Objective: To investigate the expression of peroxiredoxin 4 (PRDX4) in oral squamous cell carcinoma (OSCC) and its effect on the proliferation, migration, and invasion of OSCC cells. Methods: The Cancer Genome Atlas(TCGA) database was used to analyze the expression of PRDX4 in OSCC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blot (WB) were used to detect the mRNA and protein expression of PRDX4 in OSCC cell lines and normal oral mucosal epithelial cells. PRDX4 was knocked down in CAL-27 cells and divided into two groups: the si-PRDX4 group and si-NC group. SCC-9 cells overexpressing PRDX4 were divided into two groups: the PRDX4 overexpression group (transfected with pcDNA3.1-PRDX4 plasmid) and the vector group (the control group; transfected with pcDNA3.1-NC plasmid). A cell counting kit-8 (CCK-8) and plate colony formation assay were used to detect cell proliferation. Transwell assay and cell scratch test were used to detect cell invasion and migration ability. WB was used to detect the effects of knockdown or overexpression of PRDX4, p38MAPK agonist or inhibitor on the expression of p38MAPK-related signaling pathway proteins, and epithelial mesenchymal transition proteins in OSCC cells. Results: PRDX4 was highly expressed in OSCC tissues and cell lines. The results of qRT-PCR and WB showed that PRDX4 was highly expressed in OSCC cell lines compared with normal oral mucosal epithelial cells. The CCK-8 assay showed that the si-PRDX4 group had significantly lower OD values than the si-NC group at 24, 48, and 72 h (P<0.05). The PRDX4 overexpression group had a significantly higher OD value than the vector group at 24, 48, and 72 h (P<0.05). The plate colony formation assay showed that the si-PRDX4 group had a significantly lower number of colonies than the si-NC group (P<0.05). The number of colonies formed in the PRDX4 overexpression group was significantly higher than that in the vector group (P<0.05). The cell scratch test showed that the wound healing area of the si-PRDX4 group was less than that of the si-NC group (P<0.05). The scratch healing area of the PRDX4 overexpression group was significantly higher than that of the vector group (P<0.05). The Transwell invasion assay showed that the number of transmembrane cells in the si-PRDX4 group was lower than that in the si-NC group (P<0.05). The number of transmembrane cells in the PRDX4 overexpression group was significantly higher than that in the vector group (P<0.05). The WB results showed that knockdown and overexpression of PRDX4 could downregulate and upregulate the expression of the p38MAPK signaling pathway and epithelial-mesenchymal transition related proteins, respectively, and the addition of p38MAPK agonist and inhibitor could significantly reverse the expression of related proteins. Conclusion PRDX4 is highly expressed in OSCC. Knocking down the expression of PRDX4 in OSCC cells can downregulate the expression of p38 MAPK signal axis and EMT-related signal proteins, thereby inhibiting the proliferation, migration, invasion, and epithelial-mesenchymal transition of cells.

Objective To evaluate the economic value of fluticasone furoate/umeclidinium/vilanterol(FF/UMEC/VI)powder for inhalation in the treatment of symptomatic chronic obstructive pulmonary disease patients with acute exacerbation risk from the perspective of the Chinese health system.Methods Based on subgroup analysis of the China cohort in the IMPACT trial,a four-state lifetime Markov model was established with a 3-month cycle.The model simulation period was 11 years.Clinical efficacy,health benefits,and cost data were obtained through published literature.The health outcomes included quality adjusted life year(QALY).Using 3 times Chinas per capita gross domestic product(GDP)in 2023 as the willingness-to-pay threshold,the cost-utility analysis method was used for analysis the economic viability of FF/UMEC/VI.The scenario analysis,one-way sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the results.Results Compared with fluticasone furoate/vilanterol(FF/VI),FF/UMEC/VI in the treatment of symptomatic chronic obstructive pulmonary disease patients with acute exacerbation risk saved costs 8 118.66 yuan and obtained an additional 0.000 06 QALYs,giving it an economic advantage.Compared with umeclidinium/vilanterol(UMEC/VI),FF/UMEC/VI treatment paid 2 784.41 yuan more and received 0.000 45 QALYs less,making UMEC/VI more cost-utility.The scenario analysis results further confirmed the robustness of the model.The sensitivity analysis results showed that when the drug cost of FF/UMEC/VI per cycle decreases to 637.29 yuan,FF/UMEC/VI had economic benefits under a willingness-to-pay threshold of 3 times China's per capita GDP in 2023.Conclusion For patients with symptomatic chronic obstructive pulmonary disease at risk of acute exacerbation,FF/UMEC/VI is more cost-utility than FF/VI.Compared with UMEC/VI,FF/UMEC/VI has economic viability after price reducing.

B-cell-specific moloney murine leukemia virus integration site 1(BMI1)molecule is one of the members of the family of the Polycomb group(PcG)protein.As a crucial marker of stem cells,it maintains the normal physiological functions of the or-ganisms through regulating expression of the related genes transcriptionally.It was reported that BMI1 is also a crucial molecule which affects pathogenesis and progression of malignant tumors.Therefore,it plays an important role in regulating self-renewal,migration,invasion,drug-resistance,and as well as immune evasion of cancer stem cells(CSCs),which is associated with recurrence and metas-tasis of cancer.In this review,based on the research progresses during recent years,molecular structure and biological function of BMI1 were illustrated.Furthermore,regulation and its mechanisms of BMI1 molecule on the self-renewal,migration and invasion,drug-resistance and immune evasion of CSCs were also elaborated.It indicated that investigation of BMI1 molecule as a novel potential target in cancer immunotherapy would be much valuable and significant.

Objective:To investigate the predictive efficacy of apparent diffusion coefficient(ADC),exponential ADC(eADC)of preoperative magnetic resonance diffusion-weighted imaging(MR-DWI)combined with serum alpha fetoprotein(AFP)for microvascular invasion(MVI)in patients with hepatocellular carcinoma(HCC).Methods:A prospective study was conducted on 133 HCC patients who underwent liver cancer resection at Zhangjiagang Hospital of Traditional Chinese Medicine from January 2017 to February 2023.Based on whether occurred MVI in postoperative pathological diagnosis,they were divided into positive MVI group(62 cases)and negative MVI group(71 cases).The preoperative ADC values,ADC ratio(T/L),ratio of eADC value to eADC value(eT/L),serum AFP and other clinical pathological data were compared between the two groups.Multivariate logistic regression was used to analyze the risk factors of MVI in HCC patients.The receiver operating characteristic(ROC)curve and area under curve(AUC)were applied to assess the predictive efficacies of each indicator and the combined detection of all indicator for MVI.Results:The ADC value and T/L value of ADC in the positive MVI group were lower than those in the negative MVI group,while the eT/L value of eADC was higher than that in the negative MVI group,and the differences were statistically significant(t=3.972,5.297,3.521,P<0.05),respectively.There was no statistically significant difference in eADC values between the positive MVI group and the negative MVI group(P>0.05).The serum AFP level in the positive MVI group was higher than that in the negative MVI group,and the difference was statistically significant(U=3.615,P<0.05).The tumor diameter,alanine aminotransferase(ALT)and total bilirubin(TBil)level in the positive MVI group were higher than those in the negative MVI group,and the differences were statistically significant(t=7.686,2.083,2.923,P<0.05),respectively.The proportions of patients with multiple lesions,clinical stage Ⅲ,low differentiation and incomplete capsule in the positive MVI group were higher than those in the negative MVI group,and the differences were statistically significant(x2=6.656,4.600,9.030,5.328,P<0.05),respectively.Multivariate logistic regression analysis showed that tumor diameter>5 cm,incomplete capsule,elevated AFP,decreased T/L value of ADC,the increased eT/L value in eADC were the risk factors for MVI in HCC patients(OR=1.382,1.423,1.043,0.815,1.146,P<0.05),respectively.ROC curve analysis showed that the AUC(95％CI)values of T/L value of ADC,eT/L value of eADC and AFP were respectively 0.721(0.442-0.988),0.748(0.525-0.948)and 0.720(0.460-0.985)in predicting MVI in HCC patients.The AUC(95％CI)value of the combined prediction of them was 0.860(0.731-0.974),which was higher than the predictive efficacy of single indicator.Conclusion:The decrease in T/L value of ADC in preoperative DWI,the increases of eT/L value of eADC and serum AFP are risk factors for MVI in HCC patients.The combination of preoperative T/L value of ADC,eT/L value of eADC and serum AFP has higher predictive efficacy for MVI in HCC patients.

Objective:To propose a novel refined subtyping of Neer type Ⅵ proximal humerus fracture-dislocation and explore its clinical application.Methods:A retrospective study was conducted to analyze the data of 36 patients who had been admitted to Department of Orthopaedics, Beijing Friendship Hospital between January 2018 and December 2022 for surgical treatment with proximal humeral internal locking system (PHILOS) for Neer type Ⅵ proximal humerus fracture-dislocation. There were 25 males and 11 females with an age of (46.1±4.7) years. According to the fracture-dislocation and the separation between the humeral head and the stem, the patients with Neer type Ⅵ proximal humerus fracture-dislocation were further subdivided into 3 subtype groups (known as STAB subtypes): subtype-T group (dislocation of the shoulder joint with macro-capitellar fracture, n=14), subtype-A group (proximal humerus fracture-dislocation without separation of the humeral head from the humeral stem, n=12), and subtype-B group (dislocation of the proximal humerus fracture with separation of the humeral head from the humeral stem, n=10). STAB subtyping was performed on the same imaging data from all the patients at admission and 2 weeks later by 4 surgeons with different qualifications. Interobserver and intraobserver agreements of the STAB typing were verified. The operation time, fracture healing time, visual analogue scale (VAS) pain score, Constant-Murley score, and complications were recorded for patients in the 3 subtype groups. Results:The differences in the preoperative general data were not statistically significant between the 3 subtype groups, indicating comparability ( P>0.05). All patients were followed up for (11.2±4.2) months. The inter-observer and intra-observer Kappa values for STAB subtyping were 0.94 and 0.95, respectively. For subtype-T group, subtype-A group, and subtype-B group, respectively, the operation time was (68.9±5.6) min, (90.0±5.2) min, and (113.0±9.2) min; the fracture healing time was (9.0±0.8) weeks, (10.3±1.2) weeks, and (11.8±0.9) weeks; the VAS scores at the last follow-up were 1.0(1.0, 2.0) points, 2.0(1.0, 2.0) points, 2.0(2.0, 3.0) points; the Constant-Murley scores at the last follow-up were (83.6±2.8) points, (74.5±3.0) points, and (62.7±5.5) points. The differences between the 3 subtype groups in the above items were statistically significant ( P<0.05). The overall success rate of closed reduction was 61.1% (22/36). In subtype-T, subtype-A, and subtype-B groups, respectively, the number of patients with successful closed reduction was 13, 7, and 2, while complications occurred in 2, 3, and 6 patients. The differences in closed reduction and complications among the 3 groups were statistically significant ( P<0.05). Conclusions:The STAB subtyping proposed in this study demonstrates strong intra- and inter-group consistency. Because the refined STAB subtyping can reveal differences among all the Neer type Ⅵ proximal humeral fractures and dislocations, it may provide more precise guidance for personalized clinical decision-making.

OBJECTIVE To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism. METHODS Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group. RESULTS There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant. CONCLUSION BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.

OBJECTIVE To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism. METHODS Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group. RESULTS There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant. CONCLUSION BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.

Objective To construct a novel enzyme-free colorimetric biosensor(T-CHA)based on tri-ple-helix molecular probe(THMP)and catalytic hairpin assembly(CHA)reaction for visual detection and precise quantitative analysis of low-abundance alpha-fetoprotein(AFP).Methods The absorbance produced by AFP induced T-CHA system was recorded by gel electrophoresis and ultraviolet-visible spectrophotometer to evaluate the feasibility of T-CHA strategy.The molar concentration ratio of THMP and CHA,reaction time of CHA,temperature and pH value of buffer solution were optimized respectively.The color reaction of T-CHA was induced by different concentrations of AFP to explore the detection efficiency of T-CHA.Results Under the op-timal experimental conditions,the logarithmic values of AFP at different concentrations showed a linear rela-tionship from 5 μg/mL to 10 ng/mL,and the detection limit was 2.29 μg/mL.The T-CHA system could com-plete accurate quantitative analysis of low abundance AFP and visual free-labeled detection within 105 min,moreover the sensitivity of T-CHA was superior to that of ELISA.Conclusion Utilizing the low background leakage of THMP and the high catalytic efficiency of CHA,the T-CHA system could realize the early accurate diagnosis of hepatocellular carcinoma,moreover which has a certain application prospect in the real time detec-tion.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby strains isolated from human and food sources in Hangzhou. Methods:A total of 60 Salmonella enterica serovar Derby strains isolated in Hangzhou during the period from 2015 to 2020 were subjected to antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) typing and whole-genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and the identification of antimicrobial resistance genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the 60 genomes from Hangzhou and 379 genomes from public databases was constructed. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Hangzhou. The multidrug resistance (MDR) rate was 76.7% (46/60). All of the 60 Salmonella Derby strains were positive for the antimicrobial resistance genes aac(6′)- Iaa and fosA7. The 60 strains were subtyped into 46 molecular types by PFGE and 53 molecular types by cgMLST(HC2). Except for one strain belonging to ST3220, the other Salmonella Derby strains were ST40. The phylogenetic analysis showed that some strains isolated in Hangzhou were close to the strains in Southeast Asia, suggesting the possibility of cross-border transmission of ST40 strains, with the main food sources being pork and fish; other strains were close to those circulating in Beijing, Guangzhou, Hubei, Chongqing and other provinces, suggesting the possibility of cross-province transmission of the strains, with the main food sources being pork, beef and chicken. Conclusions:The epidemic of Salmonella Derby in Hangzhou was mainly caused by the spread of ST40 strains and MDR was common. Clinical infections might be closely related to the consumption of pork, beef, chicken and fish. There was the possibility of cross-border transmission of Salmonella Derby between Hangzhou and Southeast Asia and cross-province transmission in China.