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*

Objective:To investigate the expression level of small nucleolar RNA SNORD15A in bone marrow of patients with acute leukemia (AL) and its relationship with clinical characteristics and prognosis of patients.Methods:Bone marrow blood samples of 53 newly treated AL patients and 29 healthy subjects without clinical diagnosis of hematologic diseases or other malignant diseases (control group) at the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression of SNORD15A in bone marrow blood mononuclear cells of the two groups. The median relative expression of SNORD15A (0.148) was used as the boundary, and AL patients were divided into low expression group (<0.148) and high expression group (≥0.148). The relationship between the expression level of SNORD15A and the clinical characteristics, clinical indicators and overall survival (OS) of AL patients was analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was performed; Cox proportional hazards model was used for univariate and multivariate analyses of OS of patients.Results:The relative expression of SNORD15A was 0.148 (0.012-1.376) in newly treated AL patients and 0.921 (0.513-2.288) in the control group, and the difference was statistically significant ( Z = -6.85, P < 0.01). The differences in SNORD15A relative expression between patients with different prognostic stratification, efficacy and with or without fever and bleeding were statistically significant (all P < 0.05). The differences in platelet count, plateletcrit and albumin levels between SNORD15A low expression group and high expression group were statistically significant (all P < 0.05), and the differences in molecular biology and cytogenetic characteristics were not statistically significant (all P > 0.05). The patients in SNORD15A high expression group had better OS than the low expression group ( P < 0.05). The results of univariate Cox regression analysis showed that SNORD15A was an influencing factor for patients' OS ( HR = 0.063, 95% CI 0.005-0.766, P < 0.05); the results of multivariate Cox regression analysis showed that fatigue ( HR = 4.754, 95% CI 1.014-22.290), fever ( HR = 0.147, 95% CI 0.029-0.746) and hemoglobin ( HR = 0.970, 95% CI 0.944 -0.998) were independent influencing factors for OS (all P < 0.05). Conclusions:SNORD15A is lowly expressed in AL and may be an indicator for disease monitoring and prognostic assessment in AL patients.

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 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 explore the effect of peer support system on social anxiety and resilience among new graduate nurses. Methods:Totally 36 new graduate nurses entry in 2014 who's Interaction Anxiousness Scale (IAS) score were ＞43 were selected as control group. Totally 39 new graduate nurses entry in 2015 who's IAS score were ＞ 43 were as experimental group. The control group accepted routine standardized training. The experimental group received peer support, which consisted on conduct group intervention and twining intervention (6 months). IAS and Connor-Davidson Resilience Scale(CD-RISC) were used to investigate the nurses'social anxiety and resilienceat 3 months and 6 months after intervention. The scores were analyzed by using repeated ANVOA Results: Repeated measures analysis of variance of IAS showed that, there were significant differences on the IAS scores for interaction between measure time and group processing (P ＜0.001). The differences between the two groups in the main effects of interaction and time on the total score of CD-Rescan its three dimensions score were all statistically significant (Ps ＜ 0.001). Separate analyses showed that at baseline, there was no significant difference between two groups in all variables (Ps ＞0.05). After 3 months and 6 months of intervention, the IAS scores were lower in the intervention group than in the control group (Ps ＜0.001), the CD-RISC total scores and the three dimensions scores were higher in the intervention group than in the control group (Ps ＜0.05). Conclusion: It suggests that the peer support system could improve the social anxiety and resilience of new graduate nurses.

Objective To explore the epidemiology characteristics of endometrial cancer (EC).Methods We retrospectively analyzed 10081 patients diagnosed with EC from 62 hospitals between 2000 and 2010 in Guangdong province.Results The mean age at diagnosis was 52.8 ± 9.3.The proportion were 19.3％,64.2％,16.6％ in patients with ages ≤45,＞ 45-60,＞ 60 respectively.From 2000 to 2010,the mean ages at each year were no statistic significance.The number of cases of EC were positively correlated with years(r =0.964,P ＜ 0.001).The number of cases of patients with ≤ 30 years old (r =0.857,P =0.001),≤35 years old (r =0.866,P =0.001),≤40 years old (r =0.952,P ＜ 0.001),≤ 45 years old (r =0.952,P ＜0.001) were positively correlated with years.The ratios of patients with ≤30 years old (x2 =10.390,P =0.407),≤35 years old (x2 =11.651,P =0.309),≤ 40 years old (x2 =17.329,P =0.067),≤45 years old (x2 =5.154,P =0.881) during these eleven years were no statistic significance.The ratios of type Ⅰ EC at 2000-2010 were no statistic significance.Conclusions EC often present in patients aged from ＞ 45-60 years old.The case number of EC showed an increasing trend.However,the proportion of young patients was stable.The endometroid adenocarcinoma was the main histological type of EC.

Objective To investigate the clinical and pathological characteristics between types 1 and 2 endometrial uterine cancers.Methods The clinical materials of 9 437 patients with uterine cancer were collected with retrospective analysis from 62 hospitals during 2000 to 2010.Results The mean age of type 1 endometrial cancers was less than type 2.There were more young patients in type 1 endometrial cancers.The mean menopause age of type 2 endometrial cancers was greater than type 1.The mean age of menarche,obesity,diabetes,hypertension,infertility,and nulliparous were not significant differences between types 1 and 2 endometrial cancers.There were more patients with advanced tumor,deep myometrium invasion,estrogen receptor (ERs) negative,progesterone receptor (PR) negative,P53 positive,lymph vascular space involvement,cervical stromal invasion,adnexal metastasis,and lymph node metastasis in type 2 endometrial cancers.Conclusions Type 2 endometrial uterine cancers occurred in elder people with more pathological risk factors and more malignant biological activities.

Objective To evaluated the value of hysteroscopy and dilatation and curettage (DC) in diagnosis of endometrial cancer. Methods This retrospective analysis included clinical pathologic data of 3 676 patients with endometrial cancer from Jan. 1, 2000 to Dec. 31, 2010 in hospitals of endometrial cancer prevention projects in Guangdong Province. Results A total of 3 676 patients with endometrial cancer were divided into DC group (3 211 patients) and hysteroscopy group (465 patients). Compared to the results of pathological diagnosis, the accuracy rate between DC group and in hysteroscopy group were no statistically difference was 91.00%(2 922/3 211) vs 90.75%(422/465;χ2=0.030, P=0.862). The accuracy rate, sensitivity, specificity, positive predictive value and negative predictive value of cervical involvement between DC group and hysteroscopy group were 81.28%vs 86.45%(P<0.01), 24.78%vs 23.68%(P>0.05), 93.76%vs 98.71%(P<0.01),46.75%vs 78.26%(P<0.01) and 84.95%vs 86.88%(P>0.05), respectively. Rate of positive peritoneal cytology in DC group was 4.76%(153/3 211), and the rate was 3.23%(15/465) in hysteroscopy group, which were no statistically difference (χ2=2.206, P=0.137). There were no statistically difference in 5-year overall survival (91.02% vs 92.03%;χ2=0.033, P=0.856) and 5-year progression-free survival (89.81%vs 91.83%;χ2=1.508, P=0.219) between DC group and hysteroscopy group. Conclusions Hysteroscopy and dilatation and curettage is an effective method in diagnosis of endometrial cancer, especially hysteroscopy is better in diagnosis of cervical involvement. Hysteroscopy don′t improve risks of positive peritoneal cytology and don′t affect the prognosis of patients with endometrial cancer.

The change in serum level of 8-hydroxy-deoxyguanosine (8-OHdG),an oxidative stress biomarker,in patients with active Graves' ophthalmopathy (GO) during corticosteroid treatment was observed.The serum level of 8-OHdG was significantly increased in patients with active GO as compared with that of normal controls and patients with Graves' disease (P ＜ 0.05).After systemic corticosteroid treatment,patients with GO showed significantly lowered 8-OHdG level as compared with that before treatment and patients with Graves' disease.These changes in serum 8-OHdG level were accompanied by decreases in clinical activity score (P ＜ 0.05) during corticosteroid treatment.Oxidative stress may play a role in the pathogenesis of GO.Serum 8-OHdG level may be used as an objective and quantitative parameter in patients with GO during immunosuppressive treatment.

To investigate the role played by 8-hydroxy-deoxyguanosine (8-OHdG) in patients with Graves'ophthalmopathy(GO),and the association between 8-OHdG and the disease activity of GO.Serum levels of 8-OHdG were tested in 48 cases with GO and 30 cases with Graves' disease(GD) without ophthalmopathy.30 healthy subjects participated in this study as controls.8-OHdG was detected by enzyme-linked immunosorbent assay (ELISA).Compared with the controls,the mean level of 8-OHdG in GO patients and GD patients was increased significantly [(2.98±1.33),(2.07±1.30) vs(0.72±0.93)ng/ml,P＜0.05].Mean 8-OHdG level in GO patients was markedly higher when compared to GD patients(P＜0.05).Pearson regression analysis showed that elevated levels of 8-OHdG were significantly correlated with the Clinical Activity Score of GO (r =0.54,P＜0.01).The serum level of 8-OHdG in GO patients was raised obviously,it implies that oxidative stress plays an important role in the pathogenesis of GO,and the serum level of 8-OHdG might act as an activity index of GO.