OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

Objective To investigate the association of digit ratio with single nucleotide polymorphism(SNP)at three loci(rs17576,rs3918249,rs9509)of matrix metallopeptidase 9(MMP-9)gene.Methods A total of 804 Ningxia Han youths(399 males and 405 females)were used as the study subjects.A digital camera was used to take frontal photographs of the hands,and image analysis software was used to mark the anatomical points and measure the lengths of each finger of both hands(2D,3D,4D,5D);Multiplexed PCR was used to detect the three polymorphic sites of the MMP-9 gene,SPSS 25.0 and R Studio software were used for data analysis and plotting.Results The 2D/3D(P＜0.05)and 2D/4D(left,P＜0.01,right,P＜0.05)of both hands,2D/5D(P＜0.01),3D/5D,4D/5D(P＜0.05)of the right hand,and 3D/4D(P＜0.05)of the left hand in female youths of Ningxia Han were significantly higher than those in males,Differences in genotypes and allele frequencies at all 3 loci of the MMP-9 gene were not statistically significant between genders(P＞0.05).Right hand 2D/4D was significantly associated with genotypes at the rs17576 and rs3918249 loci in male youths(P＜0.05).Conclusion MMP-9 gene SNPs(rs17576 and rs3918249)may be associated with the formation of 2D/4D of Ningxia Han male youths.

Objective This study aims to investigate the effects of FGL2 on the immune response of EBV-infected T cells,including their activation,proliferation,exhaustion,and cytokine profile changes.Methods Primary T cells were infected with EBV at different multiplicities of infection(MOI).Expression of FGL2 in T cells,as well as T-cell activation,proliferation,exhaustion,and cytokine levels,were detected using RT-qPCR,Western blot,ELISA,CCK8,and flow cytometry(FCM),respectively.Further experiments involving FGL2 knockdown and overexpression were conducted to elucidate its specific regulatory role in EBV-infected T cells.Results FGL2 expression was significantly upregulated in EBV-infected T cells(P＜0.05).EBV infection also induced enhanced T cell activation(P＜0.001),proliferation(P＜0.001),and exhaustion(P＜0.01).Compared to the T cells+EBV group,the T cells+EBV+FGL2 overexpression group exhibited higher exhaustion levels(P＜0.01),reduced activation(P＜0.05)and proliferation(P＜0.05),decreased pro-inflammatory cytokine levels(P＜0.05),and increased anti-inflammatory cytokine levels(P＜0.05).Conversely,the T cells+EBV+FGL2 knockdown group demonstrated the opposite trends,with elevated activation(P＜0.01),proliferation(P＜0.05),pro-inflammatory cytokine levels(P＜0.05),and reduced exhaustion(P＜0.01)and anti-inflammatory cytokine levels(P＜0.05).Conclusion FGL2 suppresses T cell activation and proliferation,exacerbates T cell exhaustion,inhibits pro-inflammatory cytokine release,and promotes anti-inflammatory cytokine secretion during EBV infection,thereby modulating the immune response of T cells.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Objective:To analyze the expression of conductance calcium-activated potassium channel(IKCa1)protein in papillary thyroid carcinoma(PTC)tissues and its relationship with postoperative recovery of thyroid function.Methods:A total of 153 PTC patients who were treated from December 2020 to December 2023 were selected as the research objects.All patients were divided into a good recovery group(n=97)and a poor recovery group(n=56)according to whether they had hypothyroidism after surgery.The expression of IKCa1 protein in PTC tissues and adjacent normal tissues was compared.The relationship between the expression of IKCa1 protein in PTC tissues and the clinicopathologi-cal characteristics of the patients was analyzed.Hierarchical regression analysis was used to analyze the relationship be-tween clinicopathological features and IKCa1 mRNA level.Univariate analysis was used to analyze the influencing factors of postoperative thyroid function recovery.Spearman correlation was used to analyze the relationship between IKCa1 mRNA expression and thyroid function related factors[free triiodothyronine(FT3),free thyroxine(FT4),total triiodothyro-nine(TT3),total thyroxine(TT4)and thyroid stimulating hormone(TSH)].The independent correlation between IKCa1 mRNA expression in PTC tissues and postoperative thyroid dysfunction was analyzed.The dose on response between IKCa1 mRNA expression in PTC tissues and postoperative thyroid function was analyzed.And the relationship between IKCa1 protein expression in PTC tissues and prognosis of patients.Results:The high expression of IKCa1 protein in PTC tissues(102 cases,66.67％)was significantly higher than that in adjacent normal tissues(33 cases,21.57％),and the difference was statistically significant(P＜0.05).The expression of IKCa1 protein in PTC tissues was related to tumor diameter,lymph node metastasis,TNM stage and Ki-67(P＜0.05).Tumor diameter,lymph node metastasis,TNM stage and Ki-67 had a significant positive effect on IKCa1 mRNA level(P＜0.05).There were significant differences in lymph node metastasis,tumor diameter and IKCa1 mRNA expression between the good recovery group and the poor recovery group(P＜0.05).The results of Spearman analysis showed that the expressions of FT3,FT4,TT3,TT4 and TSH had sig-nificant effects on IKCa1 mRNA expression(P＜0.05).The expression level of IKCa1 mRNA in PTC tissues was indepen-dently correlated with postoperative thyroid function(All P＜0.05).RCS model analysis showed that with the increase of IKCa1 mRNA expression,postoperative thyroid function showed a non-linear downward trend.The overall survival of pa-tients with high expression of IKCa1 protein in PTC tissues was significantly shorter than that of patients with low ex-pression of IKCa1 protein(P＜0.05).Conclusion:IKCa1 protein is highly expressed in PTC tissues,and its expression level is closely related to postoperative thyroid function,which is a risk factor for postoperative hypothyroidism.

Objective This study aims to investigate the effects of FGL2 on the immune response of EBV-infected T cells,including their activation,proliferation,exhaustion,and cytokine profile changes.Methods Primary T cells were infected with EBV at different multiplicities of infection(MOI).Expression of FGL2 in T cells,as well as T-cell activation,proliferation,exhaustion,and cytokine levels,were detected using RT-qPCR,Western blot,ELISA,CCK8,and flow cytometry(FCM),respectively.Further experiments involving FGL2 knockdown and overexpression were conducted to elucidate its specific regulatory role in EBV-infected T cells.Results FGL2 expression was significantly upregulated in EBV-infected T cells(P＜0.05).EBV infection also induced enhanced T cell activation(P＜0.001),proliferation(P＜0.001),and exhaustion(P＜0.01).Compared to the T cells+EBV group,the T cells+EBV+FGL2 overexpression group exhibited higher exhaustion levels(P＜0.01),reduced activation(P＜0.05)and proliferation(P＜0.05),decreased pro-inflammatory cytokine levels(P＜0.05),and increased anti-inflammatory cytokine levels(P＜0.05).Conversely,the T cells+EBV+FGL2 knockdown group demonstrated the opposite trends,with elevated activation(P＜0.01),proliferation(P＜0.05),pro-inflammatory cytokine levels(P＜0.05),and reduced exhaustion(P＜0.01)and anti-inflammatory cytokine levels(P＜0.05).Conclusion FGL2 suppresses T cell activation and proliferation,exacerbates T cell exhaustion,inhibits pro-inflammatory cytokine release,and promotes anti-inflammatory cytokine secretion during EBV infection,thereby modulating the immune response of T cells.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Objective:To analyze the expression of conductance calcium-activated potassium channel(IKCa1)protein in papillary thyroid carcinoma(PTC)tissues and its relationship with postoperative recovery of thyroid function.Methods:A total of 153 PTC patients who were treated from December 2020 to December 2023 were selected as the research objects.All patients were divided into a good recovery group(n=97)and a poor recovery group(n=56)according to whether they had hypothyroidism after surgery.The expression of IKCa1 protein in PTC tissues and adjacent normal tissues was compared.The relationship between the expression of IKCa1 protein in PTC tissues and the clinicopathologi-cal characteristics of the patients was analyzed.Hierarchical regression analysis was used to analyze the relationship be-tween clinicopathological features and IKCa1 mRNA level.Univariate analysis was used to analyze the influencing factors of postoperative thyroid function recovery.Spearman correlation was used to analyze the relationship between IKCa1 mRNA expression and thyroid function related factors[free triiodothyronine(FT3),free thyroxine(FT4),total triiodothyro-nine(TT3),total thyroxine(TT4)and thyroid stimulating hormone(TSH)].The independent correlation between IKCa1 mRNA expression in PTC tissues and postoperative thyroid dysfunction was analyzed.The dose on response between IKCa1 mRNA expression in PTC tissues and postoperative thyroid function was analyzed.And the relationship between IKCa1 protein expression in PTC tissues and prognosis of patients.Results:The high expression of IKCa1 protein in PTC tissues(102 cases,66.67％)was significantly higher than that in adjacent normal tissues(33 cases,21.57％),and the difference was statistically significant(P＜0.05).The expression of IKCa1 protein in PTC tissues was related to tumor diameter,lymph node metastasis,TNM stage and Ki-67(P＜0.05).Tumor diameter,lymph node metastasis,TNM stage and Ki-67 had a significant positive effect on IKCa1 mRNA level(P＜0.05).There were significant differences in lymph node metastasis,tumor diameter and IKCa1 mRNA expression between the good recovery group and the poor recovery group(P＜0.05).The results of Spearman analysis showed that the expressions of FT3,FT4,TT3,TT4 and TSH had sig-nificant effects on IKCa1 mRNA expression(P＜0.05).The expression level of IKCa1 mRNA in PTC tissues was indepen-dently correlated with postoperative thyroid function(All P＜0.05).RCS model analysis showed that with the increase of IKCa1 mRNA expression,postoperative thyroid function showed a non-linear downward trend.The overall survival of pa-tients with high expression of IKCa1 protein in PTC tissues was significantly shorter than that of patients with low ex-pression of IKCa1 protein(P＜0.05).Conclusion:IKCa1 protein is highly expressed in PTC tissues,and its expression level is closely related to postoperative thyroid function,which is a risk factor for postoperative hypothyroidism.