Objective:To evaluate the cumulative dose of the target volume and organs at risk (OARs) in intensity-modulated radiation therapy (IMRT) for large volume non-small cell lung cancer (NSCLC) based on rigid and deformation registration methods. The dosimetric changes between the initial and second treatment plans were compared.Methods:Thirty patients treated with IMRT for large volume NSCLC with twice 4DCT scans acquired before radiotherapy and after 20 fractions of radiotherapy were recruited. The initial treatment plan (Plan 1) based on the average density projection CT (CT 1-avg) of the first 4DCT images and the second treatment plan (Plan 2) based on the average density projection CT (CT 2-avg) of the second 4DCT images were calculated. Then, the dose distributions of Plan 1 and Plan 2 were accumulated based on rigid and deformation registration methods to obtain Planrig and Plandef, respectively. Finally, the volume changes of gross tumor volume (GTV) and OARs between two CT scans were compared. The dose-volume parameters between Plan 1 and other plans (including Plan 2, Planrig and Plandef) were also statistically compared. Results:Compared with the initial CT scan, the mean volume of GTV and heart on the second CT was decreased by 44.2% and 5.5%, respectively, while the mean volume of ipsilateral lung, contralateral lung and total lung was increased by 5.2%, 6.2% and 5.8%, respectively (all P<0.05). Compared with Plan 1, the D 95%, D 98% and V 100% of target volume IGTV (GTV fusion of 10 4DCT phases) and PTV in Plan 2 did not significantly change (all P>0.05), and those in Planrig and Plandef were decreased (all P<0.05). The dose-volume parameters of spinal-cord, heart, ipsilateral lung and total lung in Plan 2, Planrig and Plandef were significantly lower than those in Plan 1(all P<0.05). Among them, the V 30Gy and D mean of heart were decreased by 27.3%, 16.5%, 15.3% and 15.2%, 6.6%, 5.6%, respectively. The V 20Gy and D mean of total lung were decreased by 15.6%, 4.5%, 3.7% and 15.7%, 6.2%, 5.1%, respectively. Some dose-volume parameters (including D 95% and D 98% of target volume, V 40Gy of heart, V 20Gy and D mean of the ipsilateral lung and the total lung) of Plandef were higher than those in Planrig (all P<0.05). The Dice similarity coefficients (DSCs) of OARs after deformation registration were significantly higher than those after rigid registration ( P<0.05). Conclusions:The dose-volume parameters of OARs significantly differ between Plan 1 and Plan 2. Hence, all these parameters have a large degree of deviation in predicting radiation-induced injury of OARs. Nevertheless, the dose-volume parameters obtained by deformation registration can enhance the prediction accuracy.

Objective To conduct a network meta-analysis on the effectiveness of first-line immunotherapy on patients with brain metastases from advanced non-small cell lung cancer (NSCLC). Methods Two investigators conducted a computerized search of Pubmed, Embase, Cochrane, and other databases to screen the literature, extract the information, and assess the risk of bias of the included studies. The included clinical trials were statistically analyzed using R (4.1.3) software. For the study outcome indicators OS and PFS, the risk ratios (HRs), and the 95% confidence intervals (CIs) were extracted from the included studies and logarithmically transformed into effect analysis statistics. Results Six randomized controlled trials were finally included, including 327 patients with non-excludable NSCLC brain metastases. Network meta-analysis suggested that PD-1 inhibitor + CTLA-4 was more advantageous than the conventional chemotherapy for enhancing patients’ OS (HR: 0.13, 95%CI: 0.03-0.71), followed by PD-L1 inhibitor (HR: 0.17, 95%CI: 0.04-0.74) and PD-1 inhibitor + chemotherapy (HR: 0.36, 95%CI: 0.2-0.63). PD-1 inhibitor + CTLA-4 was also more advantageous (HR: 0.37, 95%CI: 0.15-0.93) than the conventional chemotherapy for boosting patients’ PFS, followed by PD-L1 inhibitor + chemotherapy (HR: 0.44, 95%CI: 0.29-0.66) and PD-1 inhibitor (HR: 0.48, 95%CI: 0.27-0.86). Conclusion Immune checkpoint inhibitor therapy improves the survival of patients with brain metastases from advanced NSCLC. In particular, the combination of PD-1 inhibitor and CTLA-4 inhibitor show excellent survival benefit.

Animals ; COS Cells ; Female ; Genetic Therapy ; Interleukin-12 ; genetics ; Liver Neoplasms, Experimental ; immunology ; therapy ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Cytotoxic ; immunology

The aim of this study was to investigate the effects of gemcitabine(GEM) on apoptosis and c-myc gene expression of HL-60 cells, and feasibility of using GEM in therapy of leukemia. The HL-60 cells were cultured in vitro. The expressions of the c-myc mRNA and C-MYC protein were detected by RT-PCR and Western-blot respectively. The cell apoptosis was analyzed by TUNEL staining. The results showed that after the HL-60 cells were treated with 1.0 microg/ml GEM for 12, 24, 36 and 48 hours, the expression of c-myc mRNA was inhibited to various degree. This inhibitory effect displayed time-dependent manner and the most optimal effective time was 24 hours. Compared GEM group with Ara-C group and blank control group, there were statistical differences (p<0.05). After the HL-60 cells were treated with 1.0 microg/ml GEM for 24, 48, 72 hours, C-MYC protein significantly decreased, and the expression of C-MYC protein reached to lowest level at 48 hours after treating with GEM, and with inhibition rate of 94.16%. Compared GEM group with Ara-C group and blank control group, the differences were significant (p<0.01). There was significant difference between cells treated with GEM for 24, 48 and 72 hours (p<0.01). After the HL-60 cells were treated with 1.0 microg/ml GEM for 24 hours, the apoptotic cells increased obviously. The positive rate was 83.67% in GEM-treated group. Compared GEM group with Ara-C group (positive rate 10.67%) and untreated group (positive rate 3.00%), the differences had statistical significance (p<0.01). It is concluded that GEM can induce the apoptosis and down-regulate c-myc gene expression significantly in HL-60 cells and it may be used as a new therapeutic drug for leukemia.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Deoxycytidine ; analogs & derivatives ; pharmacology ; HL-60 Cells ; Humans ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; RNA, Messenger ; genetics

OBJECTIVETo study the effects of inhaled nitric oxide (NO) on pulmonary vascular resistance in patients after total cavopulmonary connection (TCPC).

METHODSFifty-two patients after TCPC were evaluated, of them 24 patients were administered with inhaled nitric oxide in the early postoperative period. The cardiac index (CI) and pulmonary vascular resistance (PVR) were compared before and after inhaled NO.

RESULTSIn experimental group, after inhaled NO, partial pressure of oxygen in artery/fraction of inspired oxygen increased from 161 +/- 17 to 193 +/- 23 (t = 2.75, P < 0.01); CI from (2.86 +/- 0.24) L.min(-1).m(-2) to (3.13 +/- 0.22) L.min(-1).m(-2) (t = 2.25, P < 0.05); PVR decreased from (4.2 +/- 0.5) U/m(2) to (3.8 +/- 1.4) U/m(2) (t = 2.29, P < 0.05); central venous pressure (CVP) from (17.0 +/- 1.8) mm Hg to (15.0 +/- 1.1) mm Hg, decreased 11.7%. Compared with the control group, respirator time decreased from (86 +/- 27) h to (54 +/- 18) h (t = 2.29, P < 0.05); ICU time from (6 +/- 2) d to (4 +/- 2) d (t = 2.32, P < 0.05); But hydrothorax drainage and length of stay had no significant difference.

CONCLUSIONSThough inhaled NO, there is no significant long-term effects in patients after TCPC, but it may play an important role in the management of low cardiac output syndrome and high cava pressure caused by reactive elevated pulmonary vascular resistance in the early postoperative period of TCPC.

Administration, Inhalation ; Adolescent ; Adult ; Arteriovenous Shunt, Surgical ; methods ; Cardiac Output ; drug effects ; Child ; Child, Preschool ; Female ; Humans ; Male ; Nitric Oxide ; administration & dosage ; therapeutic use ; Postoperative Period ; Pulmonary Artery ; physiology ; surgery ; Time Factors ; Vascular Resistance ; drug effects ; Vasodilator Agents ; administration & dosage ; therapeutic use ; Venae Cavae ; surgery

OBJECTIVETo summarize the experience of surgical treatment of secundum atrial septal defects in adults over 30 years old.

METHODSThere were 469 patients with secundum atrial septal defects in our study (male 144, female 325; ages 30-68, mean 38.6 years old). There were 105 cases with pulmonary hypertension and 458 cases with arrhythmia in the group. Surgical closure of defects were performed in all patients. Surgical closure of 358 cases were done by patches including 305 autologous pericardial patches. The low dose (6 x 10(-6)) nitric oxide inhalation was used in 25 postoperative patients with pulmonary hypertension. Right sided maze procedures were done in 5 cases with atrial fibrillation.

RESULTSSurgical mortality was 0.6% (3 cases), the others were healed. In the group, there were 180 cases with arrhythmia, 27 cases with left ventricular function amyoplasia, 28 cases with low cardiac output syndrome, 12 cases in secondary operation for bleeding and 1 case with air-embolism. The level of mean pulmonary artery pressure of 25 postoperative patients with pulmonary hypertension inhaled nitric oxide was down 28.5%. After right sided maze procedures were done in 5 cases with atrial fibrillation, atrial fibrillation disappeared. 352 cases were followed up from 3 months to 20 years (mean 5.6 years). Twenty-nine cases were in class I-II of cardiac function, and the others were better than class I of cardiac function.

CONCLUSIONSAtrial septal defects in adult should be operated as early as possible. When patch is needed, an autologous pericardial patch is the first selection. Inhaled nitric oxide is an effective method to postoperative pulmonary hypertension. The maze operation should be performed for atrial septal defect with atrial fibrillation while the surgical closure of defect was done. During and after operation, much attention should be paid to preventing and curing arrhythmia and protecting and supporting left heart function.

Administration, Inhalation ; Adult ; Age Factors ; Aged ; Atrial Fibrillation ; surgery ; Endothelium-Dependent Relaxing Factors ; therapeutic use ; Female ; Heart Septal Defects, Atrial ; surgery ; Humans ; Hypertension, Pulmonary ; complications ; drug therapy ; Male ; Middle Aged ; Nitric Oxide ; therapeutic use ; Postoperative Complications ; drug therapy ; Retrospective Studies

OBJECTIVETo summarize the experience in surgical treatment of residual shunt after repair of ventricular septal defect and investigate the position of the residual shunts.

METHODSBetween January 1979 and May 2003, re-operations on residual shunt after repair of ventricular septal defect were performed in 37 patients with congenital heart disease including ventricular septal defect, tetralogy of Fallot, double outlet right ventricle in 19, 17 and 1 patients, respectively. It accounted for 0.21% (37/18000) of open heart operations performed during these years. The patients included 26 males and 11 females with age from 3 months to 53 years (mean 16 +/- 12 years). The residual shunt was diagnosed by postoperative murmur and echocardiography. Twenty-six cases were repaired with patch and 11 cases were closed directly with mattresses sutures.

RESULTSTwo patients (2/37, 5%) died within 48 hrs postoperatively. The results in other 35 patients followed up after surgery from 3 months to 15 years were satisfactory.

CONCLUSIONSMost of the residual shunts occurred in base of septal leaflet of tricuspid valve, the second and the first transfer suture respectively. Effects of reoperations on residual shunts were satisfactory.

Adolescent ; Adult ; Cardiac Surgical Procedures ; methods ; Child ; Child, Preschool ; Double Outlet Right Ventricle ; surgery ; Female ; Heart Septal Defects, Ventricular ; surgery ; Humans ; Infant ; Male ; Middle Aged ; Postoperative Complications ; surgery ; Reoperation ; Retrospective Studies ; Tetralogy of Fallot ; surgery

OBJECTIVETo evaluate the indication and operative program of ventricular septal defect with pulmonary atresia (VSD-PA).

METHODSFrom June 1984 to March 2005, there were 32 patients with VSD-PA, which underwent 33 operations. Among them, 15 were males and 17 were females. The ages ranged from 6 months to 9 years. There were 9 patients with aortopulmonary collateral arteries. The operations included central aorta-pulmonary shunts 3 cases, one stage complete repair 27 cases and one stage unifocalization with VSD open 2 cases.

RESULTSThere were early 5 death including one death after aorta-pulmonary shunt and 4 deaths after one stage complete repair. The causes of death were severe low cardiac output (2 patients), respiratory function failure (1 patient), multiorgan function failure (1 patient) and severe infect (1 patient). Twenty-one patients were followed up from 3 months to 15.5 years. Heart function (NYHA) was class I or II in 19 cases and class III or IV in 2 cases.

CONCLUSIONSThe operative indication and methods mainly depend on the developing of pulmonary arteries and aortopulmonary collateral arteries. Completely surgical repair of patients with VSD-PA can be achieved with acceptable mortality.

Cardiovascular Surgical Procedures ; methods ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Heart Septal Defects, Ventricular ; complications ; surgery ; Humans ; Infant ; Male ; Pulmonary Atresia ; complications ; surgery ; Retrospective Studies ; Time Factors ; Treatment Outcome

OBJECTIVETo summarize the experience of surgical treatment of single atrium.

METHODSFrom August 1984 to August 2004, there were 33 patients with single atrium in our study. Plastic surgery for mitral valves were performed for 30 cases with mitral insufficiency. Plastic surgery for tricuspid valves were performed for 18 cases with tricuspid valve insufficiency. There were 3 cases only with complete absence of atrial septum. There were 14 cases with left superior vena cava. All new atrial septums were made with patches including 24 autologous pericardial patches and 9 terylene patches. Complicate abnormalities were corrected in the same time. Tow suture techniques were used in operations to prevent conductive system block, and plastic surgery for mitral valves were performed until the mitral valves were sufficiency.

RESULTSThere weren't death and conductive system block after operation in the group. One case was low-grade mitral insufficiency and the others weren't mitral insufficiency. Twenty-five cases were followed up from 3 months to 11 years, and they could work and study normally.

CONCLUSIONSSingle atrium should be operated as early as possible. The key of surgery is to prevent conductive system block, to properly correct mitral insufficiency and to drastically correct complicated abnormality. The new atrial septum should be made by patch and an autologous pericardial patch is the first selection.

Adolescent ; Adult ; Cardiac Surgical Procedures ; methods ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Heart Septal Defects, Atrial ; surgery ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency ; surgery ; Treatment Outcome ; Tricuspid Valve Insufficiency ; surgery

OBJECTIVETo evaluate the replication and encapsidation of HBV mutants with the truncated C gene.

METHODSThe HBV mutants with the truncated C gene were constructed by molecular cloning and PCR-based deletion in vitro. The replication and encapsidation of HBV mutants were investigated by Southern blotting, PCR and real-time fluorescence PCR respectively after transfecting the HBV mutants plasmid into HepG2 cells by using liposome.

RESULTSThe C-truncated HBV mutant vectors were constructed successfully and confirmed exactly by clone sequencing and enzymes digestion. The C-truncated HBV mutants were replication defective, however, all types of HBV DNA could be detected positive in the cytoplasm and supernatant after co-transfecting the C-truncated HBV mutants plasmid and the helper constructs into HepG2 cells. The C-truncated HBV mutants were proved to produce 3-40 folds more progeny DNA than that of the wild-type HBV by DNA quantitative assay.

CONCLUSIONThe C-truncated HBV mutants are replication-deficient and could not replicate and encapsulate in the hepatocytes when transfected solely, however, the progeny HBV-variant viruses are encapsidated more effectively to secrete into supernatant when co-transfected with the helper construct which lacks part of 5 prime-proximal HBV RNA packaging signal Epsilon.

Cell Line, Tumor ; Hepatitis B Core Antigens ; genetics ; Hepatitis B virus ; genetics ; physiology ; Humans ; Mutation ; Plasmids ; genetics ; Transfection ; Virus Replication