Effects of in vivo targeted carboxylesterase 1f gene knockdown on the Kupffer cells polarization activity in mice with acute liver failure / 中华肝脏病杂志

Objective: To investigate the effect of targeted carboxylesterase 1f (Ces1f) gene knockdown on the polarization activity of Kupffer cells (KC) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice with acute liver failure. Methods: The complex siRNA-EndoPorter formed by combining the small RNA (siRNA) carrying the Ces1f-targeting interference sequence and the polypeptide transport carrier (Endoporter) was wrapped in β-1, 3-D glucan shell to form complex particles (GeRPs). Thirty male C57BL/6 mice were randomly divided into a normal control group, a model group (LPS/D-GalN), a pretreatment group (GeRPs), a pretreatment model group (GeRPs+LPS/D-GalN), and an empty vector group (EndoPorter). Real-time fluorescent quantitative PCR and western blot were used to detect Ces1f mRNA and protein expression levels in the liver tissues of each mouse group. Real-time PCR was used to detect the expression levels of KC M1 polarization phenotypic differentiation cluster 86(CD86) mRNA and KC M2 polarization phenotypic differentiation cluster 163 (CD163) mRNA in each group. Immunofluorescence double staining technique was used to detect the expression of Ces1f protein and M1/M2 polarization phenotype CD86/CD163 protein in KC. Hematoxylin-eosin staining was used to observe the pathological damage to liver tissue. A one-way analysis of variance was used to compare the means among multiple groups, or an independent sample nonparametric rank sum test was used when the variances were uneven. Results: The relative expression levels of Ces1f mRNA/protein in liver tissue of the normal control group, model group, pretreatment group, and pretreatment model group were 1.00 ± 0.00, 0.80 ± 0.03/0.80 ± 0.14, 0.56 ± 0.08/0.52 ± 0.13, and 0.26 ± 0.05/0.29 ± 0.13, respectively, and the differences among the groups were statistically significant (F = 9.171/3.957, 20.740/9.315, 34.530/13.830, P < 0.01). The percentages of Ces1f-positive Kupffer cells in the normal control group, model group, pretreatment group, and pretreatment model group were 91.42%, ± 3.79%, 73.85% ± 7.03%, 48.70% ± 5.30%, and 25.68% ± 4.55%, respectively, and the differences between the groups were statistically significant (F = 6.333, 15.400, 23.700, P < 0.01). The relative expression levels of CD86 mRNA in the normal control group, model group, and pretreatment model group were 1.00 ± 0.00, 2.01 ± 0.04, and 4.17 ± 0.14, respectively, and the differences between the groups were statistically significant (F = 33.800, 106.500, P < 0.01). The relative expression levels of CD163 mRNA in the normal control group, the model group, and the pretreatment model group were 1.00 ± 0.00, 0.85 ± 0.01, and 0.65 ± 0.01, respectively, and the differences between the groups were statistically significant (F = 23.360, 55.350, P < 0.01). The percentages of (F4/80(+)CD86(+)) and (F4/80(+)CD163(+)) in the normal control group and model group and pretreatment model group were 10.67% ± 0.91% and 12.60% ± 1.67%, 20.02% ± 1.29% and 8.04% ± 0.76%, and 43.67% ± 2.71% and 5.43% ± 0.47%, respectively, and the differences among the groups were statistically significant (F = 11.130/8.379, 39.250/13.190, P < 0.01). The liver injury scores of the normal control group, the model group, and the pretreatment model group were 0.22 ± 0.08, 1.32 ± 0.36, and 2.17 ± 0.26, respectively, and the differences among the groups were statistically significant (F = 12.520 and 22.190, P < 0.01). Conclusion: Ces1f may be a hepatic inflammatory inhibitory molecule, and its inhibitory effect production may come from the molecule's maintenance of KC polarization phenotypic homeostasis.

Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model.@*METHODS@#The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established.@*RESULTS@#164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 μmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285).@*CONCLUSION@#Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.

The Prognostic Value of Early Relapse after Autologous Hematopoietic Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To assess the impact of early relapse (ER) after autologous hematopoietic stem cell transplan-tation (AHSCT) on overall survival (OS) for multiple myeloma (MM) patients.@*METHODS@#Clinical data of 37 patients with MM undergoing AHSCT in department of hematology of Shanxi Bethune Hospital from January 2012 to December 2017 were retrospectively analyzed. The effect of ER on OS of patients was analyzed. The effects of international staging system (ISS) staging, cytogenetics, pre-transplant efficacy, minimal residual disease, and age on OS of the patients were also analyzed respectively.@*RESULTS@#Among the 37 patients, 13 cases (35.1%) had ER, and 24 cases (64.9%) had non-ER. 3 patients with ER had extramedullary disease, but none with non-ER showed extramedullary disease. More than or equal to very good partial rate (VGPR) in patients with ER and without ER were 3 cases (23.1%) and 15 cases (62.5%), respectively, and the curative effect of the former was significantly lower than that of the latter (P<0.05). The median follow-up time was 31 (12-96) months, and median OS time was 93 months in all the patients. The median survival time of patients with ER was 17 months, and the median progression free survival was 7 months, both were significantly shorter than 93 months and 38 months of patients with non-ER (P<0.05). Univariate analysis showed that the OS was affected by ER, cytogenetic abnormalities (FISH), and ≥VGPR before transplantation. Multivariate analysis showed that ER was an independent prognostic factor.@*CONCLUSION@#The prognosis of patients with ER after AHSCT in newly diagnosed MM is poor. ER is an independent prognostic factor of survival.

Analysis of (DPY19L2 gene variant in two brothers affected with globozoospermia / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular basis for two brothers affected with globozoospermia.@*METHODS@#Whole exome sequencing was carried out for both patients. Candidate variant was verified by Sanger sequencing and quantitative real-time PCR (qRT-PCR).@*RESULTS@#Whole exome sequencing, Sanger sequencing and qRT-PCR verification revealed a heterozygous c.384dup (p.Glu129*) variant in the DPY19L2 gene in the two brothers and their mother. A large heterozygous deletion, spanning approximately 164.5 kb and encompassing the entire DPY19L2 gene, was detected on chromosome 12 of the two patients and their father.@*CONCLUSION@#The c.384dup (p.Glu129*) variant and deletion of the DPY19L2 gene probably underlie the pathogenesis of globozoospermia in the two patients, which was in keeping with the autosomal recessive inheritance of disease in this pedigree.

Distribution and characteristics of heterogeneous vancomycin-intermediate Staphylococcus aureus in blood culture / 中华微生物学和免疫学杂志

Objective:To investigate the epidemiological and molecular biological characteristics of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) in blood culture. Methods:hVISA was detected using Mueller-Hinton agar containing 5 μg/ml of teicoplanin (MHA5T) and Populats profiles/area under the curve (PAP/AUC). Staphylococcal cassette chromosome mec ( SCCmec), Staphylococcus aureus protein A ( spa) and accessory gene regulator ( agr) typing and multilocus-sequence typing (MLST) were analyzed using PCR. Difference in autolysis between hVISA and vancomycin-sensitive Staphylococcus aureus (VSSA) isolates were evaluated with Triton X-100-inducd autolysis. Expression of vraR, mgrA, icaA, icaR, pbp4 and agr genes in hVISA and VSSA strains were detected by real-time PCR. Results:The positive detection rate of methicillin-resistant Staphylococcus aureus (MRSA) in blood culture was 39.5% (136/344) in our hospital. Among the MRSA strains, there were 31 strains of hVISA (22.8%). The minimum inhibitory concentrations (MIC) of vancomycin were mainly 1.5 μg/ml (54.8%) and 2 μg/ml(25.8%)against hVISA isolates, and 0.5 μg/ml (46.7%) and 0.75 μg/ml (39.0%) against VSSA isolates. The predominant clone of hVISA was ST239- SCCmecⅢ-t030- agrⅠ accounting for 71.0% (22/31). The autolysis of hVISA isolates decreased significantly as compared with that of VSSA isolates ( χ2=13.583, P=0.032). Compared with VSSA strains, the expression of vraR, mgrA and icaA genes in hVISA strains increased by 1.58, 1.53 and 1.06 times ( P<0.01), while the expression of icaR, agr and pbp4 genes decreased by 0.85, 0.61 and 1.03 times ( P<0.05). Conclusions:The prevalence rate of hVISA in our hospital reached 22.8% and the main epidemic clone was ST239- SCCmecⅢ-t030- agrⅠ, which should be paid great attention to clinically. Rational use of antibiotics, strengthening the prevention and control of nosocomial infection, and avoiding the spread of hVISA strains and the emergence of VISA and VRSA (vancomycin-resistance Staphylococcus aureus) were also necessary.

Effect of Serum Free Light Chain Ratio and Normalization Ratio after Treatment on Diagnosis and Prognosis of Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the value of serum free light chain (sFLC) κ/λ ratio (sFLCR) on the diagnosis and prognosis of patients with newly diagnosed multiple myeloma(MM), and explore the effect of sFLCR normalization on the prognosis of patients after 4 courses of induction therapy.@*METHODS@#The clinical data of 43 newly diagnosed MM patients from January 2014 to January 2019 were analyzed retrospectively. Immunoturbidimetry was used to detect the expression levels of sFLC κ and λ. According to the ratio of involved and uninvolved sFLC, using 100 as a boundary, the MM patients were divided into the high ratio group (sFLCR≥100 or ≤0.01) and the low ratio group (0.010.05).@*CONCLUSION@#Patients in the high ratio group at the initial diagnosis have worse renal function, later stage of disease, lower deep remission rate, earlier disease progression, shorter survival time, and worse clinical prognosis.

The protective effects of cyclosporin A on vascular permeability in sepsis rats / 药学学报

The protective effects of cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPTP), on vascular permeability in sepsis rats were investigated. Cecal ligation and puncture (CLP)-induced sepsis rats were used for in vivo studies, and the effects of CsA (1 and 5 mg·kg-1) on vascular permeability of lung, kidney, and intestine, mitochondrial respiratory control ratio, and the survival of the sepsis rats were observed. Lipopolysaccharide (LPS) was used for stimulating vascular endothelial cells (VECs) in vitro, and the effects of CsA on leakage of microvascular, immunofluorescence of zonula occludes-1 (ZO-1), and transendothelial electrical resistance (TER) were observed. All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of the Army Medical University. Compared with sham-operated group, the vascular permeability of lung, kidney, and intestine in sepsis rats increased significantly (P<0.05). Compared with conventional treatment group, CsA could significantly decrease the vascular permeability of lung, kidney, and intestine (P<0.05 or P<0.01), and prolong the survival period. The results of microcirculation also showed that CsA could significantly reduce the permeability of mesenteric venules in sepsis rats. At the cellular level, LPS stimulation significantly increased the permeability of vascular endothelial cells, including the decrease of transmembrane resistance and protein expression of ZO-1 (P<0.05). CsA can significantly reduce the increase of permeability of vascular endothelial cells induced by LPS stimulation (P<0.01). The function of mitochondria in the kidneys and intestines of sepsis rats was obviously impaired, and the respiratory control ratio of mitochondria was decreased. LPS significantly increased MPTP opening of VECs, while CsA significantly inhibited MPTP opening and improved mitochondrial function. CsA may protect mitochondrial function by inhibiting the opening of MPTP and play a protective role in the vascular permeability of sepsis rats. This study will provide an insight for the treatment of sepsis vascular leakage.

Effect of Low-Dose Triptolide and Sorafenib Alone and Their Combination on AML Cell Line MV411 and the Pathway of STAT5 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of inhibiting proliferation and inducing apoptosis of low-dose triptolide and sorafenib alone or in combination on FLT3-ITD acute myeloid leukemia cell line MV4-11 and STAT5 pathway.@*METHODS@#The MV4-11 cells were treated with low dose triptolide(IC) and sorafenib(IC) alone or in combination for 48 hours. The cell proliferation and inhibition were detected by using CCK-8 kit, the cell apoptosis was detected by flow cytometry, the expression of FLT3,STAT5 in mRNA and protein levels was detected by RT-PCR and Western blot respectively.@*RESULTS@#The treatment of MV4-11 cells with low dose triptolide and sorafenib alone and in combination for 48 hours could inhibit cell proliferation and induce cell apoptosis, moreover the inhibitory rate and apoptotic rate of MV4-11 cells in drug-combination group both were higher than those in single drug group. The mRNA expression and protein expression of FLT3,STAT5 signaling pathway in drug combination group were significantly lower than those in single drug group.@*CONCLUSION@#Low-dose triptolide combined with sorafenib can synergistically inhibit the proliferation and induce the apoptosis of MV4-11 cells, which may be related with the inhibition of FLT3 and STAT5 pathway.

Management of acute pancreatitis after kidney transplantation:our experiences of 12 patients / 中华器官移植杂志

Objective To summarize the experiences of diagnosing and treating acute pancreatitis (AP) after kidney transplantation .Methods From September 2007 to December 2017 , clinical data were retrospectively analyzed for 12 AP patients after kidney transplantation .Results They were diagnosed as AP within 72 h after an onset of abdominal pain .Among 4 recurrent cases within 1 week post-transplantation ,the curative interventions included non-operative therapy (n=2) and peripancreatic puncture & drainage (n=2) .AP occurred at 1 year post-transplantation (n=8) . Three cases were cured non-surgically while another 5 cases underwent surgery . The procedures included laparoscopic cholecystectomy ( n = 1 ) , endoscopic retrograde cholangiopancreatography (ERCP) for cholelithiasis (n=1) and peripancreatic puncture & drainage (n= 2) .One patient died after surgical debridement for adjacent pancreatic tissue .Conclusions After kidney transplantation , the occurrence of AP may be associated with immunosuppressants interfering with triglyceride metabolism and pancreatic microcirculation .For those with cholelithiasis-related pancreatitis ,surgical removal of precipitating factor is required .Mini-invasive puncture and drainage are preferred for severe non-gallstone pancreatitis while surgery is performed whenever necessary .

Association between fasting blood glucose and the risk of cholelithiasis / 临床肝胆病杂志

@#ObjectiveTo investigate the association between fasting blood glucose and the risk of cholelithiasis. MethodsA total of 87513 individuals who underwent fasting blood glucose test and liver/biliary ultrasound in health examination in Kailuan from 2006 to 2007 were enrolled as subjects, and according to the results of blood glucose test, the subjects were divided into normal blood glucose group with 73456 subjects, impaired fasting blood glucose group with 7165 subjects, and diabetic group with 6892 subjects. The log-rank test was used to compare the cumulative incidence rate of cholelithiasis between groups; the Cox proportional hazards model was used to analyze the influence of different levels of fasting blood glucose on new-onset cholelithiasis and calculate hazard ratio (HR) and 95% confidence interval (CI); a stratified analysis was used to compare the risk of cholelithiasis between the individuals with different levels of fasting blood glucose in the groups with different sexes, blood lipid levels, and levels of body mass index (BMI). A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups. The chi-square test was used for comparison of categorical data between groups. ResultsThere was a significant difference in the cumulative incidence rate of cholelithiasis between the normal blood glucose group, the impaired fasting blood glucose group, and the diabetic group (10.91% vs 12.17% vs 18.86%, χ2=27.94, P＜0.05). After the continuous adjustment for the other factors in the Cox proportional hazards model analysis, compared with the normal blood glucose group, the impaired fasting blood glucose group had a risk of new-onset cholelithiasis of 0.97(95%CI: 0.85-1.11, P=0.587), and the diabetic group had a risk of new-onset cholelithiasis of 1.15(95%CI: 1.01-1.30, P=0.019). The stratified analysis showed that diabetes was a risk factor for new-onset cholelithiasis in male individuals (HR=1.16, 95%CI: 1.01-1.33, P=0.043), individuals with normal blood lipids (HR=1.22, 95%CI: 1.01-1.49, P=0.044), and individuals with overweight based on BMI (HR=1.16, 95%CI: 1.01-1.35, P=0.048). ConclusionDiabetes can increase the risk of cholelithiasis. Diabetes is an independent risk factor for cholelithiasis in men, individuals with normal blood lipids, and individuals with overweight based on BMI.

Auxo action and mechanism of tgf-β1 up-regulating smad3 phosphorylation on the expression of thymic stromal lymphopoietin in human bronchial Epithelia / 解放军医学杂志

[Abstract] Objective To discuss the effect and the corresponding mechanism of transforming growth factor β1 (TGF-β1) in promoting the bronchial epithelia synthesis and the expression of thymic stromal lymphopoietin (TSLP), so seek out a potential therapeutic target for asthma. Methods Human bronchial epithelia cells (HBEc) were cultured in vitro, and then divided into 0h group, 3h group, 6h group, 12h group, 24h group and 48h group to evaluate the effect of TGF-β1 stimulation in different time points; and divided into 0ng/ml group, 0.1ng/ml group, 1ng/ml group and 10ng/ml group to evaluate the effect of TGF-β1 stimulation in different concentrations. SB431542, a TGF-β1 antagonist, was used to block the effect of TGF-β1, HBEc were divided into negative control group, TGF-β1 group (1ng/ml TGF-β1) and TGF-β1+SB431542 group (1ng/ml TGF-β1+10μmol/L SB431542). Western blotting was performed to detect the protein expression level of TSLP, p-Smad3 and Smad3, while qRT-PCR was performed to determine the mRNA transcription level of TSLP. Concentrations of TSLP in HBEc culture supernatants were measured by ELISA. Results As the co-culture time with TGF-β1 prolonged, the expression of TSLP in HBEc increased. The relative expression of TSLP protein was significantly higher in 24h group (0.803±0.022) than in 0h group (0.350±0.032, P<0.05), and the relative expression of TSLP mRNA also increased (4.957±0.391 vs. 1.002±0.086, P<0.05). The levels of TSLP mRNA transcription and protein expression were significantly higher in 1ng/ml TGF-β1 group (7.954±2.004; 1.522±0.003) than in 0ng/ml TGF-β1 group (1.008±0.152; 0.758±0.014, P<0.05). The concentrations of TSLP in HBEc culture supernatants were markedly higher in 1ng/ml TGF-β1 group than in 0ng/ml TGF-β1 group (160.157±7.050 vs. 138.817±1.940, P<0.05). The ratio of p-Smad3/Smad3 declined obviously in TGF-β1+SB431542 group than in TGF-β1 group (0.808±0.063 vs. 1.116±0.049, P<0.05). Meanwhile, the relative expression of TSLP protein was significantly lower in TGF-β1+SB431542 group than in TGF-β1 group (1.016±0.030 vs. 1.186±0.045, P<0.05). Conclusion TGF-β1 may induce the expression of TSLP in HBEc by up-regulating Smad3 phosphorylation, which may be a novel method in curing asthma.

Effects of Serum and its components on the biofim formation of Pseudomonas aeruginosa / 临床检验杂志

Objective@#To study the effects of serum and its components on biofilm formation of Pseudomonas aeruginosa. @*Methods@#96 well microplates combined with crystal violet staining was used to detect the effects of serum, albumin and transferrin on biofilm formation of Pseudomonas aeruginosa. And confocal laser scanning microscope was used to observe the morphology of the biofilm. @*Results@#The biofilm of PAO1 was significantly enhanced from 2.26±0.42 to 3.42±0.08（t=4.71, p<0.01）with horse serum and but reduced to 0.807±0.10（t=4.71,p<0.01） by human serum; And the total biofilm biomass was significantly increased and clump-changed with horse serum, but decreased and scattered in distribution by human serum. Besides, horse serum could also enhance the biofilm formation of part of the clinical isolates of Pseudomonas aeruginosa, however, human serum could inhibit the biofilm formation of all of the clinical isolates. And 2.5g/L albumin could significantly enhance the biofilm of PAO1 from 1.96±0.22 to 2.54±0.18（t=3.55，p<0.05）, but 5 g/L could reduce the biofilm of PAO1 from 1.85±0.36 to 0.84±0.24（t=4.03，p<0.05）.@*Conclusion@#Horse serum and albumin could significantly promote the biofilm formation of Pseudomonas aeruginosa, but human serum and transferrin could decrease its biofilm formation.

Effects of IRF3 knockdown on the nuclear expression of Irak1bp1 protein in LPS-stimulated Raw 264.7 cells / 上海交通大学学报（医学版）

Objective·To amplify the interferon regulator factor 3 (IRF3) short hairpin RNA (shRNA) virus and investigate the effect of the virus on the nuclear expression of Irak1bp1 protein in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. Methods?·?Adenovirus was amplified in HEK293T cells and the virus titer was detected by TCID 50 assay. The Raw 264.7 cells were randomly divided into four groups including adenovirus (-) LPS (-) group, adenovirus (-) LPS (+) group, adenovirus (+) LPS (-) group and adenovirus (+) LPS (+) group. The expression of intracellular IRF3 mRNA was detected by real-time PCR, and the nuclear expression of IRF3 and Irak1bp1 protein were detected by Western blotting. Results?·?The titer of adenovirus was 2.2×1011PFU/mL and the best MOI was 300. The expression of IRF3 mRNA and nuclear IRF3 protein in LPS-stimulated Raw 264.7 cells were significantly higher than those of the control group. The cellular constitutive expression of IRF3 at mRNA level and the LPS-induced expression of IRF3 were significantly inhibited after transfection of Raw 264.7 cells with adenovirus strains carrying IRF3 shRNA. However, the nuclear constitutive expression of IRF3 protein was not affected by IRF3 shRNA in the unstimulated state. The expression of nuclear Irak1bp1 protein was significantly higher than that of the control group. The nuclear constitutive expression and the LPS-induced expression of Irak1bp1 protein were not affected by IRF3 shRNA. Conclusion?·?Transfection of LPS-stimulated Raw 264.7 cells with adenovirus strains carrying IRF3 shRNA could effectively inhibit the expression of IRF3, but not affect the nuclear expression of Irak1bp1 protein.

The Suppressive Effect of Carthamin Yellow on the Proliferation and Migration of Human Breast Cancer Cells and Its Related Molecular Mechanisms / 昆明医科大学学报

Objective To study the effect of Carthamin Yellow (CY) on cell proliferation, apoptosis, migration and invasion ability of breast cancer and its related molecular mechanisms. Methods CCK-8 assay was used to detect cell viability of MDA-MB-231 human breast cancer cells by different concentrations of CY at different time;flow cytometry was used to test the apoptosis rate of MDA-MB-231 cells treated by different concentrations of CY and transwell assay was used to investigate the effect of various concentrations of CY on MDA-MB-231 cell migration and invasion.After the intervention of different concentrations of CY on MDA-MB-231 cells, apoptosis-related protein Cleaved-Caspase-3, survival protein p-Akt and metastasis-related protein MMP2 were detected by western blot. Results (1) CY could inhibit the proliferation of MDA-MB-231 cells in a dose-and-time-dependent manner. (2) CY significantly promoted the apoptosis of breast cancer cells ( <0.01) . (3) CY could decrease the expression of p-Akt and increase the expression of Cleaved-Caspase-3. (4) CY impaired migration and invasion of MDA-MB-231 cells ( <0.01), and can inhibit the expression of MMP2. Conclusion CY could promote the apoptosis of breast cancer cells through activation of apoptosis signaling, and can inhibit breast cancer cell metastasis by suppressing MMP2. And CY may be a potential therapeutic drug for human breast cancer.

Application Progress of Dehydrating Agent in Acute Spinal Cord Injury(review) / 中国康复理论与实践

Acute spinal cord injury(ASCI)can be divided into primary injury and secondary injury.Spinal cord edema is important for the development of secondary injury after ASCI.Spinal cord edema can be mainly divided into cytotoxic edema and angioedema.The application of dehydrating agents in the treatment of acute spinal cord injury is obvious.This article de-scribed the application of mannitol,hypertonic saline,glycerol fructose,furosemide,human serum albumin,resveratrol and other dehydrating agents in the treatment of ASCI.

cAMP transfer across MEGJ mediates regulatory effect of Ang2 on hypo-reactivity after hypoxia in vascular smooth muscle cells / 中国病理生理杂志

AIM:To observe the cyclic adenosine monophosphate(cAMP)transfer across myoendothelial gap junctions(MEGJ)in the regulatory effect of angiopoietin-2(Ang2)on hyporeactivity after hypoxia in vascular smooth mus-cle cells(VSMCs ).METHODS:The double-sided cell co-culture model of vascular endothelial cells(VECs )and VSMCs was set up.The protein expression of inducible nitric oxide synthase(iNOS)was determined by Western blot.The contraction of VSMCs was detected via the leakage of FITC-labeled bovine serum albumin.Alexa Fluor 488-cAMP was used as the tracer to observe the cAMP transfer across MEGJ from VECs to VSMCs.RESULTS:In cultured VECs and VSMCs alone ,the cAMP concentrations were both significantly increased after exogenous Ang 2 treatment and hypoxia ,and more in VECs than that in VSMCs(P<0.05).In the double-sided cell co-culture model,the difference was weakened,and the increase in cAMP concentration in VSMCs after exogenous Ang 2 treatment and hypoxia was antagonized by connexin 43(Cx43)small interfering RNA(siRNA)(P<0.05).Alexa Fluor 488-cAMP in VECs transfered into VSMCs after exoge-nous Ang2 treatment and hypoxia,which was also antagonized by Cx43 siRNA(P<0.05).The cAMP antagonist inhibited the protein expression of iNOS in the VSMCs and the hyporeactivity of the VSMCs after exogenous Ang 2 treatment and hy-poxia(P<0.05).CONCLUSION:Ang2 may regulate the protein expression of iNOS in VSMCs and the hyporeactivity of VSMCs after hypoxia through the cAMP transfer across MEGJ.

Pulmonary papillary adenoma: report of two cases

Pulmonary papillary adenoma is a rare tumor. Two cases without any clinical symptoms were enrolled in our hospital. Both cases were incidentally detected in pulmonary area by imaging. Pathological examination revealed well-circumscribed nodules consisting of papillary growth of cuboidal to low columnar epithelial cells lining the surface of the fibrovascular stroma. Immunohistochemistry [IHC] staining showed that the lining cells were diffusely positive for TTF-1, CK, p63, CK7, and Napsin A. The Ki-67 proliferation index was approximately 2%. The morphological features and the IHC profile of the tumor were in agreement with that of pulmonary papillary adenoma. Both patients are doing well without recurrence or metastasis of the tumor

Clinical significance of peripheral blood neutrophil-lymphocyte ratio and platelet- lymphocyte ratio in patients with asthma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of peripheral blood neutrophil-lymphocyte ratio (NLR) and platelet- lymphocyte ratio (PLR) in patients in acute stage of bronchial asthma and their clinical significance.</p><p><b>METHODS</b>A total of 262 patients with acute asthma, including 97 critical and 175 non-critical patients, were recruited from our hospital between January, 2013 and May, 2016, with 130 healthy individuals as the control group. The absolute neutrophil count, absolute lymphocyte count, platelet, NLR and PLR were compared among different groups, and their diagnostic values were evaluated using the area under the receiver-operating characteristic (ROC) curve.</p><p><b>RESULTS</b>The absolute neutrophil count, absolute lymphocyte count, PLR and NLR (P<0.0001), but not platelet count (P=0.971), differed significantly among the 3 groups. The absolute lymphocyte count was significantly lower while the absolute neutrophil count, NLR and PLR were significantly higher in asthmatic patients in critical condition than in patients in non-critical condition and the control subjects (P<0.0001), and these parameters showed no significant differences between latter two groups (P>0.05). The areas under the curve of absolute neutrophil count, absolute lymphocyte count, NLR and PLR for the diagnosis of acute exacerbation of bronchial asthma were 0.802, 0.784, 0.873 and 0.795, respectively (all P<0.01); the optimal cut-off value of NLR was 2.58 for the diagnosis with a sensitivity of 82.8% and a specificity of 81.1%.</p><p><b>CONCLUSIONS</b>Peripheral blood NLR and PLR are increased in asthmatic patients, and their variations offer assistance in the diagnosis and assessment of bronchial asthma.</p>

Research progress in histone lysine demethylases inhibitors / 药学学报

The methylation of histone lysine plays a pivotal role in epigenetic regulation of gene expression. Histone lysine methylation modifications have 5 sites within histone H3(K4, K9, K27, K36, K79)and 1 site within histone H4(K20). Methylation at various sites has been shown to lead to transcriptional activation or silencing. Histone lysine methyltransferases(HKMTs)and histone lysine demethylases(HKDMs)collectively regulate the methylation modification state of histone lysine. It was reported that the mis-regulation of HKDMs is associated with the occurring and resistance of numerous malignant tumors, so more and more attention are received to HKDMs. Therefore, it is great significant in the study and development of HKDMs inhibitors. The inhibitors could be served not only as a tool in the investigation of the biological function, but also could be used as novel anti-cancer agents in the anticancer therapy. In this review, we provide a short summary of the HKDMs inhibitors recently reported and their potential in the treatment of diseases.

Latest Revision and Interpretation of International Spinal Cord Injury Bowel Function Basic Data Set / 中国康复理论与实践

Objective To study the modification of the International Spinal Cord Injury Bowel Function Basic Data Set and the signifi-cance for clinical practice. Methods The latest English version of the International Spinal Cord Injury Bowel Function Basic Data Set was compared with the previous version to find the significance of the data set. Results and Conclusion Twelve modifications were found in the latest version to make the worksheet more scientific and comprehensive for recording, and to facilitate the evaluation and comparison of var-ious published studies on intestinal dysfunction after spinal cord injury.