OBJECTIVETo investigate the molecular and functional changes in L-type Ca2+ channel of hypertrophied cardiomyocytes in neonatal rats induced by angiotensin II (Ang II).

METHODSThe in vitro model of cardiomyocyte hypertrophy was established in cultured cardiomyocytes from neonatal rats. Whole cell patch clamp was used to measure the L-type Ca2+ currents. Semi-quantitative RT-PCR was used to determine the mRNA expression of L-type Ca2+ channel alpha1C subunits.

RESULTSIn the hypertrophied cardiomyocytes induced by Ang II, I(Ca, L) densities were increased, whereas the features of I(Ca,L) activation, inactivation or recovery from inactivation were not affected. Meanwhile, Ang II increased the mRNA expression of L-type Ca2+ channel alpha1C subunits in cardiomyocytes. All these actions of Ang II could be blocked by the angiotensin II 1 type receptor blocker losartan.

CONCLUSIONDuring cardiomyocyte hypertrophy induced by Ang II, there are significant changes in the molecule and function of L-type Ca2+ channels, which are mediated by the angiotensin II 1 type receptor.

Angiotensin II ; adverse effects ; Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; metabolism ; Female ; Hypertrophy ; metabolism ; Male ; Membrane Potentials ; Myocytes, Cardiac ; metabolism ; pathology ; physiology ; Rats ; Rats, Sprague-Dawley

Objective:To investigate the predictive value of thyroid peroxidase antibody(TPOAb), thyroglobulin antibody(TgAb), and thyrotropin receptor antibody(TRAb) status prior to the first 131I treatment in the development of hypothyroidism in patients with Graves′ disease after 131I administration. Methods:The cohort of 89 males and 351 females, with a median age of 34 years (IQR 28-44) who underwent initial 131I therapy at Peking Union Medical College Hospital from December 2019 to December 2021 was established. Participants were classified into TPOAb-positive, TgAb-positive, TRAb-positive, and their respective negative groups based on pre-treatment serum levels of thyroid autoantibody. Sex, age, medical history, thyroid hormone level, thyroid autoantibodies, iodine uptake rate, thyroid estimation and 131I treatment dose were recorded. The 131I treatment dose was determined using the calculated dose method. Patients were followed up for one-year post-treatment to evaluate efficacy. Mann- Whitney U test and χ 2 test were used to compare and analyze the data between groups, and logistic regression was used to analyze the influencing factors of permanent hypothyroidism after treatment. Results:(1) In the TPOAb-positive group, transient hypothyroidism and permanent hypothyroidism occurred in 8.1%(26/321) and 44.9%(144/321), both of which were significantly higher than those in the TPOAb-negative group at 2.5%(3/119) and 31.9%(38/119); In the TRAb-negative group, permanent hypothyroidism occurred in 56.8%(25/44), which was significantly higher than that in the TRAb-positive group 39.5%(152/385). (2) After the first 131I treatment, males ( OR=0.518, 95% CI 0.314-0.855, P=0.010), TPOAb-positive ( OR=1.002, 95% CI 1.001-1.003, P=0.001), and TRAb-negative( OR=0.973, 95% CI 0.957-0.990, P=0.002) were independent influence factor, of permanent hypothyroidism. Conclusion:In the calculated dose method for treating GD, male, TPOAb-positivity, and TRAb-negativity prior to initial 131I treatment are associated with a higher likelihood of developing permanent hypothyroidism post-treatment.

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

OBJECTIVEDuring 2003-2005, an outbreak of meningitis due to Neisseria meningitidis serogroup C occurred in China. With the aim to find strain clues result in the final epidemics, the ancestral strain 053442, a clinical isolate, and a carrier strain 053426 with different gene type were analyzed.

METHODSClinical strain 053442 and carrier strain 053426 were cultured on GC agar plates under the same condition. Two-dimensional electrophoresis was performed using the pH 3-10 nonlinear IPG strips of 24 cm length, and all the protein spots were identified by matrix-assisted laser desorption/ionization time of flight spectrometry.

RESULTS502 and 380 protein spots were identified in 053426 and 053442 respectively, relating to 266 and 202 different genes covering a wide range of cellular functions. The express volume and number of proteins involved in energy metabolism, protein synthesis and amino acid biosynthesis in 053426 were higher than in 053442. Virulence factor Opa, Opc and a series of proteins involved in pilus assembly and retraction were identified in 053442, which appear to be of primary importance in colonization and invasion of human cells. Compared to 053442, virulence protein species were less in 053426, with lower express volumes too. No Opa and Opc were detected in 053426.

CONCLUSIONSThe different protein expression profiles of the clinical strain 053442 and carrier strain 053426 in the present study provide some clues of the different pathogenicity of the two strains, which may account for result in the final epidemics.

Bacterial Proteins ; analysis ; Bacterial Typing Techniques ; China ; epidemiology ; Disease Outbreaks ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Meningitis, Meningococcal ; cerebrospinal fluid ; epidemiology ; microbiology ; Neisseria meningitidis, Serogroup C ; classification ; isolation & purification ; Proteome ; analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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

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).