Simvastatin,a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,is widely prescribed to patients with hypercholesteremia and its muscular toxicity has been widely reported.The metabolism of simvastatin depends on the enzymic activity of cytochrome P450 3A4 (CYP3A4) and inhibitors of CYP3A4 can result in clinical events by interacting with simvastatin.Diltiazem is a moderate inhibitor of CYP3A4,which is known to increase the serum concentration of simvastatin.Here we report a patient with unrecognized hypothyroidism who had been stable for more than one year on low-dose simvastatin therapy of hypercholesteremia and rhabdomyolysis occurred with the addition of diltiazem.This is one of scanty reports of rhabdomyolysis induced by simvastatindiltiazem drug interaction,especially in hypothyroid patient.This case reminds the clinicians that although diltiazem as a moderate CYP3A4 inhibitor can be used cautiously with small doses of CYP3A4-dependent statius (eg,simvastatin),these two commonly used drugs should be avoided in hypothyroid patient.

Objective To establish a C57BL/6 mouse model of intestinal infection induced by S.Typhimurium.Methods In order to improve the infectious sensitivity of S.Typhimurium, C57BL/6 mice were intragastrically given 5% (w/v) NaHCO3.Then mice were challenged with S.Typhimurium.The health condition, survival and body weight of mice were observed from day 0 to day 7 after the bacterial infection.The pathological changes were also examined.Results the mice challenged with S.Typhimurium showed decreased body weight and typical clinical signs, including in appetence, piloerection and low survival rate.Macroscopic dissection revealed that intestinal hyperemia and swelling were founded in the mice challenged with S.Typhimurium.Histopathology showed intestinal epithelial and mucosal damages.Conclusions We have successfully established a C57BL/6 mouse model of S.Typhimurium infection.This model may be of crucial significance for studying the biological functions of associated immunological molecules or cytokines in the process of inflammatory bowel disease induced by S.Typhimurium.

Objective To investigate the expression of recombinant IL-37b protein and removal of the endotoxin, and identify its biological activity.Methods The prokaryotic expression vector pET28/IL-37b was constructed and to transform Escherichia coli (E.coli) Rosetta.After induction with IPTG, the recombinant protein was purified through Ni2+-NTA gel column and identified by SDS-PAGE and Coomassie brilliant blue staining.Then, the endotoxin protein was removed and was treated with LPS-stimulated RAW 264.7 cells.The culture supernatant was collected.The expression of IL-6 was detected by ELISA and the biological activity of the protein was identified.Results The recombinant IL-37b with high purity was expressed and the endotoxin produced by prokaryotic expression was reduced, and it was identified to have good biological activity.Conclusions In this study a recombinant IL-37b protein with high biological activity is successfully obtained.

OBJECTIVETo observe the clinical effect of Guilu Erxian Glue Cataplasm (GEGC) on carcinoma of the large intestine patients with myelosuppression after chemotherapy, and further to confirm its efficiency and safety.

METHODSTotally 60 patients with carcinoma of the large intestine were randomly assigned to two groups. Meanwhile, they all accepted FOLFIRI chemotherapy. Patients in the treatment group were additionally applied at Shenque (RN8), exchanging once per every other day, for 14 successive days. Patients in the control group took placebos with the same dose and dosage as the treatment group. The blood cell counts (WBC, NE, and PLT) were detected before chemotherapy, at day 7, 10, and 14. The TCM symptoms integrals, Karnofsky performance score (KPS), liver and kidney functions were observed before chemotherapy, at day 7 and day 14. Adverse skin reactions were observed each day. And the usage of hematopoietic growth factors was recorded.

RESULTS(1) The KPS score at day 7 was more stable in the treatment group than in the control group; the WBC and NE counts in the peripheral blood at day 14 were higher in the treatment group than in the control group; and TCM symptoms integrals at day 14 was lower in the treatment group than in the control group, all with statistical difference (P < 0.05). (2) Compared with the control group, the PLT count was higher in the treatment group than in the control group, the usage of rhG-CSF and antibiotics was less in the treatment group than in the control group, all with no statistical difference (P > 0.05). (3) No obvious adverse reactions such as liver injury, renal injury, or skin allergy were observed.

CONCLUSIONSAdjuvant treatment of GEGC could improve carcinoma of the large intestine patients with myelosuppression to some extent. No relevant adverse reactions were found.

Adjuvants, Immunologic ; therapeutic use ; Adult ; Aged ; Bone Marrow Diseases ; chemically induced ; drug therapy ; Colorectal Neoplasms ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged

The objective was to explore the in vitro effects of growth inhibition and apoptosis induction of 2-methoxyestradiol (2ME2), an estrogen derivative, on seven myeloma cell lines NCI-H929, HS-sultan, KM3, SKO-007, CZ-1, U266 and LP-1and to observe its synergistic effects in combination with some other drugs, such as dexamethasone, As(2)O(3), thalidomide and zoledronic acid. Seven myeloma cell lines NCI-H929, HS-sultan, KM3, SKO-007, CZ-1, U266 and LP-1 were cultured at different concentrations with or without dexamethasone, As(2)O(3), thalidomide and zoledronic acid. Cell viability was assessed by trypan blue assay, plasma cell labeling index (PCLI) was detected by BrdU assay, terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay were used to determine apoptosis cells in situ. Synergistic effects of 2ME2 in combination with other drugs were judged by King's formula. The results showed that after treatment with 1, 4, 8, 12, 16 micromol/L 2ME2 at 12, 24, 36 and 48 hours respectively, 2ME2 caused a dose- and time-dependent inhibition of the cell viability. The concentration of 50% growth inhibition (IC(50)) was between (20.8 +/- 0.27) and (34.1 +/- 0.57) micromol/L. After treatment with 12 micromol/L 2ME2 within 24 hours, 2ME2 led to a progressive decline in the fraction of S-phase cells by BrdU assay, plasma cell labeling index (PCLI) declined from (30.14 +/- 4.28)% to (14.71 +/- 6.27)% (P < 0.05). After treatment with 1, 4, 8, 12, 16 micromol/L 2ME2 at 12, 24, 36 and 48 hours respectively, 2ME2 can induce a dose- and time-dependent apoptosis of myeloma cell lines. The percentage of apoptosis was between 9% - 33% (P < 0.05). Q value of synergistic effects was between 1.13 to 1.43. It is concluded that 2ME2 can inhibit proliferation and induce apoptosis of myeloma cell lines and has synergistic effects with dexamethasone, As(2)O(3), thalidomide and zoledronic acid.
Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Proliferation ; drug effects ; Dexamethasone ; pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Estradiol ; analogs & derivatives ; pharmacology ; Humans ; Multiple Myeloma ; pathology ; Oxides ; pharmacology ; Time Factors ; Tumor Cells, Cultured

OBJECTIVETo investigate the differentiation induction effect of 2-methoxyestradiol (2ME2), an estrogen derivative on myeloma cell line CZ-1.

METHODSThe changes of CZ-1 cells in morphology, expression of surface CD49e and quantity of light chain secretion in the supernatant were observed when treated with 0.1 approximately 0.5 micromol/L 2ME2 for 48 h.

RESULTS2ME2 could induce differentiation of CZ-1 cells. The cells appeared decreased in size of nucleus, increased in cytoplasma, decreased in the ratio of nucleus to plasma, decreased in number or disappearance of nucleolus, and thickness and pyknosis of chromatin. The expression of CD49e was increased from (12.20 +/- 1.57)% to (24.80 +/- 1.26)% (P < 0.05). Light chain secretion in the supernatant was increased from (35.97 +/- 2.60) microg/ml to (79.67 +/- 1.88) microg/ml (P < 0.05).

CONCLUSIONLow concentrations of 2ME2 could induce differentiation of myeloma cell line CZ-1.

Cell Differentiation ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Estradiol ; analogs & derivatives ; pharmacology ; Flow Cytometry ; Humans ; Integrin alpha5 ; analysis ; Multiple Myeloma ; metabolism ; pathology ; Tubulin Modulators ; pharmacology

Three cases of Good's syndrome with pulmonary lesions in our hospital from June 1,2010 to June 1,2013 were retrospective analyzed and relevant literatures were reviewed.Clinical manifestation,characteristics of pulmonary lesions,diagnosis and treatment were summarized.Abnormality of lymphocyte subpopulation to varying degrees in peripheral blood was detected in all 3 cases.However none showed hypogammaglobulinemia.If thymoma patients developed recurrent respiratory infections,Good's syndrome should be considered.Pulmonary manifestations of Good's syndrome have lesions similar to those of diffuse panbronchiolitis or interstitial lung disease.Early screening of immune competency and treatment for immunodeficiency may improve prognosis.

Objective:To systematically evaluate the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) plus surgery versus neoadjuvant chemotherapy (NCT) plus surgery in the treatment of advanced esophageal squamous cell carcinoma.Methods:Clinical controlled trials of comparing the treatment of NCRT plus surgery with NCT plus surgery for esophageal squamous cell carcinoma were electronically searched from the databases including PubMed, The Cochrane Library, EMbase, CBM, CNKI, WanFang and VIP from the inception of databases to January, 2019. Two reviewers independently screened the literatures, extracted data and assessed the risk of bias of the included studies. And then, a meta-analysis was performed by using RevMan 5.3 software.Results:A total of 8 clinical control studies were included, including 995 patients with esophageal squamous cell carcinoma. Meta-analysis results showed that compared with the NCT group, the R 0 resection rate was significantly higher ( OR=2.14, 95% CI: 1.03-4.45, P=0.040) and the pathological complete response (pCR) rate was significantly higher ( OR=4.19, 95% CI: 1.71-10.28, P=0.002) in the NCRT group. The incidence of postoperative complications ( OR=1.37, 95% CI: 0.76-2.48, P=0.300) and the risk of perioperative death ( OR=1.28, 95% CI: 0.58-2.83, P=0.54) were not significantly different between two groups. The long-term survival of patients with esophageal squamous cell carcinoma in the NCRT group was significantly better compared with that in the NCT group ( HR=0.77, 95% CI: 0.64-0.92, P=0.005). Conclusions:Compared with NCT plus surgery for advanced esophageal squamous cell carcinoma, NCRT plus surgery has higher R 0 resection rate and pCR rate, does not significantly increase the risk of perioperative complications or perioperative death, and significantly improves the long-term survival of esophageal squamous cell carcinoma patients.

Objective To investigate the effect of Smad3 on cell migration of A549 and HeLa cells.Methods Primers for pCMV-Myc-Smad3 plasmid construction and siRNA targeting Smad 3 were designed and synthesized .pCMV-Myc-Smad3 plasmid was constructed with molecular cloning techniques .Overexpression of Smad 3 with Myc-tag or silencing of endogenous Smad3, and then scratch assay was used to detect the migration ability of A 549 and HeLa cells in vitro. Results pCMV-Myc-Smad3 plasmid was successfully constructed .Overexpression of Smad 3 significantly up-regulated the migration rate of A549 and HeLa cells.Conversely, in the same cells, silencing of endogenous Smad3 or treatment with Smad3 inhibitor, SIS3, down-regulated the migration rate .Conclusions Smad3 promotes cell migration of A549 and HeLa cells.

Objective To establish lentiviral expression vectors for Smurf1 silencing and assess the effects of Smurf1 silencing on cell migration.Methods HeLa and A549 cells were infected with lentiviral expression vectors for Smurf1 silencing respectively.After 7 days,the stable cell lines with Smurf1 silencing were obtained after puromycin-resistance screening,enrichment and expansion.The intracellular gene and protein levels of Smurf1 were detected by qPCR and western blot.Transwell assay was used to assess the effect of Smurf1 silencing on cell migration.Results The stable cell lines with Smurf1 silencing are constructed successfully.Silencing of Smurf1 down-regulated cell migration rate detected by Transwell assay.Conclusion Smurf1 promotes cell migration.