Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9-65 years / 中华预防医学杂志

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.

Therapeutic Effect of Modified Baitouweng Decoction Enema for Ulcerative Colitis with Damp Heat in Large Intestine and Its Influence on Levels of Inflammatory Factors / 广州中医药大学学报

Objective To investigate the therapeutic effect of enteral drip infusion with modified Baitouweng Decoction for the treatment of ulcerative colitis(UC) with damp heat in large intestine at active phase , and to observe its influence on serum levels of inflammatory factors. Methods Sixty patients suffering from mild to moderate UC with damp heat in the large intestine were randomly divided into treatment group and control group, 30 cases in each group. The treatment group was given enteral drip infusion with modified Baitouweng Decoction and the control group was given Mesalazine Enemas enema. The medication lasted for 8 continuous weeks. Before and after treatment, the scores of traditional Chinese medicine (TCM) syndromes and intestinal mucosal signs under enteroscopy, and serum levels of inflammatory factors were observed. Therapeutic effect on single TCM syndrome and clinical safety were also evaluated after treatment. Results After treatment, the scores of each TCM syndrome and intestinal mucosal signs under enteroscopy in the treatment group were much improved (P<0.05 compared with those in the control group); serum interleukin-8 (IL-8) and tumor necrosis factor beta (TNF-β) levels in both groups were decreased, serum IL-10 and IL-13 levels were increased (P <0.05 compared with those before treatment), and the effect in the treatment group was superior to that in the control group (P < 0.05). Except for the abdominal pain, the treatment group had better effect on relieving diarrhea, anal expansion, tenesmus, mucous stool and bloody purulent stool than the control group, the difference being statistically significant (P < 0.05). During the medication, no obvious adverse reaction was found in the treatment group, but 4 cases from the control group had anal burning sensation which had no effect on the mediciation. Conclusion Enteral drip infusion with modified Baitouweng Decoction can inhibit the release of proinflammatory cytokines, reduce the inflammatory response, and promote the healing of intestinal mucosa, which is effective for the treatment of UC with damp heat in large intestine at active phase.

Exogenous lipid pneumonia with hyperpyrexia: a case report / 北京大学学报(医学版)

Lipoid pneumonia (LP) is an uncommon form of pneumonia that is characterized by the presence of intra-alveolar lipid and lipid-laden macrophages on microscopy. It categorized as exogenous lipoid pneumonia (ExLP) and endogenous lipoid pneumonia (EnLP). Exogenous lipoid pneumonia caused by inhalation of liposuction substances (animal fat, vegetable oil, or mineral oil), mostly, in adult cases, they were medicines for constipation or rhinopharyngitis. Most of these patients showed mild clinical manifestations, and chronic medical condition. There were reports of lipoid pneumonia being successfully treated with corticosteroids, immunoglobulins and whole lung lavage. We report a case of exogenous lipoid pneumonia characterized by high fever and acute medical condition. A 77-year-old woman with hypertension and diabetes mellitus, accepted paraffin oil treatment for "incomplete intestinal obstruction", then, an accident of aspiration happened, as she went through the history of coughing while eating, followed by persistent hyperthermia and increases of white blood cells (WBC). Chest CT showed progressive ground-glass opacities, accompanied with fusion of consolidation, her sputum etiological examination was negative, and the therapy of broad-spectrum antibiotic was invalid. The patient was subjected to bronchofibroscopy with bronchoalveolar lavage (BAL). The bronchoalveolar lavage fluid (BALF) appeared colorless and transparent, and did not show a milky appearence. Total cell count of the BALF was 2.0×109 cell/mL, including 7.2% macrophages and 92.8% neutrophils. Cultures of the BALF were negative for bacterial, fungal, and mycobacterial pathogens. The BALF cytologic findings showed vacuolated lipid-laden macrophages (Oil Red O staining). These findings revealed exogenous lipoid pneumonia. There were reports of lipoid pneumonia being successfully treated with corticosteroids, immunoglobulins, and whole-lung lavage. So this patient was treated with methylprednisolone 120 mg/d for 3 days and 80 mg/d for 6 days, at the same time, immunoglobulins was given to infusion, but the daily peak temperature of the patients fluctuated between 38 and 39 degrees. Then, whole lung lavage was performed 28 days after admission. Unfortunately, acute pulmonary edema occurred during the operation, as the tracheal intubation problems, and 6 days later, the patient died at last. The clinical manifestations of exogenous lipid pneumonia vary greatly, from asymptomatic to life-threatening symptoms, and as febrile low fever is the main manifestation, but hyperthermia may also be the remarkable presentation.

Implementation of toxicologic pathology peer review based on the new edition of China Good Laboratory Practice / 国际药学研究杂志

The Chinese Food and Drug Administration issued the new Good Laboratory Practice(GLP)for nonclinical safety studies in September 2017,which emphasizes the peer review during the pathology practice.Pathology peer review could verify and im?prove the accuracy and quality of pathology diagnoses and interpretations in discussion.Pathology peer review is recommended when important risk assessment or business decisions are based on nonclinical studies.The objectives of this review are to provide a unified interpretation of the new regulation and recommend compliant processes for organizations to implement.

Recent Advances of Researches on Expression, Function and Regulation of CD22 / 中国实验血液学杂志

CD22 is a type I transmembrane protein expressed on most mature B lymphocyte, and plays a significant role in signal transduction pathways. CD22 acts as a co-receptor of the B-cell receptor (BCR) that inhibits the BCR signaling by antigen-receptor interaction. The phosphorylation of CD22 can be triggered by cross-linking of CD22 with the BCR through antigen, then predominantly triggers the dephosphorylation and inactivation of downstream proteins and inhibit the BCR signaling. Autoimmune disease could be caused by the abnormal expression or dysfunction of CD22 which interrupts BCR signaling and then influences the quantity and function of B cells. The further study of the function and regulation of CD22 would help us understanding the pathogenesis of autoimmune disease and setting theoretical basis for its targeting treatment. In this article, the structure and expression of CD22, the ligands of CD22, the regulation of BCR and transmenbrane signaling, the effect of CD22 on B cells, and CD22 and autoimmune diseases were reviewed.

Mutations in UGT1A1 gene in neonates with hyperbilirubinemia of Guangxi Heiyi Zhuang nationality / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the distribution of mutations of UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and its relationship with hyperbilirubinemia among neonates with hyperbilirubinemia of Guangxi Heiyi Zhuang nationality.</p><p><b>METHODS</b>Total genomic DNA was extracted from the blood of 100 neonates with hyperbilirubinemia (case group) and 100 neonates without hyperbilirubinemia (control group), all of whom were selected from Guangxi Heiyi Zhuang population. TATA box and all exons of UGT1A1 gene were amplified by PCR and directly sequenced.</p><p><b>RESULTS</b>(TA)7 insertion mutation in TATA box, G71R missense mutation in exon 1, and 4 single nucleotide polymorphisms (SNPs) (rs199539868, rs114982090, rs1042640 and rs8330) in exon 5 were observed. The allele frequency of G71R mutation in the case group was significantly higher than that in the control group (P<0.01). There were no significant differences in the genotype distribution and allele frequency of TATA box mutation and SNPs (rs1042640 and rs8330) between the two groups (P>0.05). The logistic regression analysis showed that the odds ratios (95% confidence intervals) of UGT1A1 TATA box mutation, G71R mutation, and SNPs (rs1042640 and rs8330) associated with the development of neonatal hyperbilirubinemia were 0.846 (0.440, 1.629), 3.932 (1.745, 8.858), 0.899 (0.364, 2.222), respectively.</p><p><b>CONCLUSIONS</b>(TA)7 insertion mutation and G71R missense mutation of UGT1A1 gene are common mutation types in neonates with hyperbilirubinemia of Guangxi Heiyi Zhuang nationality. Four SNPs (rs199539868, rs114982090, rs1042640, and rs8330) was first reported in China. UGT1A1 G71R missense mutation is a risk factor for hyperbilirubinemia in neonates of Guangxi Heiyi Zhuang nationality.</p>

The correlation of cytomegalovirus gB genotype with viral DNA load and treatment time in patients with CMV infection after hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of CMV gB genotypes on viral load and treatment time in patients with CMV infection after hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>Viral load was detected by real-time (RT) quantitative polymerase chain reaction (PCR) (Q-PCR), CMV gB genotypes by PCR restriction fragment length polymorphism (RFLP) (PCR-RFLP) in 115 patients with CMV infection (CMV-DNA positive) after HSCT during July 2004 and May 2010.</p><p><b>RESULTS</b>(1) The distribution of CMV gB genotypes in HSCT recipients were as following: gB1, 42/115 (36.52%); gB2, 3/115 (2.61%); gB3, 43/115 (37.39%); gB4, 2/115 (1.74%). 20 patients (17.39%) had a combination of 2 different CMV genotypes and 5 patients (4.35%) had a CMV variant that lacked an RsaI digestion site, herein named gB5. (2) The median viral load were 2.7×10(3)(1.81×10(3) ∼ 6.03×10(4)) in gB1, 4.0×10(3) (1.32×10(3) ∼ 6.39×10(4)) in gB3 and 1.2×10(4)(2.28×10(3) ∼ 6.50×10(5)) in mixed gB. There was no statistical difference in viral load between gB1 and gB3 (P > 0.050). There was significantly statistical difference in viral load between single-gB (gB1 or gB3) and mixed-gB (P < 0.05). (3) The median treatment time was 17 days in mixed-gB and 14 days in single-gB. There was significantly statistical difference between two groups (P < 0.05). Conclusion gB genotype may have an impact on CMV DNA load and treatment time in HSCT recipients with CMV infection.</p>

Effects of penehyclidine hydrochloride on apoptosis of lung tissues in rats with traumatic acute lung injury / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effects of penehyclidine hydrochloride on apoptosis of lung tissue cells and its mechanism in acute lung injury following blunt chest trauma in rats.</p><p><b>METHODS</b>Sprague Dawley (SD) rats (n equal to 54) weighing (250+/-5) g were divided equally and randomly into three groups: normal control group (C group, n equal to 18), trauma model group (T group, n equal to 18) and penehyclidine hydrochloride treatment group (P group, n equal to 18). Each group was further divided into three subgroups according to the time points of 3, 12 and 24 hours after experiment (at each time point, n equal to 6 for each subgroup). Rats of P group were intraperitoneally injected with penehyclidine hydrochloride for 2 mg/kg immediately after blunt chest trauma and rats in its 24 hours subgroup were once again injected with penehyclidine hydrochloride in the same dose 12 hours after injury. Lung tissue samples were collected at every time point and cell apoptosis in lung tissues were measured by TUNEL. Apoptotic index (AI) was calculated, expressions of bax and bcl-2 were detected by immunohistochemical staining of SABC, and lung tissue sections were taken for light and electron microscopic observation.</p><p><b>RESULTS</b>As compared with C group, at every time point, AI and expressions of bax and bcl-2 in T group were higher (P less than 0.05), and the ratio of bcl-2/bax markedly decreased (P less than 0.05), especially in the 24 hours subgroup. The ratio in T group (0.468+/-0.007) was lower than that in C group (1.382+/-0.058, t equal to 12.5, P less than 0.01). Lung tissue injuries were significant under a light microscope, and the number of apoptotic cells increased obviously under a transmission electron microscope. As compared with T group at the same phase, AI and expression of bax decreased in P group (P less than 0.05 and P less than 0.01), while the expression of bcl-2 increased significantly (P less than 0.01), and the ratio of bcl-2/bax markedly increased (P less than 0.05), especially in the 24 hours subgroup. The ratio in P group (1.012+/-0.070) was much higher than that in T group (0.468+/-0.007, t equal to 8.3, P less than 0.01). The injury of lung tissues was relieved, and apoptosis of cells decreased obviously under a transmission electron microscopic observation.</p><p><b>CONCLUSIONS</b>Apoptosis and expressions of bax and bcl-2 in lung tissues might be involved in the pathogenesis of lung injury induced by blunt chest trauma. Penehyclidine hydrochloride can alleviate lung injuries by inhibiting apoptosis of lung tissue cells, during which effects of penehyclidine hydrochloride on regulating expressions of bax and bcl-2 may play an important role.</p>

The preparation of series of the controllable degradation coral-hydroxyapatite (SCHA-200R) and the on its application as the scaffold in bone tissue-engineering / 中华整形外科杂志

<p><b>OBJECTIVE</b>Fabricate series of the controllable degradation coral-hydroxyapatite.</p><p><b>METHODS</b>The natural coral undergo a chemical reaction with (NH4)2 HPO4 at high temperature and pressure for different time-lengths. After getting the products, the components and the special structures were analyzed. Observe the biologic degradation of the reaction products and analyze the metal elements and their contents. Haemolysis tests, cytotoxity tests and bone compatibility tests were performed to assess the biocompatibility of the products.</p><p><b>RESULTS</b>When hydrothermal reactions happened under different conditions, the different gradients of CaCO3/hydroxyapatite materials were produced. These types of materials kept the characteristic of interconnected micro-porous network structures. A thin layer of compact material can be seen on the surface of its trabecula ultra-micro structure. The SCHA-200R has a good biocompatibility.</p><p><b>CONCLUSIONS</b>Gradient HA (SCHA-200R) materials can be formed by adjusting the same temperature, same pressure and different time-length of the reaction. This kind of gradient material keeps the quality of micro-porous network structures. The SCHA-200R is a potential candidate scaffold for bone tissue engineering.</p>

Relationship between aging and the number and function of bone marrow-derived endothelial progenitor cells in rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between aging and the number and function of bone marrow-derived endothelial progenitor cells (EPC) in rats.</p><p><b>METHODS</b>The number and function of bone marrow-derived EPC were measured in 4, 10 and 18 months old rats (n = 10 in each group). Mononuclear cells (MNC) were isolated from rat bone marrow by Ficoll density gradient centrifugation and cultured for 7 days, EPC were identified as adherent cells double positive stained for FITC-UEA-I and DiI-acLDL under laser confocal immunofluence microscopy. Boyden chamber was used to determine the migration capacity of EPC and the number of recultured EPC was counted to test the adherent function of EPC.</p><p><b>RESULT</b>The number (42.0 +/- 5.8 vs 30.8 +/- 4.7 vs 21.5 +/- 4.7 per field) and the migration and adhesion capacities of EPC were significantly reduced with aging.</p><p><b>CONCLUSION</b>This study shows that the number and function of EPC are decreased with aging.</p>

Beneficial effects of probucol on endothelial function in patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>The study investigate the antioxidant probucol on endothelial function in patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>A total of 49 ACS patients randomly received standard therapy plus probucol (P, n = 24) or standard therapy (C, n = 25). Plasma oxidized low-density lipoprotein (ox-LDL), nitric oxide (NO) and circulating endothelial cells (CEC) were measured. The brachial arterial hyperemia-induced flow mediated dilation (FMD) and sublingual nitroglycerin (NTG) mediated vasodilatations were measured by high resolution ultrasound. These variables were analyzed before and after 3 months therapy.</p><p><b>RESULTS</b>Plasma NO and FMD was significantly increased after 3 months therapy than before therapy [(80.46 +/- 10.24) micromol/Lvs (48.46 +/- 12.24) micromol/L, P < 0.01; (13.46 +/- 1.20)% vs (7.45 +/- 1.02)%, P < 0.05, respectively], while the number of CEC and ox-LDL were significantly decreased (P < 0.01) in P group. These values were similar before and after 3 months in C group. The linear correlation analysis showed that plasma ox-LDL negatively correlated with NO (r = -0.574, P < 0.01) and FMD (r = -0.517, P < 0.01) and positively correlated with CEC (r = 0.385, P < 0.01) in patients received 3 months probucol therapy.</p><p><b>CONCLUSIONS</b>Chronic antioxidant probucol therapy could improve endothelial function in patients with ACS.</p>

The role of cyclooxygenase on angiogenesis and endothelial progenitor cell mobilization in rat ischemic myocardium / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of COX1 and COX2 on angiogenesis and endothelial progenitor cell mobilization in rats with experimental myocardial infarction (MI).</p><p><b>METHODS</b>The rats were randomly divided into 3 groups: MI group, MI plus rofecoxib group and MI plus valeryl salicylate group. At the 7th day after operation, circulating EPCs, plasma VEGF and HIF-1alpha mRNA of ischemic myocardium were measured. At the 28th day post operation, capillary densities were also measured in ischemic myocardium.</p><p><b>RESULT</b>Compared with the MI group and the MI plus valeryl salicylate group, circulating EPCs, plasma VEGF, HIF-1alpha mRNA and capillary densities of ischemic myocardium were all decreased in MI plus rofecoxib group.</p><p><b>CONCLUSION</b>The present study revealed that COX2 play an important role with angiogenesis and endothelial progenitor cell mobilization in rat with experimental MI by modulating expression of VEGF and HIF-1alpha.</p>

Effects of paclitaxel combined with bone marrow stromal stem cells implantation on vascular endothelial repair and smooth muscle cells growth in vitro / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of paclitaxel combined with bone marrow stromal stem cells (MSCs) implantation on inhibiting the smooth muscle cells (SMCs) growth and promoting endothelial repair by developing an endothelial repair model in vitro.</p><p><b>METHODS</b>In a cell coculture system, rabbit endothelial cells (ECs) and human MSCs were seeded in the lower chamber and rabbit SMCs were seeded in the upper chamber. 3H-TdR incorporation and PCNA protein expression were used to evaluate SMCs proliferation at the 10th day after paclitaxel application (1, 10, 100 nmol/L; 20 min). Fluorescence immunocytochemistry was employed to observe the Flk-1 and vWF protein expression on MSCs.</p><p><b>RESULTS</b>The SMCs 3H-TdR incorporation of the MSCs implant group was significantly lower than that of the proliferative ECs group (1 nmol/L: 12 265 +/- 991 vs. 14 505 +/- 1013 cpm/well; 10 nmol/L: 8401 +/- 783 vs. 10 511 +/- 934 cpm/well; 100 nmol/L: 5880 +/- 569 vs. 7457 +/- 768 cpm/well, n = 6, P < 0.05), but higher than that of the confluent ECs group (1 nmol/L: 12 265 +/- 991 vs. 8671 +/- 642 cpm/well; 10 nmol/L: 8401 +/- 783 vs. 6175 +/- 743 cpm/well; 100 nmol/L: 5880 +/- 569 vs. 4423 +/- 406 cpm/well, n = 6, P < 0.05). The expression of SMCs PCNA protein in MSCs implant group was lower than that of the proliferative ECs group (1 nmol/L: 0.92 +/- 0.06 vs. 1.15 +/- 0.07; 10 nmol/L: 0.97 +/- 0.07 vs. 1.07 +/- 0.08; 100 nmol/L: 0.91 +/- 0.05 vs. 1.18 +/- 0.11, n = 6, P < 0.05), but higher than that of the confluent ECs group (1 nmol/L: 0.92 +/- 0.06 vs. 0.74 +/- 0.07; 10 nmol/L: 0.97 +/- 0.07 vs. 0.78 +/- 0.06; 100 nmol/L: 0.91 +/- 0.05 vs. 0.71 +/- 0.05, n = 6, P < 0.05). The MSCs did not express vWF or Flk-1 protein before coculture. Although none cell expressed vWF, some of the MSCs began to express Flk-1 protein after cocultured with mature ECs for 10 days.</p><p><b>CONCLUSION</b>MSCs implantation can partly inhibit the delayed SMCs proliferation. The MSCs cocultured with paclitaxel-treated mature ECs have the ability to differentiate into ECs.</p>

Effects of endothelial cell growth states on the proliferation and migration of vascular smooth muscle cells in vitro / 生理学报

Endothelial injury, smooth muscle cells (SMCs) proliferation and migration are the same common pathophysiological processes of many cardiovascular diseases, such as atherosclerosis, hypertension, diabetes and restenosis. It is important to determine the functional interactions between endothelial cells (ECs) and SMCs under pathologic conditions. This work was to study the effects of ECs growth states on the proliferation and migration of vascular SMCs in cell coculture system. (3)H-TdR incorporation and flow cytometry were used to determine the effects of ECs growth states on the proliferation of SMCs. The number of migrating SMCs was counted. RT-PCR was used to analyze the expression of alpha-SM-actin mRNA. The results showed that (3)H-TdR incorporation decreased significantly from 14,900+/-1035 cpm/well in the control group to 8,575+/-749 cpm/well in the confluent ECs group (n=6, P<0.01), and increased to 27,268+/-2310 cpm/well in the proliferative ECs group ( n=6, P<0.01). The transition of SMCs from G(0)/G(1) phase to G(2)/M and S phases was blocked in the confluent ECs group but promoted in the proliferative ECs group. Compared with the control group, the number of migrating cells was about 4 times higher in the proliferative ECs group (n=6, P<0.01), while it in the confluent ECs group was only the half of the number of the control(n=6, P<0.05). The expression of alpha-SM-actin mRNA was increased significantly in the confluent ECs group(2.3+/-0.11 vs 1.4+/-0.12, P<0.05), but decreased significantly in the proliferative ECs group(0.92+/-0.08 vs 1.4+/-0.12, P<0.05). The results suggest that the biologic features of SMCs are influenced by ECs growth states. The proliferative ECs promote SMCs proliferation, migration and downregulate alpha-SM-actin mRNA expression significantly.