Objective To identify the relationship between sorafenib's efficacy and its side effects in treatment of advanced renal cell carcinoma patients. Methods Fifty-one patients having measurable diseases were diagnosed with advanced renal cell carcinoma. Of whom, 26 patients were in stage T1Nx,0,1M1, 12 patients in stage T2Nx,0 M1, 8 patients in stage T3NxM1, 5 patients in stage T4NxM1. These 46 patients of T1 -T3 had their primary diseases removed, but the 5 T~ patients didn"t have their primary diseases removed. These 51 patients received oral sorafenib 400 mg Bid continual-ly and they had CT scan every two months to evaluate the progression. The dosage of sorafenib wasmodified according to efficacy and toxicity. Two patients changed the dosage to 200 mg Bid due to se-vere side effects. Sixteen patients increased the dosage to 600 mg Bid or 800 mg Bid. The response ofSorafenib and toxicities as well as their severity were recorded. The toxicity severity was graded ac-cording to National Cancer Institute Common Toxicity Criteria version 3.0. The efficacy was deter-mined by RECIST criteria. The efficacy and progression free survival (PFS) were recorded. The sta-tistics analysis was conducted between sorafenib's side effects and efficacy as well as their severity by multi-faetor Logistic regression. Results The rates of adverse events in the patients receiving oral sorafenib were hand-foot skin reaetion 68. 6% (35/51), diarrhea 39. 2% (20/51), rash 25. 5% (13/ 51), mucositis 23.5% (12/51), hypertension 17.6% (9/51), and myelosuppression 13. 7%(7/51). The response rate in the patients who had toxicity of grade 3-4 was 33.3%(12/36), and that in the patients who had slight toxicity was 12.0%(3/25). The rate of hand-foot skin reaction was higher than that of diarrhea, rash, mucositis, hypertension and bone marrow suppression (P<0.01). Sor-afenib's efficacy was eorrelated to rash and mueositis (P=0.048, 0.045 respectively). More grade 3 4 side effects occurred in the patients who would have better response to sorafenib (P=0.008). The median PFS was 15.0 months and PFS was not related to the toxicity and its severity. Conclusions It may help to predict the response for sorafenib's side effects and efficacy in the treatment of the patients with advaneed renal cell earcinoma.

Objective To analyze the effect and related factors of sorafenib in the treatment of metastatic renal cell carcinoma(MRCC), and identify the potential predictive factors of sorafenib re-sponse. Methods The data of 51 MRCC patients who received sorafenib therapy, with or without combination with interferon or chemotherapy were retrospectively reviewed. After two cycles of treat-ment, patients were evaluated for progression or response. Pearson Chi-square test and Logistic re-gression test were performed respectively as univariate and multivariate analyses of sorafenib response. Results The overall objective response rate was 29.4%(95% confidence interval 16.9% to 41.9%, with 1(2.0%) complete response and 14(27.4%) partial responses. Twenty-nine(56.9%) had stable disease, and 7 (13.7%) had progression disease (PD). Significant independent predictive factors asso-ciated with good response in multivariate analysis were lung metastasis only(P=0.021, HR=5.127). Conclusions Sorafenib is effective in MRCC patients. Lung metastasis only is predictive factor in mul-tivariate analysis for sorafenib response.

The biomimetic drug system can effectively reduce the immunogenicity of traditional nanoparticles and make the drug have good targeting and safety by imitating the structure and function of biological system.Therefore,the biomimetic drug system has become an ideal candidate drug delivery system and has been widely concerned as a new drug delivery system.Now domestic and international bionic delivery system research has been involved in different types of pharmaceutical preparations,including nanoparticles,liposomes,microcapsules,polymer micelles and so on.This paper reviews the latest research progress of biomimetic nanoparticles at home and abroad.

Objective To investigate the better regimen of combined cyclophosphamide pulse therapy with corticosteroids in the treatment of Pemphigus. Methods Intravenous cyclophosphamide was given weekly in a dosage of 600 mg to those Pemphigus patients whose conditions couldn't be improved by corticosteroids (oral prednisone 1.2～1.5 mg/kg/d) alone. Results Ten patients with Pemphigus received weekly cyclophosphomide therapy in addition to corticosteroid. Patients conditions improved quickly, without side effects. Conclusions Cyclophosphamide weekly pulse therapy combined with corticosteroids is a good regimen in the treatment of Pemphigus.

BACKGROUNDLactate dehydrogenase (LDH) is a crucial regulator of energy metabolism in many organs including the heart. Lovastatin is widely used in prevention and treatment of coronary heart disease and is a drug with substantial metabolic influences. Our study aimed to determine the activities of the lactate dehydrogenase A and B (LDHA and LDHB) genes following lovastatin treatment.

METHODSThe rat myocardial cell line H9c2(2-1) in culture was exposed to 100 nmol/L lovastatin for 24 hours or for five days. The functions of the LDHA and LDHB genes were examined at the transcriptional (mRNA) level with quantitative real-time polymerase chain reaction (Q-RT-PCR), and at the translational (protein) level with immunoblotting.

RESULTSWhen compared with control levels, the LDHA mRNA went up by (151.65 ± 16.72)% (P = 0.0132) after 24 hours and by (175.28 ± 56.54)% (P = 0.0366) after five days of lovastatin treatment. Although 24 hours of lovastatin treatment had no significant effects on LDHB mRNA levels, when the treatment was extended to five days, LDHB mRNA levels were significantly down-regulated to (63.65 ± 15.21)% of control levels (P = 0.0117). After 24 hours of treatment with lovastatin, there were no significant changes in protein levels of either LDHA or LDHB. When treatment time was extended to five days, the protein levels of LDHA were up-regulated by (148.65 ± 11.81)% (P = 0.00969), while the protein levels of LDHB were down-regulated to (64.91 ± 5.47)% of control levels (P = 0.0192).

CONCLUSIONSLovastatin affects gene activities of LDHA and LDHB differently, which may reveal novel pharmacological effects of lovastatin.

Animals ; Anticholesteremic Agents ; pharmacology ; Blotting, Western ; Cell Line ; Isoenzymes ; genetics ; metabolism ; L-Lactate Dehydrogenase ; genetics ; metabolism ; Lovastatin ; pharmacology ; Myocytes, Cardiac ; drug effects ; enzymology ; Rats ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo study the impacts of exposure to electromagnetic radiation (EMR) on liver function in rats.

METHODSTwenty adult male Sprague-Dawley rats were randomly divided into normal group and radiated group. The rats in normal group were not radiated, those in radiated group were exposed to EMR 4 h/ d for 18 consecutive days. Rats were sacrificed immediately after the end of the experiment. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and those of malondialdehyde (MDA) and glutathione (GSH) in liver tissue were evaluated by colorimetric method. The liver histopathological changes were observed by hematoxylin and eosin staining and the protein expression of bax and bcl- 2 in liver tissue were detected by immunohistochemical method. Terminal-deoxynucleotidyl transferase mediated nick and labelling (TUNEL) method was used for analysis of apoptosis in liver.

RESULTSCompared with the normal rats, the serum levels of ALT and AST in the radiated group had no obvious changes (P>0.05), while the contents of MDA increased (P < 0.01) and those of GSH decreased (P < 0.01) in liver tissues. The histopathology examination showed diffuse hepatocyte swelling and vacuolation, small pieces and focal necrosis. The immunohistochemical results displayed that the expression of the bax protein was higher and that of bcl-2 protein was lower in radiated group. The hepatocyte apoptosis rates in radiated group was higher than that in normal group (all P < 0.01).

CONCLUSIONThe exposure to 900 MHz mobile phone 4 h/d for 18 days could induce the liver histological changes, which may be partly due to the apoptosis and oxidative stress induced in liver tissue by electromagnetic radiation.

Animals ; Apoptosis ; Cell Phone ; Electromagnetic Radiation ; Liver ; pathology ; radiation effects ; Male ; Oxidative Stress ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Staining and Labeling

BACKGROUNDGlucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.

METHODSEighty hospitalized patients (average age (59.0 +/- 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment.

RESULTSImmunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.

CONCLUSIONSBoth the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.

Aged ; Blotting, Western ; Coronary Disease ; drug therapy ; metabolism ; Female ; Humans ; Isosorbide Dinitrate ; therapeutic use ; Lovastatin ; therapeutic use ; Male ; Metoprolol ; therapeutic use ; Middle Aged ; Nifedipine ; therapeutic use ; Receptors, Glucocorticoid ; metabolism

Objective:To investigate whether the existence of thoracic artery blood supply in peripheral pulmonary lesions is the key factor affecting the accuracy of contrast-enhanced ultrasound in differentiating benign and malignant lesions.Methods:From June 2020 to December 2021, a total of 170 patients with peripheral pulmonary lesions were consecutively enrolled in Xi′an Chest Hospital, and all patients underwent conventional ultrasound and contrast-enhanced ultrasound(CEUS). Taking ΔAT(lesion-lung arrival time difference ) of 2.5 seconds as the cut-off point for differentiating benign and malignant lesions(ΔAT<2.5 s for benign, ΔAT≥2.5 s for malignant), and the final pathological results as the gold standard, these patiens were divided into correct classification group and wrong classification group, and the main influencing factors of wrong classification were analyzed.Results:Compared with the correct classification group, the proportion of thoracic artery blood supply in the wrong classification group was significantly higher ( P<0.001). After adjusting the dendritic venous reflux, thoracic artery blood supply was an independent influencing factor for CEUS misclassification ( OR=3.531, 95% CI=1.805-6.908, P<0.001). In the patients with thoracic artery blood supply, the sensitivity of the absence of dendritic venous reflux in judging malignant peripulmonary lesions was 75.0%, the specificity was 91.3%, and the area under the ROC curve (AUC) was 0.832 (95% CI=0.715-0.915, P<0.001), while the sensitivity, specificity and AUC of CEUS in judging malignant peripulmonary lesions were 68.7%, 67.4% and 0.659 (95% CI=0.528-0.775, P=0.006), and there was significant statistical difference in the AUC between them( P<0.001). In the group of patients without thoracic arterial blood supply, the sensitivity of the absence of dendritic venous reflux in judging malignant peripulmonary lesions was 82.8%, the specificity was 63.3%, and the AUC was 0.730 (95% CI=0.636-0.811, P<0.001), while the sensitivity, specificity and AUC of CEUS in judging malignant peripulmonary lesions were 62.1%, 81.0% and 0.684 (95% CI=0.587-0.770, P=0.003), and there was no significant difference in the AUC between them ( P=0.425). Conclusions:The presence of thoracic artery blood supply significantly decrease the diagnostic efficiency of CEUS in differentiating benign and malignant of peripheral pulmonary lesions. For peripheral pulmonary lesions with thoracic arterial blood supply, the diagnostic efficiency of dendritic venous reflux is better than CEUS, while for lesions without thoracic artery supply, the diagnostic efficiency of dendritic venous reflux is equivalent to CEUS.

A 68-year-old female patient was treated for unhealed ulcer in the fourth toe of the left foot. Clinical examinations identified severe stenosis of the proximal segment and occlusion of the distal segment of the left anterior tibial artery, and occlusion of the left posterior tibial artery and the peroneal artery. The proximal stenotic segment of the left anterior tibial artery was dilated, but the distal occlusive part failed to be re-canalized. Left anterior tibial artery to dorsal pedal artery bypass was performed on the patient with an epoxide-crosslinked, special radicals antigen-sealed, porcine-derived biological graft; debridement of the left 4th digiti pedis was also performed. Postoperation course was uneventful. The pulse of the left dorsal pedal artery was strong. The ankle brachial index (ABI) increased from 0.60 to 1.09. Warfarin and two antiplatelet drugs were given after the operation. Six months after operation, computed tomographic angiogram (CTA)identified the patent graft.

AIMTo study the influence of astragalus and zinc sulfate on the viscosity in erythrocyte membrane during intestinal I/R and their mechanism of action.

METHODSModels of rabbits intestinal I/R injury were made. The effect of astragalus and zinc sulfate on the viscosity and malondialdehyde (MDA) in erythrocyte membrane, superoxide dismutase (SOD) in erythrocyte, oxidase (XO) in plasma and MDA tissues homogenate were observed.

RESULTSThe administration of astragalus and zinc sulfate decreased viscosity and MDA and XO, prevented the reduction of SOD, and alleviated I/R injury.

CONCLUSIONLipid peroxidation injury of the erythrocyte membrane was one of the pathogenesis of I/R injury, and astragalus and the zinc sulfate possessed effects of anti-lipid peroxide, stabilized erythrocyte membrane, increased red blood cell deform ability and raised microcircular perfusion.

Animals ; Astragalus Plant ; Blood Viscosity ; Drugs, Chinese Herbal ; pharmacology ; Erythrocyte Membrane ; drug effects ; Female ; Intestines ; blood supply ; pathology ; Lipid Peroxidation ; Male ; Malondialdehyde ; analysis ; Oxidoreductases ; analysis ; Rabbits ; Reperfusion Injury ; metabolism ; pathology ; Superoxide Dismutase ; analysis ; Zinc Sulfate ; pharmacology