异位甲状腺癌的诊断和治疗

目的　探讨异位甲状腺癌的发病特点、诊断和治疗方法。方法　对 2 9例异位甲状腺癌的临床及病理资料进行回顾性分析。结果　 2 9例均行手术治疗 ,术后辅以放、化疗。术后随访 ,5年存活率为 5 2 .0 % ,最长 1例已存活 2 4年。结论　早期发现并及时手术治疗是提高异位甲状腺癌患者生存率的关键 ,术后给予辅助性放、化疗有助于提高生存率。     

Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL-6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis. We set out to test if anti-IL-6 therapy using tocilizumab can decrease hip synovitis and improve bone healing in the piglet model of LCPD. Fourteen piglets were surgically induced with ischemic osteonecrosis and assigned to two groups: the no treatment group (n = 7) and the tocilizumab group (15 to 20 mg/kg, biweekly intravenous injection, n = 7). All animals were euthanized 8 weeks after the induction of osteonecrosis. Hip synovium and femoral heads were assessed for hip synovitis and bone healing using histology, micro-CT, and histomorphometry. The mean hip synovitis score and the number of synovial macrophages and vessels were significantly lower in the tocilizumab group compared with the no treatment group (p < .0001, p = .01, and p < .01, respectively). Micro-CT analysis of the femoral heads showed a significantly higher bone volume in the tocilizumab group compared with the no treatment group (p = .02). The histologic assessment revealed a significantly lower number of osteoclasts per bone surface (p < .001) in the tocilizumab group compared with the no treatment group. Moreover, fluorochrome labeling showed a significantly higher percent of mineralizing bone surface (p < .01), bone formation rate per bone surface (p < .01), and mineral apposition rate (p = .04) in the tocilizumab group. Taken together, tocilizumab therapy decreased hip synovitis and osteoclastic bone resorption and increased new bone formation after ischemic osteonecrosis. This study provides preclinical evidence that tocilizumab decreases synovitis and improves bone healing in a large animal model of LCPD. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Development of Hip Bone Geometry During Gender-Affirming Hormone Therapy in Transgender Adolescents Resembles That of the Experienced Gender When Pubertal Suspension Is Started in Early Puberty

Bone geometry can be described in terms of periosteal and endocortical growth and is partly determined by sex steroids. Periosteal and endocortical apposition are thought to be regulated by testosterone and estrogen, respectively. Gender-affirming hormone (GAH) treatment with sex steroids in transgender people might affect bone geometry. However, in adult transgender people, no change in bone geometry during GAH was observed. In this study, we investigated changes in bone geometry among transgender adolescents using a gonadotropin-releasing hormone agonist (GnRHa) and GAH before achieving peak bone mass. Transgender adolescents treated with GnRHa and subsequent GAH before the age of 18 years were eligible for inclusion. Participants were grouped based on their Tanner stage at the start of GnRHa treatment and divided into early, mid, and late puberty groups. Hip structure analysis software calculating subperiosteal width (SPW) and endocortical diameter (ED) was applied to dual-energy X-ray absorptiometry scans performed at the start of GnRHa and GAH treatments, and after ≥2 years of GAH treatment. Mixed-model analyses were performed to study differences over time. Data were visually compared with reference values of the general population. A total of 322 participants were included, of whom 106 were trans women and 216 trans men. In both trans women and trans men, participants resembled the reference curve for SPW and ED of the experienced gender but only when GnRHa was started during early puberty. Those who started during mid and late puberty remained within the reference curve of the gender assigned at birth. A possible explanation might be sought in the phenomenon of programming, which conceptualizes that stimuli during critical windows of development can have major consequences throughout one's life span. Therefore, this study adds insights into sex-specific bone geometry development during puberty of transgender adolescents treated with GnRHa, as well as the general population. © 2021 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

开心胶囊对大鼠垂体后叶素心肌缺血模型的影响

临床发现,由西洋参,川苍,苍术,香附,蒲黄,红花,山楂等组成的呀约开心胶囊对心肌缺血有改善作用。为探讨其作用机理,建立垂体后叶素（Ｐｉｔ）造成的心肌缺血大鼠模型,观察中药开心胶囊不同剂量对心肌缺血大鼠的防治作用,并以肠溶阿斯匹林作阳性对照,结果中药开心胶囊高剂量组可改善Ｐｉｔ引起的心肌缺血并提高大鼠６－酮－前列腺素Ｆ１α－（６－Ｋｅｔｏ－ＰＧＦ１α）的含量（与模型组比Ｐ〈０．０１）;中、高剂量组可     

不同证候的注意缺陷多动障碍患儿多巴胺D2受体基因携带情况检测

注意缺陷多动障碍（ａｔｔｅｎｔｉｏｎｄｅｆｉｃｉｔｈｙｐｅｒｃａｔｉｖｉｔｙｄｉｓｏｎｒｄｒ,ＡＤＨＤ）是常见的儿童行为障碍,目前病因尚未明确,国外近年由于分子生物学方法的介入,发现多巴胺Ｄ２受体ＴａｑＩＡ１等位基因与本病相关,通过对广州市城镇学龄儿童多巴胺Ｄ２受体基因ＴａｑＩＡ多态性的检测,支持Ａ１等位基因与本病的关系（Ｐ＝０．００６５２０）并发现病该基因与中医辨证的“肾虚肝亢”证候关系更为密切     

Uptake of Enzymatically-Digested Hyaluronan by Liver Endothelial Cells in Vivo and in Vitro

Intravenously-injected hyaluronan (HA) is distributed into liver in which endothelium is a site of uptake and degradation of HA. The role and fate of HA have been widely investigated; however, effects of size and dose of HA on its metabolism have not been well documented yet. To investigate these effects, we prepared fluorescein-labeled HAs, according to the modified methods described by de Belder and Wik, which were enzymatically digested. The 90 kDa fluorescein-labeled HA gradually accumulated in a liver that was distributed into the endothelium; however, 10 kDa or less HA did not. Cell fractionation and flow cytometry further demonstrated the cell of uptake in the liver is an endothelial cell, both in vivo and in vitro. Interestingly, the largest uptake by liver endothelial cells in vitro was observed in 10 kDa HA, even though which did not accumulate in liver in vivo. These results suggest that the result observed with 10 kDa HA in vivo is due to the rapid excretion in urine. Thus, inhibiting of the digestion or suppressing of the urinary excretion would enhance uptake of HA in vivo. These ideas may help to deliver drugs or genes targeting to liver endothelium.     

A novel controlled drug-delivery system for growth hormone applied to healing skin wounds in diabetic rats

Controlled release systems for drugs, hormones and growth factors can be particularly useful in tissue repair processes. These systems act as a biodegradable support containing the substance to be delivered, allowing their gradual release. In the past years, the local application of growth factors has acquired special relevance as a therapeutic option for use in subjects who show deficient tissue scarring, the hormone dose being the limiting factor for its success. In this study, the in vitro biocompatibility of a copolymer formed by vinylpyrrolidone and 2-hydroxyethyl methacrylate, used as an administration vehicle for hGH, was evaluated. The system was then tested in vivo in terms of its capacity for healing incisional wounds in healthy and diabetic rats. For the in vitro studies, polymer and hormone degradation rates were determined, and polymer biocompatibility was evaluated in fibroblast cultures. In the in vivo experiments, an incision was made in the back of the animals, and polymers discs with/without hGH, were introduced in the aperture. Morphological, immunohistochemical and morphometric evaluations were performed on wound tissue specimens 3-10 days after surgery. In vitro, the polymer was found to be biodegradable and showed no toxic effects on fibroblasts, the hormone being slowly released to the culture medium. In untreated diabetic rats, a delayed skin scarring and cell response were observed, compared to that noted in healthy animals. Skin closure, keratinisation and fibrosis occurred earlier in the presence of the polymer-hGH system. The use of this co-polymer as an administration vehicle for hGH improves the wound scarring process in the pathological setting of diabetes.     

Prevalence and Incidence of Hypoparathyroidism in the United States Using a Large Claims Database

Hypoparathyroidism is a rare endocrine disorder whose incidence and prevalence have not been well defined. This study aimed to 1) estimate the number of insured adult patients with hypoparathyroidism in the United States and 2) obtain physician assessment of disease severity and chronicity. Prevalence was estimated through calculation of diagnoses of hypoparathyroidism in a large proprietary health plan claims database over a 12‐month period from October 2007 through September 2008 and projected to the US insured population. Incidence was also calculated from the same database by determining the proportion of total neck surgeries resulting in either transient (≤6 months) or chronic (>6 months) hypoparathyroidism. A physician primary market research study was conducted to assess disease severity and determine the percentage of new nonsurgical patients with hypoparathyroidism. Incidence data were entered into an epidemiologic model to derive an estimate of prevalence. The diagnosis‐based prevalence approach estimated 58,793 insured patients with chronic hypoparathyroidism in the United States. The surgical‐based incidence approach yielded 117,342 relevant surgeries resulting in 8901 cases over 12 months. Overall, 7.6% of surgeries resulted in hypoparathyroidism (75% transient, 25% chronic). The prevalence of chronic hypoparathyroidism among insured patients included in the surgical database was estimated to be 58,625. The physician survey found that 75% of cases treated over the past 12 months were reported due to surgery and, among all thyroidectomies and parathyroidectomies and neck dissections performed in a year, 26% resulted in transient hypoparathyroidism and 5% progressed to a chronic state. In conclusion, the two claims‐based methods yielded similar estimates of the number of insured patients with chronic hypoparathyroidism in the United States (～58,700). The physician survey was consistent with those calculations and confirmed the burden imposed by hypoparathyroidism. © 2013 American Society for Bone and Mineral Research.     

Functional evaluation of poly-(N-ρ-vinylbenzyl-O-β-Dgalactopyranosyl-[1-4]-D-gluconamide)(PVLA) as a liver specific carrier

Hepatocytes express the specific C-type lectin, asialoglycoprotein (ASGP) receptor, on the surface to remove the ligand-bearing proteins from circulation. The specific expression and ligand specificity are thought to be the ideal characters for the target of drug or gene delivery. Various galactose-bearing molecules were synthesized for this purpose. However, the biological or functional interaction of these molecules with the ASGP receptor still remains to be elucidated. In this study, we evaluated the functional ability of synthetic galactose polymer ligand, poly-(N-ρ-vinylbenzyl-O-β-Dgalactopyranosyl-[1-4]-D-gluconamide) (PVLA), to interact with recombinant ASGP receptors using mouse ASGP receptor (mouse hepatic lectin; MHL) gene-transfected CHO cells. PVLA-coated beads bound to and were endocytosed by the whole (MHL-1/-2) ASGP receptor-expressing CHO cells like hepatocytes while PVMA (poly-(N-ρ-vinylbenzyl-O-β-D-glucopyranosyl-[1-4]-D-gluconamide) did not. Interestingly, PVLA-coated beads were also endocytosed by either MHL-1 or MHL-2 alone expressing cells, which are known to be incapable of endocytosing natural ligands. In addition, the endocytosis of PVLA-coated beads by MHL-expressing CHO cells or primary hepatocytes was inhibited only by soluble PVLA but not by the same galactose molecular concentration of soluble asialofetuin. Furthermore, PVLA-coated beads were endocytosed by primary hepatocyte to a significantly higher degree than asialofetuin-coated beads in vitro. These results suggest that PVLA has higher affinity to the ASGP receptor than the natural ligands in blood. Consistently, it was demonstrated that intravenously injected FITC-labeled PVLA but not PVMA drastically accumulated in parenchymal cells of the liver in vivo. Taken together, PVLA exhibiting higher affinity with hepatocytes than natural ligands is thought to be an attractive and practical carrier-ligand for liver targeting.     

Reproductive Hormones and Longitudinal Change in Bone Mineral Density and Incident Fracture Risk in Older Men: The Concord Health and Aging in Men Project

The objectives of this study were to examine relationships between baseline levels of reproductive hormones in older men and (1) change in bone mineral density (BMD) over 5 years and (2) incident fractures over an average of 6 years' follow‐up. A total of 1705 men aged 70 years and older from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005–2007), 2 years follow‐up (2007–2009), and 5 years follow‐up (2010–2013). At baseline, testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) were measured by liquid chromatography–tandem mass spectrometry (LC‐MS/MS), and sex hormone–binding globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) by immunoassay. Hip BMD was measured by dual X‐ray absorptiometry (DXA) at all three time‐points. Fracture data were collected at 4‐monthly phone calls and verified radiographically. Statistical modeling was by general estimating equations and Cox model regression. Univariate analyses revealed inverse associations for serum SHBG, FSH, and LH and positive association for E1 but not DHT or E2 with BMD loss at the hip across the three time points. Serum levels of SHBG (β = –0.071), FSH (β = –0.085), LH (β = –0.070), and E1 (β = 0.107) remained significantly associated with BMD loss in multivariate‐adjusted models; however, we were unable to identify any thresholds for accelerated BMD loss according to reproductive steroids. Incident fractures (all, n = 171; hip, n = 44; and nonvertebral, n = 139) were all significantly associated with serum SHBG, FSH, and LH levels in univariate models but none remained significantly associated in multivariate‐adjusted model. Serum T, DHT, E2, and E1 levels were not associated with incident fractures in univariate or multivariate‐adjusted analyses. In older men, lower serum SHBG, FSH, and LH and higher E1 levels protected against loss of BMD without increasing fracture rate. This means these reproductive variables may be considered as novel biomarkers of bone health during male aging. © 2015 American Society for Bone and Mineral Research.