Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Pulmonary hypertension (PH) is a rare and severe progressive disease. It results from hypertrophic remodeling of distal pulmonary arterioles that increases pulmonary arterial pressure and pulmonary vascular resistance in the absence of left heart, pulmonary parenchymal, or thromboembolic disease. Hypoxia-inducible factor-1 (HIF-1) regulates a large number of genes related to the occurrence and development of PH, and induces pulmonary angiogenesis, cell proliferation and migration, cellular energy metabolism and utilization. HIF-1 is an important component of the pathogenesis of hypoxic PH and plays an important role in driving the pathological process of pulmonary vascular and right ventricular remodeling. This article systematically elucidated the role and regulation of HIF-1 in hypoxic PH and its potential in targeted therapy of PH.

In recent years, obesity has become a global public health problem, and the incidence of obesity among children and adolescents in China has been gradually increasing.Obesity in childhood will affect the development and health of children and may lead to an increased incidence of multiple chronic diseases in adulthood.The current main strategy for weight reduction in obese children is to change their dietary habits and increase physical activity, but it is prone to relapseand has a high failure rate.Obese patients exhibit persistent hunger and lack of satiety.Glucagon-like peptide-1 receptor agonists, which suppress appetite and increase satiety, have successfully treated adult obesity with good results.This article will discuss the feasibility and safety of using glucagon-like peptide-1 receptor agonists for obesity in children and adolescents by reviewing the possible mechanisms of action of glucagon-like peptide-1 receptor agonists for weight reduction and the clinical data of glucagon-like peptide-1 receptor agonists on obesity in children and adolescents.

Obesity is a major risk factor for the generation and development of diabetes, atherosclerosis, hyperlipidemia and cancer. Obesity is accompanied with remodeling of adipose tis-sue, such as changed cell component and function, angiogene-sis, extracellular matrix remodeling and infiltration of inflamma-tory cells. It is important for the prevention of obesity to study adipose tissue remodeling. This review summarizes recent ad-vances in adipose tissue remodeling.

Aim To explore micro RNAs-integrated pathogenic signaling to control endothelial-mesenchy-mal transition ( EndMT ) in pulmonary hypertension ( PH) by a network bioinformatic approach. Methods Literature-mining method was used to find PH-relat-ed genes and EndMT/EMT-related miRNAs. Bioinfor-matic prediction approach ( DIANA3 , Miranda4 , PicT-ar5 , TargetScan6 , miRDB7 and microT-CDS8 ) was used for miRNA target prediction. Hypergeometric a-nalysis was used to predict miRNAs related to EndMT in PH. The analysis of interactions between PH-rele-vant genes( PH network) was performed with the use of Biological General Repository for Interaction Datasets ( BioGRID ) . These miRNAs were ranked with the highest probability of substantial overlap among their gene targets in the PH-network, the relationship be-tween their targets and the PH functional categories which include hypoxia, inflammation, and transforming growth factor/BMP signaling. Then, the part of results was validated by animal experiment. Lastly the miR-NA-Target network was built using Cytocape 3 . Results List of 230 genes was compiled that were directly im-plicated in the development of PH and 189 miRNAs were related to EndMT in PH. Among 189 miRNAs, only 22 microRNAs(miR-let-7 family, miR-124, miR-130 family, miR-135, miR-144, miR-149, miR-155, miR-16-1, miR-17, miR-181 family, miR-182, miR-200 family, miR-204, miR-205, miR-21, miR-224, miR-27, miR-29 family, miR-301a, miR-31, miR-361 and miR-375) were related to hypoxia, inflamma-tion, and transforming growth factor/BMP signaling. Among these miRNAs, the levels of let-7g, miR-21, miR-124 and miR-130 family were significantly changed in the pulmonary artery in hypoxia-induced PH rats. Conclusions Among numerous miRNAs,22 of which may be involved in hypoxia, inflammation, and transforming growth factor/BMP signaling and re-lated to EndMT in PH by network bioinformatic ap-proach, which provides a theoretical basis for further investigation of EndMT in PH.

The air quality of simulated moxibustion clinic was tested, which could provide references for the evaluation on air pollution in moxibustion clinic. After the clinical environment of moxibustion was established,the contents of CO,NO, PM 10 and PM 2.5 in the air at 5 different time points (0.5 h, 1 h and 2 h after 10 moxa sticks were ignited as well as 5 min ventilation after 0.5 h moxibustion burning and 5 min ventilation after 1 h moxibustion burning) were measured by testing organizations.0.5 h, 1 h and 2 h after 10 moxa sticks were ignited, the content ranges of CO,NO, PM 10 and PM 2.5 in the air were 15.9 to 37.0 mg/m,0.012 6 to 0.022 4 mg/m,0.22 to 1.28 mg/mand 0.13 to 0.53 mg/m, respectively; the contents of CO, PM 10 and PM 2.5 were higher than national standard. With 5 min ventilation after 0.5 h moxibustion burning and 5 min ventilation after 1 h moxibustion burning, the content ranges of CO,NO,PM 10 and PM 2.5 were 0.3 to 0.4 mg/m,0.015 5 to 0.018 0 mg/m,0.11 to 0.13 mg/mand 0.04 mg/m, respectively; the contents of CO, PM 10 and PM 2.5 were lower than national standard. It is concluded that long-time moxibustion could cause relatively high concentration of moxa smoke, and the contents of CO, PM 10 and PM 2.5 in the air will exceed the national standard. However, by keeping good ventilation, the contents of CO,NO,PM 10 and PM 2.5 in the air can be controlled within safe ranges.

OBJECTIVE: To explore the role of calpain in pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension and the underlying mechanisms.
 METHODS: Sprague-Dawley rats were randomly divided into the hypoxia group and the normoxia control group. Right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored by a method with right external jugular vein cannula. Right ventricular hypertrophy index was presented as the ratio of right ventricular weight to left ventricular weight (left ventricle plus septum weight). Levels of calpain-1, -2 and -4 mRNA in pulmonary artery were determined by real-time PCR. Levels of calpain-1, -2 and -4 protein were determined by Western blot. Primary rat pulmonary arterial smooth muscle cells (PASMCs) were divided into 4 groups: a normoxia control group, a normoxia+MDL28170 group, a hypoxia group and a hypoxia+MDL28170 group. Cell proliferation was detected by MTS and flow cytometry. Levels of Ki-67 and proliferating cell nuclear antigen (PCNA) mRNA were determined by real-time PCR.
 RESULTS: RVSP, mPAP and right ventricular remodeling index were significantly elevated in the hypoxia group compared to those in the normoxia group. In the hypoxia group, pulmonary vascular remodeling was significantly developed, accompanied by up-regulation of calpain-1, -2 and -4. MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs concomitant with the suppression of Ki-67 and PCNA mRNA expression.
 CONCLUSION Calpain mediates vascular remodeling via promoting proliferation of PASMCs in hypoxia-induced pulmonary hypertension.
Animals ; Calpain ; genetics ; physiology ; Cell Proliferation ; Dipeptides ; physiology ; Hypertension, Pulmonary ; chemically induced ; genetics ; physiopathology ; Hypertrophy, Right Ventricular ; Hypoxia ; Ki-67 Antigen ; drug effects ; Myocytes, Smooth Muscle ; physiology ; Proliferating Cell Nuclear Antigen ; drug effects ; Pulmonary Artery ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Up-Regulation ; Vascular Remodeling ; genetics ; physiology

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Humans ; Lymphoma, Follicular ; drug therapy ; Rituximab

OBJECTIVEA prospective, multicenter and non-interventional prospective study was conducted to evaluate the clinical features of rituximab combined with chemotherapy (R-Chemo) as first-line treatment on newly diagnosed Chinese patients with diffuse large B-cell lymphoma (DLBCL).

METHODSThis was a single arm, prospective, observational multicenter and phase IV clinical trial for 279 patients, who were newly diagnosed as CD20-positive DLBCL from 24 medical centers in China 2011 and 2012, no special exclusion criteria were used. All patients received rituximab based R-Chemo regimes, such as R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone) and other regimes as the first-line treatment. The treatment strategies were determined by physicians and patients without detailed description for treatment course, dose, interval time and examination. Clinical response and safety of all patients were investigated in 120 days after completion of last dose of rituximab.

RESULTSOf 279 patients, 258 with stage I-IV who received at least 1 cycle of rituximab treatment and completed at least one time of tumor assessment were enrolled into intention-to-treat analysis, including 148 male and 110 female. The median age of all patients was 57.2(12.8-88.4) years. ECOG performance statuses of 0 or 1 were observed in 91.1% of patients, international prognostic index levels in the low-risk and low-middle-risk groups in 76.4% of patients, the tumor diameters smaller than 7.5 cm in 69.0% of patients. All patients received 6 median cycles of R-Chemo treatment every 24.4 days. R-CHOP treatment was shown to improve the clinical response with overall response rates of 94.2%. Common adverse events included anemia, marrow failure, leukopenia, thrombocytopenia, digestive diseases, infection and liver toxicity. All adverse events are manageable.

CONCLUSIONNon-interventional clinical trial of R-Chemo remains the standard first-line treatment for newly diagnosed patients with DLBCL in real clinical practice, which is consistent with international treatment recommendations for DLBCL patients. R-Chemo can provide the clinical evidence and benefit as the first-line standard treatment for Chinese patients with DLBCL.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; Treatment Outcome

Objective To evaluate the clinical efficacy and adverse effects of brucea javanica oil emulsion combined with DP chemotherapy in treating advanced non-small-cell lung cancer.Methods Totally 48 patients with advanced non-small-cell lung cancer were divided into two groups randomly by mechanical sampling method.Twenty-four cases in treatment group were treated by brucea javanica oil emulsion combined with DP chemotherapy, while 24 cases in control group were treated by DP chemotherapy only.The clinical effects were evaluated after treatment of two cycles.Results The short-term effective rate was 54.2% (13/24) in treatment group and 45.8% (11/24) in control group, and there was no significant difference between two groups ( χ2 = 0.333, P = 0.564).The rate of increased and stable life quality was 87.5%(21/24) in treatment group and 58.3%(14/24) in control group,and there was significant difference between two groups (χ2 = 5.169,P = 0.023).The rate of increased and stable weight was 79.2% (19/24) in treatment group and 45.8%( 11/24) in control group, and there was significant difference between two groups (χ2 = 5.689,P = 0.017).The incidence of nausea or vomiting was 45.8% (11/24) in treatment group and 41.7%( 10/24 ) in control group, and there was no significant difference between two groups (χ2 = 0.085, P = 0.771 ).Compared with those in control group, patients in treatment group had less adverse effects in decreasing of peripheral blood leucocytes and showed better immune function.Conclusion Brucea javanica oil emulsion combined with DP chemotherapy in treating advanced non-small-cell lung cancer has good clinical effect, especially enhances the quality of life, improves immune function and decreases the adverse effects of chemotherapy.