The F-box protein (FBP) family is a large and diverse protein family that is present in all eukaryotes. Based on the secondary structure of the C-terminal, FBPs can be classified as FBXW, FBXL, and FBXO. FBPs can form the SCF complex by binding with S-phase kinase-associated protein 1 (SKP1), cullin 1 (CUL1), and ring-box 1 (Rbx1), functioning as E3 ubiquitin ligase. They specifically recognize substrate proteins via the ubiquitin-proteasome pathway and participate in various biological activities, such as cell cycle regulation, transcriptional regulation, apoptosis, and cell signaling transduction. Numerous studies have shown that FBPs play important roles in host-virus interactions. Being the substrate recognition component of the SCF complex, FBPs bind, ubiquitinate (at K-48), and transport substrates for proteasomal degradation. Based on the type of substrate, F-Box family proteins can either exert antiviral or proviral (immune evasive) effects. Some FBPs can specifically recognize and degrade interferon pathway-associated signal molecules via the ubiquitin-proteasome pathway, thereby upregulating or inhibiting interferon signals and regulating host-related immune responses. Additionally, some FBPs can recognize and degrade viral proteins via the ubiquitin-proteasome pathway, thereby inhibiting viral replication and transmission. However, viruses can hijack FBPs to promote the degradation of immunogenic host proteins, resulting in immune evasion. Although several FBP-targeting inhibitors have been developed, there are limited reports on the application of FBPs in antiviral drug research. Given the large number of FBP family members, further research is required on the functions and mechanisms of FBPs in virus-host interactions, to provide novel directions for the development of antiviral drugs.

ObjectiveTo analyze the epidemiological trends and characteristics of brucellosis in humans (hereinafter referred to as brucellosis) in Tangshan City, Hebei Province from 2016 to 2023, and to provide a scientific basis for formulating brucellosis prevention and control strategies in the region. MethodsThe incidence data of human brucellosis in Tangshan City from 2016 to 2023 were collected from the China Disease Prevention and Control Information System. The diagnosis time, infection route, and clinical characteristics of the cases were obtained from the case investigation reports. Descriptive epidemiological methods were used to analyze the temporal, spatial, demographic distributions, and clinical characteristics of human brucellosis. Brucella species were identified using agglutination tests with bacterial suspension and A/M antigen-positive serum. ResultsA total of 2 193 cases of human brucellosis were confirmed and clinically diagnosed in Tangshan City from 2016 to 2023, with the peak incidence occured from March to August, and which exhibited distinct geographic distribution patterns. The highest incidence rate was found in people aged 60‒<70 years. The occupation of cases were primarily farmers. The incidence rate in males (528/100 000) was higher than that in females (184/100 000). All cases had confirmed exposure to infected animals or contaminated animal products. ConclusionThe epidemic of human brucellosis in Tangshan exhibited an overall steady downward trend from 2016 to 2023, except for a slight increase in 2016 and 2021, with the incidence rate controlled at 289/100 000‒335/100 000. The prevention and control situation of human brucellosis still remains severe, with the highest incidence rate in the eastern region of Tangshan, which are characterized by the breeding, slaughtering, and processing of cattle and sheep. Therefore, it it is necessary to enhance the prevention and control of human brucellosis among the personnel engaged in these industries in the eastern areas.

Objective:To explore the protective effect of Yiqi Fumai Lyophilized Injection (YQFM) on myocardial cell injury induced by doxorubicin and its mechanism.Methods:H9c2 cells were divided into the control group, the doxorubicin group, and the YQFM group. Cells in the control group were given routine incubated. H9c2 cells in the doxorubicin group were given doxorubicin (1 μmol/L) and incubated for 24 h. Cells in the YQFM group were given doxorubicin (1 μmol/L) and YQFM (1.5 mg/L) and incubated for 24 h. The cell viability, cell surface area, atrial natriuretic peptide, and brain natriuretic peptide protein expression levels were detected in each group. The levels of oxidative stress factors, including superoxide dismutase (SOD), malondialdehyde, glutathione peroxidase (GSH-Px) and catalase (CAT) were detected in each group. The apoptosis level, mitochondrial membrane potential, apoptotic associated protein such as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and c-cysteinyl aspartate specific proteinase-3 (c-Caspase-3), p53 and protein expression level of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway were detected in each group.Results:YQFM increased the viability ( P < 0.01), decreased the cell surface area ( P < 0.001), and the levels of atrial natriuretic peptide and brain natriuretic peptide proteins ( P < 0.05) of H9c2 cell in the doxorubicin group. In addition, the SOD, GSH-Px, and CAT levels in the YQFM group were higher than those in the doxorubicin group ( P < 0.05, 0.01), while the malondialdehyde level in the YQFM group was lower than that in the doxorubicin group ( P < 0.05). YQFM also reduced the apoptosis level of H9c2 cell in the doxorubicin group ( P < 0.01), increased the level of mitochondrial membrane potential ( P < 0.01) and the Bcl-2/Bax protein expression level ( P < 0.05), and decreased c-Caspase-3 and p53 protein expression levels ( P < 0.05). It was further found that the p-PI3K and p-Akt protein expression levels in the YQFM group were higher than those in the doxorubicin group ( P < 0.05, 0.01). Conclusions:YQFM can inhibit myocardial cell injury induced by doxorubicin, and its mechanism may be related to the inhibition of oxidative stress and activation of PI3K/Akt pathway.

Objective To explore the efficacy and safety of balloon-occluded hepatic artery infusion chemotherapy(b-HAIC)based on FOLFOX regimen for unresectable hepatocellular carcinoma(uHCC).Methods Data of 20 uHCC patients who underwent FOLFOX-based b-HAIC were retrospectively analyzed.According to the dose of fluorouracil in FOLFOX regimen,the patients were divided into low-(600 mg/m2·22 h,n=8),medium-(1200 mg/m2·44 h,n=6)and high-dose group(2400 mg/m2·44 h,n=6).The number of b-HAIC cycles were recorded.Clinical efficacy was evaluated,the objective response rate(ORR)and disease control rate(DCR)were calculated,and changes of alpha-fetoprotein(AFP)after treatment were observed to evaluate the efficacy of b-HAIC.And b-HAIC treatment-related adverse events were recorded.Results One to four cycles of b-HAIC were performed in 20 cases,with the median of 2 cycles.The follow-up times were 7-31 weeks,with the median of 15 weeks.There were 4 cases(4/20,20.00%)of complete response(CR),12(12/20,60.00%)of partial response(PR)and 4(4/20,20.00%)of stable disease(SD),ORR was 80.00%(16/20)and DCR was 100%(20/20).The time for the optimal response ranged from 4 to 16 weeks,with a median of 6 weeks.After treatment,ORR in low-,medium-and high-dose group was 75.00%(6/8),83.33%(5/6)and 83.33%(5/6),respectively,and DCR was 100%in all 3 groups.AFP in 17 cases elevated before b-HAIC reduced at different degrees after treatment.Treatment-related adverse events included upper abdominal pain,nausea and vomiting during perfusion,as well as elevated transaminases and total bilirubin,neutrophil percentage and bone marrow suppression after b-HAIC,all relieved after symptomatic treatment.Conclusion FOLFOX-based b-HAIC had good short-term efficacy and controllable adverse reactions for treating uHCC.

Objective:To investigate the impact of body mass index (BMI) on delayed extubation of patients with acute Stanford type A aortic dissection (ATAAD).Methods:A total of 400 ATAAD patients who were admitted to our hospital from October 2021 to October 2023 and underwent surgical treatment were selected as the research objects. According to BMI, they were divided into obese group (BMI≥28 kg/m 2, 119 cases) and non-obese group (BMI<28 kg/m 2, 281 cases). The differences of preoperative clinical characteristics, intraoperative and postoperative data between the two groups were compared. Starting from transferring to the ICU and ending with the first successful extubation, The risk factors of postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients were analyzed, and the predictive efficacy of related factors for postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients was evaluated. Results:Compared with the non-obese group, the proportion of hypertension, diabetes, admission heart rate, admission systolic blood pressure, admission diastolic blood pressure and preoperative white blood cell count in the obese group were significantly increased, and the differences were statistically significant ( P<0.05). The cardiopulmonary bypass time, aortic cross-clamp time, operation time, red blood cell transfusion volume, invasive mechanical ventilation time, secondary operation rate and total hospitalization cost in the obese group were significantly higher than those in the non-obese group, and the differences were statistically significant ( P<0.05). Univariate logistic regression analysis showed that BMI, cardiopulmonary bypass time, ascending aortic cross-clamp time, operation time, age, hypertension, and red blood cell transfusion were related factors for postoperative invasive mechanical ventilation time ≥48 h in ATAAD patients ( P<0.05). Logistic multivariate regression analysis showed that increased BMI ( OR=1.213, P<0.05) and increased age ( OR=1.020, P<0.05) were independent risk predictors of postoperative invasive mechanical ventilation time≥48 h in ATAAD patients. Receiver operating characteristic curve ( ROC) analysis showed that the area under the ROC curve ( AUC) of BMI for predicting the duration of postoperative invasive mechanical ventilation in ATAAD patients≥48 h was 0.682 ( P<0.05), and the best predictive cut-off value was 25.64 kg/m 2. Conclusion:BMI≥28kg/m 2 increases the difficulty of surgery and the duration of invasive mechanical ventilation in ATAAD patients. BMI has a high predictive value for the duration of invasive mechanical ventilation in ATAAD patients after surgery ≥48 h, and effective intervention measures can be formulated to improve the treatment effect of patients.

Objective:To study the effects of modified maxillary protraction therapy on the changes in facial soft tissue in patients with maxillary hypoplasia using cephalometric measurements.Methods:26 cases(16 males and 10 females)of Class Ⅲ skeletal malocclu-sion with maxillary hypoplasia during the later period of pubertal peak(CVM Ⅴ to Ⅵ)were included.Treatment was carried out using modified palatal anchorage with a combination of a modified bite-jumping appliance and bilateral maxillary anterior traction.Cephalo-metric measurements were taken before and after treatment using lateral cephalograms,the changes in facial soft tissue-related parame-ters were compared.Results:(1)After treatment,the measurements of soft tissue landmarks in the midfacial region showed a signifi-cant increase(P＜0.05),with the average anterior movement exceeding 3 mm for the nasal tip,subnasale,soft tissue A point and upper lip protrusion point.(2)The changes in the G-Sn-Pos,Ns-Prn-Pos,and S-Ns-Sn were highly significant(P＜0.01),with an average increase in the G-Sn-Pos of 3.23°±3.74°,a decrease in Ns-Prn-Pos of 2.56°±4.99°,and an average increase in S-Ns-Sn of 2.63° ±3.39°.(3)Changes in soft tissue tension and facial height proportion after treatment were not statistically significant(P＞0.05).Con-clusion:The use of a modified pad type intraoral appliance in conjunction with bilateral maxillary anterior traction can effectively pro-mote the improvement of mid facial soft tissue profile in patients with maxillary underdevelopment during the peak growth and develop-ment period,and coordinate the relationship between nasal,lip and chin soft tissue.

The mechanical load generated during running impact the microstructures of knee joint.Quantitative MRI can be used to observe the microstructures of knee joint,which is an important imaging method for evaluating changes of knee joint after long-distance race.The progresses of quantitative MRI for evaluating microscopic injuries of knee joint after long-distance race were reviewed in this article.

Portal vein thrombosis （PVT） refers to thromboembolism that occurs in the extrahepatic main portal vein and/or intrahepatic portal vein branches. PVT is the result of the combined effect of multiple factors， but its pathogenesis remains unclear. Animal models are an important method for exploring the pathophysiological mechanism of PVT. Based on the different species of animals， this article reviews the existing animal models of PVT in terms of modeling methods， principles， advantages and disadvantages， and application.

Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.

Objective:To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B.Methods:Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test.Results:A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance.Conclusion:Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log 10IU/ml), HBsAg level at 24 weeks (≤ 0.92 log 10IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log 10IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log 10IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.