2012～2017年我州土家族及汉族患者药品不良反应分析

摘 要 目的：探讨恩施地区药品不良反应发生特点及土家族与汉族发生抗菌药物不良反应（ADR）的差异。方法：选取2012年1月～2017年7月恩施地区上报的ADR报告,从患者一般情况、ADR严重程度及发生时间、β 内酰胺类ADR、给药途径及ADR转归等方面,比较土家族及汉族患者发生的ADR的差异。结果：土家族与汉族患者发生的ADR,在β 内酰胺类尤其是头孢菌素类药物所致ADR分布、口服与静脉滴注用药分布,以及ADR转归情况等方面的差异有统计学意义（P<0.01）。两者发生ADR严重程度无差异（P﹥0.05）。结论：ADR的发生存在种族差异,少数民族地区在使用抗菌药物及给药途径方面应关注民族差异,减少ADR发生。     

Participating in an exercise group after anterior cruciate ligament reconstruction (ACLR) is perceived to influence psychosocial factors and successful recovery: a focus group qualitative study

ObjectivesTo explore the patients’ experiences of participating in an exercise group following anterior cruciate ligament reconstruction (ACLR).DesignHermaneutic phenomenological qualitative study of two focus groups.SettingOutpatient care, private rehabilitation centre.ParticipantsNine adults who had participated in an exercise group led by a physiotherapist following ACLR.ResultsThree major themes emerged from the data: psychosocial factors, physical outcomes and identity of the exercise group. The most significant perception of engaging in an exercise group following ACLR was its influence on psychosocial factors, especially motivation, self-confidence and social support. The group influenced the participants’ motivation, enjoyment and commitment to exercise during their rehabilitation. Social support, self-confidence and reassurance were mostly gained. The participants taking part in sport experienced the ACLR group as a substitute for sport trainings. The group was perceived to help enhance speed of recovery and facilitate the return to normal life, especially for participants with lower reported motivation and adherence to home-exercises. The authors interpreted that the subjective physical outcomes’ improvements described by all the participants was potentially an increased level of self-efficacy.The challenging role of the physiotherapist was highlighted as well as the promotion of shared accountability between patients and the group’s leader. The exercise group’s identity was questioned within the rehabilitation process, and the need for more knowledge of its existence in order to promote exercise group therapy was suggested.ConclusionParticipating in an exercise group therapy influences psychosocial factors such as motivation, self-confidence, social support, potentially self-efficacy and helps enhance a faster successful recovery following ACLR. Our findings indicate that participants with a lower reported adherence to home-exercises may especially benefit from it.     

兰州市城关区HIV新发感染调查分析

目的了解甘肃省兰州市城关区艾滋病疫情特征和流行趋势,为卫生行政部门制定艾滋病防治措施和疫情监测管理策略提供依据。方法用Excel软件统计分析2009─2013年城关区网络直报的艾滋病病毒（HIV）新发感染病例。结果 2009─2013年城关区报告新发病例468例,发病率4.40/10万,2009─2011年发病稳中有降,但2011─2013年呈现出逐年增长的趋势;感染人群以性活跃期的青壮年为主,16-45岁占82.26%,男女性别比6.67∶1;传播途径以性接触为主,占92.31%;职业分布前三位依次是家务及待业（19.44%）、农民（15.60%）、其他（13.68%）。结论农民工、妇女等易感人群面临感染HIV的威胁,应大力推广覆盖人群面广的社区艾滋病干预模式;制定符合本地区现状的防治策略和措施,提高干预工作效率,遏制艾滋病进一步蔓延。     

Recombinant adenoviral vector expressing HCV NS4 induces protective immune responses in a mouse model of Vaccinia-HCV virus infection: A dose and route conundrum

Hepatitis C virus (HCV) leads to chronic infection in the majority of infected patients presumably due to failure or inefficiency of the immune responses generated. Both antibody and cellular immune responses have been suggested to be important in viral clearance. Non-replicative adenoviral vectors expressing antigens of interest are considered as attractive vaccine vectors for a number of pathogens. In this study, we sought to evaluate cellular and humoral immune responses against HCV NS4 protein using recombinant adenovirus as a vaccine vector expressing NS4 antigen. We have also measured the effect of antigen doses and routes of immunization on the quality and extent of the immune responses, especially their role in viral load reduction, in a recombinant Vaccinia-HCV (Vac-HCV) infection mouse model. Our results show that an optimum dose of adenovirus vector (2 × 10⁷ pfu/mouse) administered intramuscularly (i.m.) induces high T cell proliferation, granzyme B-expressing CD8⁺ T cells, pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-2 and IL-6, and antibody responses that can significantly reduce the Vac-HCV viral load in the ovaries of female C57BL/6 mice. Our results demonstrate that recombinant adenovirus vector can induce both humoral and cellular protective immunity against HCV-NS4 antigen, and that immunity is intricately controlled by route and dose of immunizing vector.     

Biocompatibility of silk-tropoelastin protein polymers

Blended polymers are used extensively in many critical medical conditions as components of permanently implanted devices. Hybrid protein polymers containing recombinant human tropoelastin and silk fibroin have favorable characteristics as implantable scaffolds in terms of mechanical and biological properties. A firefly luciferase transgenic mouse model was used to monitor real-time IL-1β production localized to the site of biomaterial implantation, to observe the acute immune response (up to 5 days) to these materials. Significantly reduced levels of IL-1β were observed in silk/tropoelastin implants compared to control silk only implants at 1, 2 and 3 days post-surgery. Subsequently, mice (n = 9) were euthanized at 10 days (10D) and 3 weeks (3W) post-surgery to assess inflammatory cell infiltration and collagen deposition, using histopathology and immunohistochemistry. Compared to control silk only implants, fewer total inflammatory cells were found in silk/tropoelastin (∼29% at 10D and ∼47% at 3W). Also fewer ingrowth cells (∼42% at 10D and ∼63% at 3W) were observed within the silk/tropoelastin implants compared to silk only. Lower IL-6 (∼52%) and MMP-2 (∼84%) (pro-inflammatory) were also detected for silk/tropoelastin at 10 days. After 3 weeks implantation, reduced neovascularization (vWF ∼43%), fewer proliferating cells (Ki67 ∼58% and PCNA ∼41%), macrophages (F4/80 ∼64%), lower IL-10 (∼47%) and MMP-9 (∼55%) were also observed in silk/tropoelastin materials compared to silk only. Together, these results suggest that incorporation of tropoelastin improves on the established biocompatibility of silk fibroin, uniquely measured here as a reduced foreign body inflammatory response.     

Therapeutic efficacy of antibiotic-loaded gelatin microsphere/silk fibroin scaffolds in infected full-thickness burns

Despite advances in burn treatment, burn infection remains a major cause of morbidity and mortality. In this study, an antibacterial silk fibroin (SF) scaffold for burn treatment was designed; gelatin microspheres (GMs) were impregnated with the antibiotic gentamycin sulfate (GS), and the GS-impregnated GMs were then embedded in a SF matrix to fabricate GS/GM/SF scaffolds. The developed GS/GM/SF scaffolds could serve as a dermal regeneration template in full-thickness burns. The average pore size and porosity of the GS/GM/SF scaffolds were 40–80 μm and 85%, respectively. Furthermore, the drug release rate of the scaffolds was significantly slower than that of either GS/GM or GS/SF scaffolds. And the composite scaffold exhibited stronger antimicrobial activities against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Hence, we evaluated the wound-healing effects and antibacterial properties of the GS/GM/SF scaffolds in a rat full-thickness burn infection model. Over 21 days, the GS/GM/SF scaffolds not only significantly reduced burn infection by P. aeruginosa but also accelerated the regeneration of the dermis and exhibited higher epithelialization rates than did GS/SF and SF scaffolds. Thus, GS/GM/SF scaffolds are potentially effective for treatment of full-thickness infected burns, and GS/GM/SF scaffolds are a promising therapeutic tool for severely burned patients.     

Woven silk fabric-reinforced silk nanofibrous scaffolds for regenerating load-bearing soft tissues

Although three-dimensional (3-D) porous regenerated silk scaffolds with outstanding biocompatibility, biodegradability and low inflammatory reactions have promising application in different tissue regeneration, the mechanical properties of regenerated scaffolds, especially suture retention strength, must be further improved to satisfy the requirements of clinical applications. This study presents woven silk fabric-reinforced silk nanofibrous scaffolds aimed at dermal tissue engineering. To improve the mechanical properties, silk scaffolds prepared by lyophilization were reinforced with degummed woven silk fabrics. The ultimate tensile strength, elongation at break and suture retention strength of the scaffolds were significantly improved, providing suitable mechanical properties strong enough for clinical applications. The stiffness and degradation behaviors were then further regulated by different after-treatment processes, making the scaffolds more suitable for dermal tissue regeneration. The in vitro cell culture results indicated that these scaffolds maintained their excellent biocompatibility after being reinforced with woven silk fabrics. Without sacrifice of porous structure and biocompatibility, the fabric-reinforced scaffolds with better mechanical properties could facilitate future clinical applications of silk as matrices in skin repair.     

Effects of clodronate and alendronate on osteoclast and osteoblast co-cultures on silk–hydroxyapatite films

The goal of this study was to explore the effects of osteoporosis-related therapeutics on bone remodeling in vitro. A previously established bone-tissue mimetic system consisting of silk protein biomaterials in combination with hydroxyapatite and human cells was used for the study. Silk–hydroxyapatite films were pre-complexed with the non-nitrogenous bisphosphonate clodronate or the nitrogenous bisphosphonate alendronate and cultured with THP-1 human acute monocytic leukemia cell line-derived osteoclasts, human mesenchymal stem cell derived osteoblasts or a direct co-culture of the two cell types. Metabolic activity, calcium deposition and alkaline phosphatase activity were assessed over 12 weeks, and reconstructed remodeled biomaterial surfaces were also evaluated for quantitative morphological changes. Increased metabolic activity and increased roughness were found on the clodronate-complexed biomaterial substrates remodeled by osteoblasts and co-cultures of osteoblasts with osteoclasts, even at doses high enough to cause a 90% decrease in osteoclast metabolic activity. Films complexed with low doses of alendronate resulted in increased metabolic activity and calcium deposition by osteoblasts, while higher doses were similarly toxic among osteoclasts, osteoblasts and co-cultures. These results point to the utility of these well-defined bone-mimetic in vitro cultures as useful screens for therapeutics for bone-related diseases, particularly with the ability to conduct studies for extended duration (here for 12 weeks) and with pre-complexed drugs to mimic conditions found in vivo.     

Genetically engineered silk–collagen-like copolymer for biomedical applications: Production,characterization and evaluation of cellular response

Genetically engineered protein polymers (GEPP) are a class of multifunctional materials with precisely controlled molecular structure and property profile. Representing a promising alternative for currently used materials in biomedical applications, GEPP offer multiple benefits over natural and chemically synthesized polymers. However, producing them in sufficient quantities for preclinical research remains challenging. Here, we present results from an in vitro cellular response study of a recombinant protein polymer that is soluble at low pH but self-organizes into supramolecular fibers and physical hydrogels at neutral pH. It has a triblock structure denoted as C₂S^H₄₈C₂, which consists of hydrophilic collagen-inspired and histidine-rich silk-inspired blocks. The protein was successfully produced by the yeast Pichia pastoris in laboratory-scale bioreactors, and it was purified by selective precipitation. This efficient and inexpensive production method provided material of sufficient quantities, purity and sterility for cell culture study. Rheology and erosion studies showed that it forms hydrogels exhibiting long-term stability, self-healing behavior and tunable mechanical properties. Primary rat bone marrow cells cultured in direct contact with these hydrogels remained fully viable; however, proliferation and mineralization were relatively low compared to collagen hydrogel controls, probably because of the absence of cell-adhesive motifs. As biofunctional factors can be readily incorporated to improve material performance, our approach provides a promising route towards biomedical applications.     

Characterization of dielectrophoresis-aligned nanofibrous silk fibroin–chitosan scaffold and its interactions with endothelial cells for tissue engineering applications

Aligned three-dimensional nanofibrous silk fibroin–chitosan (eSFCS) scaffolds were fabricated using dielectrophoresis (DEP) by investigating the effects of alternating current frequency, the presence of ions, the SF:CS ratio and the post-DEP freezing temperature. Scaffolds were characterized with polarized light microscopy to analyze SF polymer chain alignment, atomic force microscopy (AFM) to measure the apparent elastic modulus, and scanning electron microscopy and AFM to analyze scaffold topography. The interaction of human umbilical vein endothelial cells (HUVECs) with eSFCS scaffolds was assessed using immunostaining to assess cell patterning and AFM to measure the apparent elastic modulus of the cells. The eSFCS (50:50) samples prepared at 10 MHz with NaCl had the highest percentage of aligned area as compared to other conditions. As DEP frequency increased from 100 kHz to 10 MHz, fibril sizes decreased significantly. eSFCS (50:50) scaffolds fabricated at 10 MHz in the presence of 5 mM NaCl had a fibril size of 77.96 ± 4.69 nm and an apparent elastic modulus of 39.9 ± 22.4 kPa. HUVECs on eSFCS scaffolds formed aligned and branched capillary-like vascular structures. The elastic modulus of HUVEC cultured on eSFCS was 6.36 ± 2.37 kPa. DEP is a potential tool for fabrication of SFCS scaffolds with aligned nanofibrous structures that can guide vasculature in tissue engineering and repair.