补肾壮骨胶囊对去卵巢大鼠骨质疏松症骨密度和相关细胞因子的影响

目的：研究补肾壮骨胶囊对去卵巢大鼠骨质疏松症的骨密度和细胞因子等的影响,探索该药对绝经后骨质疏松症的防治功效及作用机理。方法：将大鼠随机分为6组：假手术组、卵巢切除组、切除卵巢＋牡蛎碳酸钙组、切除卵巢＋补肾壮骨胶囊低剂量组、切除卵巢＋补肾壮骨胶囊中剂量组、切除卵巢＋补肾壮骨胶囊高剂量组,观察骨密度、血清E2和IL-6、子宫指数和股骨指数等指标,了解其对去卵巢大鼠骨骼的影响。结果：1）骨密度的变化：去卵巢16周后,卵巢切除组大鼠右股骨骨密度和骨矿含量均明显低于假手术对照组,差异有显著性（P〈0.01）,表明造模成功。与卵巢切除组比较,补肾壮骨胶囊中剂量组和高剂量组可明显提高模型大鼠股骨BMC含量（P〈0.05）,高剂量组可明显提高模型大鼠股骨BMD的含量（P〈0.05）。2）血清E2和IL-6的变化：去卵巢16周后,卵巢切除组大鼠血清E2含量显著低于假手术对照组,差异有显著性（P〈0.05）。中药中剂量组及高剂量组E2含量明显高于模型组,差异有显著性（P〈0.05）。3）子宫指数和股骨指数：与假手术组比较,卵巢切除组子宫指数和股骨指数明显降低,具有统计学意义（P〈0.05）,提示造模成功。与卵巢切除组比较,高剂量组子宫指数明显增加（P〈0.05）;高、中、低三个剂量组股骨指数均明显增加（P〈0.05）。结论：补肾壮骨胶囊能增加去卵巢大鼠子宫湿重,但对干重无明显影响,可以显著提高去卵巢大鼠离体骨骨密度及改善其生物力学性能,提高去卵巢大鼠血清E2和IL-6含量,具有类性激素样作用。     

An accidental case of aconite poisoning due to Kampo herbal medicine ingestion

An accidental case of aconite intoxication occurred after a patient took a therapeutic dose of Kampo herbal medicine containing Aconiti tuber, Uzu but had used the wrong decoction procedure. The poisoning was likely caused by an increased level of Aconitum alkaloids in the decoction; the patient developed aconite intoxication due to incomplete decoction. Aconitum alkaloid levels in the leftover solution which the patient had drunk and in the decoction extracted from 3 g Uzu were determined. It was found that decoction makes the medicine safer to drink. Older individuals, especially those with dementia, have a higher risk of aconite poisoning because they sometimes do not boil the medicine appropriately.     

AFP-producing Xp11 translocation renal cell carcinoma: Case report and review of the literature

Alpha-fetoprotein (AFP) is a useful tumor marker for hepatocellular carcinomas and yolk sac tumors. Rare extrahepatic visceral malignancies may be associated with AFP production and those exhibiting a hepatoid differentiation by morphology and immunohistochemical are classified as hepatoid adenocarcinoma. Renal cell carcinoma (RCC) producing AFP is a rare entity. To date, only one case of AFP-producing Xp11 translocation RCC has been reported. We reported another case of Xp11 translocation RCC, in which the tumor cells displayed strong immunostaining for AFP, HepPar1, and GPC-3. Additionally, the other published cases are reviewed.     

Does the efficacy of regorafenib differ in chemotherapy refractory metastatic colorectal cancer patients who had mucinous pathology compared to those who had non-mucinous pathology?

Purpose: To investigate the importance of mucinous histopathology on the assessment of tumor response in patients with metastatic colorectal cancer (mCRC) receiving regorafenib. Materials and method: All patients diagnosed with histologically confirmed mCRC in 2 oncology centers between 2013 and 2018 were retrospectively analyzed. Among 678 patients diagnosed with mCRC, 103 patients were treated with regorafenib. Ninety-four of these patients who had used at least 2 cycles of regorafenib and evaluable for treatment response were included in the analysis. Histopathologically, 18 patients with mucinous adenocarcinoma and 76 patients with nonmucinous adenocarcinoma were compared in terms of response rate and survival durations. Results: Median follow-up duration of 6 months, median age of the patients was 61 (34-77) years. While 19.1% of the patients had mucinous histology, 80.9% had nonmucinous histology. The overall response rate was significantly lower in the mucinous subgroup than the nonmucinous subgroup (5.6% vs 43.4%, respectively, P = 0.003). Similarly, both progression-free survival (3.0 vs 4.0 months, respectively, P = 0.011) and overall survival duration were shorter in the mucinous subgroup (3.0 vs 7.0 months, P = 0.016, respectively) compared with the nonmucinous subgroup. Conclusion: The histological subgroup may predict tumor response in mCRC patients receiving regorafenib. Its efficacy on nonmucinous histology had significantly more favorable than mucinous subtype.     

Lung sounds classification using convolutional neural networks

Lung sounds convey relevant information related to pulmonary disorders, and to evaluate patients with pulmonary conditions, the physician or the doctor uses the traditional auscultation technique. However, this technique suffers from limitations. For example, if the physician is not well trained, this may lead to a wrong diagnosis. Moreover, lung sounds are non-stationary, complicating the tasks of analysis, recognition, and distinction. This is why developing automatic recognition systems can help to deal with these limitations. In this paper, we compare three machine learning approaches for lung sounds classification. The first two approaches are based on the extraction of a set of handcrafted features trained by three different classifiers (support vector machines, k-nearest neighbor, and Gaussian mixture models) while the third approach is based on the design of convolutional neural networks (CNN). In the first approach, we extracted the 12 MFCC coefficients from the audio files then calculated six MFCCs statistics. We also experimented normalization using zero mean and unity variance to enhance accuracy. In the second approach, the local binary pattern (LBP) features are extracted from the visual representation of the audio files (spectrograms). The features are normalized using whitening. The dataset used in this work consists of seven classes (normal, coarse crackle, fine crackle, monophonic wheeze, polyphonic wheeze, squawk, and stridor). We have also experimentally tested dataset augmentation techniques on the spectrograms to enhance the ultimate accuracy of the CNN. The results show that CNN outperformed the handcrafted feature based classifiers.     

Identification of key transporters mediating uptake of aconitum alkaloids into the liver and kidneys and the potential mechanism of detoxification by active ingredients of liquorice

Aconite as a commonly used herb has been extensively applied in the treatment of rheumatoid arthritis, as pain relief, as well as for its cardiotonic actions. Aconitum alkaloids have been shown to be the most potent ingredients in aconite, in terms of efficacy against disease, but they are also highly toxic. Apart from neurological and cardiovascular toxicity exposed, the damage to hepatocytes and nephrocytes with long-term use of aconitum alkaloids should also be carefully considered. This study attempted to investigate the critical role of uptake transporters mediating the transport of aconitum alkaloids into the liver and the kidneys. The resulting data revealed that hOATP1B1, 1B3, hOCT1 and hOAT3 were mainly involved in the uptake of aconitum alkaloids. Additionally, the inhibitory effects of bioactive ingredients of liquorice on uptake transporters were screened and further confirmed by determining the IC₅₀ values. The in vitro study suggested that liquorice might lower the toxicity of aconite by reducing its exposure in the liver and/or kidneys through inhibition of uptake transporters. Eventually, the in vivo study was indicative of detoxification of liquorice by decreasing the exposure of aconitine as representative compound in liver after co-administration, even though the exposure in kidney altered was less significant. In summary, hOATP1B1, 1B3, hOCT1 and hOCT3 were determined as the key uptake transporters mediating the transport process of aconitum alkaloids into the liver and/or kidneys, and liquorice may alleviate the toxicity caused by reduction of exposure through inhibition of those key uptake transporters.

Liquorice may alleviate the toxicity of bioactive ingredients of aconite by inhibiting transporters mediating uptake in the liver/kidneys.     

Non-cognitive outcomes in trials of disease-modifying drugs for Alzheimer's disease

Alzheimer's disease (AD) constitutes a major challenge for healthcare systems in countries with ageing populations. The clinical signs include the progressive loss of memory and other cognitive functions. However, AD also has non-cognitive features, such as decline in functional abilities, inducing a spectrum of psychological and behavioural symptoms. There is considerable clinical interest in non-cognitive abnormalities of AD, due to their high prevalence and because non-cognitive features complicate patient management, increasing the burden on caregivers and frequently leading to institutionalisation. Efforts are currently being made to investigate AD pathology and to develop appropriate treatment strategies. These strategies focus on the long-term preservation of cognitive and functional abilities and/or the slowing of disease progression, together with the attenuation of behavioural symptoms and the maintenance of quality of life for the patient and the caregiver. The non-cognitive features of AD are often neglected, but are important outcomes when evaluating the “real-life” benefits of disease-modifying treatments for dementia. We discuss the non-cognitive outcomes of interest, in particular, activities of daily living, nutritional parameters, mood and behavioural features, falls, patient's and caregiver's quality of life and use of health system; and the instruments that can be used to measure them.