Brain/diagnostic imaging* ; Head

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

BACKGROUND: Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations. METHODS: This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL. RESULTS: Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively. CONCLUSIONS: Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation. TRIAL REGISTRATION ChiCTR-EOC-17010553.
Case-Control Studies ; China/epidemiology* ; Esophageal Neoplasms/pathology* ; Humans ; Precancerous Conditions/pathology* ; Risk Factors ; Stomach Neoplasms

Objective To investigate the epidemiological characteristics and interruption of 228 hepatitis B virus (HBV) positive pregnant women, and to provide more references for clinical education and treatment. Methods A total of 228 chronic HBV pregnant women underwent maternal-neonatal transmission blocking treatment in Third Affiliated Hospital of Sun Yat-sen University from January 2015 to April 2019 were enrolled. Self-designed follow-up questionnaires were used to collect pregnant women's data. Then the relationship of epidemiological characteristics and HBV-DNA load levels with the genotype, hepatitis B e antigen (HBeAg), and alanine aminotransferase (ALT) was analyzed, moreover, the prevention of mother-to-child transmission was also analyzed. Results A total of 228 HBV-positive pregnant women were mainly over 30 years old, with a family history of liver disease, low education level (

Objective To evaluate the safety of morphine hydrochloride injection. Methods Ear verin injection was used to evaluate the vascular irritation using the comparison of left side with right side in rabbits. Quadriceps femoris injection was used to evaluate the muscle irritation using the comparison of left side with right side in rabbits. Guinea pigs were intravenously injected with morphine hydrochloride injection at a dose of 2.8 mg·kg-1 once daily 3 times, stimulation was performed on 14 d after the last sensitization and the booster dose was 2 times the sensitization dose. The allergic reactions were observed. The different concentrations of morphine hydrochloride injection were placed in 2％ rabbit erythrocyte suspension, and then the hemolyzation and agglutination were observed. Results There were no significant vascular or muscular irritation and injury effects of morphine hydrochloride injection in rabbits. There were no evidenceof hemolyzation and agglutination in rabbit erythrocytes in vitro. No allergic reactions on guinea pigs in vivo were observed. Conclusion After treatment of morphine hydrochloride injection, neither obvious vascular /muscle stimulation or sensitization, nor hemolyzation or agglutination appeared in rabbits. The research results provide basic reference for the clinical rational and safe application of morphine hydrochloride injection.

OBJECTIVE: To investigate the association between pre-treatment thrombocytosis and prognosis in patients with ovarian cancer (OC). METHODS: PubMed, EMBASE, and the Cochrane Library were searched for articles regarding the prognosis of OC patients with pre-treatment thrombocytosis by the end of March 2018. Pooled estimates for overall survival (OS) and progression-free survival (PFS) events were calculated as hazard ratios (HRs) either on a fixed or random effect model by Stata 13.0 software. Funnel plot and Egger's test were applied to evaluate publication bias and sensitivity analyses were undertaken to estimate the strength of outcomes. RESULTS: Eleven studies that met the inclusion criteria were enrolled, including a total of 4,953 patients. Pooled results showed that pre-treatment thrombocytosis was significantly associated with OS (HR=1.722; 95% confidence interval [CI]=1.437–2.064) and PFS (HR=1.452; 95% CI=1.323–1.593) in the cohort. Significant correlation was found in OS and PFS between pre-treatment thrombocytosis and both epithelial OC (all stages and differentiation degrees of OC) and advanced epithelial OC (III or IV) by subgroup analyses, which were performed according to publication year, country, case numbers, OC category, International Federation of Gynecology and Obstetrics stage, and cut-off value. However, subgroup analyses indicated no significant correlation between pre-treatment thrombocytosis and OS for patients with high-grade serous (poorly differentiated or undifferentiated) OC (HR=1.220; 95% CI=0.946–1.573; p=0.125). Egger's test demonstrated no obvious publication bias in the articles enrolled in this study (OS: p=0.226; PFS: p=0.071). CONCLUSION: Pre-treatment thrombocytosis might be taken as an independent prognostic indicator for patients with OC.
Cohort Studies ; Disease-Free Survival ; Gynecology ; Humans ; Obstetrics ; Ovarian Neoplasms* ; Prognosis* ; Publication Bias ; Publications ; Thrombocytosis*

Objective To observe the clinical efficacy of Kechuanning capsules for the treatment of chronic obstructive pulmonary disease (COPD) in stable phase.Methods Totally 110 patients with stable COPD were randomly divided into the therapy group and the control group, 55 cases in each group. Patients in both groups were given ipratropium bromide solution for inhalation. On the basis of western medicine treatment, the therapy group took Kechuanning capsules orally at the same time, 4 softgels for each time, 3 times a day;on the basis of western medicine treatment, the control group took the same amount of placebo capsules. The treatment lasted three months. Meanwhile, the clinical efficacy, BODE index, CAT score and ADRs of patients in the two groups were observed.Results The clinical efficacy in the therapy group was 96.00% (48/50), and 88.24% (45/51) in the control group, with statistical significance (P<0.05). BODE index and CAT score in the two groups decreased and the therapy group was lower than the control group (P<0.05). Liver and kidney function had no obvious abnormalities in the treatment group before and after treatment.Conclusion Kechuanning capsules can effectively reduce the BODE index and CAT score in patients with stable COPD, improve patients' life quality and clinical outcomes, and no obvious side effect has been found.

Objective To observe the effects of Kechuanning capsules on airway inflammation cells and inflammatory mediators in patients with COPD.Methods Totally 110 patients with stable COPD were randomly divided into therapy group and control group, 55 cases in each group. Both of the groups were given compound ipratropium bromide solution for inhalation, at the same time, patients in the therapy group took Kechuanning capsules orally, 4 softgels each time, 3 times a day, and patients in the control group took the same amount of placebo capsules. The treatment lasted three months. Differential counting of inflammatory cells and levels of inflammatory factors in serum and sputum supernatant were observed.Results In terms of differential counting of inflammatory cells, the sputum neutrophils of the therapy group decreased significantly (P<0.05) and macrophages increased (P<0.05) after treatment, with statistical significance compared with the control group (P<0.05). In terms of inflammatory mediators, the levels of IL-6, IL-8, LTB4 in serum did not change significantly (P>0.05) in two groups before and after treatment;IL-6, IL-8, LTB4 levels in the sputum supernatant of the therapy group were lower than those before treatment (P<0.05), with statistical significance compared with the control group (P<0.05). Conclusion Kechuanning capsules have an obvious inhibitory effect on airway inflammatory cells in patients with stable COPD as well as the release of inflammatory mediators.

Objective To improve detection rate and diagnostic accuracy of single ventricle(SV) in obstetric fetal echocardiography,to investigate the common types and complicated malformations of SV in the fetus,and to summarize the differential announcements in diagnosing fetal SV.Methods In 345 fetal hearts which were diagnosed as congenital heart disease by fetal echocardiography in our hospital,73 cases diagnosed as SV,including 3 cases appeared as ones of twins,were included in this study.Systemic scanning and multiple-views fetal echocardiography were used to examine these enrolled fetuses.Results In all 73 SV eases,3 cases were diagnosed as simple SV,the others were diagnosed as SV accompanied with other abnormalities,among them 44 cases accompanied with single atrium,18 cases with single atrium and persistent truncus arteriosus,2 cases with pulmonary atresia,20 cases with pulmonary artery stenosis,4 cases with partial atrioventricular septal defect,3 eases with aorta dysplasia or aortic valve dysplasia.SV types were classified as 24.7％ in type A,13.7％ in type B,46.6％ in type C and 15.0％ in type D respectively.68.2％ of the cases were diagnosed with aortic D-transposition,and 45.2 ％ with common inlet,42.5 ％ with single inlet and 12.3 ％ with double inlet respectively.42 SV cases were executed termination of pregnancy which 11 cases were confirmed by pathology and the other 31 cases were out of following-up.Conclusions Most cases of fetal SV were accompanied other abnormalities and simple SV was rare.Type C in which ventricular structure was combined with left and right ventricle was the most common type.To avoid the false diagnosis,much attention must be paid to distinguish big papillary muscle and abnormal muscle bundle from interventricular septum during ultrasonic examination.

Objective To investigate the common types of fetal cardiac malformations and complicated malformations,and to assess the value of classifying on these types.Methods 3201 pregnant women were undergone with fetal echocardiography (FECG),239 fetuses of them were diagnosed to be suffered with congenital heart disease(CHD),and 8 cases were one of twins with abnormal heart confirmed by FECG.All new-births were examined by echocardiography within half year after their births.Results 155 complex CHD in 239 fetuses were diagnosed by FECG,in them the common malformations were in turn 59 cases with diagnosed univentricular heart,29 cases with double outlet right ventricle,19 with atrio ventricular septum defect,12 with tetralogy of Fallot or quinalogy of Fallot,11 with persistent truncus arteriosus,6 with right ventricular dysplasia syndrome,6 cases transposition of the great vessels.100 cases were induced labor,41 of them were comfirmed by pathology.16 fetuses were born,123 cases were being pregnanted or un-followed up.Conclusions Complex and multi-malformation were common in fetal cardiocascular abnormalities.Diagnosing rate of fetal CHD(FCHD) in our enroll fetuses was 7.47 ％,rate of complex CHD vs CHD was 64.85 ％.According different types of FCHD,able to be operated or not after birth,surgery methods,as well as prognosis evaluations,all FCHD cases were classified into three subtypes:curable type,curable palliative type and untreatable type.This newly viewpoint will help pregnant women and their family to make reasonable selection.