OBJECTIVES: To investigate the association between insulin resistance and uterine volume in girls with idiopathic central precocious puberty (ICPP). METHODS: A retrospective study was conducted involving 61 girls diagnosed with ICPP who visited the pediatric growth and development clinic of the Third Affiliated Hospital of Zhengzhou University between January 2022 and September 2024, designated as the ICPP group, and 61 normally developing girls as the control group. The differences in insulin resistance index (homeostasis model assessment of insulin resistance, HOMA-IR), uterine volume, and other indicators between the two groups were compared, and the relationship between insulin resistance and uterine volume in these girls was analyzed. RESULTS: The uterine volume and HOMA-IR level in the ICPP group were significantly higher than those in the control group (P<0.05). Correlation analysis revealed that there was a positive correlation between HOMA-IR level and uterine volume in the ICPP group (r_s=0.643, P<0.001). Multiple linear regression analysis indicated that as HOMA-IR increased,uterine volume in the girls tended to increase (P<0.05). CONCLUSIONS There is an association between insulin resistance and uterine volume in girls with ICPP, and as HOMA-IR increases, uterine volume in the girls also increases.
Humans ; Female ; Insulin Resistance ; Puberty, Precocious/metabolism* ; Uterus/pathology* ; Child ; Retrospective Studies ; Organ Size ; Linear Models

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

OBJECTIVE: The molecular biology of alleles of ABO blood group A_el and B_el subtype from two samples was analyzed to explore the effect of mutations on the structure of glycosyltransferase. METHODS: The ABO phenotypes were identified by serological techniques, then exons 6 and 7 of ABO gene were amplified and sequenced, combined with haplotype analysis to determine the genotypes. Finally, homology modeling of the mutated A/B glycosyltransferase were conducted by Modeller software and the effect of mutations on the spatial structure was analyzed by PyMol software. RESULTS: The serological phenotypes of the two samples were A_el and B_el, and their genotypes were ABO*AW.37/ABO*O.01.01 and ABO*BEL.03/ABO*O.01.01, respectively. The three-dimensional structure modeling of the protein showed that, compared to the wild-type glycosyltransferase, two hydrogen bonds between the side chain of p.Glu314 and surrounding amino acid disappeared in the p.Lys314Glu mutant GTA; the hydrogen bonds between the side chain of p.Trp168 and surrounding amino acid also disappeared, and the hydrogen bond between the main chain of p.Trp168 and p.Gly165 was shortened to 3.3 Å in the p.Arg168Trp mutant GTB. CONCLUSION Mutations in exon 7 of ABO gene c.940A>G and c.502C>T are keys to the formation of AW.37 and BEL.03 alleles, resulting in decreased expression of A and B antigens, respectively.
ABO Blood-Group System/classification* ; Humans ; Genotype ; Mutation ; Alleles ; Glycosyltransferases/genetics* ; Exons ; Haplotypes ; Phenotype ; Models, Molecular

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.

Objective To investigate the mechanism by which long non-coding RNA(lncRNA)AI662270 regulates insulin resistance in adipocytes in aging mice.Methods(1)Twenty male C57BL/6 mice were randomly divided into youth(4-month-old)group and aged(18-month-old)group(n=10).Mice in youth group were raised to 4 months of age and euthanized by orbital exsanguination under urethane anesthesia,while aged mice were euthanized at 18 months using the same sacrifice method.Epididymal white adipose tissue(eWAT)and liver tissue were rapidly dissected.Western blotting was employed to detect the protein expression levels of tumor suppressor gene 1(p16ink4a)and cyclin-dependent kinase inhibitor p21(p21kip1),RT-qPCR was used to measure the expression of 4 differentially expressed lncRNAs(C4a,AI662270,BATE1 and Gm29719).Mouse embryonic fibroblasts(3T3-L1)were cultured and divided into a normal control group(no treatment after induced differentiation into mature adipocytes)and a senescence model group[doxorubicin(ADR)-treated group;0.2 μmol/L ADR was used to induce senescent adipocytes].β-galactosidase staining was performed to assess adipocyte senescence.RT-qPCR was applied to evaluate the expression of AI662270 and senescence markers(p16ink4a,p21kip1,p53),while Western blotting was utilized to detect the expression levels of phosphorylated H2A histone family member X(γ-H2AX),p16ink4a,and p21kip1 proteins.(2)Hexokinase method was adopted to measure glucose content in mouse serum and 3T3-L1 adipocyte culture medium.RT-qPCR was performed to analyze mRNA expression levels of insulin sensitivity-related gene protein kinase B(Akt),insulin receptor substrate 1(IRS1),phosphatidylinositol 3 kinase(PI3K)and glucose transporter 4(GLUT4)in mouse eWAT and adipocytes.Western blotting was conducted to determine the protein expression levels of IRS 1,PI3K,Akt,and p-Akt.(3)Spearman correlation analysis was applied to examine the correlation between AI662270 expression levels and IRS1/PI3K mRNA expression levels.A low-expression model of AI662270 in senescent adipocytes was constructed,and RT-qPCR was used to verify the knockdown efficiency.Hexokinase method was employed to assess glucose content in the cell culture medium of senescent adipocytes after AI662270 knockdown.RT-qPCR was performed to measure the mRNA expressions of Akt,IRS1,IRS2,and PI3K,while Western blotting was utilized to detect the expressions levels of Akt and p-Akt proteins.(4)Bioinformatics analysis was performed to predict downstream target genes of AI662270 and their binding sites.RT-qPCR and Western blotting were subsequently applied to validate the expression of these downstream target genes following AI662270 knockdown.Results(1)Compared with youth group,the protein expression levels of p16ink4a and p21kip1 in eWAT of aged mice were significantly increased(P＜0.05).Additionally,the expression levels of C4a,AI662270,BATE1,and Gm29719 in both eWAT and liver tissues were significantly increased in aged group(P＜0.05).β-galactosidase staining revealed enhanced blue-green coloration and enlarged,flattened cellular morphology in ADR-treated senescent adipocytes compared with normal control group.Compared with normal control group,ADR-treated senescent adipocytes significantly increased the mRNA expression levels of AI662270,p16ink4a,and p21kip1,and significantly elevated protein expression levels of γ-H2AX,p16ink4a,and p21kip1(P＜0.05).(2)Serum glucose content was significantly higher in aged group mice compared with youth group(P＜0.01),and glucose content in the adipocyte culture medium in ADR group was significantly increased(P＜0.05).The expression levels of IRS1 and PI3K in eWAT in aged group were significantly reduced compared with youth group(P＜0.01).Compared with normal control group,the expression levels of IRS 1 and PI3K in adipocytes in ADR-treated group were also significantly reduced(P＜0.05).(3)Spearman correlation analysis demonstrated that the expression level of AI662270 was negatively correlated with the mRNA expression levels of IRS1 and PI3K(P＜0.05).RT-qPCR showed that AI662270 expression level was significantly reduced in the siAI662270-transfected senescent adipocytes compared with siNC group(P＜0.05),indicating the low expression model of aged adipocytes AI662270 was successfully constructed.Hexokinase assay results showed that glucose content in the cell culture medium was significantly reduced after the AI662270 was knocked down by senescent adipocytes(P＜0.05).Furthermore,the mRNA expression levels of IRS1,IRS2 and PI3K(P＜0.05)and the p-Akt/Akt ratio in senescent adipocytes was significantly increased after knockdown of AI662270(P＜0.01).(4)Bioinformatics analysis predicted miR-3073b-3p as a downstream target gene of AI662270,and heme oxygenase 1(Hmox1)was identified as a target molecule of miR-3073b-3p.The expression level of miR-3073b-3p in senescent adipocytes in siAI662270 group was significantly increased,while the mRNA and protein expression level of Hmox1 were significantly decreased compared with siNC group(P＜0.01).Conclusions Aging significantly increases the expression of AI662270 in eWAT of mice,and the expression of AI662270 was negatively correlated with insulin sensitivity.AI662270 knockdown can reduce glucose content in senescent adipocyte culture medium,upregulate the expression of IRS1 and PI3K,and increase insulin sensitivity in senescent adipocytes,which may be mediated through the AI662270/miR-3073b-3p/Hmox1 pathway.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.