膦甲酸钠抗乙型肝炎病毒近期疗效观察

为观察磷甲酸钠抗乙型肝炎病毒（HBV）的近期疗效，将67例慢性乙型肝炎患者随机分为2组：治疗组47例，在常规保什治疗的基础上加用膦用甲酸钠；对照组20例，仅用常规保肝药物治疗。治疗前后观察患者功能、血清HBVDNA含量、乙肝病毒免疫学标志等的变化。结果显示，治疗2周后，治疗组肝功能均有恢复；47例患者中42例HBVDNA水平下降，以第1周明显，第2周时10例反跳；13例HBVDNA转阴，其中5例在用药1周后即转阴。30例HBeAg阳性患者中，2例出现血清转换，1例转为弱阳性。提示磷甲酸钠具有明显和快速的抑制乙肝病毒复制、降低病毒量的作用，可作为抗病毒序贯疗法的首程用药或联合用药的选择之一。     

人半月板纤维软骨细胞培养及生物学特性研究

为探索分离培养人半月板纤维软骨细胞的简便实用方法，采用胰蛋白酶和胶原酶联合消化的方法，简便快速地获得大量成活率高的人半月板纤维软骨细胞，在F－12培养液中进行原代和传代培养，并对传代培养纤维软骨细胞进行了免疫组化鉴定，光镜及超微结构的观察，结果显示，光镜下，原代培养细胞呈线形，单层排列，电镜可见细胞内有丰富的粗面内质网及线粒体，细胞呈多极性，表面有突起，纤维软骨细胞免疫组化Ⅱ型胶原染色阳性，提示本实验建立的人纤维软骨细胞分离培养方法是一种可行的方法。，     

利福平药动学对药物性肝损害的影响研究

目的：本文通过对利福平导致药物性肝损害机理的研究，寻找治疗结核病而不致造成药物性肝损-害的合理给药方案。方法：采用药动学和免疫学对利福平导致药物性肝损害机理进行研究。结果与结论：药物性肝损害可能是由于利福平代谢物引起，减少用量，提高血药浓度，减少代谢物形成是预防药物肝损害的有效途径。     

MK2 plays an important role for the increased vascular permeability that follows thermal injury

We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase > p38 > MK2 > HSP27.     

Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis

Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate‐limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT‐mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self‐renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration.     

FOXP3在激素受体阳性乳腺癌中的表达及其对MCF-7细胞侵袭和迁移的影响

目的 探讨转录因子FOXP3在激素受体阳性乳腺癌组织中的表达及其对MCF-7细胞侵袭和迁移的影响.方法 收集2010年9月-2011年10月河北医科大学第四医院乳腺中心收治的66例激素受体阳性乳腺癌患者的石蜡标本,采用免疫组化检测组织中FOXP3的表达情况,分析FOXP3表达与临床病理特征的关系;采用Kaplan-Me...     

氢吗啡酮自控镇痛应用于子宫肌瘤动脉栓塞术的有效性和安全性

目的 评价氢吗啡酮经静脉患者自控镇痛泵应用于子宫肌瘤动脉栓塞术（UAE）围手术期镇痛的有效性和安全性。方法 选取2021年6月至12月在郑州大学第一附属医院接受UAE术治疗的27例子宫肌瘤患者。将氢吗啡酮10 mg+0.9%氯化钠溶液配至100 mL镇痛泵中,术前15 min开始挂泵给药,术中根据患者疼痛情况调整用药剂量。采用疼痛数字评价量表（NRS）评估患者栓塞即刻、栓塞后5 min、手术结束时及术后6、12、24、48、72 h疼痛情况,并观察不良反应发生情况。结果 栓塞即刻、栓塞后5 min、手术结束时,术后6、12、24、48、72 h疼痛控制良好,中位住院时间为5 d,患者对镇痛治疗结果满意。术后简明疼痛评估量表（BPI）评分除“对行走能力的影响”与术前比较差异无统计学意义（P=0.861）外,其他生活质量评价项差异有统计学意义（均P<0.05）。5例（18.52%）发生不良反应,未发生呼吸抑制等严重不良反应。结论 子宫肌瘤动脉栓塞术中氢吗啡酮自控镇痛泵应用安全有效,可显著减轻患者疼痛并缩短住院时间。自控泵操作简便,不良反应发生率低,有一定的推广价值。     

Thirteen Chinese patients with sporadic Paget’s disease of bone: clinical features, SQSTM1 mutation identification, and functional analysis

To increase awareness of the rarity of Paget's disease of bone (PDB) in the Chinese population, we characterized the clinical manifestations and features of 13 Chinese sporadic PDB patients. The clinical features of our Chinese PDB patients show similarities with cases reported in Western countries. The most common lesion sites were the pelvis, femur, and tibia; the next most common lesion sites were the spine and skull. Most patients had a higher serum alkaline phosphatase (ALP) level. Treatment with bisphosphonates was effective. In addition, we screened for PDB-causing mutations and performed a functional analysis in an attempt to elucidate the molecular pathogenesis of PDB. A total of 216 persons, including 13 sporadic PDB patients, three unaffected relatives of 1 patient, and 200 healthy donors, were recruited. All eight exons and exon-intron boundaries of the SQSTM1 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. We identified a 53-year-old man who harbored a heterozygous T-to-C transversion at position 1250 in exon 8 (1250T?>?C), which resulted in a methionine-to-threonine (ATG?>?ACG) substitution at codon 404 (M404T). The M404T mutant SQSTM1 protein exhibited increased NF-κB activation and drove a significantly increased number of osteoclast-like cells (OLCs) that formed in response to RANKL and an increased number of OLC nuclei. This is the first report of an SQSTM1 genetic mutation that contributes to the pathogenesis of PDB in Chinese patients. These results may partially explain the mechanism by which this SQSTM1 mutation contributes to the pathogenesis of sporadic PDB in Chinese patients.     

Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy

Inflammation contributes to the tubulointerstitial lesions of diabetic nephropathy. Toll-like receptors (TLRs) modulate immune responses and inflammatory diseases, but their role in diabetic nephropathy is not well understood. In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. We observed similar effects using a TLR4-neutralizing antibody. Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. Taken together, these data suggest that a TLR4-mediated pathway may promote tubulointerstitial inflammation in diabetic nephropathy.     

Application of humanistic care to the reengineering of nursing process at maternity hospital

目的 从流程管理入手,探讨保证护理服务与人文关怀有机融合的有效途径.方法 依据卓越护理流程设计的原则、华生人文关怀理论、患者需求、患者权利,对所有直接服务于患者的护理项目中的人文关怀措施进行个性化设计,对设计后的流程试运行3个月,并在实施过程中不断征求患者的意见,定稿后进行培训和执行.结果 流程再造实施后患者对护理服务11项指标评价及舒适达标、护理质量、安全评价显著优于实施前(均P＜0.01).结论 将人文关怀融入各项护理流程再造中,有利于提高护理服务质量和患者满意度.