Chemistry, manufacturing and controls regulatory considerations for marketing authorization application of therapeutic antibody in China / 药学学报

The marketing authorization application is a milestone of drug life cycle, which indicates a candidate has potential to become a commercial drug. As of now, there are only 12 domestic therapeutic antibodies approved in China. The chemistry, manufacturing and controls (CMC) development and evaluation of monoclonal antibody were more challenging for both industry and authority agency. As the result of domestic biopharmaceutical industry development and implement of priority review system, the marketing authorization application of domestic antibody biosimilar and imported antibodies had dramatic increased in recent years. Thus, the CMC evaluation of monoclonal antibody become the important task of biological product's marketing authorization registration management. In the article, the CMC regulatory considerations for marketing authorization application based on author's review experience was proposed, in order to accelerate development and registration of commercial antibody in China.

Application of elevating the root of tongue bare-handed to assist ProSeal laryngeal mask airway insertion in patients with tongue body hypertrophy / 实用医学杂志

Objective To investigate the effect of elevating the root of tongue bare-handed to assist ProSeal laryngeal mask airway insertion in patients with tongue body hypertrophy under general anesthesia. Methods Sixty ASAⅠ~Ⅲgrade patients with tongue body hypertrophy undergoing surgery in general anesthesia were randomly divided into two groups:30 cases in each group. After anesthesia induction ,laryngeal mask airway was inserted in the observation group with assistance of elevating the root of tongue bared-handed ,while inserted in the control group by standard method.Insertion time ,success rate of the first and secondary and total insertion ,pharyngolaryneal complications at 24 hours after removal were recorded ,as well as the success rate of gastric tube intubation was recorded. Results Compared with the control group ,insertion time was significantly shortened (P < 0.05). Success rate of the first and total insertion were increased (P < 0.05).Success rate of gastric tube intubation was increased(P < 0.05),and pharyngolaryneal complications were decreased (P < 0.05) in the observation group. Conclusions Elevating the root of tongue bare-handed to assist ProSeal laryngeal mask airway insertion in patients with tongue body hypertrophy is a simple and fast method with high success rate ,good apposition and less complications. Its efficacy is better than that of the standard method.

Grape Seed Procyanidin Extract Reduces Arsenic-Induced Renal Inflammatory Injury in Male Mice / 生物医学与环境科学（英文）

The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.

Paeoniflorin inhibits macrophage-mediated lung cancer metastasis / 中国天然药物

Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages (M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages (stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P < 0.01 or P < 0.05 vs control group). Paeoniflorin could decrease the cell populations at S phases (paeoniflorin 10, 30, 100 μmol·L(-1), P < 0.05 vs control group) and increase the cell populations at G0-G1 phases of Lewis lung cancer cells (paeoniflorin 100 μmol·L(-1), P < 0.05 vs control group) and reduce the numbers of M2 macrophages in peritoneal macrophages induced by IL-4 (paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P < 0.01 vs Control group). Paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo (paeoniflorin 20, 40 mg·kg(-1), P < 0.01 vs control group). These results suggest that paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages.

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity.</p><p><b>METHODS</b>Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed.</p><p><b>RESULTS</b>ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST.</p><p><b>CONCLUSION</b>GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.</p>

Expressions of HIF-1α and VEGF in rhabdomyosarcoma and their clinical significance / 肿瘤

Objective: To investigate the expressions of HIF-1α (hypoxia inducible factor-1α) and VEGF (vascular endothelial growth factor) in rhabdomyosarcoma and their clinical significance. Methods: The expressions of HIF-1α and VEGF preteins in 70 cases of rhabdomyosarcoma were detected by immunohistochemistry, and the correlations of the expressions of HIF-1α and VEGF with the clinicopathological characteristics and the prognosis were analyzed. Results: The positive-expression rates of HIF-1α and VEGF in rhabdomyosarcoma tissues were 75.7% (53/70) and 72.9% (51/70), respectively. HIF-1α expression was positively correlated to VEGF expression (r = 0.554, P = 0.000). HIF-1α expression was significantly associated with the factors of gender (P = 0.035), tumor size (P = 0.016) and clinical staging (P = 0.008), but it was not associated with the age (P = 0.555), pathological type (P = 0.625) and lymph node metastasis (P = 0.750). The three-year overall survival rates of HIF-1α-negative patients and HIF-1α-positive patients were 54.5% and 38.0%, respectively (P = 0.045). VEGF expression was significantly associated with clinical stage (P = 0.026), but it was not associated with the age (P = 0.478), gender (P = 0.944), tumor size (P = 0.535), pathological type (P = 0.399) and lymph node metastasis (P = 0.356). The three-year overall survival rates of VEGF-negative patients and VEGF-positive patients were 68.1% and 31.1% (P = 0.011). COX regression model showed that the factors of VEGF expression (P = 0.005), clinical staging (P = 0.004) and tumor size (P = 0.000) were independent predictors of poor prognosis of rhabdomyosarcoma. HIF-1α could not be considered as an independent prognostic factor of rhabdomyosarcoma (P = 0.845). Conclusion: The overexpression of HIF-1α and VEGF in rhabdomyosarcoma is related to clinical staging. HIF-1α expression is associated with VEGF expression, and VEGF is an independent predictor of poor prognosis of rhabdomyosarcoma. Copyright © 2012 by TUMOR.

The design of precision measure circuit for frequency & duty cycle of bioelectrical signal and its application in neuron-threshold stimulator / 中国医疗器械杂志

This paper mainly introduces the principles of a type of circuit for measuring frequency & duty cycle of low-frequency signals, and its applications in neuron-threshold stimulator. The circuit has the advantages of simple structure and accurate measurement.

The method and implementation of measuring the peak of bioelectrical signals / 中国医疗器械杂志

It is always very difficult to process the bioelectrical signals, sampling, amplifying and quantifying because of the different sources it comes from and the mechanism it depends on. This paper mainly introduces a method of measuring the peak value of bioelectrical signals, expatiates on the structure, testing result, analysis for error and measure taken for improvement of the circuit designed by this method. At last, the paper also points out that the method is wonderful, simple, easy to carry out, and can be used in many medical systems.