锁阳抑制良性前列腺增生的作用机制研究

目的研究锁阳对大鼠前列腺增生(BPH)模型的作用及相关机制研究。方法用雌/雄激素诱导大鼠前列腺增生。按体重将去势3周后大鼠随机分为3组:模型组,锁阳组(3 g·kg^-1·d^-1),氟他胺组(30 mg·kg^-1·d^-1),每组10只。另外取10只健康大鼠作为假手术组,模型组和假手术组给等量0. 9%Na Cl,均灌胃给药,每天1次,连续给药45 d。以蛋白免疫印迹检测增殖细胞核抗原(PCNA)蛋白变化;用Cyto Scape3. 5. 1软件构建和分析锁阳"化合物-靶点-前列腺增生"复杂网络。结果给药后,假手术组、模型组、锁阳组的PCNA蛋白表达灰度比值分别是0. 58±0. 11,1. 37±0. 21,0. 94±0. 31,模型组与假手术比较,差异有统计学意义(P <0. 05);锁阳组与模型组比较,差异有统计学意义(P <0. 05)。网络药理学揭示,锁阳直接作用于BPH疾病的靶点有7个,4个新发现的靶点分别为细胞周期素D1(CCND1)、磷脂酰基醇(PIK3CA)、氧化物酶体增殖物激活受体(PPARG)和过氧化物合成酶(PTGS2)。结论锁阳抑制大鼠前列腺增生可能与细胞增殖等通路以及调节细胞周期素D1(CCND1)与磷脂酰基醇(PIK3CA)等蛋白表达相关。     

Clinical ultrasound stimulating angiogenesis following drug-release from polymersomes on the ischemic zone for peripheral arterial occlusive disease

Peripheral Arterial Occlusive Disease (PAOD) is an aging disease that affects the quality of life of many people by its intermittent claudication and critical limb ischemia presentations. Traditional treatment and management of PAOD are asking patients to make a life change and medication with antiplatelet, statins and cilostazol, which decrease the possibility of clot formation. Our strategy has employed a magnetic Fe₃O₄-PLGA polymersome to carry the cilostazol into the ischemic area by magnetic attraction following remote-control drug release through low-energy ultrasound exposure. In the animal studies, the cilostazol-loaded Fe₃O₄-PLGA polymersomes were injected and accumulated at ischemic leg through magnetic attraction. Then, using a clinical-use ultrasound machine the leg was irradiated to forward cilostazol release from the accumulated polymersomes. Dramatically, we found an observable result of bloody flux recovery in the leg after 7?days compared to the non-treated leg that showed no evidence of the blood recovery.     

Three months of rifapentine and isoniazid for latent tuberculosis infection in hemodialysis patients: High rates of adverse events

The consequences of once-weekly rifapentine plus isoniazid for 3 months (3HP) against latent tuberculosis infections in hemodialysis patients have not been studied before. This is the first study to evaluate the safety and tolerability of 3HP in this population and revealed a completion rate of 65.4%. The therapy was not associated with hepatotoxicity, but with high rates of adverse events (69.2%).     

Systemic lupus erythematosus and thyroid disease – Experience in a single medical center in Taiwan

BackgroundTo investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan.MethodsThis is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia.ResultsCompared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p < 0.0001). The average age of SLE patients with thyroid diseases patients were older than those without thyroid diseases (p = 0.002). Those had euthyroid AITD were younger than other patients with thyroid diseases (p = 0.02). Up to 30.3% SLE patients had overlap syndrome and had higher relative risk of thyroid diseases than those without overlap syndrome, in terms of hypothyroidism and AITD, but not hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p < 0.0001).ConclusionSLE patients had significantly higher rate of hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement.     

Mutation spectrum of MMACHC in Chinese pediatric patients with cobalamin C disease: A case series and literature review

Cobalamin (cbl) C disease is a rare autosomal recessive inheritance disease, which is the most common cobalamin metabolic disorder. Its clinical phenotype involves multiple systems with varying degrees of severity, where in mild cases can be asymptomatic for many years, whereas severe cases may cause death during the neonatal period. The disease is caused by mutations in the MMACHC gene located on chromosome 1p34.1 that contains 5 exons; among which, exons 1–4 have an 849 bp coding sequence that encodes a protein containing 282 amino acids. Through clinical physical examination and laboratory tests, especially blood and urine screening, we found 28 cblC pediatric patients with clinical manifestations, such as mental retardation, motor development delay, epilepsy, metabolic acidosis, vomiting and diarrhea. By Sanger sequencing, we found homozygous or compound heterozygous mutations of MMACHC in 27 of the patients, and single heterozygous mutation of MMACHC in one of them. The c.609G > A, c.658-660delAAG, c.80A > G and c.482G > A mutations accounted for 43.64% (24/55), 10.91% (6/55), 9.09% (5/55) and 7.27% (4/55) of all the mutations, respectively. This spectrum finding is basically consistent with the previously reported data in Chinese patients. The most common c.609G > A mutation may likely lead to early-onset cblC disease. In previous literature involving a large sample of Caucasian cblC cases, the mutation spectrum of MMACHC gene is almost completely different from that of the Chinese population. The most common mutations in the Caucasian population were c.271dupA, c.394C > T and c.331C > T, which account for 48.05% (542/1128), 13.65% (154/1128) and 7.36% (83/1128) of all the mutant alleles, respectively. The c.271dupA mutation and c.331C > T mutation were mainly associated with early-onset cblC in children less than 1 year old, whilst the c.394C > T mutation was mainly associated with late-onset cblC patients characterised by isolated acute nervous system abnormalities. We also analysed the cause behind the different mutation spectrum of MMACHC gene between the Chinese and Caucasian populations.     

Clinicoepidemiologic characteristics of scrub typhus and murine typhus: A multi-center study in southern Taiwan

BackgroundThis study aimed to offer key features to differentiate scrub typhus (ST) and murine typhus (MT) at the early stage of the diseases and provide clinicoepidemiologic characteristics of ST and MT in southern Taiwan, a region where both diseases are endemic. Comparison of doxycycline treatment efficacy between the two diseases by matching disease severity and delayed treatment had never been investigated.MethodsWe reviewed the medical records of cases of ST and MT in four hospitals in southern Taiwan. Propensity-score matching was used to analyze the defervescence curves between patients with doxycycline-treated ST and MT by log-rank test.ResultsBetween 2004 and 2016, 265 ST and 63 MT cases were diagnosed. The number of cases of ST was significantly related to temperature (Rs = 0.77) and rainfall (Rs = 0.63). Island area exposure, arthropod bite, eschar, and lymphadenopathy were only recorded in ST patients. Multivariate analysis revealed that mountainous area exposure (odds ratio [OR], 11.0; 95% confidence interval [CI], 4.4–27.2) was an independent predictor for ST, while contact with rats (OR, 8.4; 95% CI, 3.3–21.3) was that for MT. After propensity-score matching, there was no difference in defervescence curves between these two rickettsioses treated with doxycycline (p = 0.24).ConclusionIn the present study, island area exposure, arthropod bite, eschar, and lymphadenopathy were unique manifestations of ST. Mountainous area exposure is a predictive factor for ST, while contact with rats predicted MT. There was no difference in defervescence time between these two rickettsioses after doxycycline treatment.     

Results of the First Clinical Study in Humans That Combines Hyperbaric Oxygen Pretreatment with Autologous Peripheral Blood Stem Cell Transplantation

Patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation (auto-HCT) are at risk for multiple morbidities, including mucosal inflammation and neutropenic fever, both related to neutropenia. Evidence from our preclinical work in an umbilical cord blood (UCB) transplantation murine model suggests that treatment with hyperbaric oxygen (HBO) before UCB infusion improves UCB CD34⁺ cell engraftment by reducing erythropoietin levels. A pilot clinical trial using HBO in patients undergoing UCB transplantation showed improvement in kinetics of blood count recovery. In this study, we evaluated HBO in combination with auto-HCT. Our primary aim was to determine the safety of HBO in this setting and secondarily to determine its efficacy in reducing time to neutrophil and platelet engraftment compared with matched historic controls. Patients with multiple myeloma, non-Hodgkin lymphoma, and Hodgkin disease eligible for auto-HCT were included. On day 0, patients received HBO treatment consisting of exposure to 2.5 atmosphere absolutes for a total of 90 minutes, in a monoplace hyperbaric chamber, breathing 100% oxygen. Six hours after the start of HBO, peripherally mobilized stem/progenitor cells were infused and patients were followed daily for toxicity and blood count recovery. All patients received daily granulocyte colony-stimulating factor starting on day +5 and until absolute neutrophil count (ANC) of ≥1500 or ANC of 500 for 3 consecutive days. A matched historic cohort of 225 patients who received auto-HCT between January 2008 and December 2012 was chosen for comparison and matched on sex, age, conditioning regimen, and disease type. We screened 26 patients for this study; 20 were treated and included in the primary analysis, and 19 completed the HBO therapy and were included in the secondary analysis. Although the median time to neutrophil count recovery was 11 days in both the HBO and control cohorts, the Kaplan-Meier estimates of the full distributions indicate that the time to neutrophil recovery was generally about 1 day sooner for HBO versus historical controls (log-rank P = .005; range, 9 to 13 for HBO patients and 7 to 18 for controls). The median time to platelet count recovery was 16 days (range, 14 to 21) for HBO versus 18 days (range, 11 to 86) for controls (log-rank P < .0001). In the secondary analysis comparing the HBO cohort who completed HBO therapy (n = 19) with our historical cohort, we evaluated neutropenic fever, growth factor use, mucositis, day +100 disease responses, and blood product use. HBO was associated with less growth factor use (median 6 days in HBO cohort versus median 8 days in controls, P < .0001). Packed RBC and platelet transfusion requirements were not statistically different between the 2 cohorts. Mucositis incidence was significantly lower in the HBO cohort (26.3% in HBO cohort versus 64.2% in controls, P = .002). HBO therapy appears to be well tolerated in the setting of high-dose therapy and auto-HCT. Prospective studies are needed to confirm potential benefits of HBO with respect to earlier blood count recovery, reduced mucositis, and growth factor use, and a cost-benefit analysis is warranted.© 2019 American Society for Blood and Marrow Transplantation.     

G-CSF-Mobilized Blood and Bone Marrow Grafts as the Source of Stem Cells for HLA-Identical Sibling Transplantation in Patients with Thalassemia Major

As an inherited anemia, thalassemia major (TM) is currently only curable with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here we report an allo-HSCT protocol for patients with TM who received a combination of granulocyte colony-stimulating factor-primed bone marrow and peripheral blood stem cells (G-BM & PBSCs) from a matched sibling donor (MSD). The conditioning regimen consisted of i.v. busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin. Chimerism analysis was performed for all patients. Immunosuppressive treatment was terminated if rejection was suspected, and donor lymphocyte infusion was administered once no response was observed. A total of 184 patients with TM were enrolled in the study between July 2007 and July 2018. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 13.1%, and that of moderate or severe chronic GVHD was 5.7%. The cumulative incidence of graft rejection was .6%. In the total cohort, the 3-year overall survival, thalassemia-free survival, and GVHD-free, relapse-free survival were 97.8%, 97.3%, and 89.5%, respectively. Collectively, our results indicate that G-BM & PBSCs from an MSD is be a good stem cell source for patients with TM undergoing allo-HSCT.