Parkin and PINK1 play an important role in mitochondrial quality control, whose malfunction may also be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Excessive TDP-43 accumulation is a pathological hallmark of ALS and is associated with Parkin protein reduction in spinal cord neurons from sporadic ALS patients. In this study, we reveal that Parkin and PINK1 are differentially misregulated in TDP-43 proteinopathy at RNA and protein levels. Using knock-in flies, mouse primary neurons, and TDP-43Q331K transgenic mice, we further unveil that TDP-43 downregulates Parkin mRNA, which involves an unidentified, intron-independent mechanism and requires the RNA-binding and the protein–protein interaction functions of TDP-43. Unlike Parkin, TDP-43 does not regulate PINK1 at an RNA level. Instead, excess of TDP-43 causes cytosolic accumulation of cleaved PINK1 due to impaired proteasomal activity, leading to compromised mitochondrial functions. Consistent with the alterations at the molecular and cellular levels, we show that transgenic upregulation of Parkin but downregulation of PINK1 suppresses TDP-43-induced degenerative phenotypes in a Drosophila model of ALS. Together, these findings highlight the challenge associated with the heterogeneity and complexity of ALS pathogenesis, while pointing to Parkin–PINK1 as a common pathway that may be differentially misregulated in TDP-43 proteinopathy.

In order to mine information from medical health data and develop intelligent applicationrelated issues, the multi-modal medical health data feature representation learning related content was studied, and several feature learning models were proposed for disease risk assessment. In the aspect of medical text feature learning, a medical text feature learning model based on convolutional neural network is proposed. The convolutional neural network text analysis technology is applied to the disease risk assessment application. The medical data feature representation adopts the deep learning method. The learning and extraction of different disease characteristics use the same method to realize the versatility of the model. A simple preprocessing of the experimental data samples, including its power frequency denoising and lead convolution regularization, constructs a convolutional neural network for medical data feature advancement and intelligent recognition. On the basis of it, several sets of experiments were carried out to discuss the influence of the convolution kernel and the choice of learning rate on the experimental results. In addition, comparative experiments with support vector machine, BP neural network and RBF neural network are carried out. The results show that the convolutional neural network used in this paper shows obvious advantages in recognition rate and training speed compared with other methods. In the aspect of time series data feature learning, a multi-channel convolutional self-encoding neural network is proposed. Analyze the connection between fatigue and emotional abnormalities and define the concept of emotional fatigue. The proposed multi-channel convolutional neural network is used to learn the data features, and the convolutional self-encoding neural network is used to learn the facial image data features. These two characteristics and the collected physiological data are combined to perform emotional fatigue detection. An emotional fatigue detection demonstration platform for multi-modal data feature fusion is established to realize data acquisition, emotional fatigue detection and emotional feedback. The experimental results verify the validity, versatility and stability of the model.

Background: Mycobacterium fortuitum is a rapidly growing non-tuberculous mycobacterium (NTM) with weak pathogenicity. Here, we present a rare case of disseminated M. fortuitum and Talaromyces marneffei coinfection in a human immunodeficiency virus (HIV) negative patient. Case Presentation: A 28-year-old female was admitted to our hospital due to 2 months of swelling of lymph nodes on the right side of her cervix, accompanied by repeated low fever for more than 1 month. Biopsy of the right cervical lymph node and endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) both suggested granulomatous inflammation. The bacterial culture and mycobacteria examination of the lesion as well as HIV antibody test were all negative. Disseminated T. marneffei infection was diagnosed by the quantitative polymerase chain reaction (qPCR) results from the blood showing 1798 copies/ul. In the meantime, treatment with amphotericin B combined with cefoxitin was administered for suspected NTM infection. However, the once-dropped fever recurred and the lymph nodes continued to swell. Metagenomics next-generation sequencing (mNGS) detection of the lymph nodes indicated M. fortuitum. After combination treatment with amphotericin B, voriconazole, linazolamide, and imipenem, the patient's body temperature returned to normal, the lymph node swelling was gradually reduced, and the lung lesion was absorbed. Conclusion:We report the first case of an HIV-negative patient diagnosed with disseminated M. fortuitum and T. marneffei coinfection with nonspecific clinical manifestation, in order to heighten awareness of these infections.

Hemangioendothelioma (HE) is a type of angiomatous lesions that features endothelial cell proliferation. Understanding the mechanisms orchestrating HE angiogenesis can provide therapeutic insights. It has been shown that platelets can support normal and malignant endothelial cells during angiogenesis. Using the mouse endothelial-derived EOMA cell line as a model of HE, we explored the regulatory effect of platelets. We found that platelets stimulated EOMA proliferation but did not mitigate apoptosis. Furthermore, direct platelet-EOMA cell contact was required and the proliferation was mediated via integrin β3/Akt signaling in EOMA cells. SiRNA knockdown of integrin β3 and inhibition of Akt activity significantly abolished platelet-induced EOMA cell proliferation in vitro and tumor development in vivo. These results provide a new mechanism by which platelets support HE progression and suggest integrin β3 as a potential target to treat HE.

<strong>Objective: </strong>Study clinical curative effect of levonorgestrel treatment on perimenopausal dysfunctional uterine bleeding. Method: Selected 126 outpatient of dysfunctional uterine bleeding which hospitalize from December 2010 to December 2012 at department of gynaecology to undergo levonorgestrel treatment on the 5‒7 days of menstruation. The endometrial thickness, hemoglobin, and the PBAC score of before and 3, 6, and 12 months after placement were observed and recorded. To observation the adverse reactions after levonorgestrel treatment. <strong>Results: </strong>After treatment, the thickness of the endometrium, the amount of menstruation and the hemoglobin concentration increased in 126 patients. During the treatment, 21 patients experienced mild dizziness and nausea, but did not affect the drug use and efficacy. <strong>Conclusion: </strong>Effects of levonorgestrel on intrauterine treatment of perimenopausal dysfunctional uterine bleeding can effectively reduce the amount of menstruation and increase hemoglobin levels. It is economic, simple, less adverse reaction, and widely entrenched in clinical practice.