A high-throughput Gaussia luciferase reporter assay for screening potential gasdermin E activators against pancreatic cancer

It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC. This screening system neatly quantifies the oligomerization of GSDME-N to characterize whether pyroptosis occurs under the stimulation of chemotherapy drugs. Based on this system, ponatinib and perifosine are screened out from the FDA-approved anti-cancer drug library containing 106 compounds. Concretely, they exhibit the most potent luminescent activity and cause drastic pyroptosis in PDAC cells. Further, we demonstrate that perifosine suppresses pancreatic cancer by promoting pyroptosis via caspase-3/GSDME pathway both in vitro and in vivo. Collectively, this study reveals the great significance of hGLuc-hGSDME-PCA in identifying compounds triggering GSDME-dependent pyroptosis and developing promising therapeutic agents for PDAC.

Paired box 5 increases the chemosensitivity of esophageal squamous cell cancer cells by promoting p53 signaling activity / 中华医学杂志(英文版)

BACKGROUND@#Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear.@*METHODS@#To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification.@*RESULTS@#PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = -0.189, P = 0.011 for cg00464519 and r = -0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.@*CONCLUSIONS@#As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.

Advances in diagnosis and treatment of chronic subdural hematoma complicated with subdural empyema after trepanation and drainage / 中华创伤杂志

Most patients with chronic subdural hematoma (CSDH) have a history of craniocerebral trauma.Avulsion of intracranial pontine vein is the main pathogenesis after craniocerebral injury.CSDH drilling and drainage is the most widely used surgical method,with low recurrence and mortality rate.However,the postoperative complication of subdural pyometra is extremely rare,which leads to high mortality and disability rate and thus representing a very challenging disease in trauma surgery.Old age,diabetes mellitus,drainage with foreign body,craniocerebral surgery,open wound,chronic systemic infectious diseases (sinusitis,otitis media,abdominal abscess,lung infection,urinary tract infection),tumor or immune deficiency diseases are all the high risk factors.This paper reviews the pathogenesis,pathogenic bacteria,clinical manifestations,auxiliary examination,treatment and prognosis of subdural empyema after CSDH drilling and drainage in recent years,and provides suggestions for clinical management.

Advances in diagnosis and treatment of chronic subdural hematoma complicated with subdural empyema after trepanation and drainage / 中华创伤杂志

Most patients with chronic subdural hematoma (CSDH) have a history of craniocerebral trauma. Avulsion of intracranial pontine vein is the main pathogenesis after craniocerebral injury. CSDH drilling and drainage is the most widely used surgical method, with low recurrence and mortality rate. However, the postoperative complication of subdural pyometra is extremely rare, which leads to high mortality and disability rate and thus representing a very challenging disease in trauma surgery. Old age, diabetes mellitus, drainage with foreign body, craniocerebral surgery, open wound, chronic systemic infectious diseases (sinusitis, otitis media, abdominal abscess, lung infection, urinary tract infection), tumor or immune deficiency diseases are all the high risk factors. This paper reviews the pathogenesis, pathogenic bacteria, clinical manifestations, auxiliary examination, treatment and prognosis of subdural empyema after CSDH drilling and drainage in recent years, and provides suggestions for clinical management.

Study on the relationship between 25-hydroxyl vitamin D deficiency and food allergy in children with atopic dermatitis / 重庆医学

Objective The purpose of this study was to detect serum 25-hydroxyvitamin D [25-(OH) VitD] levels in children with atopic dermatitis (AD) and to explore its association with food allergy (FA).Methods Sixty cases of infant patients with AD have been collected.The morning fasting venous blood were obtained to check the 25-(OH)VitD level in serum.Moreover,IgE in 6 kinds of common food was also tested.Multiple regression analysis was used to analyze the relation between 25-(OH)VitD level in serum and FA.The potential risks and confounding factors were adjusted.Results Among the 60 AD children,67.4％ of them had FA,and the majority of them had milk allergy (86.84％),no wheat allergy was found.There was a positive correlation between 25-(OH) VitD levels and age (r=0.46,P＜ 0.01),but no statistical correlation with total IgE levels (P＞0.05).25-(OH)VitD deficiency may significantly increase the risk of suffering from FA (OR=11.20,95％CI:1.35-73.66,P=0.023).Conclusion The decrease of the 25-(OH)VitD level in infant patients with AD is associated with FA.What's more,25-(OH)VitD deficiency may be a risk factor for increasing FA.

Effects and Safety of Metformin Combined with Vildagliptin on the Glycemic Control for Patients with Newly Diagnosed Type 2 Diabetes Mellitus / 现代生物医学进展

Objective:To study the effects and safety of metformin combined with vildagliptin on the glycemic control for patients with newly diagnosed type 2 diabetes mellitus.Methods:60 patients with type 2 diabetes mellitus who were treated from February 2015 to April 2016 were selected and divided into the control group and the observation group according to different treatment methods.The control group was treated with routine treatment.The observation group was treated with vildagliptin based on the control group.The blood glucose,glycosylated hemoglobin,two-hour postprandial blood glucose and serum as well as urinal amylase were measured before and after treatment,and the clinical curative effect of the two groups and the levels of interleukin-6,tumor necrosis factor and C-reactive protein were compared.Results:After treatment,the total effective rate of observation group was 90％,which was significantly higher than that of the control group(66.7％,P＜0.05).After treatment,the serum interleukin-6,tumor necrosis factor,C-reactive protein and fasting blood glucose,glycosylated hemoglobin and postprandial blood glucose levels were significantly lower than those of the control group[(7.63± 1.12)dvs(8.68± 1.30)d;(7.23± 0.95)d vs(7.89± 1.20)d;(11.14± 1.56)d vs(12.12± 1.89)d];[(12.12± 1.89)d vs(ll.20± 1.34)d;(6.89± 0.96)d vs(8.23± 1.10)d;(1.65± 0.23)d vs(3.65± 0.48)d] (P＜0.05).After treatment,the INS level of observation group was significantly lower than that of the control group (P＜0.05) and the GLP-1 level was significantly higher than that of the control group (P＜0.05).Conclusion:Metformin combined with vildagliptin could effectively control the blood glucose of patients with newly diagnosed type 2 diabetes and enhance the safety.

Robot-assisted upper limb therapy improves shoulder joint proprioception after stroke / 中华物理医学与康复杂志

Objective To explore the effect of robot-assisted therapy on the shoulder joint proprioception of convalescent stroke survivors.Methods Forty stroke survivors were enrolled and randomized into an experimental group (n =20) and a control group (n =20).Both groups received routine drug treatment and rehabilitation,including the traditional kinesitherapy,occupational therapy and physical therapy,but the experimental group was additionally provided with 20 minutes of robot-assisted upper limb therapy 6 times a week for 8 weeks.Before the intervention and at 4 and 8 weeks the multi-joint system (MJS) upper limb proprioception test system was used to evaluate the average trace error and test execution time of the upper limb.Shoulder joint proprioception was measured at 30° and 60° in intorsion and extorsion using an isokinetic dynamometer.Results Before the training there were no significant differences between the two groups in terms of any of the assessments.After 4 and 8 weeks of training,significant improvement was observed in the measurements,and those of the experimental group were significantly better than those of the control group at the same time points.Conclusion Robot-assisted therapy can facilitate the recovery of shoulder joint proprioception after a stroke.It is worthy of application in clinical practice.

Surgical and interventional treatment for superior mesenteric artery thrombosis / 中华老年医学杂志

Objective To observe the operation process implementation and the therapeutic effect of interventional therapy for the superior mesenteric artery thrombosis.Methods 21 cases with superior mesenteric arterial thrombosis who had the diagnosis and clinical treatment in our hospital from January 2005 to December 2013 were retrospectively analyzed.Results Among 21 cases,19 cases had obvious risk factors,and their early symptoms and signs were not consistent.The artery angiography showed that 17 cases had superior mesenteric artery thrombosis,2 cases had ileum arterial thrombosis,2 cases had inferior mesenteric arterial thrombosis.All surgeries were performed successfully.The length of hospital stay was 10 14 days with an average of 11 days.After interventional treatment,the symptom of abdominal pain had obvious remission.The follow-up period was 12 to 36 months and no recurrence was found.Conclusions The diagnosis of mesenteric arterial thrombosis is difficult.Mesenteric arterial thrombosis needs the early diagnosis and timely interventional treatment.

Imaging features of Ewing sarcoma and primitive neuroectodermal tumor in sacrum / 中华放射学杂志

Objective To investigate the imaging features of Ewing's sarcoma and primitive neuroectodermal tumor (ES and PNET) in sacrum.Methods Imaging data were retrospectively collected and reviewed in 17 patients with ES and PNET confirmed by pathology.X-ray was performed in all patients,CT scans in 13 patients,and MR scans in 10 patients.Results All lesions were detected solitary and lateral.X-ray and CT features were lytic bone destruction in 12 cases,2 of them with bone sclerosis; one patient showed diffuse sclerosis.Soft tissue mass in pelvic cavity can be seen in 11 cases,9 of them with adjacent large blood vessels invasive and 4 patients with sacroiliac joints invasive.On post-contrast images,mild enhancement was found in 8 cases,and 5 patients with marked enhancement.MR images showed intermediate signal intensity on T1WI in 8 cases and heterogeneous moderate to high signal intensity on T2WI/fat suppression in 10 cases.DWI showed high signal intensity in 4 cases.Unlike CT scan,contrastenhanced MR images showed significant enhancement in 7 cases.Conclusions Ewing's sarcoma and primitive neuroectodermal tumor (ES and PNET) in sacrum have some specific imaging features.Imaging examination could provide reliable evidence for clinical diagnosis.

A pilot study of different thrombolytic therapies for acute cerebral infarction due to occlusion of middle cerebral artery / 中华放射学杂志

ObjectiveTo evaluate the effect and safety of different thrombolytic therapies for acute cerebral infarction due to occlusion of middle cerebral artery(MCA).MethodsOne hundred and thirty-two cases of acute cerebral infarction in territory of MCA were randomly divided into 3 groups,all of which were treated with alteplase.Group A (48 cases) was treated by intra-venous therapy with alteplase,group B (43 cases) was treated by infusing alteplase at the site of the internal carotid artery,and group C(41 cases) was treated by infusing alteplase into the thrombus.The improvement of neurological function,complications and mortality rate were recorded and statistically compared,with analysis of variance for counting data of normal distribution,x2 test for quantitative data,and the mean difference was significant at the 0.05level.ResultsThe effective rates of group A,B and C at 2 h,24 h,2 w were 18.8％ (9/48),39.6％ ( 19/48),45.8％ (22/48) ;39.5％ (17/43),53.5％ (23/43),58.1％ (25/43) ;78.0％ (32/41),85.4％ (35/41 ),87.8％ (36/41)respectively.The effective rate of group C was obviously better than group A( x2 =12.809,9.979,9.289,P ＜ 0.01 ) and B (x2 =31.295,19.425,17.161,P ＜ 0.01 ) with statistical significance.The effective rate of group B was better than group A at 2 h after thrombolytic therapy with statistical significance (x2 =4.801,P ＜ 0.05 ).The effective rate of group A and B did not have significant difference at 24 h,2 w after therapy ( x2 =1.765,1.375,P ＞ 0.05 ).The hemorrhage rates of group A,B and C were 14.6％ (7/48),14.0％ (6/43),7.3％ (3/41 ),the mortality rates of group A,B and C were 6.2％ (3/48),4.6％ (2/43),2.4％ (1/41),and there was no significant difference among the 3 groups ( x2 =1.328,0.786,P ＞ 0.05 ).ConclusionIt is suggested that the thrombus-imbeded thrombolytic therapy is a better way in treating acute cerebral infraction due to occlusion of MCA for its rapid and better therapeutic effect.

The Interaction Between the Symbiotic Genes pJB5JI of Rhizobium Leguminosarum bv. Viciae and the Symbiotic Plasmid of Mesorhizobium huakuii 7653R / 微生物学通报

Mesorhizobium huakuii strain 7653R,isolated from nodules of A.sinicus L,contains two indige-nous plasmids,p7653Ra and p7653Rb,the latter being the symbiotic plasmid.We eliminated the plasmids via Tn5-sacB insertion and obtained its symbiotic plasmid-cured derivative 7653RD.Then,we transferred the symbiotic plasmid pJB5JI of Rhizobium leguminosarum bv.Viciae T83K3 into 7653R and 7653RD.The pot plant test showed an increase in competitive ability and symbiotic nitrogen fixation of transconjugant 7653R-197(pJB5JI) compared to 7653R.pJB5JI could not restore the ability of 7653RD to nodulate Astra-galus sinicus.7653RD(pJB5JI) could form ineffective nodules on peas,implying that the symbiotic plasmid pJB5JI could express its function at the chromosomal background of Mesorhizobium huakuii 7653R.We checked the stability of plasmid in transconjugants under free-living and during symbiosis.The results indi-cated pJB5JI could not be detected in some nodule isolates.We amplified kan resistance gene from all transconjugants and nodule isolates which suggested that pJB5JI might fully or partially integrated into the chromosome of recipients.