Objective:To investigate whether radiotherapy should be delivered before the application of immune checkpoint inhibitor PD-1 in patients with advanced non-small cell lung cancer (NSCLC) and evaluate the effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor.Methods:Clinical data of patients with stage Ⅳ NSCLC who received immunotherapy in Henan Cancer Hospital from March 2015 to September 2019 were retrospectively analyzed. The baseline data of patients, the status of radiotherapy and immunotherapy and the pulmonary toxicity were collected. According to whether radiotherapy was given before PD-1 inhibitor application, all patients were divided into the previous radiotherapy and non-radiotherapy groups. Survival analysis was performed by Kaplan- Meier method. Results:A total of 90 patients were enrolled including 39 cases in the previous radiotherapy group and 51 cases in the non-radiotherapy group. The median follow-up time was 22.9 months. The median progression-free survival (mPFS) in the previous radiotherapy group was 7.5 months (95% CI 5.4-9.5 months), significantly longer compared with 4.1 months (95% CI 3.1-5.1 months) in the non-radiotherapy group ( P=0.003). The median overall survival (mOS) significantly differed between two groups[15.2 months (95% CI 12.3-18.1 months) vs. 9.3 months (95% CI 6.1-12.5 months)]( P=0.040). The incidence of pulmonary toxicity showed no significant difference between two groups ( P=0.154). Conclusions:Patients with stage Ⅳ NSCLC patients in the previous radiotherapy group obtain significantly better mPFS and mOS and similar pulmonary toxicity compared with their counterparts in the non-radiotherapy group. Nevertheless, the findings remain to be validated by subsequent investigations with larger sample size.

OBJECTIVE: To establish the electricity plate digestion and inductively coupled plasma-mass spectrometry (ICP-MS) method for determination of 33 inorganic elements in human hair. METHODS: Lithium (6Li), Germanium (72Ge), Yttrium (89Y), Indium (115In), and Terbium (159Tb) were used as internal standards. The electric heating board digestion in a mixture of nitric acid and hydrogen peroxide was used as the pre-treatment of the hair. Thirty-three inorganic elements in human hair were analyzed by ICP-MS method. RESULTS: The detection limit of ICP-MS was 0.0001 microg/g(Th)-10.9 microg/g (Ca) and the limit of quantitation was 0.0005 microg/g (Th)-25 microg/g (Ca). The recovery rate of this method was 86%-113%. The RSD for the intra-day and inter-day were less than 9.2%. The method was not statistically different from microwave digestion method. CONCLUSION This method is highly efficient and accurate. It can be used for analysis of 33 inorganic elements in human hair.
Electricity ; Hair/chemistry* ; Humans ; Limit of Detection ; Mass Spectrometry/methods* ; Microwaves ; Reference Standards ; Sensitivity and Specificity ; Trace Elements/analysis*

OBJECTIVE: To determine the normal reference values of 33 elements, Ag, Al, As, Au, B, Ba, Be, Ca, Cd, Co, Cr, Cs, Cu, Fe, Ga, Hg, Li, Mg, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, Th, Ti, Tl, U, V, Zn and Zr, in the blood and urine samples from the general population in Sanmen County of Zhejiang province, a typical coastal area of eastern China. METHODS: The 33 elements in 272 blood and 300 urine samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS). The normality test of data was conducted using SPSS 17.0 Statistics. The data was compared with other reports. RESULTS: The normal reference values of the 33 elements in the blood and urine samples from the general population in Sanmen County were obtained, which of some elements were found to be similar with other reports, such as Co, Cu, Mn and Sr, while As, Cd, Hg and Pb were generally found to be higher than those previously reported. There was a wide variation between the reports from different countries in blood Ba. CONCLUSION The normal reference values of the 33 elements in the blood and urine samples from the general population in Sanmen County are established, and successfully applied to two poisoning cases.
Blood Chemical Analysis ; China ; Elements ; Environmental Monitoring ; Humans ; Urinalysis

Aim To investigate the effects of TRPV4-Nox2 complex on ROS production and aortic vasodilatory function in mice fed with high-fat diet.Methods Male C57 BL/6J mice and TRPV4 KO mice were randomly divided into seven groups, with 10 mice in each group: normal diet group(ND), high-fat diet group(HFD), TRPV4 KO mice fed with high-fat diet group(TRPV4 KO-HFD), HFD+AAV-Flt1-Vector/Nox2 ▵3 group, TRPV4 KO-HFD+AAV-Flt1 -Vector/Nox2 ▵3 group.Body weight and blood pressure were recorded.14 weeks later primary aortic endothelial cells were isolated for CM-H2DCFDA staining and immuno-FRET assay, and aortic rings were isolated for vascular tone assay.Results ① Obesity significantly increased ROS production, triggered vasodilatory dysfunction and increased the strength of physical coupling between TRPV4-Nox2 complex(P<0.05); ② Decreasing the physical association of TRPV4-Nox2 complex could help reduce obesity-induced increased ROS production and vasodilatory dysfunction(P<0.05); ③ Entrectinib had no effect on the expression and function of TRPV4 and Nox2, but only decreased the physical association of the TRPV4-Nox2, which in turn improved obesity-induced oxidative stress and restored vasodilatory function.Conclusions Reducing the physical association of TRPV4 and Nox2 through Entrectinib can help reduce obesity-induced increase in ROS production and improve vasodilatory function of obese mice.

The objective of study was to investigate the expressions of CD80, CD86 and its ligand CD28 on peripheral lymphocytes in patients with idiopathic thrombocytopenic purpura (ITP), to explore the effect of interleukin 18 (IL-18) and its clinical significance in ITP. The expressions of co-stimulatory molecules (CD80, CD86 and its ligand CD28) on peripheral lymphocytes from 34 ITP patients and 34 normal humans were detected by immunofluorescence and flow cytometry. The IL-18 in the plasma was detected by using enzyme linked immunosorbent assay (ELISA). The results showed that the expressions of CD80 and CD86 on peripheral lymphocytes from ITP patients were higher than that of the normal control (4.21 +/- 2.27%, 7.19 +/- 5.16% vs 2.34 +/- 0.87%, 4.08 +/- 1.96%) (P < 0.01); the concentration of IL-18 in plasma of ITP patients was (538.31 +/- 111.33) pg/ml, but the concentration of IL-18 in plasma of controls was (489.44 +/- 49.07) pg/ml. The level of IL-18 negatively correlated with the platelet counts in peripheral blood (r = -0.395, P < 0.05). It is concluded that the CD28/CD80 and CD28/CD86 costimulatory molecules are overexpressed, when the IL-18 level in ITP patients is obviously higher than that in normal controls. When ITP occurred, and the co-stimulatory molecules CD80 and CD86 are closely associated with ITP, it seems that IL-18 may play an important role in ITP pathogenesis.
B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; CD28 Antigens ; metabolism ; Humans ; Interleukin-18 ; blood ; Lymphocytes ; metabolism ; Purpura, Thrombocytopenic, Idiopathic ; blood ; immunology

OBJECTIVETo delineate the characteristics of the clinical manifestation, pathology of skeletal muscle and gene mutations of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) in children.

METHODThe clinical manifestation, laboratorial data, brain images, muscle pathology and mitochondrial gene mutations were analyzed in 24 patients with MELAS who were diagnosed in Department of Pediatrics, Peking University First Hospital. Their prognosis was evaluated by following up.

RESULTSymptoms of central nervous system such as stroke-like episodes, vomiting, convulsion and headache were present in all the 24 cases. Nine cases had the symptoms of myopathy. Twenty cases had developmental delay. Short stature, being thin and hairy was very common in these cases. Serum lactate level increased in all the cases, pyruvate increased in 17 cases. Elevated CSF lactate was found in 2 cases. Magnetic resonance imaging (MRI) was performed on 24 cases, out of them 23 were abnormal. The lesions mainly involved cerebral lobes. Occipital lobe was the most common site of lesions. Computed tomography (CT) was performed on 13 cases, low density lesions were present in 10 cases, basal ganglia calcifications in 5 cases. Muscle biopsy was performed on 8 cases, ragged-red fibers (RRF) were found in 4/8 cases, and abnormal accumulation of mitochondria were found in 3/8 cases. The mtDNA gene mutational analysis showed A3243G mutation in these patients. The mutation rates varied from 11.6% to 75.0%. The same mutation were found in 4/5 mothers who had the genetic tests, and the mutation rates of the mothers varied from 15.0% to 23.6%. The clinical information of 11 cases was available through recent following up. Three cases died, the others had some degrees of mental retardation.

CONCLUSIONChildren with MELAS had various clinical manifestations. Central nervous system and skeletal muscle were usually involved. Short stature and hypertrichosis were common signs. The prognosis of this disease was disappointing. mtDNA A3243G was the most common mutation in MELAS. Fully understanding the characteristics of its clinical manifestation, laboratory tests, brain image, muscle pathology and molecular features can be helpful to the early diagnosis and treatment.

Acidosis, Lactic ; blood ; Adolescent ; Brain ; diagnostic imaging ; pathology ; Child ; Child, Preschool ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Electroencephalography ; Female ; Follow-Up Studies ; Humans ; Infant ; MELAS Syndrome ; diagnosis ; genetics ; pathology ; Magnetic Resonance Imaging ; Male ; Muscle, Skeletal ; diagnostic imaging ; pathology ; Point Mutation ; Pyruvic Acid ; blood ; Stroke ; diagnostic imaging ; genetics ; pathology ; Syndrome ; Tomography, X-Ray Computed

OBJECTIVETo observe the effects of Ganoderma lucidum spores on Cytochrome C (Cyt-C) and mitochondrial calcium in the testis of NIDDM rats.

METHODSFifty male Wistar rats were divided randomly into three groups: model, ganoderma and normal control, the first two groups injected with 2% STZ through vena caudalis, and the last one with half-and-half sodium citrate/citrate buffer solution. Two weeks after normal diet, glucose tolerance tests were performed and the rats with abnormal glucose tolerance from the model and ganoderma groups received high-fat and high-carbohydrate food, the ganoderma group given Ganoderma lucidum spores (250mg/[ kg x d] ) in addition, both for 10 weeks. Glucose tolerance tests were repeated 1 day before the end of the experiment and the rats were castrated and relevant indexes measured.

RESULTSThe NIDDM model was successfully constructed. In the model group, the levels of mitochondrial Cyt-C and mitochondrial calcium were significantly lower (P <0. 05) while that of the plasma Cyt-C was significantly higher than in the ganoderma and the control groups.

CONCLUSIONCyt-C and calcium ion are involved in the damage of the testis. Ganoderma lucidum spores can protect the testis of NIDDM rats.

Animals ; Calcium ; metabolism ; Cytochromes c ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Male ; Mitochondria ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Reishi ; Testis ; drug effects ; metabolism

Adult ; Biopsy ; Female ; Graft Rejection ; pathology ; Humans ; Intestinal Mucosa ; pathology ; Intestine, Small ; injuries ; pathology ; transplantation ; Male ; Organ Transplantation ; adverse effects ; Reperfusion Injury ; etiology ; pathology ; Young Adult

Roscovitine is a specific inhibitor of cyclin-dependent kinases (cdks) cdc2/cyclin B, cdk2/cyclin A, cdk2/cyclin E and cdk5/p35. The studies on the enzyme inhibitory properties and cellular effects of roscovitine revealed that it arrests cells in G(2)/M and G(1)/S phase, inhibits the proliferation of mammalian cells and induces cell death. However, the characteristics of cell death and exact mechanism by which this cdk inhibitor kills transformed cells are unknown. We previously investigated that the roscovitine induces apoptotic death of mitotic PC12 cells. The present study was to identify whether the roscovitine-induced death is related with the specific elements of caspases in pathway of apoptosis. The morphological data of caspase-3 immunofluorocytochemistry double staining with hoechst 33342 indicated that apoptotic nuclei were identified as nuclei with chromatin condensation and nuclear fragmentation, and that caspase-3 active p17 subunit co-existed in PC12 cells treated with roscovitine 50 micromol/L for 4 h. The number of the caspase-3 positive cells increased significantly to about 42%, as compared with the normal control (P<0.001). The data of MTT assay showed that the number of viable cells treated by roscovitine (50 micromol/L) alone for 12 h was 29.03%, of the untreated controls. Both a broad-spectrum caspase inhibitor Z-VAD-FMK (50 mumol/L) and a specific caspase-3 inhibitor Z-DEVD-FMK (100 micromol/L) increased viable PC12 cells to 45.16%, (Z-DEVD-FMK) and 58.06%, (Z-VAD-FMK), respectively, in the presence of roscovitine. Non-erythroid a-spectrin is a cytoskeleted protein that is a substrate of caspase-3 cysteine proteases. To confirm the activity of caspase-3 that produced in roscovitine (50 micromol/L for 12 h)-induced PC12 cell death, activated caspase-3 specific 120 kDa spectrin breakdown products (SBDP) were detected by Western bloting using the mouse anti-non-erythroid a-spectrin monoclonal antibody. The mean relative density of bands corresponding to caspase-3 specific SBDP levels were significantly increased in the cytosolic fractions treated with roscovitine, as compared to the normal control (P<0.001). These results indicate that caspase signals, especially caspase-3 signal are necessary for the progression of proliferating PC12 cell apoptotic death evoked by roscovintine.
Animals ; Apoptosis ; drug effects ; physiology ; Caspase 3 ; physiology ; Cyclin-Dependent Kinases ; antagonists & inhibitors ; PC12 Cells ; Protein Kinase Inhibitors ; pharmacology ; Purines ; pharmacology ; Rats