotion campaigns.

OBJECTIVETo determine the expression of connexin 43 (Cx43) protein and explore the functional modulation of gap junction intercellular communication in astrocytes.

METHODSCultured neonatal SD rat astrocytes were divided into normal control group, all-trans retinoic acid (ATRA) group (treated with 10 µmol/L ATRA for 24 h) and oleamide group (treated with 25 µmol/L oleamide for 2 h). Western blotting and immunofluorescence assay were used to detect total cellular Cx43 protein expression and Cx43 expression on the surface of the astrocytes, respectively. Parachute assay was used to evaluate the functional changes of gap junction intercellular communication of the astrocytes.

RESULTSCompared with the normal control cells, ATRA treatment resulted in a significantly increased expression of total Cx43 protein in the astrocytes (P<0.01), and oleamide significantly suppressed its expression (P<0.01). Similarly, ATRA obviously enhanced while oleamide suppressed Cx43 protein expression on the surface of the astrocytes. The gap junction intercellular communication of the astrocytes was enhanced by ATRA (P<0.01) and inhibited by oleamide (P<0.01).

CONCLUSIONATRA and oleamide can modulate gap junction intercellular communication of the astrocytes possibly by regulating the expression of Cx43 protein.

Animals ; Astrocytes ; metabolism ; Cell Communication ; drug effects ; Cells, Cultured ; Connexin 43 ; metabolism ; Gap Junctions ; metabolism ; Oleic Acids ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; pharmacology

Objective:To discuss the perioperative symptom change rule of patients with myasthenia gravis(MG), and to provide a theoretical basis for preventing and reducing the surgical risk of patients with MG.Methods:The clinical data of 104 patients who underwent thymectomy in the Department of Thoracic Surgery of the Second Affiliated Hospital of Zhengzhou University from 2015 to 2019 were retrospectively analyzed. According to the degree of the impact of MG symptoms on the body's physiology and life, the "MG dynamic classification standard" was formulated, which was divided into type 0-type Ⅳ according to the severity of MG symptoms. The symptoms of each patient of "admission", "preoperative" and "postoperative" are classified according to the "dynamic classification criteria", and the number of "admission", "preoperative" and "postoperative" were counted respectively. Based on the statistical analysis of each patient's type changes, the perioperative symptom changes of myasthenia gravis patients were summarized.Results:1. "Admission" classification: 12 cases of type 0, 42 cases of type Ⅰ, 32 cases of type Ⅱ, 12 cases of type Ⅲ, 5 cases of type Ⅳa, and 1 case of type Ⅳb. 2. "Preoperative" classification: 44 cases of type 0, 34 cases of type Ⅰ, 14 cases of type Ⅱ, 12 cases of type Ⅲ; 68 cases of preoperative symptom reduction (65.4%, 68/104), 36 cases of preoperative symptom stable (34.6%, 36/104). Asymptomatic aggravation. 3. "Postoperative" classification: 49 cases of type 0, 21 cases of type Ⅰ, 11 cases of type Ⅱ, 10 cases of type Ⅲ, 9 cases of type Ⅳa, 4 cases of type Ⅳb; 33 cases (31.7%, 33/104) had postoperative symptoms aggravated. Among the patients with worsening symptoms after surgery, 5 cases (15.2%, 5/33) worsened on the first day after surgery, 9 cases (27.2%, 9/33) worsened on the second day after surgery, and 13 cases (39.4%, 13/33) worsened on the third day after surgery. There were 4 cases (12.1%, 4/33) worsened on the 4th day, and 2 cases (6.1%, 2/33) worsened on the 5th day after surgery.Conclusion:MG patients had different conditions at admission. After individualized perioperative treatment, more than half of the patients' symptoms alleviated to varying degrees. After the operation, the symptoms of MG will be temporarily aggravated due to the effects of surgery and anesthesia, and the aggravation period is mostly on 1-3 days. Reasonable selection of low-risk MG patients for surgery, avoiding the superposition of other influencing factors in the postoperative exacerbation period, is expected to reduce the occurrence of postoperative crises in MG patients.

Objective:To investigate the effect of IKKε on autophagy during abdominal aortic aneurysm formation in mice.Methods:We stimulated ApoE -/- mice and ApoE -/-IKKε -/- mice with AngⅡ and saline for 28 days. Metaboilic levels and aortic diameter of ApoE -/- mice and ApoE -/-IKKε -/- mice were measured. The arterial fibrosis of mice was detected by Masson staining and HE staining, mitochondrial reactive oxides were detected by fluorescence assay, the expression levels of autophagy factors LC3B and Beclin-1 were detected by immunohistochemistry, and the protein level of LC3B was detected by Western blot. Results:There was no significant difference in metaboilic levels between ApoE -/- mice and ApoE -/- IKKε -/- mice. However, the aortic diameterf ApoE -/-IKKε -/- mice was significantly less than that of ApoE -/- mice. The fibrosis level of ApoE -/-IKKε -/- mice was significantly lower than that of ApoE -/- mice. Furthermore, ROS in ApoE -/-IKKε -/- mice was lower than that in ApoE -/- mice. In addition, immunohistochemical and western blot showed that the expression levels of LC3B and Beclin-1 in ApoE -/-IKKε -/- mice were significantly lower than in ApoE -/- mice. Conclusion:IKKε -/- deficiency can significantly inhibit autophagy, thus reducing the development of abdominal aortic aneurysm in mice.

Objective:To evaluate the reliability and repeatability of thoracolumbar AOSpine injury score (TLAOSIS)and thoracolumbar injury severity score (TLICS) classification scoring system in guiding thoracolumbar fracture surgery, and to explore the main reasons for the consistency of classification scoring systems.Methods:Fifty-five thoracolumbar fracture patients with complete clinical data and radiologic data admitted to Second Affiliated Hospital of Zhejiang Chinese Medical University from January 2018 to December 2018 were enrolled. Based on their preoperative X-ray films, CT and MRI, six physicians were assigned to independently determine the classification using the TLAOSIS and TLICS.For the same patient, the classification was identified as inconsistency among 6 observers if there was an observer in a different type.After a 4-week interval, the 55 patients were presented in a random sequence to the same evaluators for repeated evaluation.All data did not contain any marks related to the type. The Cohen's Kappa coefficient was used to determine the interobserver reliability and intraobserver repeatability concerning fracture morphology, posterior ligament classification (PLC) injury classification and neurological function score. Kappa coefficients were used to observe the consistency of pre- and post-measure measurements within each observer.Results:The two classification scoring systems had good consistency and reproducibility in guiding surgery. For TLAOSIS classification scoring system, the interobserver and intraobserver Kappa values for fracture morphology were 0.806 and 0.667; neurological status were 0.937 and 0.891; PLC injury classification were 0.873 and 0.779; the final recommendation surgery were 0.816 and 0.764. For TLICS classification scoring system, the interobserver and intraobserver Kappa values for fracture morphology were 0.878 and 0.788; neurological status were 0.936 and 0.888; PLC injury classification were 0.809 and 0.691; the final recommendation surgery were 0.811 and 0.705. The two classification scoring systems were statistically significant in fracture morphology and PLC injury classification both in the reliability and repeatability analysis ( P<0.05), but there was no significant difference in the neurological function score ( P>0.05). Conclusions:TLAOSIS and TLICS have good consistency and reproducibility in guiding surgery. The fracture morphology and PLC injury classification are the factors influencing the consistency of surgical guidance for the two classification scoring systems.

Objective:To compare the differences between thoracolumbar AO spine injury score (TL AOSIS) and thoracolumbar injury classification and severity score system (TLICS) in guiding thoracolumbar fracture surgery.Methods:A retrospective study was conducted of the 55 patients with complete preoperative imaging data who had been treated for thoracolumbar injuries at Department of Spinal Surgery, The Second Affiliated Hospital to Zhejiang Chinese Medical University from January 2015 to December 2016. They were 34 men and 21 women, aged from 21 to 55 years (average, 37.5 years). Of them, 31 were identified as having normal neurological function and 24 as having impaired neurological function. TL AOSIS and TLICS were used to evaluate respectively all the patients, those with normal neurological function and those with impaired neurological function, and consequently made suggestions whether surgery should be performed or not.Results:Among the 55 patients, by the guidance of TL AOSIS and TLICS respectively, conservative treatment was suggested for 19 and 25 cases, either conservative treatment or surgery for 12 and 13 cases, and surgery for 24 and 17 cases. There was fine consistency between the 2 scoring systems in surgery suggestion for thoracolumbar fracture ( P=0.358). Among the 31 patients with normal neurological function, by the guidance of TL AOSIS and TLICS respectively, conservative treatment was suggested for 19 and 25 cases, either conservative treatment or surgery for 6 and 0 cases, and surgery for 6 and 6 cases. TLICS suggested surgery for significantly more patients than TL AOSIS did ( P=0.033). Among the 24 patients with impaired neurological function, by the guidance of TL AOSIS and TLICS respectively, either conservative treatment or surgery was suggested for 6 and 13 cases, and surgery for 18 and 11 cases. TL AOSIS suggested surgery for significantly more patients than TLICS did ( P=0.039). Conclusion:There is fine consistency between TL AOSIS and TLICS in surgery suggestion for thoracolumbar fracture, but TL AOSIS may lead to more surgery suggestions for the patients with complete burst fracture or impaired neurological function than TLICS.

Objective To explore the expression profile of the JAK/STAT pathway in patients with acute myeloid leukemia(AML)and to analyze its impact on the survival prognosis of patients.Methods This study compared differentially expressed genes between AML patients and healthy controls in 2 independent cohorts(n=64,n=121),and these genes were enriched by pathways.The expression levels of JAKs and STATs genes were compared between AML patients and healthy controls.The clinical values of JAK/STAT genes were analyzed using gene expression data,patients'clinical and prognostic information from 2 AML cohorts(n=163,n=403).Results Gene microarray expression results in 26 AML patients and 38 healthy controls showed 1266 genes with significantly differential expression(Padj≤0.05,| log2FC| ≥0.5),of which 426 genes were significantly upregulated in AML patients and 840 genes were significantly downregulated in AML patients.Pathway enrichment of these genes was performed in the JAK/STAT pathway,which was found to be active in AML patients(P＜0.05).Comparison of mi-croarray data from the GSE1159 cohort(n=121)showed AML patients had higher levels of JAK1(P=0.019),J AK2(P=0.047)and STAT4(P＜0.001)gene expression than the healthy controls,and their STAT5A(P=0.028)and STAT6(P=0.022)gene expression levels were lower than those in the healthy controls.Univariate survival analysis identified shorter over-all survival(P=0.02,HR=1.463;P=0.041,HR=1.293)and event-free survival(P=0.01,HR=1.510)in patients with high STAT4 expression than in those with a lower STAT4 expression in the TCGA and GSE6891 cohorts(n=163;n=403).Univa-riate and multifactorial COX analyzes confirmed that high STAT4 expression was an independent prognostic risk factor for AML patients(EFS:P=0.002,HR=1.958;OS:P=0.036,HR=1.556).Conclusion In AML patients,the JAK/STAT path-way is activated,and the STAT4 expression level is higher than that of the healthy controls.High expression of STAT4 suggest poor prognosis,wihich is an independent risk factor for the prognosis of AML patients.