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

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.

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.

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.

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.

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.

Objective:To understand the epidemiological characteristics and post-exposure prophylaxis (PEP) situation of rabies exposure population in the animal injury outpatient department of Lishui Central Hospital, so as to provide reference for rabies prevention and control in this region.Methods:The epidemiological data of 6 471 rabies-exposed persons in Lishui Central Hospital from 2021 to 2023 were retrospectively analyzed, including the gender and age of exposed persons, the month and location of injury, the species of injured animals, the exposure grade, rabies vaccination, rabies passive immunization agents, etc.Results:From 2021 to 2023, a total of 6 471 cases of rabies exposure were treated in the animal injury outpatient department of Lishui Central Hospital. From 2021 to 2023, 1 133 cases, 2 135 cases and 3 203 cases were treated respectively. April to November was the peak period of exposure. The population of 21 to 30 years had the highest rate of treatment, reaching 27.79% (1 798/6 471), and was a high-risk group of exposure. The age composition ratio of rabies exposure in the three years was statistically significantly different ( χ2=43.82, P<0.001); the male to female ratio was 1∶1.14 ( χ2=1.63, P=0.442); 3 317 cases (51.26%, 3 317/6 471) were injured by cats, and 2 614 cases (42.16%, 2 614/6 471) were injured by dogs, cats and dogs were the main injured animals ( χ2=18.63, P=0.098). The upper limbs (4 131/6 471, 63.84%) and lower limbs (1 848/6 471, 28.56%) were the most exposed sites, and there was a statistically significant difference in the exposure composition ratio of each site in three years ( χ2=105.79, P<0.001). Grade II exposure accounted for 31.79% (2 057/6 471), grade III exposure accounted for 62.31% (4 032/6 471). Among grade III exposure individuals, those who used passive immune preparations accounted for 55.13% (2 232/4 032). Conclusions:The number of rabies-exposed patients in the animal injury outpatient department of Lishui Central Hospital has been increasing year by year, and the population of patients injured by cats and dogs is particularly prominent. The utilization rate of passive immune preparations for grade III exposure patients still needs to be further improved.

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:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To analyze the confirmation results of initial screening positive for human immunodeficiency virus (HIV) antibodies and to investigate the rationality of the gray zone for the signal-to-cutoff (S/CO) ratio values obtained by chemiluminescence assay. Methods A total of 184 specimens with positive HIV antibody screening results were collected. Confirmation was conducted using the Western blot (WB) method and viral nucleic acid testing, and the confirmation outcomes and band distribution were observed. The receiver operating characteristic (ROC) curve was employed to predict the optimal cutoff value, and the rationality of S/CO values in establishing a gray zone for HIV antibody was analyzed. Results Among the 184 HIV antibody screening positive samples, 153(83.15%) were initially screened by chemiluminescence, and 31 (16.85%) were screened by colloidal gold method. Male cases (57.07%) and those aged 40 years or older (75.00%) had higher proportion of initial screening positivity than females and other age groups. Supplemental WB testing revealed that 101 (54.89%) cases were confirmed as HIV-1 antibody positive, 56(30.43%) were negative, and 27(14.67%) were indeterminate. Of the 27 indeterminate cases, one was confirmed positive by NAT (initial S/CO value by chemiluminescence5.60), while the remaining 26 were negative. The positive agreement rates between chemiluminescence, colloidal gold and supplemental WB testing were 65.36% and 3.23%, respectively, with statistically significant difference (χ²=40.191, P < 0.05). Among 27 cases with indeterminate HIV-1 antibody results, upon further nucleic acid testing for viral load, one case exhibited WB banding pattern of P24+gp160, and the nucleic acid load confirmed this case as positive. In the distribution of band patterns among indeterminate samples, P24 had the highest occurrence (74.07%), followed by P66 (11.11%), gp160 (7.41%) as well as P17 and gp41 (both 3.70%). The ROC curve predicted the optimal S/CO cutoff value to be 5.15, with an area under the curve (AUC) of 0.904, sensitivity and specificity of 83.30% and 76.40%, respectively, and 95%CI of 0.861 to 0.948. There was a good correlation between the WB band patterns and confirmation results for initial screening positive cases (P < 0.05), with the highest correlation found for the P24 band (r=0.910). Conclusion There is a certain rate of false positives among HIV antibody initial screening positive cases, and effective screening can be achieved through WB testing. Additionally, based on the current testing platform, the gray zone for HIV antibody S/CO values in the chemiluminescence assay is set at 1.00 to 5.15, which exhibits high sensitivity.