Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective To investigate the clinical characteristics in an elderly patient with sellar multiple myeloma.Methods Clinical features,laboratory data and radiologic profile of an elderly patient with sellar multiple myeloma were collected.Results The patient was an 85-year-old male.The main clinical manifestations were fatigue,poor appetite and polyuria.Laboratory examinations showed a significant decrease in blood sodium,several anterior pitu-itary hormones and an increase in total protein,mass of pituitary lesion and concentration of prolactin.During etio-logical screening,it was found that the blood immunoglobulin G(IgG)level was significantly increased,the blood M protein was positive and the bone marrow smear showed myeloma cells accompanied by multiple osteolytic lesions in the bones of the whole body.Considering the diagnosis of multiple myeloma,the pituitary lesion was likely to be the extra-medullary involvement.Conclusions The intrasellar plasmacytoma is not common.The disease onset is insidious with clinical features and imaging findings lacking specificity.Therefore,diagnosis relies on biopsy which poses risks for elderly patients and increases diagnostic challenges leading to misdiagnosis.

Objective To explore the home rehabilitation experience of individuals with fully magnetically levitated left ventricular assist device,and to provide a basis for developing scientific nursing intervention plans and follow-up strategies for clinical practice.Methods Using phenomenological research methods,a semi-structured interview was conducted on 13 patients with fully maglev left ventricular assist device implantation in a tertiary A comprehensive hospital in Wuhan from September to October 2022.Colaizzi's 7-step analysis method was used to analyze the data and extract themes.Results A total of 3 themes and 9 subthemes were extracted,including complex emotions in home rehabilitation(challenges for new characters,anxieties and concerns,regaining new life and full of confidence),difficulties in home self-management(lack of professional knowledge,insufficient exercise,difficulty in managing pump cable bag wounds,weak ability to recognize and respond to external controller alarms),and needs for home rehabilitation(need for continuity of care,desire for more social support).Conclusion Complex emotional experiences and many difficulties and needs exist in the home rehabilitation process of patients after implantation of full magnetic levitation left ventricular assist device.Healthcare professionals should actively pay attention to the postoperative psychological changes of patients,strengthen pre-discharge training to improve patients'self-management ability,and actively build a multi-party Internet home rehabilitation management platform to improve the rehabilitation quality of patients.

Objective To explore the home rehabilitation experience of individuals with fully magnetically levitated left ventricular assist device,and to provide a basis for developing scientific nursing intervention plans and follow-up strategies for clinical practice.Methods Using phenomenological research methods,a semi-structured interview was conducted on 13 patients with fully maglev left ventricular assist device implantation in a tertiary A comprehensive hospital in Wuhan from September to October 2022.Colaizzi's 7-step analysis method was used to analyze the data and extract themes.Results A total of 3 themes and 9 subthemes were extracted,including complex emotions in home rehabilitation(challenges for new characters,anxieties and concerns,regaining new life and full of confidence),difficulties in home self-management(lack of professional knowledge,insufficient exercise,difficulty in managing pump cable bag wounds,weak ability to recognize and respond to external controller alarms),and needs for home rehabilitation(need for continuity of care,desire for more social support).Conclusion Complex emotional experiences and many difficulties and needs exist in the home rehabilitation process of patients after implantation of full magnetic levitation left ventricular assist device.Healthcare professionals should actively pay attention to the postoperative psychological changes of patients,strengthen pre-discharge training to improve patients'self-management ability,and actively build a multi-party Internet home rehabilitation management platform to improve the rehabilitation quality of patients.

Objective To investigate the needs and feedback from clinical medical students on the diversified teaching mode adopted by the Department of Endocrinology in Peking Union Medical College Hospital.Methods Questionnaires were distributed to the medicine students who were in clinical rotation in Peking Union Medical Col-lege,and the teaching status and teaching effect was investigated.Results A total of 95 valid questionnaires were received.The attending physicians and the teaching resident physicians performed well in the daily teaching activi-ties.The medical students believed that outpatient training was necessary in addition to ward rotations.After the ro-tation in the endocrinology department,the self-evaluated score of mastery of endocrinology knowledge had been significantly improved,especially in those who rotated in outpatient clinic,suggesting that outpatient teaching was of great significance.In addition,the establishment of a self-learning platform including clinical cases and videos in endocrinology could be used as an important supplementary means for clinical teaching.Conclusions Outpatient training improves learning outcomes of medical students,so must be kept and further strengthened in the future.Building a database of typical clinical cases and teaching videos can improve the training quality.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

This article reports the diagnosis and treatment of a case of acromegaly in a pregnant patient who took bromocriptine during pregnancy and delivered successfully. A retrospective summary of the clinical data and treatment outcomes before and after two pregnancies of the patient is provided. The patient took bromocriptine during the second pregnancy, and her condition remained stable. A baby girl was delivered by caesarean section at full term. The article suggests that pregnancy in acromegaly patients, after the stabilization of the condition, can lead to favorable outcomes. The use of dopamine receptor agonists during pregnancy does not increase adverse events during the perinatal period.

Objective To investigate the clinical prognosis value of serum microRNA(miR)-138-5p and miR-212-5p levels in prostate cancer.Methods A total of 95 cases of prostate cancer patients admitted to the First Hospital of Handan from July 2020 to June 2021 were collected.Based on follow-up records for two years after surgery,these patients were separated into a poor prognosis group(n=52)and a good prognosis group(n=43),and 48 healthy volunteers who underwent a physical examination at the hospital were collected as the healthy control group.In addition,quantitative real-time fluorescence-PCR(qRT-PCR)was applied to detect the relative expression levels of miR-138-5p and miR-212-5p in the serum of study subjects,and the clinical data of the patients were collected and analyzed.Multivariate COX regression was applied to analyze factors that affected the prognosis of prostate cancer patients.The predictive value of serum miR-138-5p and miR-212-5p for the prognosis of prostate patients was tested,and receiver operating characteristic(ROC)curves were plotted.Pearson method was applied to analyze the correlation between the expression of serum miR-138-5p and miR-212-5p and the Gleason score.Results Compared to the healthy control group,the serum levels of miR-138-5p(0.88±0.10,0.83±0.09 vs 1.01±0.10),and miR-212-5p(0.75±0.09,0.71±0.08 vs 1.02±0.11)were lower in the good prostate cancer prognosis group and poor prostate cancer prognosis group,and the differences were significant(t=14.021,22.275;9.825,18.063,all P＜0.05).The prognosis of prostate cancer patients was related to TNM staging,bone metastasis,tissue differentiation degree,preoperative PSA level,and Gleason score(x2=4.417～7.187,t=14.235,all P＜0.05).Serum miR-138-5p[HR(95％CI):0.871(0.785～0.966)],and miR-212-5p[HR(95％CI):0.822(0.725～0.932)]were protective factors for poor prognosis(all P＜0.05).While Gleason score[HR(95％CI):1.253(1.026～1.530)],TNM stage[HR(95％CI):1.224(1.024～1.463)],bone metastasis[HR(95％CI):1.398(1.036～1.887)],tissue differentiation degree[HR(95％CI):1.520(1.146～2.016)]and PSA level[HR(95％CI):1.426(1.094～1.858)]were all risk factors for poor prognosis(all P＜0.05).The AUC(95％CI)of serum miR-138-5p and miR-212-5p were 0.883(95％CI:0.801～0.940)and 0.863(95％CI:0.777～0.925),respectively.Serum miR-138-5p and miR-212-5p were negatively correlated with the Gleason score(r=-0.610,-0.420,all P＜0.05).Conclusion Serum miR-138-5p and miR-212-5p levels are elevated in patients with poor prostate cancer prognosis and may have a certain auxiliary predictive value for prostate cancer patient prognosis.

Objective The objective of this study is to examine the expression level of the S100A7A protein in both gastric cancer tissues and cells,as well as to evaluate its impact on the malignant phenotype of gastric cancer(GC)cells.Methods Immunohistochemical assay was used to detect the expression characteristics of S100A7A in 21 gastric cancer tissues and their corresponding paracancerous tissues,as well as to investigate its correlation with gastric cancer clinicopathological factors.Gastric cancer cells were genetically modified to overex-press S100A7A through plasmid transfection.Subsequently,the impact of S100A7A on the proliferation,migra-tion,and invasion capacities of gastric cancer cells was assessed using cell proliferation assays(EdU assay and plate cloning assay)as well as cell migration and invasion assays(Transwell assay and scratch assay).Results The expression of S100A7A protein was higher in GC tissues than in paracancerous tissues;Overexpression of S100A7A may increase gastric cancer cell proliferation,migration,and invasion.Conclusion S100A7A is a possible oncogene in GC and is predicted to serve as a new diagnostic and therapeutic target for the disease.