Hepatocellular carcinoma （HCC） is a common primary malignant tumor. In recent years， the role of ubiquitin-specific proteases （USPs） in HCC has attracted widespread attention. USPs are a class of key deubiquitinating enzymes that affect a variety of biological processes by regulating the ubiquitination status of proteins. Studies have shown that USPs participate in the regulation of cell proliferation， apoptosis， migration， and invasion by deubiquitinating various tumor-related proteins. In addition， the abnormal expression of USPs is closely associated with the prognosis of HCC patients and may thus be used as potential biomarkers and therapeutic targets. This article reviews the research advances in USPs in HCC and explores their key roles in the development， progression， and metastasis of HCC. A deep understanding of the mechanism of action of USPs in HCC not only helps to reveal the pathogenesis of HCC， but also provides a scientific basis for developing new diagnostic tools and treatment strategies. Future research should further explore the regulatory effect of USPs in HCC， in order to provide more effective means for the clinical treatment of HCC.

Liver cancer has high prevalence and mortality rates around the world， and its development and progression are closely associated with the interaction between the tumor microenvironment and tumor-associated macrophages （TAMs）. TAMs play a significant role in immune suppression， immune escape， cell proliferation， invasion， metastasis， and drug resistance in liver cancer. Traditional Chinese medicine （TCM）， with its unique therapeutic concepts and methods， has shown great potential in regulating TAMs and improving the prognosis of liver cancer. This article reviews the role and molecular mechanisms of TCM in regulating TAMs for the treatment of liver cancer， discusses the key role of TAMs in the progression of liver cancer， and analyzes the impact of Chinese medicinal components on the recruitment， polarization， and activity of TAMs and the expression of related factors based on TCM theory. Studies have shown that TCM can regulate the polarization state of TAMs， promote the formation of M1-type antitumor macrophages， and inhibit the activity of M2-type tumor macrophages， thereby playing a role in inhibiting the proliferation of liver cancer cells， promoting apoptosis， inhibiting angiogenesis， and enhancing immune response. In addition， this article also summarizes the molecular targets and mechanisms of action of TCM monomers， compound prescriptions， and novel preparations in the treatment of liver cancer， such as inhibiting the secretion of cytokines by TAMs， regulating signaling pathways， and affecting metabolic pathways， in order to provide a scientific basis for the application of TCM in liver cancer treatment and offer new ideas for immunotherapy for liver cancer.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Objective:A subunit vaccine against SARS-CoV-2 BA.2 variant was prepared by prokaryotic expression system and its immunogenicity was evaluated.Methods:The recombinant plasmid of BA.2 variant RBD and the tandem of RBD and TT-P2 epitopes was constructed by molecular cloning technology, and recombinant proteins So and Sot were obtained by protein purification technology. Mice were immunized by intramuscular injection after mixing protein So/Sot as immunogens with Al(OH) 3 adjuvant to evaluate the effect of cellular and humoral immunity. Results:High purity soluble protein were obtained by dialysis and renaturation after expressed by prokaryotic system. The number of antigen-specific T lymphocytes secreting IFN-γ and IL-4 (213.7±0.6 and 311.7±1.5) in the Sot group induced by mice was significantly higher than that in the So group (94.3±16.8 and 185.7±4.2) ( P<0.001). The serum antibody level induced by Sot group was higher than that in the So group, the geometric mean titer (GMT) of neutralizing antibodies against BA.2 strain were 588 and 337, respectively ( P<0.05). Sot protein induced Th1/Th2 mixed type immune response with the predominance of Th2 type. Conclusions:The protein subunit vaccine expressed by the prokaryotic system have excellent cellular and humoral immunogenicity, which provides a strong theoretical basis for the development of the protein subunit vaccines of the SARS-CoV-2 Omicron variant.

Objective:To explore the value of predicting new-onset heart failure events in patients with hypertrophic cardiomyopathy (HCM) using clinical and cardiac magnetic resonance (CMR) features based on machine learning algorithms.Methods:The study was a retrospective cohort study. Patients with a confirmed diagnosis of HCM who underwent CMR examinations at Beijing Anzhen Hospital from May 2017 to March 2021 were selected and randomly divided into the training set and the validation set in a ratio of 7∶3. Clinical data and CMR parameters (including conventional parameters and radiomics features) were collected. The endpoint events were heart failure hospitalization and heart failure death, with follow-up ending in January 2023. Features with high stability and P value<0.05 in univariate Cox regression analysis were selected. Subsequently, three machine learning algorithms—random forest, decision tree, and XGBoost—were used to build heart failure event prediction models in the training set. The model performance was then evaluated using the independent validation set, with the performance assessed based on the concordance index. Results:A total of 462 patients were included, with a median age of 51 (39, 62) years, of whom 332 (71.9%) were male. There were 323 patients in the training set and 139 in the validation set. The median follow-up time was 42 (28, 52) months. A total of 44 patients (9.5% (44/462)) experienced endpoint events (8 cases of heart failure death and 36 cases of heart failure hospitalization), with 31 events in the training set and 13 in the validation set. Univariate Cox regression analysis identified 39 radiomic features, 4 conventional CMR parameters (left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left ventricular ejection fraction, and late gadolinium enhancement ratio), and 1 clinical feature (history of non-sustained ventricular tachycardia) that could be included in the machine learning model. In the prediction models built with the training set, the concordance indices for the random forest, decision tree, and XGBoost models were 0.966 (95% CI 0.813-0.995), 0.956 (95% CI 0.796-0.992), and 0.973 (95% CI 0.823-0.996), respectively. In the validation set, the concordance indices for the random forest, decision tree, and XGBoost models were 0.854 (95% CI 0.557-0.964), 0.706 (95% CI 0.399-0.896), and 0.703 (95%CI 0.408-0.890), respectively. Conclusion:Integrating clinical and CMR features of HCM patients through machine learning aids in predicting heart failure events, with the random forest model showing superior performance.

In order to facilitate the accurate comprehension and correct implemention of the national occupational health standard Health standard for operators of nuclear power plants (GBZ/T 164-2022), this article presents an in-depth elucidation encompassing the significance of the standard promulgation, the background of its revision, the current status of the relevant domestic and international standards, the basis for revision of the principal technical inclusion and the application scope of the standard. The aim is to provide a guidance the selection, appropriate evaluation, and occupational health monitoring of nuclear power plant operators, ultimately ensuring the safe operation of nuclear facilities.

Objective:To discuss the protective effect of sodium butyrate(NaB)on acute liver injury in the mice induced by lipopolysaccharide(LPS)combined with D-galactosamine(D-Gal),and to clarify its mechanism.Methods:Thirty male Kunming mice were randomly divided into control group,model group,and NaB group,and there were 10 mice in each group.The mice in NaB group were given 200 mg·kg-1·d-1 NaB,while the mice in control group and model group were given an equal volume of sterile water.The mice in model group and NaB group were intraperitoneally injected with 20 μg·kg-1 LPS and 600 mg·kg-1 D-Gal to induce the acute liver injury models.The body weights and liver weights of the mice in various groups were detcted,and the liver index was calculated.HE staining was used to observe the pathomorphology of liver tissue of the mice in various groups;kits were used to detect the activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum,and the activities of total superoxide dismutase(T-SOD)and catalase(CAT),and the levels of malondialdehyde(MDA)in liver tissue of the mice in various groups;Western blotting method was used to detect the expression levels of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in liver tissue of the mice in various groups.Results:There were no significant differences in body weights of the mice among various groups(P>0.05).Compared with control group,the liver index of the mice in model group was significantly increased(P<0.01).Compared with model group,the liver index of the mice in NaB group was significantly decreased(P<0.01).The HE staining results showed that the liver tissue of the mice in control group exhibited normal structure,with clear boundaries of hepatocytes,consistent size,radially arranged around the central vein,and the nucleus located in the center of the cells;in model group,the arrangement of hepatocytes was disordered,the cells were swollen,there were multiple foci of hepatocellular necrosis,inflammatory cell infiltration,and hemorrhage;compared with model group,the cells in NaB group showed improved hepatocellular structure and reduced inflammatory infiltration.Compared with control group,the activities of ALT and AST in serum of the mice in model group were significantly increased(P<0.01);compared with model group,the activities of ALT and AST in serum of the mice in NaB group were significantly decreased(P<0.05 or P<0.01).Compared with control group,the activities of T-SOD and CAT in liver tissue of the mice in model group were significantly decreased(P<0.01),and the level of MDA was significantly increased(P<0.01);compared with model group,the activities of T-SOD and CAT in liver tissue of the mice in NaB group were significantly increased(P<0.05 or P<0.01),and the level of MDA was significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in model group were significantly decreased(P<0.05);compared with model group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in NaB group were significantly increased(P<0.01).Conclusion:NaB has a protective effect on LPS/D-Gal induced acute liver injury in the mice,and its mechanism may be related to the upregulation of the expressions of Nrf2 and HO-1 proteins and the increas of the activity of oxidant enzyme in liver tissue by NaB,thereby reduces the liver oxidative stress level of liver.

Background and purpose:Human epidermal growth factor receptor 2(HER2)serves as one of the paramount drivers of breast cancer metastasis,with roughly 20%-30%of breast cancer patients exhibiting high expression of HER2.The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells;however,the manner in which HER2 expression is modulated at the mRNA level remains ambiguous.Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2,and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported.This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression.Methods:In this study,a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells.RNA fluorescence in situ hybridization(FISH)was utilized to detect the subcellular localization of circ-0007766.The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance.Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro.The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments,and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured.Additionally,it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972.A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972.The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment.RIP detection was performed in MDA-MB-231 cells,and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).Western blot was used to detect the protein expressions.Results:Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells,with the preponderance being in the cytoplasm.The expression level of circ-0007766 was strikingly higher in breast cancer tissues than in para-cancerous tissues.The expression of circ-0007766 was significantly elevated in HER2-positive breast cancer samples compared with HER2-negative samples.The overexpression(knockdown)of circ-0007766 in HER2-negative breast cancer cells(in HER2-positive breast cancer cells)was capable of promoting(inhibiting)the migration and invasion of breast cancer cells.Circ-0007766 directly bound to miR-1972,which inhibited breast cancer cell migration and invasion,thereby forming an endogenous competitive RNA(ceRNA)regulatory network and impeding the downregulation of HER2 mRNA and protein expression mediated by miR-1972.Circ-0007766 could potentiate the inhibitory effect of miR-1972 on HER2-mediated breast cancer cell migration and invasion that was negatively regulated by miR-1972.CircRNAs sequestered miRNAs to function as ceRNAs,thereby regulating gene expression at both the transcriptional and translational levels.Finally,we discovered that the expressions of circ-0007766 and HER2 were positively correlated in breast cancer cell and tissue samples,while the expression levels of miR-1972 and HER2 were negatively correlated.Circ-0007766 could specifically target miR-1972 to hinder its regulatory effect on HER2 expression.Conclusion:This study discovers that circ-0007766 facilitates the migration and invasion of breast cancer cells via the miR-1972/HER2 signal axis,offering a novel biomarker and potential therapeutic target for patients with metastatic HER2-positive breast cancer.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective To describe and analyze the current situation of the four same type of departments in an hospital in order to provide a reference for the construction of"the most cost-effective medical care".Methods The CN-DRG were used to automatically group and compare the medical capacity and inpatient service efficiency of the hospital department groups,and in the refined analysis,one DRG disease group of in situ cancer and non-malignant disease loss uterine surgery and single species uterine fibroid was included,and the Kruskal-Wallis H test was used to further compare the differences in length of stay and various costs.Results It included a total of 22630 patients,whose weights varied from a maximum of 3948.62 in diagnostic group 1 to a minimum of 133.55 in diagnostic group 11.The cost consumption indexes ranged from a minimum of 0.89 in diagnostic group 5 to a maximum of 1.04 in diagnostic group 2,while the time consumption indexes ranged from a minimum of 0.48 in diagnostic group 11 to a maximum of 0.81 in diagnostic group 5.When comparing the diagnostic groups,there were statistically significant differences(P＜0.05)in hospitalization days,total cost,diagnostic cost,therapeutic cost,and cost of supplies.Specifically,when comparing the diagnostic and treatment groups within departments,the differences in hospitalization days and all costs were statistically significant(P＜0.05)in departments 1 and 2,the differences in diagnostic cost,therapeutic cost,and cost of supplies were statistically significant(P＜0.05)in department 3.Conclusion There exists a notable disparity in the extent to which each diagnostic and treatment group contributes to the hospital's service capacity and cost variability.Consequently,it is necessary to reasonably evaluate the length of hospital stay and medical cost of patients to achieve the highest cost-effective medical treatment.