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.

Continuing medical education for general practitioners is an important measure to upgrade the quality of primary health care services in China, which is still facing various challenges and need to be further developed and improved. This article analyzes the status quo and existing problems of continuing medical education for general practitioners in China, and proposes suggestions based on the concept of people centered and integrated health care (PCIC), including faculty development, training contents, assessment methods, and experience learning, to provide references for the improvement of continuing medical education for general practitioners.

Objective:To investigate the clinicopathological features and the prognosis of IgA nephropathy (IgAN) in children with massive proteinuria.Methods:It was a retrospective cohort study. Clinical data of IgAN children with massive proteinuria admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2008 to December 2021 were retrospectively analyzed. Patients were divided into effective group and ineffective group according to whether urine protein turned negative after 6 months of initial treatment. The follow-up endpoint event was defined as a reduction in proteinuria of less than 50% or end-stage renal disease (ESRD) achievement. MedCalc software was used to perform Kaplan-Meier survival analysis, and Log-rank test was used to compare the difference of renal survival between the two groups.Results:A total of 127 patients were diagnosed as primary IgAN by renal biopsy, of whom 57 patients with IgAN showed massive proteinuria. These 57 IgAN patients with macroproteinuria accounted for 44.9% of the total IgAN patients and were enrolled in the study. Among the 57 cases, 33 cases (57.9%) were Lee's grade Ⅲ, 11 cases (19.3%) were below Lee's grade Ⅲ, and 13 cases (22.8%) were above Lee's grade Ⅲ. The follow-up time was 4.0 (3.0,5.8) years. In the initial treatment, among 57 patients, 46 (80.7%) were effective (effective group) and 11 (19.3%) were ineffective (ineffective group). Compared with the effective group, the ineffective group had a higher proportion of concurrent AKI at the onset of disease and longer recovery time of renal function, with significant difference (7/11 vs. 13/46, χ2=4.878, P=0.027). Compared with the effective group, the proportion of Lee grade Ⅲ or above was higher in the ineffective group, and the difference was statistically significant (5/11 vs. 8/46, χ2=3.971, P=0.046). There were significant differences in endocapillary hypercellularity (E1), segmental glomerulosclerosis or adhesion (S1) and cellular/fibrocellular crescents (C2) of Oxford classification between IgAN children with Lee grade Ⅲ or below and those over Lee grade Ⅲ (11/13 vs. 20/44, χ2=6.204, P=0.013; 12/13 vs. 17/44, χ2=11.566, P=0.001; 9/13 vs. 7/44, χ2=14.131, P=0.001). Among 57 patients, endpoint events occurred in 2 patients who both were urinary protein unmitigated, and none of the children progressed to ESRD. There was no significant difference in cumulative renal survival between the two groups by Kaplan-Meier survival analysis and Log-rank test ( χ2=0.537, P=0.460) after addition of calcineurin inhibitors (CNIs) to the initial treatment ineffective group. Conclusions:Macroproteinuria is the prominent manifestation of IgAN in children. The pathological type is mainly Lee grade Ⅲ. Children with macroproteinuria have a good prognosis in the short and medium term after active treatment. For IgAN with macroproteinuria that does not respond well to initial treatment, AKI is more common at onset, and renal function recovery time is longer. The application of CNIs may have a certain effect on improving the renal outcome of IgAN with massive proteinuria.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

OBJECTIVE To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis. METHODS Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval. CONCLUSION This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.

Objective To explore the pathological features of lung tissue in mild chronic obstructive pulmonary disease(COPD)and their association with inflammatory factors.Methods A total of 70 patients who underwent surgery for small lung nodule were prospectively included,and were divided into the normal group(n=10),the mild COPD group(n=50)and the moderate and severe COPD group(n=10).The pathological changes of lung tissue were evaluated after HE,Masson and EVG staining.The expression levels of SMA,Actin and CD31 proteins were detected by immunohistochemistry staining.Tumor necrosis factor α(TNF-α),interleukin-10(IL-10)protein and mRNA levels were detected by immunohistochemistry and qPCR.Results Pulmonary tissue in mild COPD showed widening of alveolar septum,dilation of small airways,mild thickening of blood vessel wall and inflammatory reaction dominated by lymphocyte infiltration.Immunohistochemistry staining showed that contents of SMA and Actin proteins in mild COPD lung tissue were higher than those in the normal group(P＜0.05).In addition,the TNF-α mRNA and the positive rate of TNF-α in lung tissue of mild COPD were significantly higher than those in the normal group,while the IL-10 mRNA was significantly lower than that of the normal group(all P＜0.05).SMA and Actin were positively correlated with the positive expression of inflammatory cytokine TNF-α,but negatively correlated with the positive expression of IL-10(all P＜0.05).Conclusion The main pathological changes of lung tissue in mild COPD include small lung blood vessel remodeling ocharacterized by thickening of small blood vessel smooth muscle layer and lymphocyte-dominated inflammatory response,while the increase of pro-inflammatory factor TNF-α and decrease of anti-inflammatory factor IL-10 are associated with pathological changes of COPD.

Objective To investigate the incidence and risk factors for acute kidney injury(AKI)in children with primary nephrotic syndrome(PNS),as well as the role of neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(KIM-1)in the early identification of AKI in these children.Methods A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted.The children were divided into two groups based on the presence of AKI:the AKI group(47 cases)and the non-AKI group(169 cases).The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis.Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups,as well as among the different stages of AKI.Results The incidence of AKI in children with PNS was 21.8%.Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome,gastrointestinal infections,and heavy proteinuria were independent risk factors for AKI in these children with PNS(P<0.05).Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group(P<0.05),and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup(P<0.017).Conclusions KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS.Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.

Objective To preliminarily investigate the related factors influencing the size of vestibular schwannomas.Methods The clinical data of patients with vestibular schwannomas who underwent retrosigmoid approach surgery at the department of neurosurgery of First Affiliated Hospital of Xinjiang Medical University from June 2013 to June 2023 were retrospectively analyzed.The tumor size of the patients was evaluated based on their preoperative imaging data.Univariate and multiple linear regression analyses were performed to explore the factors affecting the size of vestibular schwannomas.Results The tumor size of patients was ranging from 0.63 to 6.60 cm,with a median size of 2.97(2.20,3.80)cm.Univariate analysis showed that gender(P=0.010),ethnicity(P=0.001),age(P=0.049)and cystic solid tumor(P<0.001)were related to the size of vestibular schwannomas.Large-sized vestibular schwannomas were most commonly cystic-solid,and small and medium-sized vestibular schwannomas were most commonly solid.BMI,surgical side and place of residence were not correlated with the size of vestibular schwannomas(P>0.05).Multiple linear regression results showed that male(B=0.390,P=0.001)and Uyghur(B=0.611,P<0.001)patients were more likely to develop large tumors;with every 1-year increase in age,the maximum diameter of the tumor was reduced by an average of 0.011 cm(B=-0.011,P=0.027).Conclusion The gender,age,and ethnicity of patients are correlated with the size of vestibular schwannomas,and male,Uyghur,or younger patients were at higher risk of developing larger vestibular schwannomas.

Objective:To explore the characteristics of gene mutation in patients with myelodysplastic syndrome (MDS) and its correlation with clinical features. Methods:From January 2017 to December 2021,172 patients with MDS in The First Affiliated Hospital of Bengbu Medical University were analyzed retrospectively. Fourteen high frequency genes related to MDS were detected,and the relationship between gene mutation and clinical characteristics of patients as well as revised International Prognostic Scoring System (IPSS-R) was analyzed. The impact of gene mutations on prognosis was explored. Results:Among 172 patients,there were 101 males and 71 females,with a median age of 67 (15-89) years old,and gene mutations were detected in 88 cases (51.2％). The genes with mutation incidence>5％ were arranged in descending order as follows:TET2 (16.9％),RUNX1 (12.8％),ASXL1 (12.2％),CEBPA (8.1％),TP53 (7.0％) and DNMT3A (6.4％). According to biological functional classification,the genes with the highest mutation frequency were epigenetic regulatory genes (36.6％). The proportion of primitive bone marrow cells in mutation group was higher than that in non-mutation group (P<0.001). The incidence of gene mutation varied in different MDS subtypes,and the difference was statistically significant (P<0.05). The mutation incidence in IPSS-R higher risk group (IPSS-R score>3.5) was 65.7％,which was significantly higher than 30.0％ in IPSS-R lower risk group (IPSS-R score ≤3.5) (P<0.05),and there was a statistically significant difference in the incidence of TP53 gene mutation between the two groups (P<0.05). Multivariate Cox survival analysis showed that TP53,NPM1 and TET2 gene mutation were independent risk factors affecting prognosis. Conclusion:MDS patients are prone to gene mutation,and the increasing number of mutations and the presence of TP53,NPM1 and TET2 gene mutation may be factors affecting the prognosis.

Objective:To study the effect of tertiary lymphoid structures(TLS)on the pathological response and prognosis of patients with non-small cell lung cancer(NSCLC)receiving neoadjuvant therapy.Methods:We retrospectively collected the data of 132 patients with NSCLC who underwent neoadjuvant therapy and surgery at Tianjin Chest Hospital between January 2019 and December 2023,including 40 in the neoadjuvant chemotherapy(NC)group and 92 in the NC plus immunotherapy(NCI)group.The percentage of residual viable tumor(RVT)and tumor infiltrating lymphocyte(TIL)counts were evaluated by hematoxylin and eosin(H&E)staining,while TLS number and matur-ity were assessed by H&E and immunohistochemical staining.The differences in TLS number and maturity and effects on patient pathologic-al response and prognosis were compared between groups.Results:TIL count,total TLS number,pathological complete response and major pathological response rates were significantly higher in the NCI versus NC group(P<0.001).Moreover,a multivariate Logistic analysis sho-wed that TLS number and maturity and TIL count affected pathological response in the NCI group(P<0.05).A multiple linear regression ana-lysis indicated that a low TIL count was a risk factor for a high RVT in the NC group,while a low number of mature TLS,low TIL count,and N stage were independent risk factors for a high RVT in the NCI group(all P<0.05).In the NCI group,a multivariate Cox regression analysis showed that a low number of mature TLS(P=0.001)and low TIL count(P=0.009)were independent predictors of disease-free survival(DFS),while a survival analysis showed that patients in the NCI group with high(vs.low)numbers of mature TLS and a high(vs.low)TIL count had significantly longer DFS(all P<0.001).Conclusions:A low number of mature TLS and low TIL count were associated with an adverse patholo-gical response and short DFS in patients with NSCLC.Thus,TLS maturity and TIL count can predict the pathological response and prognosis of patients with NSCLC treated with NCI.