Adolescent ; Adult ; Altitude ; Exercise ; Free Radicals ; metabolism ; Humans ; Male ; Placebos ; Tyrosine ; pharmacology ; Young Adult

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.

OBJECTIVETo constitute a model of B immunoblastic lymphomas in the Hu-PBL-SCID mice.

METHODSThe SCID mice were reconstituted by intraperitoneal injection (i.p.) of 5 x 10(7) human lymphocytes from Epstein-Barr virus (EBV) seronegative individuals. After one week, the SCID mice were inoculated with EBV by i.p. injection, and subjected to the investigation of whether there was any tumor in the abdomen of such SCID mice four weeks later. The characteristics of the found tumor was observed by the methods of Hematoxylin-eosin (HE) stain, immunohistochemical staining and polymerase chain reaction (PCR).

RESULTSCompared with the control groups, all the EBV-infected Hu-PBL-SCID mice had abdominal solid tumors [(32 +/- 12.5) mm3] developed, often located in the liver. HE staining and immunohistochemical staining showed the tumors were human B cell lymphomas. EBV DNA could be detected in the tumors by the PCR.

CONCLUSIONSThe model of B immunoblastic lymphomas in the Hu-PBL-SCID mice is successfully constituted, and may well be useful to the human tumor immunological study.

Animals ; Disease Models, Animal ; Herpesvirus 4, Human ; physiology ; Humans ; Lymphoma, Large-Cell, Immunoblastic ; Mice ; Mice, SCID

BACKGROUNDNumerous studies have shown that reducing the level of tumor necrosis factor-alpha (TNFα) through the use of anti-TNF antibodies or soluble TNF receptor is a safe and efficacious treatment to inflammatory diseases such as rheumatoid arthritis. Therefore, novel approaches to achieve this outcome are desired. The aim of this study was to investigate the characterization of a small molecule inhibitor, Y316, which blocks TNF mRNA upregulation and TNF production by lipopolysaccharides (LPS) stimulated monocytes.

METHODSPeripheral blood mononuclear cells (PBMC) from healthy volunteers were plated in 24-well plates and stimulated with LPS (1 µg/ml), phorbol-12-myristate-13-acetate (PMA) (100 ng/ml), zymosan (10 µg/ml) and Tsst (100 ng/ml). Supernatants were collected after 4-hour culture at 37°C, and quantitative determination of TNFα, interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and IL-2 production in the supernatants was performed by colorimetric enzyme-linked immunosorbent assay (ELISA). Total RNA of PBMC was isolated and cytokine mRNA quantitation was performed by using a RNA level measuring kit (R & D Systems). PBMC were pretreated with Y316 (10 µmol/L, 1 µmol/L, 0.1 µmol/L, 0.01 µol/L and 0.001 µmol/L) or dimethyl sulfoxide at 37°C for 10 minutes, and then stimulated with LPS or PMA, protein concentrations of p44.42, IKBα, P38 and Jun NH2-terminal kinase were determined by Western blotting. Cyclic adenosine-3',5'-monophosphate (cAMP) of PBMC was measured by enzyme immunoassay kit (Amersham Pharmacia Biotech).

RESULTSY316 blocked TNF production and inhibited the upregulation of TNF mRNA levels in response to LPS, and also prevented the production of IL-1 and IL-6. In contrast, Y316 augmented the production of IL-10 in LPS-stimulated monocytes. Y316 failed to prevent the production of IL-2 and TNF in antigen-stimulated T cells, suggesting that its effects may be cell-type specific. Y316 prevented the phosphorylation and activation of the MAPK, ERK, and therefore appeared to mediate its effects on TNF by acting at an early point in the signaling cascade induced in response to LPS. There was no effect of Y316 on cAMP levels either alone or in the presence of LPS.

CONCLUSIONSY316 appears to be a small molecule inhibiting TNF production, which may act via a novel mechanism. Identification of the target of Y316 may lead to the development of alternative strategies for achieving selective cytokine inhibition.

Anti-Inflammatory Agents ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Interleukin-1 ; antagonists & inhibitors ; biosynthesis ; Interleukin-6 ; antagonists & inhibitors ; biosynthesis ; Lipopolysaccharides ; pharmacology ; Monocytes ; drug effects ; immunology ; Phosphorylation ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; biosynthesis

Objective To explore whether autoreactive antibody presents in patients with sporadic idiopathic hypoparathyroidism(sIHP).Methods The subjects including 26 patients with sIHP and 112 genealogical members as well as 60 age-and sex-matched healthy controls.Anti-parathyroid antibodies in the sera were assayed by indirect immunofluorescence.The levels of calcium,phosphorus and magnesium as well as intact parathyroid hormone(iPTH)in the sera were tested.Results Positive autoantibodies against parathyroid tissue were demonstrated in 10 patients(38%)with sIHP,significantly higher than that of in genealogical members(10%,?~2=13.42,P

Abstract: To analyze the clinical, therapeutic and laboratory characteristics of disseminated cryptococcosis caused by Cryptococcus neoformans invading the blood stream in patient with liver cirrhosis and splenectomy. A 30-year-old male underwent splenectomy plus pericardial devascularization due to "splenomegaly and hypersplenism" in March in 2016. The patient had intermittent fever after operation for many times, and successively accompanied with back pain, left lower limb abscess and right hip pain. The highest body temperature was 39 ℃. CT and MRI revealed the lung lesion and multiple bone destruction. During that period, the effect of antibiotics was not good. On April 19th, 2017, Gram's stain, India ink stain, API 32C, Vitek 2 Compact, ribosomal ITS and IGS sequence analysis were performed to identify the strain isolated from the pus and blood stream. The serum of the patient was detected for cryptococcal antigen. Antifungal susceptibility test was used to determine drug sensitivity and minimum inhibitory concentration (MIC). The Cryptococcus neoformans isolated from fresh pus specimen showed a prominent, thick capsule after India ink stain. The colonies isolated from pus and blood stream were identified Cryptococcus neoformans using API 32C, Vitek 2 Compact, and sequence analysis of rDNA ITS and IGS. Cryptococcal capsule antigen was positive. The minimal inhibitory concentrations of 5-Flucytosine, amphotericin B, fluconazole, itriconazole, voriconazole against the isolate were <4 μg/mL, <0.5 μg/mL, 4 μg/mL, ≤0.25 μg/mL, 0.125 μg/mL respectively. The patient was initially treated with intravenous amphotericin B and flucytosine. After anti-Cryptococcus treatment for two months, the patient clinically improved, and the lesions were reduced on a follow-up CT scan. The patient made a full functional recovery after treatment for six months. Cryptococcosis has hidden onset, atypical clinical symptoms and lack of specificity. Blood stream is the main channel for Cryptococcus to spread and involve many organs of the whole body, including skin, bone and so on. Therefore, early use of blood culture to monitor blood flow dissemination, actively removing the primary focus and cutting off the infection route in time and carrying out effective anti-Cryptococcus treatment are conducive to the patient's early recovery.

Objective To investigate the difference of blood sampling methods from heparin maintained arterial catheter for blood gas analysis and activated partial thromboplastin time (APTT).Methods Conventional and modified arterial catheter blood sampling methods were applied at the same period of time to 30 cases with arterial pressure measurement.3-5 ml blood containing heparin was disposed in conventional method.No blood was disposed for the modified method.The samples were used for blood gas analysis and APTT.The operation time of the sampling by two methods were compared.Results No significant difference was seen for the blood gas analysis and APTT from the blood samples collected by two different methods (P ＞ 0.05).The operation time of modified method was significantly shorter than that of the conventional method [(187.87 ±15.05)s vs (275.73 ±14.75)s,t =22.84;P＜0.01].Conclusions Arterial catheter blood sampling from heparin maintained blood by the modified method gives accurate clinical laboratory results,in this case,the blood gas analysis and the APTT.No blood is wasted and the operation time for the nurses is reduced.The modified method could be an alternative to the conventional blood collection method.

OBJECTIVETo report the prenatal diagnosis of 2 cases of pregnancy with the risk of chromosomal disorders. In Case 1, the pregnant woman had a daughter with testicular regression syndrome and a segmental duplication of Ypter --> Yp11.2 and a deletion of Yq11.23 --> Yqter. In Case 2, both the pregnant woman and her husband were carriers of chromosomal balanced translocation.

METHODSTwo samples of amniotic fluid were obtained at the 19th week of gestation for fetal karyotype analysis. For Case 1, FISH with a probe of Xp/Yp subtelomere was performed on the metaphase of the amniotic fluid, genomic DNA of the amniotic fluid extracted and multiplex PCR conducted for AZF regions. Both the pregnant women underwent sonography to confirm the karyotypic diagnosis.

RESULTSCytogenetic, FISH and multiplex PCR analysis of the cultured amniotic fluid cells from Case 1 showed a normal male karyotype, and ultrasound scan of the fetus showed normal male external genitalia and normal development. Cytogenetic analysis of the cultured amniotic fluid cells from Case 2 revealed a karyotype of balanced translocation with t(13 ; 14) from the father, and no abnormality of the fetus was found by ultrasound scan.

CONCLUSIONIt is helpful to perform cytogenetical and molecular prenatal diagnosis in combination with ultrasound scan for the fetus with the risk of chromosomal disorders and subsequently for genetic counseling.

Adult ; Amniotic Fluid ; cytology ; Chromosome Disorders ; diagnosis ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic

BACKGROUNDTherapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis. This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis.

METHODSTwenty-four mice were randomly allocated to normal control group (n = 6), blank control group (n = 6), VEGF gene transfection group (n = 6), and NGF gene transfection group (n = 6). The model of left hindlimb ischemia model was established by ligating the femoral artery. VEGF165plasmid (125 μg) and NGF plasmid (125 μg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively. Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction. The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining. NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay.

RESULTSOn the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group. The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P < 0.05). The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P < 0.05). Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P < 0.05), but there was no significant difference of the NGF protein expression between VEGF group and blank control group (P > 0.05). The type I skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group (P < 0.05).

CONCLUSIONSNGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type I muscle fiber expression in ischemic limbs.

Animals ; Antigens, CD34 ; metabolism ; Female ; Hindlimb ; metabolism ; pathology ; Ischemia ; metabolism ; pathology ; Mice ; Muscle, Skeletal ; metabolism ; pathology ; Neovascularization, Physiologic ; genetics ; physiology ; Random Allocation ; Vascular Endothelial Growth Factor A ; genetics ; physiology