Drug-induced Parkinsonism (DIP) is a common complication of antipsychotic drugs, calcium channel antagonists, gastrointestinal prokinetic drugs, and antiepileptic drugs and the most common secondary Parkinsonism in the elderly. DIP caused by various drugs is not uncommon in clinic. However, it is easy to omit diagnosis and treatment. Withdrawal of offending drugs is the main treatment and lower risk drugs should be switched if the drug in use cannot be discontinued. The advances in definition, risk factors, pathogenesis, clinical features, diagnosis and treatment, and prognosis of DIP are reviewed in this paper, in order to improve cognition for this curable iatrogenic disease in clinical practice.

[Abstract] Objective: To explore the expression of PSME3 (proteasome activator complex subunit 3) in gastric cancer (GC) tissues and its correlation with the prognosis of GC patients, and to further analyze its effect and mechanism in the occurrence and development of GC. Methods: The expression level of PSME3 gene in GC tissues was analyzed with TCGA and UALCAN database. qPCR was used to verify the expression of PSME3 in GC tissues and corresponding adjacent normal tissues that resected from 40 GC patients who were surgically treated in the Fourth Hospital of Hebei Medical University from January 2017 to December 2018. ROC curve and KaplanMeier plotter method were used to analyze the value of PSME3 mainly in diagnosing and predicting the prognosis of GC patients. The biological processes and pathways that PSME3 involved in were further analyzed. Results: The expression level of PSME3 in GC tissues was significantly higher than that in normal tissues, and it’s high expression was significantly correlated with the tumor stage, pathological subtype, status of lymph node metastasis and Helicobacter pylori infection in GC patients (all P<0.01). PSME3 was also highly expressed in GC tissue samples collected by the qPCR confirmatory detection group (P<0.01). PSME3 could distinguish gastric cancer patients from normal people with an AUC value of 0.808. The overall survival time, the first progression survival time and post progression survival time of the GC patients with low PSME3 expression were longer than those in the patients with high PSME3 expression (all P<0.01). Mechanism research found that PSME3 mainly played an oncogenic role of the development of GC by regulating cell cycle, mTORC1 signaling pathway, PI3K/AKT/mTOR signaling pathway and TGF- β signaling pathway etc. Conclusion: PSME3 is highly expressed in GC tissues, and it is significantly related to the poor prognosis of GC patients. It plays an oncogenic role in the occurrence and development of GC.

The COVID-19 has had a profound impact on human society, the elderly, as a vulnerable group, are the most affected. Based on two cases of disease narrative collected by the department of neurology of a hospital in Guiyang, this paper analyzed the shortcomings of elderly care in the context of epidemic prevention and control. The overall health information literacy of the elderly was low, which made it difficult to obtain correct epidemic related information. The lifestyle of the elderly has changed during the epidemic prevention and control stag. The long time isolation at home has reduced their constitution and made them prone to illness, thus affecting the quality of healthy elderly care. In this stage, the psychological burden of the middle-aged and elderly people has been increasing, which reduced the life satisfaction and subjective well-being of the elderly, and increased the risk of depression. In view of these outstanding problems, this paper proposed corresponding measures, aiming to improve the quality of life and physical and mental health of the elderly during the epidemic prevention and control stage, and provide reference for realizing healthy aging in China.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.