ObjectiveTo establish and characterize an inducible， CD4+ T cell-specific ablation mouse model （CD4-iDTR） using the Cre-loxP and diphtheria toxin receptor （DTR） systems， and to evaluate its depletion efficacy and specificity. MethodsCD4-iDTR mice were generated through cross-breeding， with genotypes confirmed via PCR-based screening. Mice were categorized into an untreated （control） group and a diphtheria toxin （DT） induction group. Flow cytometry was employed to compare the baseline distribution of CD4⁺ T cells between untreated CD4-iDTR and wild-type C57BL/6 mice.In the DT group， CD4⁺ T cell ablation was induced by subcutaneous DT administration. The depletion efficiency in skin tissues and skin-draining lymph nodes （sdLNs） was quantified at 24 h and 1 week post-injection. Furthermore， the proportions of neutrophils， macrophages， dendritic cells， and other CD11b⁺ immune cell subsets in the skin were monitored to assess the model specificity. ResultsGenomic profiling confirmed the successful generation of the CD4-iDTR line. Under steady-state conditions， no significant differences were observed in the frequency or absolute number of CD4⁺ T cells in the skin and sdLNs between CD4-iDTR and C57BL/6 mice （P>0.05）. Following DT induction， the CD4⁺ T cell population in the skin exhibited decline within 24 h and 1 week （P<0.05）， whereas the CD4⁺ T cell counts in sdLNs remained stable. The percentages of cutaneous neutrophils， macrophages， and other CD11b⁺ myeloid populations were not significantly altered following DT treatment （P>0.05）. ConclusionThe CD4-iDTR mouse model is successfully established and bred， achieving efficient， specific， and inducible ablation of cutaneous CD4⁺ T cells without significant interference with the skin immune microenvironment. This model serves as an ideal experimental tool for investigating skin-specific immunological mechanisms.

In recent years, the novel tracer mitoxantrone hydrochloride has been increasingly applied in thyroid cancer surgery. As a safe tracer, mitoxantrone hydrochloride enables the detection of more lymph nodes and better protection of the parathyroid glands during thyroid cancer surgery. It assists surgeons in achieving more precise treatment, thereby improving the prognosis of patients. However, research on the use of mitoxantrone in thyroid cancer surgery remains limited, and standardized operating protocols are lacking. This article explores the current applications and future development of mitoxantrone in thyroid cancer surgery, aiming to provide a reference for clinical practice.

In recent years, the novel tracer mitoxantrone hydrochloride has been increasingly applied in thyroid cancer surgery. As a safe tracer, mitoxantrone hydrochloride enables the detection of more lymph nodes and better protection of the parathyroid glands during thyroid cancer surgery. It assists surgeons in achieving more precise treatment, thereby improving the prognosis of patients. However, research on the use of mitoxantrone in thyroid cancer surgery remains limited, and standardized operating protocols are lacking. This article explores the current applications and future development of mitoxantrone in thyroid cancer surgery, aiming to provide a reference for clinical practice.

AIM:To investigate the association between single nucleotide polymorphisms(SNPs)in the silent information regulator 1(SIRT1)gene and breast cancer risk in the Han Chinese population.METHODS:A total of 105 Han Chinese patients with breast cancer and 90 healthy controls were enrolled.Sequenom MassARRAY was used to detect the genotypes of SIRT1 gene loci,rs3740051,rs3758391,rs12778366 and rs2394443.The Hardy-Weinberg equilibrium(HWE)was analysed using the chi-square test.Multivariate logistic regression was employed to analyze the correlation be-tween each SNP and breast cancer susceptibility,as well as the relationship between the rs3758391 genotype and the clini-copathological characteristics of breast cancer in Han Chinese women.SHEsis software was used to assess linkage disequi-librium and haplotypes of the selected SNPs.The impact of genotypes at rs3758391 locus on SIRT1 protein expression was examined using Western blot.An additional 150 Han Chinese women with breast cancer and 150 healthy controls were en-rolled,and SIRT1 protein expression was assessed using immunohistochemistry.Logistic regression was performed to as-sess the relationship between high and low SIRT1 expression and the clinical characteristics of breast cancer.Kaplan-Mei-er website was used to determine the association between SIRT1 expression and patient prognosis.RESULTS:All four SNP loci conformed to the HWE test(P>0.05).The TC/TC+CC genotype of the SIRT1 rs3758391 locus significantly re-duced the risk of breast cancer compared with the TT genotype(TT vs TC:ORadj=0.348,95%CI:0.157～0.773,Padj=0.010;TT vs TC+CC:ORadj=0.381,95%CI:0.179～0.811,Padj=0.012),and correlated with earlier disease course(stage I/II),smaller tumor volume,and higher SIRT1 protein expression levels(P<0.05).SIRT1 expression was signifi-cantly lower in breast cancer tissues,and low SIRT1 expression was associated with larger tumor size,lymph node metasta-sis,and reduced recurrence-free survival(P<0.05).CONCLUSION:The TC/TC+CC genotype of the SIRT1 rs3758391 locus may be a protective factor for breast cancer in Han Chinese women,potentially reducing the risk of breast cancer and delaying disease progression by regulating SIRT1 expression.In addition,SIRT1 expression level is closely related to the clinical characteristics and prognosis of breast cancer.

AIM:To investigate the association between single nucleotide polymorphisms(SNPs)in the silent information regulator 1(SIRT1)gene and breast cancer risk in the Han Chinese population.METHODS:A total of 105 Han Chinese patients with breast cancer and 90 healthy controls were enrolled.Sequenom MassARRAY was used to detect the genotypes of SIRT1 gene loci,rs3740051,rs3758391,rs12778366 and rs2394443.The Hardy-Weinberg equilibrium(HWE)was analysed using the chi-square test.Multivariate logistic regression was employed to analyze the correlation be-tween each SNP and breast cancer susceptibility,as well as the relationship between the rs3758391 genotype and the clini-copathological characteristics of breast cancer in Han Chinese women.SHEsis software was used to assess linkage disequi-librium and haplotypes of the selected SNPs.The impact of genotypes at rs3758391 locus on SIRT1 protein expression was examined using Western blot.An additional 150 Han Chinese women with breast cancer and 150 healthy controls were en-rolled,and SIRT1 protein expression was assessed using immunohistochemistry.Logistic regression was performed to as-sess the relationship between high and low SIRT1 expression and the clinical characteristics of breast cancer.Kaplan-Mei-er website was used to determine the association between SIRT1 expression and patient prognosis.RESULTS:All four SNP loci conformed to the HWE test(P>0.05).The TC/TC+CC genotype of the SIRT1 rs3758391 locus significantly re-duced the risk of breast cancer compared with the TT genotype(TT vs TC:ORadj=0.348,95%CI:0.157～0.773,Padj=0.010;TT vs TC+CC:ORadj=0.381,95%CI:0.179～0.811,Padj=0.012),and correlated with earlier disease course(stage I/II),smaller tumor volume,and higher SIRT1 protein expression levels(P<0.05).SIRT1 expression was signifi-cantly lower in breast cancer tissues,and low SIRT1 expression was associated with larger tumor size,lymph node metasta-sis,and reduced recurrence-free survival(P<0.05).CONCLUSION:The TC/TC+CC genotype of the SIRT1 rs3758391 locus may be a protective factor for breast cancer in Han Chinese women,potentially reducing the risk of breast cancer and delaying disease progression by regulating SIRT1 expression.In addition,SIRT1 expression level is closely related to the clinical characteristics and prognosis of breast cancer.

OBJECTIVE To explore the synergistic effect of clorgiline and voriconazole on inhibition of bacteria and formation of biofilms in vitro so as to provide experiment bases for clinical treatment of drug-resistant Candida albicans infection.METHODS Minimum inhibitory concentrations(MICs)of voriconazole and clorgiline against two strains of C.albicans were explored by broth microdilution method.The synergistic effect of the two drugs on inhibition of bacteria were evaluated by chessboard method,and the fractional inhibitory concentration index(FICI)was calculated.The potential mechanisms of clorgiline for synergistically boost the effect of voriconazole were studied by rhodamine 6G(R6G)efflux pump test;the effects of the single and combined use of the two drugs on inhibition of the biofilms were explored by crystal violet staining method.RESULTS The MICs of the sin-gle voriconazole against the 2 strains of C.albicans were 0.25 μg/ml and 8 μg/ml,respectively;the MICs were decreased to 0.0625 μg/ml and 0.5 μg/ml,respectively,after its combination with clorgiline.The FICIs of the combined use of the two drugs against the two strains were both less than 0.5,showing synergistic antibacterial effect.The result of R6G efflux pump experiment indicated that clorgiline inhibited the efflux of R6G within 2 hours.The biofilm formation experiment showed that the single use of voriconazole or clorgiline had limited effect on inhibition of biofilm formation,and the combined use of the two drugs could inhibit the biofilm formation.CONCLUSIONS Clorgiline can enhance the antibacterial activity of voriconazole by inhibiting the efflux pump func-tion of the C.albicans strains.The two drugs show remarkable synergistic effect on inhibition of the biofilm for-mation,which may provide novel strategies for combined use of drugs and theoretical bases for treatment of the drug-resistant C.albicans infection.

OBJECTIVE To explore the synergistic effect of clorgiline and voriconazole on inhibition of bacteria and formation of biofilms in vitro so as to provide experiment bases for clinical treatment of drug-resistant Candida albicans infection.METHODS Minimum inhibitory concentrations(MICs)of voriconazole and clorgiline against two strains of C.albicans were explored by broth microdilution method.The synergistic effect of the two drugs on inhibition of bacteria were evaluated by chessboard method,and the fractional inhibitory concentration index(FICI)was calculated.The potential mechanisms of clorgiline for synergistically boost the effect of voriconazole were studied by rhodamine 6G(R6G)efflux pump test;the effects of the single and combined use of the two drugs on inhibition of the biofilms were explored by crystal violet staining method.RESULTS The MICs of the sin-gle voriconazole against the 2 strains of C.albicans were 0.25 μg/ml and 8 μg/ml,respectively;the MICs were decreased to 0.0625 μg/ml and 0.5 μg/ml,respectively,after its combination with clorgiline.The FICIs of the combined use of the two drugs against the two strains were both less than 0.5,showing synergistic antibacterial effect.The result of R6G efflux pump experiment indicated that clorgiline inhibited the efflux of R6G within 2 hours.The biofilm formation experiment showed that the single use of voriconazole or clorgiline had limited effect on inhibition of biofilm formation,and the combined use of the two drugs could inhibit the biofilm formation.CONCLUSIONS Clorgiline can enhance the antibacterial activity of voriconazole by inhibiting the efflux pump func-tion of the C.albicans strains.The two drugs show remarkable synergistic effect on inhibition of the biofilm for-mation,which may provide novel strategies for combined use of drugs and theoretical bases for treatment of the drug-resistant C.albicans infection.

In recent 20 years, the incidence of thyroid cancer has shown an obvious upward trend, especially in female patients. As the second most common molecular marker of thyroid cancer, RAS mutation affects the occurrence and development of thyroid cancer mainly through RAS-RAF-MEK-ERK and PI3K-Akt signaling pathways. However, the effect of RAS mutation on the invasive characteristics, prognosis and survival rate of thyroid cancer is still controversial. This article reviews the research progress of RAS gene mutation in thyroid cancer.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Objective:To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma.Methods:The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model.Results:Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome ( HR=8.50,95% CI: 1.679-8.328, P=0.001), serum albumin ( HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy ( HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions:Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.