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 To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.

Objective:To study the effects of low-dose dexmedetomidine via nasal spray on preoperative anxiety and tracheal intuba-tion induced stress response in elderly patients with maxillofacial surgery using heart rate variability(HRV).Methods:60 elderly pa-tients underwent maxillofacial surgery were randomly divided into the dexmedetomidine group(group D)and the control group(group C).Patients in the group D were treated with nasal spray of dexmedetomidine at 45 min preoperatively.Those in the group C were giv-en the same dose of normal saline spray at the same time.All patients were given intravenous combined with inhalation general anes-thesia.The hemodynamics,HRV index,sedation score and BIS value of the 2 groups of patients were compared at 3 time points,be-fore operation(T0),entrance(T1)and tracheal intubation(T2)respectively.Results:At T1,the average score of Ramsay in group D and group C was 2.8±0.7 and 1.1±0.39,BIS 87.3±6.1 and 97.4±0.5,SD1 20.9±7.0 and 15.4±5.4,SDNN 30.9±6.6 and 37.1±7.0,LF/HF 1.3±0.3 and 2.6±0.4,respectively(P＜O.01).At T2,the average score of SD1 in group D and group C was 10.4±3.5 and 7.7±3.1,SDNN 59.2±6.5 and 70.1±7.1,LF/HF 5.l±0.5 and 7.5±0.5,respectively(P＜0.01).Conclusion:Low-dose dexmedetomidine nasal spray can effectively relieve the preoperative anxiety of elderly patients in maxillofacial surgery and reduce the stress response of tracheal intubation.

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.

Objective To systematically evaluate the efficacy and safety of single and bilateral lung transplantation in the treatment of end-stage chronic obstructive pulmonary disease (COPD). Methods Chinese and English databases were searched by computer, including PubMed, Web of Science, The Cochrane Library, EMbase, CNKI, Wanfang database, VIP database and CBM. Case-control studies on single lung transplantation or bilateral lung transplantation for COPD were collected from the inception to July 31, 2022. We evaluated the quality of the literature via Newcastle-Ottawa Scale (NOS). All results were analyzed using Review Manager V5.3 and STATA 17.0. Results A total of 8 studies were included covering 14076 patients, including 8326 patients in the single lung transplantation group and 5750 patients in the bilateral lung transplantation group. NOS scores were≥6 points. The results of meta-analysis showed that there was no statistical difference in the postoperative 1-year survival between the two groups (P=0.070). The 2-year survival rate (P=0.002), 3-year survival rate (P<0.001), 5-year survival rate (P<0.001), overall survival rate (P＜0.001), postoperative forced expiratory volume in one second/predicted value (P<0.001), postoperative forced vital capacity (P<0.001), and postoperative 6-minute walking distance (P=0.002) were lower or shorter than those in the bilateral lung transplantation group, the postoperative intubation time (P=0.030) was longer than that in the bilateral lung transplantation group. Bilateral lung transplantation group showed better surgical results. There was no statistical difference in the mortality, obliterative bronchiolitis, length of hospitalization, primary graft dysfunction, or postoperative adverse events (P>0.05). Conclusion Bilateral lung transplantation is associated with better long-term survival and postoperative lung function compared with single lung transplantation. In-hospital mortality and postoperative complications are similar between them.

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.