达英-35治疗多囊卵巢综合征合并不孕症的疗效及对患者血清FSH、LH、TOS、TAS水平的影响

摘要 目的：研究达英-35治疗多囊卵巢综合征合并不孕症的疗效及对患者血清卵泡刺激素(FSH)、促黄体生成素(LH)、总氧化态(TOS)、抗氧化态(TAS)水平的影响。方法：选取2015年8月至2016年7月我院收治的76例多囊卵巢综合征合并不孕症患者,根据随机数字法分为观察组和对照组,38例每组。对照组使用克罗米芬,观察组在此基础上加以达英-35。比较两组患者临床疗效,治疗前后血清FSH、LH、TOS、TAS水平、卵泡数、卵巢体积、体重指数的变化及不良反应的发生情况。结果：治疗后,观察组临床总有效率显著高于对照组[89.47%(34/38) vs. 60.53%(23/38)](P<0.05);两组患者的血清FSH、LH、TOS水平、卵泡数、卵巢体积、体重指数明显减少较治疗前均显著降低(P<0.05),而血清TAS水平较治疗前显著上升(P<0.05),且观察组的血清FSH、LH、水平明显低于对照组(P<0.05),而血清TAS水平显著高于对照组(P<0.05)。观察组和对照组的不良反应的发生率比较无明显差异(P>0.05)。结论：达英-35治疗多囊卵巢综合征合并不孕症患者能有效提高患者的临床疗效和改善其临床症状,且安全性高,这可能与其有效改善患者血清FSH、LH、TOS、TAS水平有关。     

A Prognostic Model to Predict Recovery of COVID-19 Patients Based on Longitudinal Laboratory Findings

Virologica Sinica - The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19. This study aimed to evaluate longitudinal change patterns of key...     

青少年多囊卵巢综合征的临床、超声和生化特征及其诊断意义

青春期多囊卵巢综合征(PCOS)的诊断具有一定的临床挑战性。迄今未有报道青少年人群PCOS的患病率以及临床、超声和生化特征。为了评估PCOS的临床和生化特征在14~16岁月经初潮女孩中的普遍程度,确定内循环雄激素水平在卵泡期早期的正常范围。本研究进行了一项前瞻性群组研究,研究群组是244名未经选择的月经初潮后的女孩,平均年龄在15.2岁。从一个大的以人口为基础的出生群组(Raine队列)中招募受试者。临床高雄激素血症(HA)使用Ferriman-Gallwey评分进行量化。在卵泡期的初期(第2~第6天),本研究使用免疫法测定循环雄激素和性激素结合球蛋白,并通过经腹部超声检查来评估卵巢形态,得到了青少年女性群体卵泡期初期的雄激素的正常范围。循环游离睾酮水平的前5%和10%分别为45.6 pmol/L和34.5 pmol/L。51%的女孩报告月经不规律。临床HA是罕见的,仅观察到3.5%的女孩罹患此病。平均卵巢体积大于其他报道中成年妇女的卵巢体积,35%的女孩在经腹超声时显示有多囊卵巢形态。按照游离睾酮数值排序,取前5%作为HA。42名女孩(18.5%)符合PCOS的Rotterdam标准,11个女孩(5%)雄激素超出社会标准。本研究表明,月经不规律在青春期是常见的,不涉及临床或生化HA。卵巢体积和形态的PCOS诊断在青春期可能有局限性。     

The protective effects of C16 peptide and angiopoietin-1 compound in lipopolysaccharide-induced acute respiratory distress syndrome

C16 peptide and angiopoietin-1 (Ang-1) have been found to have anti-inflammatory activity in various inflammation-related diseases. However, their combined role in acute respiratory distress syndrome (ARDS) has not been investigated yet. The objective of this study was to investigate the effects of C16 peptide and Ang-1 in combination with lipopolysaccharide (LPS)-induced inflammatory insult in vitro and in vivo. Human pulmonary microvascular endothelial cells and human pulmonary alveolar epithelial cells were used as cell culture systems, and an ARDS rodent model was used for in vivo studies. Our results demonstrated that C16 and Ang-1 in combination significantly suppressed inflammatory cell transmigration by 33% in comparison with the vehicle alone, and decreased the lung tissue wet-to-dry lung weight ratio to a maximum of 1.53, compared to 3.55 in the vehicle group in ARDS rats. Moreover, C  +  A treatment reduced the histology injury score to 60% of the vehicle control, enhanced arterial oxygen saturation (SO₂), decreased arterial carbon dioxide partial pressure (PCO₂), and increased oxygen partial pressure (PO₂) in ARDS rats, while also improving the survival rate from 47% (7/15) to 80% (12/15) and diminishing fibrosis, necrosis, and apoptosis in lung tissue. Furthermore, when C  +  A therapy was administered 4 h following LPS injection, the treatment showed significant alleviating effects on pulmonary inflammatory cell infiltration 24 h postinsult. In conclusion, our in vitro and in vivo studies show that C16 and Ang-1 exert protective effects against LPS-induced inflammatory insult. C16 and Ang-1 hold promise as a novel agent against LPS-induced ARDS. Further studies are needed to determine the potential for C16 and Ang-1 in combination in treating inflammatory lung diseases.     

Histoplasmosis diseminada y síndrome hemofagocítico en pacientes VIH: serie de casos en un hospital peruano

BackgroundDisseminated histoplasmosis (DH) is an opportunistic fungal infection in severely immunocompromised patients with HIV infection. Haemophagocytic syndrome (HFS), which can occur in these co-infected patients when the immune response is significantly altered, is often associated with high mortality.AimsTo describe the epidemiological, clinical, analytical and microbiological characteristics, along with studying the presence of HFS, in patients with DH-HIV.MethodsA retrospective study was conducted on a case series using data from the clinical records of patients diagnosed with DH and HIV infection during the years 2014 and 2015.ResultsDH was diagnosed in 8 (1.3%) of 597 HIV patients. All patients were in stage C3, and 75% (6/8) were not receiving combined antiretroviral therapy (CART). The remaining two patients had recently begun CART (possible immune reconstitution syndrome). Five (62.5%) of the 8 patients met criteria for HFS. The most frequent clinical symptoms were lymphoproliferative and consumptive syndrome, respiratory compromise, and cytopenia. Histoplasma was isolated in lymph nodes of 75% (6/8) of the patients, in blood samples in 25% (2/8), and also in intestinal tissue in one patient. The antifungal therapy was amphotericin B deoxycholate, without adjuvants. The overall mortality was 50%.ConclusionsIn this case series, DH-HIV co-infection frequently progressed to HFS with high mortality. The clinical picture may resemble that of other systemic opportunistic infections, such as tuberculosis, or can take place simultaneously with other infections. Clinical suspicion is important in patients with severe cytopenia and lymphoproliferative and consumptive syndrome in order to establish an early diagnosis and prescribing a timely specific therapy.     

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.     

Hypomorphic zebrafish models mimic the musculoskeletal phenotype of β4GalT7-deficient Ehlers-Danlos syndrome

β4GalT7 is a transmembrane Golgi enzyme, encoded by B4GALT7, that plays a pivotal role in the proteoglycan linker region formation during proteoglycan biosynthesis. Defects in this enzyme give rise to a rare autosomal recessive form of Ehlers-Danlos syndrome (EDS), currently known as ‘spondylodysplastic EDS (spEDS-B4GALT7)’. This EDS subtype is mainly characterized by short stature, hypotonia and skeletal abnormalities, thereby illustrating its pleiotropic importance during human development. Insights into the pathogenic mechanisms underlying this disabling disease are very limited, in part due to the lack of a relevant in vivo model.As the majority of mutations identified in patients with spEDS-B4GALT7 are hypomorphic, we generated zebrafish models with partial loss of B4galt7 function, including different knockdown (morphant) and mosaic knockout (crispant) b4galt7 zebrafish models and studied the morphologic, functional and molecular aspects in embryonic and larval stages.Morphant and crispant zebrafish show highly similar morphological abnormalities in early development including a small, round head, bowed pectoral fins, short body-axis and mild developmental delay. Several craniofacial cartilage and bone structures are absent or strongly misshapen. In addition, the total amount of sulfated glycosaminoglycans is significantly diminished and particularly heparan and chondroitin sulfate proteoglycan levels are greatly reduced. We also show impaired cartilage patterning and loss of chondrocyte organization in a cartilage-specific Tg(Col2a1aBAC:mcherry) zebrafish reporter line. The occurrence of the same abnormalities in the different models confirms these are specifically caused by B4galt7 deficiency. A disturbed actin pattern, along with a lack of muscle tone, was only noted in morphants in which translation of b4galt7 was blocked.In conclusion, we generated the first viable animal models for spEDS-B4GALT7, and show that in early development the human spEDS-B4GALT7 phenotype is faithfully mimicked in these zebrafish models. Our findings underscore a key role for β4GalT7 in early development of cartilage, bone and muscle. These models will lead to a better understanding of spEDS-B4GALT7 and can be used in future efforts focusing on therapeutic applications.     

Synthesis of 18F-labeled streptozotocin derivatives and an in-vivo kinetics study using positron emission tomography

Glucose transporter 2 (GLUT2) is involved in glucose uptake by hepatocytes, pancreatic beta cells, and absorptive cells in the intestine and proximal tubules in the kidney. Pancreatic GLUT2 also plays an important role in the mechanism of glucose-stimulated insulin secretion. In this study, novel Fluorine-18-labeled streptozotocin (STZ) derivatives were synthesized to serve as glycoside analogs for in-vivo GLUT2 imaging. Fluorine was introduced to hexyl groups at the 3′-positions of the compounds, and we aimed to synthesize compounds that were more stable than STZ. The nitroso derivatives exhibited relatively good stability during purification and purity analysis after radiosynthesis. We then evaluated the compounds in PET imaging and ex-vivo biodistribution studies. We observed high levels of radioactivity in the liver and kidney, which indicated accumulation in these organs within 5 min of administration. In contrast, the denitroso derivatives accumulated only in the kidney and bladder shortly after administration. Compounds with nitroso groups are thus expected to accumulate in GLUT2-expressing organs, and the presence of a nitroso group is essential for in-vivo GLUT2 imaging.     

肠道微生物与性激素相关疾病研究进展

数以万亿计的微生物生活在人类肠道中,形成了一个复杂的微生态群落。肠道微生物可为宿主提供营养和能量,并与人类疾病的发生发展密切相关。随着研究的不断深入,越来越多的证据表明肠道微生物的改变可引起性激素水平变化,进而导致一系列相关的疾病发生。本文就肠道微生物与多囊卵巢综合征、乳腺癌、卵巢癌等性激素相关疾病之间的关系进行阐述,旨在为人类疾病诊疗提供新思路。