In public health emergencies,medical emergency response efforts face governance challenges such as complex and variable tasks,difficulties in team organization,and uncertain working areas.The establishment of temporary party organiza-tions plays a crucial role in efficiently achieving the goals of medical emergency teams and stabilizing social order.This paper an-alyzes the functional positioning,key tasks,and operational mechanisms of temporary party organizations within Guangdong's medical teams aiding in the pandemic response.The study finds that these temporary party organizations effectively address the complex challenges of public health emergencies through functions such as strengthening political leadership,mobilizing public support,coordinating organization,and serving the community.This provides important insights for advancing the construction of governance systems for public health emergencies in China.

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribo-somopathy genes have also been found to be intimately associated with cancer development.The cor-relation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

Objective:To analyze the clinical characteristics of patients suffering from acute ischemic stroke (AIS) complicated with obstructive sleep apnea-hypopnea syndrome (OSAHS).Methods:Data of patients with AIS who visited the Second Affiliated Hospital of Soochow University from January 2015 to June 2020 and underwent polysomnography monitoring (PSG) in the sleep center were collected retrospectively. Patients were divided into OSAHS group and AIS only group. Demographic information of patients, general clinical data, hematological indicators of glucose and lipid metabolism and inflammatory markers, PSG parameters and neurological function scores were collected, including the National Institutes of Health Stroke Scale (NIHSS) on admission and the modified Rankin Scale (mRS) on discharge. We compared the differences between the two groups. In addition, OSAHS group were divided into good prognosis and poor prognosis subgroups according to mRS score. The differences between the two subgroups were compared.Results:A total of 112 AIS patients combined with OSAHS and 89 AIS only patients were included. The proportion of non-rapid eye movement stages 1+2 [(N1+N2) %], arousal index, the oxygen desaturation index (ODI), percentage of total sleep time with oxygen saturation<90% (TS90) in the OSAHS group were higher than those in the AIS only group, while N3%, lowest nocturnal oxygen saturation (LSaO 2) were lower (all P<0.05). There was no statistical difference in the distribution of cerebral apoplexy lesions (cortex, subcortical, brainstem, cerebellum) between the two groups, but the proportion of patients with multifocal cerebral apoplexy in the OSAHS group was higher ( P=0.032). There was no statistical difference in NIHSS score on admission between the two groups, but the neutrophil/lymphocyte ratio (NLR) score ( P=0.004) and mRS score on discharge ( P=0.010) of the OSAHS group were significantly higher than those in the AIS only group. There were 74 patients in the good prognosis group and 38 in the poor prognosis group. The analysis showed that the NIHSS and NLR scores of the poor prognosis group were higher than the good prognosis group, admission NIHSS score was a risk factor for poor prognosis, all P<0.01. Conclusions:AIS patients complicated with OSAHS are characterized by disordered sleep structure, more severe nocturnal hypoxia, higher risk of developing multiple lesions, poor neurological function recovery at discharge, and high inflammatory index of NLR. Among them, patients with poor prognosis have poorer sleep efficiency, and high admission NIHSS score is a risk factor for poor prognosis.

Objective To observe the characteristics of brain activation of multiple sclerosis (MS) patients and healthy controls at functional magnetic resonance imaging (fMRI) with olfactory stimulation,determine the locations of activation in areas of olfactory center and explore the MS olfactory related network.Methods Eighteen MS patients from the Affiliated Hospital of North Sichuan Medical College from February 2017 to March 2018 were enrolled as MS group,and 20 matched healthy adults during the same period served as controls.The Visual Analogue Scale was used to evaluate olfactory function in all subjects,the rest structure MRI was performed first,and volatile gases of lavender and rose solution were used to alternately stimulate olfactory during fMRI scanning.The brain activation was obtained by using matlab2013a and SPM8 softwares.The distribution and quantity of demyelination lesions were counted on T2 weighted image,and Spearman correlation analysis was done with SPSS 17.0 software package.Results The activated brain areas in the healthy control group included bilateral middle frontal gyrus,bilateral insula,bilateral supramarginal gyrus,bilateral orbitofrontal gyrus,right thalamus,right central anterior gyrus,bilateral cingulated gyrus,bilateral hippocampus,bilateral amygdala and bilateral superior frontal gyrus (t =2.11,P＜0.05).The activated brain areas in the MS group included right cerebellum,left insula,left superior temporal gyrus,right inferior frontal gyrus (t=2.19,P＜0.05).Compared with the control group,the MS group showed statistically significant decrease in activated values in right insula,right amygdala,right inferior frontal gyrus,right frontal middle gyrus,and the left supramarginal gyrus (t=2.04,P＜0.05).The distribution and number of demyelination lesions and major activation of brain regions with olfactory in the MS group demonstrated no significant correlation (r=-0.524,P=0.054).Conclusions Multiple brain areas involved in the olfactory processing and olfactory-related brain network existed.The activation of olfactory center had dominance in the right brain.The activation of the brain area in the MS group was significantly reduced,and the activation voxel and activation intensity were weakened.The olfactory-related brain network changed in MS patients.The distribution and number of demyelination lesions had no significant effect on the major activation of brain regions with olfactory stimulation.

Parkinson's disease (PD) is one of the most common forms of neurodegenerative diseases and increases in incidence with aging.Low mortality and high disability rates bring huge economic and psychological burden to society and families.PD manifested as motor symptoms and non-motor symptoms.Recent studies have shown that non-motor symptoms,such as sensory disorder,are the significant symptoms in early stages of PD and influence quality of life of PD patients.This review focuses on the characteristics and electrophysiological changes of sensory disorders (olfactory,visual,auditory,vestibule function,pain,etc) in PD patients to provide help for the early diagnosis,disease monitoring and efficacy evaluation of PD.