骨碎补治疗骨质疏松症的实验研究进展

骨碎补作为补肾强骨、活血化瘀类的代表中药,被广泛应用于临床,尤其是在治疗骨质疏松症方面具有重要作用。关于骨碎补的基础研究已成为近年来的研究热点。众多学者从细胞生物学和分子生物学的方向出发,研究骨碎补对间充质干细胞、成骨细胞和破骨细胞分化水平的调节能力,并在信号传导通路方面探讨骨碎补通过BMP-Smads信号通路、OPG/RANKL/RANK信号通路、雌激素信号通路等对机体骨代谢水平的调控机制。大量的实验研究从不同层面论证了骨碎补在调节骨代谢平衡、改善骨质疏松方面的作用。虽然骨碎补在临床治疗与实验中被广泛研究,但是其对于细胞的机制研究及信号通路研究仍待总结,尤其是对于激活还是抑制Notch信号通路来发挥作用尚需进一步深入探究。     

骨碎补总黄酮的实验及临床研究概况

骨碎补总黄酮作为从中药骨碎补中提取的有效成分,被广泛应用于实验及临床研究。特别是在骨质疏松方面的研究尤为突出,从分子通路,如BMP-Smads信号通路、Wnt/β-catenin通路、MAPK信号通路、CTSK信号通路及OPG/RANKL/RANK信号通路等,到体内雌激素水平、体外细胞、骨组织及临床研究等,从不同的层面论证了骨碎补总黄酮抗骨质疏松的作用。骨碎补总黄酮还可以治疗骨折、骨缺损、膝骨关节炎、类风湿关节炎、股骨头坏死、骨牵张技术等。骨碎补总黄酮在治疗各种不同骨科疾病时,可通过相同的分子蛋白通路发挥作用,从微观角度体现了中医异病同治的治疗特点。虽然骨碎补总黄酮在基础研究及临床治疗方面应用广泛,但是其作用机理仍有待探究,不同分子通路之间的相互作用需要进一步明确。另外,骨碎补总黄酮仍然属于混合成分,其中柚皮苷的作用较为突出,但是并不能完全代替骨碎补总黄酮的作用,需要进一步分离提取,更精准地找到治疗不同骨科疾病不同靶点的有效成分。     

骨碎补防治骨质疏松症的研究进展

随着我国人口老龄化,骨质疏松症的发病率逐年增加,严重影响着老年人的生活质量,其预防及治疗巳成为全球性公共卫生问题。近年来对骨碎补防治骨质疏松症有了一定深人研究,主要包括骨碎补及其有效成分在细胞、动物、临床个体水平防治骨质疏松症的疗效和作用机理。本文综述了国内外关于骨碎补防治骨质疏松症的相关研究,分析了目前研究过程中存在的问题,并对其未来发展进行了展望。     

骨碎补活性单体成分调控骨质疏松症相关信号通路的研究进展

骨质疏松症相关分子信号通路的发现及其各通路中关键靶点的明确,为骨质疏松症的防治开辟了新的方向。骨碎补是防治骨质疏松症的一味常用中药,目前骨碎补中被证明具有抗骨质疏松活性的单体成分包括柚皮苷、柚皮素和新北美圣草苷。研究显示,骨碎补通过调控骨代谢相关分子信号通路,如OPG/RANKL/RANK通路、组织蛋白酶K通路、Wnt/β-catenin通路、骨形成蛋白通路上相关靶点,发挥抑制骨吸收或促进骨形成的作用,最终达到防治骨质疏松症的目的。本文综述了骨碎补活性单体成分调控骨质疏松症相关信号通路的研究进展,发现研究者使用的干预药物以骨碎补总黄酮为主,其次是单体成分柚皮苷,尽管有研究表明柚皮素及新北美圣草苷可能比柚皮苷具备更强的抗骨质疏松活性,但相关研究较匮乏。另外,目前相关研究仅停留在单一分子信号通路中的一个或数个调控靶点上,为了阐明骨碎补活性单体成分抗骨质疏松的多靶点、多环节生物学机制,发掘中药防治骨代谢疾病的潜在价值,今后有必要进行骨碎补活性单体成分的进一步分离、鉴定以及各信号通路间的相互交联研究。     

骨碎补总黄酮与骨质疏松症的研究

为研究骨碎补总黄酮对骨质疏松症的治疗作用,笔者查阅了近几年来最新发表的相关文献资料,结合在临床中应用含有中药骨碎补的自拟方剂强骨饮的经验。现对骨碎补总黄酮对骨质疏松症在分子水平和细胞水平的治疗作用做一综述,以期对今后的临床用药提供一种新的选择。     

骨碎补含药血清对成骨细胞增殖、成骨的影响

目的研究骨碎补含药血清对成骨细胞的增殖、成骨的影响。方法取乳鼠颅骨,利用二型胶原酶反复消化,离心,提取成骨细胞。利用骨碎补含药血清干预,分别测定细胞增殖率、ALP活性、钙盐沉积量、骨钙素分泌量等,研究骨碎补含药血清对成骨细胞的增殖、成骨分化及其抗氧化性的影响;结果用含药血清干预,测定增殖率、ALP活性、钙盐沉积量、骨钙素分泌量、钙化结节量均高于空白对照组。结论骨碎补含药血清可以促进成骨细胞的增殖、成骨分化及其增强其抗氧化性。     

骨碎补总黄酮对去卵巢大鼠骨超微结构及脯氨酸羟化程度的影响

目的：研究应用骨碎补总黄酮后骨超微结构及脯氨酸羟化程度的变化,从骨胶原的超微结构来研究骨碎补总黄酮对骨强度的影响。方法：40只10月龄SD雌性大鼠（体重350～380g）,随机分成假切除组（空白组）、模型组、药物组、对照组,每组10只。假切除组只切除腹部的少许脂肪,其余各组采用双侧卵巢切除的方法进行动物造模。药物组每天灌服中药骨碎补总黄酮浓缩剂2ml（相当于骨碎补总黄酮0.02g）,共6个月;对照组每天灌服培美力悬剂2ml（相当于倍美力0.017mg）,共6个月。灌胃6个月后取L2进行扫描电镜观察,并以碱水解法测单位重量脯氨酸羟化程度。结果：骨碎补总黄酮能明显改善骨胶原的排列,减少断裂的骨胶原。药物组脯氨酸羟化程度为（58.77±0.56）%,对照组为（60.90±0.53）%,模型组为（47.34±0.52）%,药物组和对照组比较差异无统计学意义,但较模型组脯氨酸羟化程度提高（P〈0.05）。结论：骨碎补总黄酮能改善松质骨的超微结构及脯氨酸羟化程度,从而为药物防治骨质疏松的研究提供思路。     

骨碎补提取物对骨髓间充质干细胞向成骨细胞分化Cbfα-1表达的影响及意义

目的：体外实验研究中药骨碎补对大鼠骨髓间充质干细胞增殖分化及对Cbfα-1表达的影响。方法采用中药干预培养细胞的方法,利用骨碎补单味药物与培养基联合培养大鼠骨髓间充质干细胞（ BMSCs ）,通过Ⅰ型胶原免疫组化染色检测其促BMSCs成骨分化能力,通过RT-PCR方法进行半定量分析Cbfα-1的表达,探讨中药骨碎补促成骨能力的机制。结果骨碎补药物各组Ⅰ型胶原免疫组化染色检测BMSCs成骨分化能力及RT-PCR检测Cbfα-1的表达均明显优于空白组及条件培养组（P＜0.01）,0.002 g/ml药物组优于0.02 g/ml及0.0002 g/ml药物组（P＜0.05）。结论中药骨碎补可促进BMSCs增殖及成骨分化,使Cbfα1的表达加强。     

丹参与骨碎补注射液防治激素诱发股骨头坏死的实验研究

目的探讨丹参和骨碎补对激素性股骨头坏死的防治机理及其交互作用.方法选用家兔50只,随机分成五组:模型组、丹参组、骨碎补组、丹参 骨碎补组、对照组.8周后观察五组家兔血液流变学、脂代谢、股骨头组织学等指标的改变.结果与对照组相比,模型组股骨头疏松,易于凿切,血液粘度和血脂升高,骨小梁变细、稀疏,空骨陷窝率增高,髓腔脂肪细胞增多;而其余各组上述病变有不同程度的减轻,其中以丹参 骨碎补组病理改变最轻.结论①丹参、骨碎补均能预防激素所致的高粘滞血症和高脂血症;②骨碎补能提高血钙血磷,激活成骨细胞,提高股骨头的骨密度,能预防激素性骨质疏松;③两药在预防SANFH方面有协同作用.     

Elimination of HCV as a public health concern among people who inject drugs by 2030 – What will it take to get there?

Introduction : Globally, there is a considerable burden of HCV and HIV infections among people who inject drugs (PWID) and transmission of both infections continues. Needle and syringe programme (NSP) and opioid substitution therapy (OST) coverage remains low, despite evidence demonstrating their prevention benefit. Direct‐acting antiviral therapies (DAA) with HCV cure >95% among PWID provide an opportunity to reverse rising trends in HCV‐related morbidity and mortality and reduce incidence. However, HCV testing, linkage to care, and treatment remain low due to health system, provider, societal, and patient barriers. Between 2015 and 2030, WHO targets include reducing new HCV infections by 80% and HCV deaths by 65%, and increasing HCV diagnoses from <5% to 90% and number of eligible persons receiving HCV treatment from <1% to 80%. This commentary discusses why PWID should be considered as a priority population in these efforts, reasons why this goal could be attainable among PWID, challenges that need to be overcome, and key recommendations for action. Discussion : Challenges to HCV elimination as a global health concern among PWID include poor global coverage of harm reduction services, restrictive drug policies and criminalization of drug use, poor access to health services, low HCV testing, linkage to care and treatment, restrictions for accessing DAA therapy, and the lack of national strategies and government investment to support WHO elimination goals. Key recommendations for action include reforming drug policies (decriminalization of drug use and/or possession, or providing alternatives to imprisonment for PWID; decriminalization of the use and provision of sterile needles‐syringes; and legalization of OST for people who are opioid dependent), scaling up and improving funding for harm reduction services, making health services accessible for PWID, supporting community empowerment and community‐based programmes, improving access to affordable diagnostics and medicines, and eliminating stigma, discrimination, and violence against PWID. Conclusions : The ambitious targets for HCV elimination set by WHO are achievable in many countries, but will require researchers, healthcare providers, policy makers, affected communities, advocates, the pharmaceutical and diagnostics industries, and governments around the world to work together to make this happen.     

Physiology of malabsorption

Malabsorption occurs when the function of the gastrointestinal tract is suboptimal and nutrient absorption is reduced. Malnutrition, weight loss, diarrhoea, steatorrhoea, anaemia and other specific nutrient deficiencies can be produced. This article will review the principles of normal nutrient absorption and the pathophysiology in disorders which result in malabsorption. Normal absorption needs coordinated processes of motility, hormone release, digestive secretion from the salivary glands, stomach, pancreas, liver and intestine, and the expression of specific enzymes and transporter molecules. Gastric, pancreatic and intestinal disorders can all produce malabsorption. These can be complications of surgical procedures, or be due to inflammatory and autoimmune disorders such as coeliac disease, Crohn's disease, small intestinal bacterial overgrowth, chronic pancreatitis, or autoimmune gastritis. Understanding the mechanisms involved and how these are affected by surgical procedures and disease will enable malabsorption to be recognized, investigated and treated appropriately.     

Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia

BACKGROUND: Time-frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. METHODS: Response entropy, SE [S/5 Entropy Module, M-ENTROPY (later in text: Entropy), Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A-2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg-1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg-1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. RESULTS: Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 +/- 22%, 75 +/- 26%, and 59 +/- 18% (mean +/- SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86+/-21%, 88 +/- 13%, and 63 +/- 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P < 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. CONCLUSIONS: All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.     

Interactions among age, adiposity, bodyweight, lifestyle factors and sex steroid hormones in healthy Singaporean Chinese men

Aim： To examine the inter-relationships among age, lifestyle factors, anthropometric parameters, percent body fat and steroid hormone parameters in 531 healthy Singaporean Chinese men aged between 29 and 72 years old. Methods： Various lifestyle parameters were quantified through a survey, and testosterone （T）, estradiol （E2）, dehydroepiandrosterone sulphate （DHEAS） and sex hormone binding globulin （SHBG） were measured using established methods. Anthropometric parameters were collected and computed, and percent body fat （Siri） was measured using the DEXA scanner. Results： SHBG, DHEAS, bioavailable-T （Bio-T）, E2, Siri, Ht, W/H, W/Ht and work stress were independently correlated with age. Using multivariate analyses and adjusting for age and other related factors, exercise, smoking and alcohol consumption have positive impacts on androgen levels and body composition. However, black and green tea consumption was associated with negative effects on body composition and with higher levels of E2 and Free Estradiol Index （FEI）. Men with shorter sleep duration had significantly lower T levels as compared to those with 6 h or more of nightly sleep. Higher T levels were associated with lower levels of adiposity and other indices of adiposity, whereas higher E2 levels were related to higher levels of adiposity. Men with higher DHEAS were significantly taller and heavier than those with low DHEAS levels. Conclusion： The study showed the close interactions among the gonadal/adrenal and metabolic compartments, with age being a key determinant in their interactions. Lifestyle factors such as exercise, smoking, sleeping and alcohol and tea consumption might play significantly roles in determining the status of health in men.     

Advanced endoscopic technologies

The use of endoscopy for diagnosing and treating ailments of the alimentary tract has evolved steadily over the past few decades, with tremendous growth and innovation in the past few years. Initially, endoscopy relied on rigid telescopes, direct visualization, and dangerously exothermic sources of illumination. The introduction of fiber optics, charge-coupled-device cameras, and increasingly efficient light sources has enabled researchers to investigate areas of the human gastrointestinal tract through flexible endoscopy not previously thought to be reachable without formal surgical exploration. The more recent advances in scope platforms, devices, and techniques have allowed researchers to push the envelope of endoscopic diagnostics and therapeutics to greater heights. Specific new platforms include ColonoSight and mother–daughter endoscopes such as the ShapeLock TransPort and the SpyGlass direct visualization system. Specific devices include the EndoCinch suturing system, the full-thickness Plicator procedure, Esophyx, the Stretta system, and the HALO³⁶⁰ system. Specific new techniques include small-caliber endoscopy, endoscopic mucosal and submucosal resection, and natural orifice translumenal endoscopic surgery (NOTES). This article describes the most relevant recent advances in endoscopic innovation with regard to platform design, devices, and techniques anticipated to serve as the foundation for further research and design for developing generations of endoscopic technologies to come.     

Apigenin drives the production of reactive oxygen species and initiates a mitochondrial mediated cell death pathway in prostate epithelial cells

BACKGROUND: Phytoestrogens may reduce tumorigenesis in prostate cancer. We screened five phytoestrogens for their effect on cell growth and apoptosis in PWR-1E, LNCaP, PC-3, and DU145 prostate epithelial cells in vitro. METHODS: We assessed cell number, proliferation, and apoptosis using crystal violet assays, flow cytometric analysis, and TUNEL. Focusing specifically on apigenin we assessed the ability of calpain, serine protease, caspase, estrogen receptor, and ceramide synthase inhibitors to block apigenin induced apoptosis. We also analyzed caspase 3, 7, 8, 9, Bcl-2, Bax, Bid, and cytochrome C by Western analysis, and mitochondrial permeability and reactive oxygen species production by flow cytometry using mitosensor(TM) and DCFH-DA, respectively. RESULTS: Apigenin and silybinin significantly reduced cell number, with apigenin inducing apoptosis in PWR-1E, LNCaP, PC-3, and DU145 cells. The PC-3 and DU145 cells were less susceptible to apigenin induced apoptosis then LNCaP and PWR-1E cells. The induction of apoptosis by apigenin was caspase dependent. Apigenin generated reactive oxygen species, a loss of mitochondrial Bcl-2 expression, mitochondrial permeability, cytochrome C release, and the cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor of apoptosis protein, cIAP-2. The overexpression of Bcl-2 in LNCaP B10 cells reduced the apoptotic effects of apigenin. CONCLUSIONS: Apigenin induces cell death in prostate epithelial cells using a mitochondrial mediated cell death pathway. Bcl-2 has a role in inhibiting apigenin induced cell death in prostate epithelial cells.     

Transforming Growth Factor-β, Bioenergetics, and Mitochondria in Renal Disease

The transforming growth factor-β (TGF-β) family comprises more than 30 family members that are structurally related secreted dimeric cytokines, including TGF-β, activins, and bone morphogenetic proteins/growth and differentiation factors. TGF-β are pluripotent regulators of cell proliferation, differentiation, apoptosis, migration, and adhesion of many different cell types. TGF-β pathways are highly evolutionarily conserved and control embryogenesis, tissue repair, and tissue homeostasis in invertebrates and vertebrates. Aberrations in TGF-β activity and signaling underlie a broad spectrum of developmental disorders and major pathologies in human beings, including cancer, fibrosis, and autoimmune diseases. Recent observations have indicated an emerging role for TGF-β in the regulation of mitochondrial bioenergetics and oxidative stress responses characteristic of chronic degenerative diseases and aging. Conversely, energy and metabolic sensory pathways cross-regulate mediators of TGF-β signaling. Here, we review TGF-β and regulation of bioenergetic and mitochondrial functions, including energy and oxidant metabolism and apoptotic cell death, as well as their emerging relevance in renal biology and disease.     

Vomiting, retching, headache and restlessness after halothane-, isoflurane- and enflurane-based anaesthesia: An analysis of pooled data following ear, nose, throat and eye surgery

Background: Isoflurane has exceeded halothane and enflurane in usage. A literature search, however, revealed no data comparing the effects on emesis, headache and restlessness of these three agents.
Methods: With hospital ethics committee approval and patient consent, a prospective, randomised, double-blind study of 556 patients undergoing ENT and eye surgery was undertaken to evaluate the effects of halothane, isoflurane and enflurane on vomiting, retching, headache and restlessness until 24 h after anaesthesia. Balanced general anaesthesia was administered comprising benzodiazepine premedication, induction with thiopentone-atracurium-morphine (ENT patients) or fentanyl (eye patients), controlled ventilation and maintenance with either halothane 0.4–0.6 vol% (n = 186), isoflurane 0.6–0.8 vol% (n = 184) or enflurane 0.8–1 vol% (n=186) in nitrous oxide 67% and oxygen.
Results: The three study groups were comparable, and comprised comparable subgroups having ear, nose, throat, intraocular and non-intraocular surgery. During early recovery from anaesthesia, the respective requirements for halothane, isoflurane and enflurane for analgesia (7%, 9% and 10%), frequency of emesis (6%, 8% and 8%), antiemetic requirements (1%, 1% and 2%), restlessness-pain scores and time spent in the recovery ward (27 SD 10, 31 SD 12 and 26 SD 9 min) were similar. During the ensuing 24-h postoperative period, patients who had isoflurane experienced emesis less often than those who had halothane (36% vs 46%, P <0.025) but did so with similar frequency to those who had enflurane (46% vs 41%). Antiemetic requirements were least in those given isoflurane (isoflurane 12%, halothane and enflurane 23% each, P <0.005), but headache and analgesic requirements were similar.
Conclusion: Isoflurane induces less postoperative emesis than halothane, but headache is similarly frequent after anaesthesia with any of these agents.     

Microbiology of male urethroadnexitis: diagnostic procedures and criteria for aetiologic classification

Summary. Common pathogens and unconventional, fastidious bacteria, viruses, parasites, and fungi are causative agents in male urethroadnexitis. Uropathogens and sexually transmitted organisms must be considered. Diagnostic procedures and criteria for aetiologic classification in cases of balanitis, urethritis, prostatitis, epididymitis, and orchitis are described and evaluated.