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 evaluate the application value of X-ray,echocardiogram,pulmonary perfusion scintigraphy,EBCT,Magnetic resonance Pulmonary angiography in diagnosis of PTE.Methods Twenty-five consecutive patients clinically diagnosed of having PTE were examined from july 2003 through March 2004. Patients underwent X-ray chest plain film, echoeardiogram, electronic beam computed tomographie (EBCT)angiography,ventilation-perfusion (V-P)seintigraphy,Magnetic resonance Pulmonary angiography (MRPA)and puhnonary angiography according to a strict diagnostic protocol.Two of the independent readers reviewed the pulmonary angiography and record all of the lobe and segmental involved in PTE and compared with other image method.Results Pulmonary angiography:all of the patients success underwent the technique,the pulmonary artery branch with PTE was in 556 of 775 branches (71.7%). Chest radiography had hints of diagnosis in 12 of 25 patients.Nine patients diagnosed with echocardiogram. Right heart enlargement was in 21,and pulmonary hypertension in 18.V-P scintigraphy revealed 247 segmental involved with PTE of 500 (52.0% ),and the sensitivity was 64.66% compare with the pulmonary angiography.There were 523 pulmonary branches involved PTE with EBCT pulmonary angiograpy of 775 branches,and the sensitivity was 94.06%.MRPA: 8 of 10 patients succeed in the technique, 155 branches of 248 were detected with PTE(62.5% ),the sensitivity was 81.29%.Conclusions EBCT is a high sensitivity method in diagnosis of PTE.Chest radiography and echocardiogram are the first-line modality of PTE.V-P scintigrapby is the valid compensation in diagnosis subsegmental pulmonary artery with PTE when EBCT miss diagnosis.Gd-CE-MRPA may be the second-line modality in diagnosis of PTE.

OBJECTIVETo report and assess the efficacy of a coupled exofixator in the treatment of comminuted fracture of the humeral shaft.

METHODSFrom June 1999 to September 2003, 24 patients with comminuted fracture of the humeral shaft were treated in our department, in whom 11 were involved in left humerus fractures and 13 in right humerus fractures. Closed reduction or open reduction with a small incision as well as a coupled exofixator was used to treat these patients.

RESULTSAll cases got anatomical reduction after 6-12 months follow-up. The time for fracture union averaged 5.8 months with a good functional recovery of the shoulder-elbow joints.

CONCLUSIONSThe coupled exofixator is favorable to the treatment of comminuted humeral shaft fractures. It can shorten union time and avoid nonunion occurrence.

Adolescent ; Adult ; External Fixators ; Female ; Fracture Fixation ; methods ; Fractures, Comminuted ; surgery ; Humans ; Humeral Fractures ; surgery ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVEIsobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry were used to screen differentially expressed plasma proteins in cold stress rats.

METHODSThirty health SPF Wistar rats were randomly divided into cold stress group A and control group B, then A and B were randomly divided into 3 groups (n = 5): A1, A2, A3 and B1, B2, B3. The temperature of room raising was (24.0 +/- 0.1) degrees C, and the cold stress temperature was (4.0 +/- 0.1) degrees C. The rats were treated with different temperatures until 12 h. The abdominal aortic blood was collected with heparin anticoagulation suction tube. Then, the plasma was separated for protein extraction, quantitative, enzymolysis, iTHAQ labeling, scx fractionation and mass spectrometry analysis.

RESULTSTotally, 1085 proteins were identified in the test, 39 differentially expressed proteins were screened, including 29 up-regulated proteins and 10 down-regulated proteins. Three important differentially expressed proteins related to cold stress were screened by bioinfonnatics analysis (Minor histocompatihility protein HA-1, Has-related protein Rap-1b, Integrin beta-1).

CONCLUSIONIn the experiment, the differentially expressed plasma proteins were successfully screened in cold stress rats. iTRAQ technology provided a good platform to screen protein diaguostic markers on cold stress rats, and laid a good foundation for further. study on animal cold stress mechanism.

Animals ; Blood Proteins ; chemistry ; Cold Temperature ; Mass Spectrometry ; Rats ; Rats, Wistar ; Stress, Physiological

OBJECTIVETo study the incidences of comorbidities and behavioral problems in children with functional articulation disorders.

METHODSOne hundred and twelve children with functional articulation disorders (aged 4-11 years) were enrolled. Their comorbidities were identified based on clinical investigations and the DSM-IV diagnosis criteria of attention deficit hyperactivity disorder (ADHD), stuttering, tic disorders and enuresis. Behavioral problems were evaluated by the Conners Parent Symptom Questionnaire and the Child Behavior Checklist.

RESULTSSixty-nine patients (61.6%) had one or more comorbidities. The incidence of comorbidity in children with middle-severe functional articulation disorders was higher than in those with mild disorders. The most common comorbidity was language impairment (30.4%), followed by stuttering (16.1%), enuresis (13.4%), and tic disorders (6.3%). In school age children, ADHD (47.5%) was the most common comorbidity. The incidence of behavioral problems was 40.2% by the Child Behavior Checklist and 57.1% by the Parent Symptom Questionnaire.

CONCLUSIONSThe children with functional articulation disorders have high incidence of comorbidity and many behavioral problems.

Articulation Disorders ; psychology ; Attention Deficit Disorder with Hyperactivity ; epidemiology ; Child ; Child Behavior Disorders ; epidemiology ; Child, Preschool ; Comorbidity ; Enuresis ; epidemiology ; Female ; Humans ; Incidence ; Language Disorders ; epidemiology ; Male

OBJECTIVETo study the therapeutic effect of agonistic CD40 monoclonal antibody combined with tumor specific cytotoxic T lymphocyte (CTL) on B lymphoma.

METHODSHuman B lymphoma cell line, Daudi cells, were cultured with CD40 mAb (5C11) for 24 and 48 hours, respectively. Annexin V/PI-binding assay was employed to analyze apoptosis, and FCM to analyze Fas (CD95) expression. Human peripheral monocyte-derived DC were loaded with apoptotic Daudi cells and stimulated by SC11 for further maturation. Tumor specific CTL were generated in vitro by co-culture of mature DC with autologous T lymphocytes. DNA fragmentations of Daudi cells treated with 5C11, CTL or 5C11 combined with CTL were determined by JAM assay. To establish the B lymphoma model, Daudi cells were subcutaneously injected into humanized SCID mice (hu-SCID). 1 or 3 weeks after tumor transfer. tumor-bearing mice were respectively treated with SC11, CTL, 5C11 combined with CTL by intraperitoneal injection. Tumor volume in differently treated mice was measured every week after therapy, and the survival of tumor-bearing mice was recorded.

RESULTS5C11 significantly up-regulated FAS expression in Daudi cells, but had no significant effect on apoptosis rate of Daudi cells. Tumor-specific CTL could effectively kill Daudi cells. Fragmentation of Daudi cells co-cultured with CTL was remarkably enhanced by combination with SC11. Tumor growth in hu-SCID mice was apparently delayed by treatment with SC11, CTL, or SC11 combined with CTL. Moreover, minimal tumor burden mice got 30.0% or 70.0% complete remission (CR), respectively, when received CTL treatment or combination treatment of SC11 with CTL, and the lifespan of tumor bearing mice was also prolonged significantly.

CONCLUSIONSC11 may enhance the sensitivity of Daudi cells to apoptosis by up-regulation of Fas expression and promote cytotoxicity of CTL in vitro and therapeutic effect in vivo.

Animals ; Antibodies, Monoclonal ; immunology ; therapeutic use ; Apoptosis ; immunology ; CD40 Antigens ; immunology ; Cell Line, Tumor ; Coculture Techniques ; Female ; Flow Cytometry ; Humans ; Immunotherapy, Adoptive ; methods ; Lymphoma, B-Cell ; immunology ; pathology ; therapy ; Mice ; Mice, SCID ; Remission Induction ; Survival Analysis ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; Xenograft Model Antitumor Assays ; fas Receptor ; immunology

BACKGROUNDMacrophage stimulating protein (MSP) is produced by human bone marrow endothelial cells. In this study, we sought to observe its effects on inducing the expansion of early hematopoietic progenitor cells which were cultured in a liquid culture system in the presence of the combination of stem cell factor (SCF), interleukin 3 (IL-3), interleukin 6 (IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO) (Cys) and MSP or of Cys and bone marrow endothelial cell conditioned medium (EC-CM).

METHODSHuman bone marrow CD34(+) cells were separated and cultured in a liquid culture system for 6 days. Granulocyte-macrophage colony forming unit (CFU-GM) and colony forming unit-granulocyte, erythrocyte, macrophage, megakaryocyte (CFU-GEMM) were employed to assay the effects of different treatment on the proliferation of hematopoeitic stem/progenitor cells. The nitroblue tetrazolium (NBT) reductive test and hoechest 33258 staining were employed to reflect the differentiation and apoptosis of the cells respectively.

RESULTSMSP inhibited the proliferation of CFU-GM and CFU-GEMM in semi-solid culture and the inhibitory effect on CFU-GEMM was stronger than on CFU-GM. MSP inhibited the differentiation of early hematopoietic progenitor cells induced by hematopoietic stimulators. Bone marrow (BM) CFU-GEMM was 2.3-fold or 1.7-fold increase or significantly decreased in either Cys + EC-CM, Cys + MSP or Cys compared with 0 hour control in liquid culture system after 6 days.

CONCLUSIONMSP, a hematopoietic inhibitor, inhibits the differentiation of early hematopoietic progenitor cells induced by hematopoietic stimulators and makes the early hematopoietic progenitor cells expand in a liquid culture system.

Antigens, CD34 ; analysis ; Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cells, Cultured ; Chemokine CCL3 ; Chemokines, CC ; pharmacology ; Hematopoietic Stem Cells ; drug effects ; Hepatocyte Growth Factor ; pharmacology ; Humans ; Proto-Oncogene Proteins ; pharmacology

Objective:To evaluate the value and identify the prognosic factors of postoperative radiotherapy (PORT) in completely resected stage Ⅲ(pN 2) lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) wild-type who received adjuvant chemotherapy. Methods:Clinical data of 172 patients with stage Ⅲ(pN 2) EGFR wild-type lung adenocarcinoma who underwent radical resection and adjuvant chemotherapy from 2009 to 2016 were retrospectively analyzed. All patients received platinum-based adjuvant chemotherapy combining two drugs for>4 cycles, and divided into the PORT group and the non-PORT group. The survival rate was calculated by Kaplan- Meier method and log-rank test, and multivariate prognostic analysis was performed by Cox’s regression model. Results:Among 172 patients, the median overall survival (OS), 3-year and 5-year OS rates were 40 months, 55.9% and 28.3%, respectively. The median disease-free survival (DFS), 3-year and 5-year DFS rates were 17 months, 24.5% and 13.0%, respectively. DFS was significantly improved in the PORT group (29 months vs. 13 months, P=0.001), whereas OS did not significantly differ between two groups (51 months vs. 38 months, P=0.151). In subgroup analysis, DFS of patients with multistation N 2 or the number of N 2 metastases of≥3 or skip N 2 in the PORT group was significantly longer ( P<0.05), whereas PORT exerted no significant effect on OS ( P>0.05). Conclusions:For patients with completely resected stage Ⅲ(N 2) EGFR wild-type lung adenocarcinoma receiving adjuvant chemotherapy, PORT might increase DFS and have a trend toward longer OS. However, these findings remain to be validated by large sample size investigations.

OBJECTIVETo observe the mechanism of the optimized traditional acupuncture prescription for accouchement on cervical ripening based on the molecular biology by observing related indices of cervical ripening in late-stage pregnant rats.

METHODSTwenty initial pregnant Wistar rats were randomly divided into an electroacupuncture (EA) group (n = 10) and a model group (n = 10), and other 10 non-pregnancy female rats with same lot were selected as a blank control group. EA group was treated with the optimized traditional acupuncture prescription for accouchement on the 20th day of pregnant, which performed EA at bilateral "Hegu" (LI 4) for 20 min and then at bilateral "Sanyinjiao" (SP 6) for 5 min with 2 Hz/50 Hz sparse-dense wave, while the other groups without acupuncture intervention. The contents of matrix metalloproteinase 9 (MMP-9) and interleukin 8 (IL-8) in cervix tissue were detected by ELISA method.

RESULTSCompared with the blank control group, the contents of MMP-9 and IL-8 in the model group were increased significantly (both P < 0.01). Compared with the model group, the contents of MMP-9 and IL-8 in the EA group were increased significantly (P < or = 0.05).

CONCLUSIONOptimized traditional acupuncture prescription for accouchement can increase the contents of MMP-9 and IL-8 in cervix tissue of late-stage pregnant rats so as to promote cervical ripening, and the mechanism of EA in promoting cervical ripening is explained from the perspective of molecular biology.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Cervical Ripening ; metabolism ; Cervix Uteri ; enzymology ; Female ; Humans ; Interleukin-8 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Models, Animal ; Pregnancy ; Rats ; Rats, Wistar

AIMTo prepare heart-protecting musk pH-dependent gradient-release pellets and investigate the drug release in vitro and in vivo.

METHODSThe pH-dependent gradient-release pellet system was prepared by using HPMC, Eudragit L-30D-55 and Eudragit L100-Eudragit S100 (1:5) combinations as coater. The release of borneol and total ginsenoside from pH-dependent gradient-release pellets were determined according to the method of Pharmacopoeia of the People's Republic of China (2000) in the simulated gastrointestinal pH conditions. The gastrointestinal transit and disintegration of pellets was investigated by using gamma-scintigraphic trace in volunteers. The pharmacokinetics of borneol of heart-protecting musk pH-dependent gradient-release pellets was studied in 6 healthy volunteers by GC methods.

RESULTSThe f2 value of release data of borneol and total ginsenoside of the heart-protecting musk pH-dependent gradient-release pellets was 79.6 in the simulated gastrointestinal pH conditions. The gamma-scintigraphic trace evaluation demonstrated that the pellets coated with HPMC, Eudragit L-30D-55 or Eudragit L100-Eudragit S100 (1:5) combinations can disintegrate in stomach, duodenum and jejunum or ileum. The gastrointestinal transit time of pellets was about 5 hours in fasted state and about 6 hours in fed state. The concentration-time curves of borneol of heart-protecting musk pills fit in two-compartment model. The pharmacokinetics data showed that borneol had a short time of absorption and elimination. The mean residence time (MRT) of borneol of heart-protecting musk pills was 2.61 hours. The plasma concentration of borneol of heart-protecting musk sustained-release capsule which consisted of three kinds of pellets coated with HPMC, Eudragit L-30D-55 or Eudragit L100-Eudragit S100 (1:5) combinations was steadier than those of heart-protecting musk pills, its Cmax was lower than and Tmax was near to those of heart-protecting musk pills, its MRT was 4.0 hours, and its relative bioavailability was 96%.

CONCLUSIONThe lipidsoluble borneol and watersoluble total ginsenoside of heart-protecting musk pH-dependent gradient-release pellets can release simultaneously while sustained-releasing in vitro. The heart-protecting musk pH-dependent gradient-release pellets had the characteristics of pH-dependent gradient-releasing and disintegration while transiting in gastrointestinal tract. A characteristic of gradient sustained-release was shown in the concentration-time curves of borneol of heart-protecting musk sustained-release capsule in volunteers.

Adult ; Bornanes ; pharmacokinetics ; Delayed-Action Preparations ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Fatty Acids, Monounsaturated ; administration & dosage ; Gastrointestinal Transit ; Ginsenosides ; pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Lactose ; analogs & derivatives ; Male ; Materia Medica ; administration & dosage ; pharmacokinetics ; Methylcellulose ; analogs & derivatives ; Oxazines ; Polymethacrylic Acids ; Random Allocation