Objective:To investigate the clinical application value of cystatin C(CysC), neutrophil gelatinase-associated lipocalin(NGAL), urea nitrogen(UREA), blood creatinine(Scr)and urinary neutrophil gelatinase-associated lipocalin(NGAL)in early diabetic nephropathy and their relationship with aging.Methods:A total of 140 diabetic patients aged 60 and above who were admitted to Beijing Hospital from July 2022 to November 2022 and 59 healthy people aged 60 and above who underwent physical examination in Beijing hospital during the same period were selected as the study subjects.In January 2023, 157 healthy people over 20 years old who underwent physical examination in Beijing Hospital were used as another group of research objects to explore the relationship between various indicators and aging.According to the urinary microalbumin/urinary creatinine(UACR)ratio, the patients were divided into three groups: 40 patients with simple diabetes mellitus(DM), 57 patients with early diabetic nephropathy(EDN), and 43 patients with diabetic nephropathy(DN).59 healthy subjects were used as control group(NC group).Serum NGAL, Scr, Cys C, UREA and urinary NGAL were detected, and NGAL was determined by latex immunoturbidimetry.Scr was determined by sarcosine oxidase method.Cys C was determined by immunoturbidimetry.Urease-glutamate dehydrogenase method was used to determine UREA.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of urea alone and combined diagnosis in EDN.The relationship between serum NGAL, Scr, Cys C, UREA and urinary NGAL and gender and aging were analyzed in 157 healthy individuals.Results:Compared to the NC group, serum NGAL, Scr, CysC, and UREA levels were significantly higher in the EDN and DN groups(all P<0.01), and the differences between EDN group, DN group and NC group were statistically significant( P<0.01).The values of these markers increased across the NC, DM, EDN, and DN groups.ROC curve shows: The area under curve(AUC)of serum NGAL, Scr, Cys C, UREA, urine NGAL, combined diagnosis 1 and combined diagnosis 2 were 0.655, 0.760, 0.789, 0.753, 0.628, 0.831, 0.827, respectively.The sensitivity of combined diagnosis 1 and combined diagnosis 2 was higher(63.2% and 66.7%), and the specificity of serum NGAL was higher(96.6%).The AUC values of Cys C, co-diagnosis 1, and co-diagnosis 2 were large and correlated(AUC=0.789, 0.831, 0.827, rs=0.501, 0.573, 0.567), and the diagnostic value of Cys C, co-diagnosis 1, and co-diagnosis 2 for EDN was high(AUC=0.789, 0.831, 0.827, Yoden index=0.442, 0.530, 0.531; sensitivity 56.1%, 63.2%, 66.7%; specificity 88.1%, 89.8%, 86.4%).Healthy individuals over 20 years of age: serum NGAL[(127.5±35.5)μg/L vs.(111.5±32.4)μg/L, P=0.004], Scr[(83.4±11.2)μmol/L versus(63.4±11.0)μmol/L, P<0.001], Cys C[(0.8±0.2)mg/L vs.(0.7±0.2)mg/L, P<0.001], and UREA levels were higher in males than females[(5.1±1.1)mmol/L vs.(4.6±1.1)mmol/ L, P=0.002]; urinary NGAL was higher in females than males[22.0(13.0, 37.8)μg/L vs.15.0(10.0, 30.5)μg/L, P=0.025].Cys C( F=16.582, P<0.001), urinary NGAL levels( F=-3.533, P<0.001)basically increased with age. Conclusions:CysC showed a higher diagnostic value for EDN than UREA, Scr, blood NGAL, and urine NGAL in patients aged 60 and above Combined diagnosis 1 and combined diagnosis 2 have higher value in monitoring the progress of DN.The levels of Cys C and urinary NGAL showed a gradually increasing trend with the increase of age, and the levels of serum NGAL, Scr, Cys C and UREA were higher in males than in females.Urinary NGAL was higher in females than males.

Objective:To compare the clinical and laboratory characteristics and survival between Chinese and Western patients with myelodysplastic neoplasms (MDS) .Methods:Clinical and laboratory data were collected from 1,464 primary adult patients diagnosed with MDS at the Institute of Hematology & Blood Diseases Hospital from August 2016 to June 2024. Collected data were retrospectively analyzed and compared with 2,191 patients from the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) .Results:Chinese patients were significantly younger (median age: 56 years vs. 72 years, P<0.001) and experienced more severe hematopenia ( P<0.001) compared with patients from the IWG-PM. Further, Chinese patients exhibited a higher percentage of isolated del (20q), +8, and complex karyotypes as well as a lower percentage of normal karyotypes, del (5q), and -Y ( P<0.001). Higher U2AF1, NRAS, and NPM1 mutation rates and lower ASXL1, SF3B1, and RUNX1 mutation rates were observed in Chinese patients than in participants from the IWG-PM ( P<0.05). No significant difference in overall survival (OS) was found between the two groups (median OS: 48 [95% CI: 40 - 56]months, vs. 45[95% CI: 40 - 49] months; P=0.449). Among participants aged ≤45 years, Chinese patients demonstrated more trisomy 8 ( P=0.070) and U2AF1 mutation ( P<0.001) and higher 4-year OS rate compared with those from the IWG-PM (75.5% vs. 62.1%, P=0.001). Among participants aged ≥70 years, Chinese patients exhibited more complex karyotypes but fewer del (5q) as well as more NPM1 but less SF3B1 and TET2 compared with those from the IWG-PM ( P<0.05). Chinese patients demonstrated shorter survival (median OS: 20 [95% CI: 13 - 27] months vs. 37 [95% CI: 32 - 42] months, P<0.001) . Conclusion:Chinese and Western MDS patients differ in age of onset, clinical features, and cytogenetic or molecular genetic abnormalities, with significant differences persisting in age-matched groups. Although the OS is similar, disparities exist in survival for younger and older patients between the two populations.

Objective:To investigate the association between pre- and post-treatment gene mutation profiles and clinical outcomes (treatment response and prognosis) in patients with myelodysplastic syndromes with excess blasts (MDS-EB) receiving hypomethylating agent (HMA) monotherapy.Methods:The clinical characteristics, treatment efficacy, and survival outcomes of 69 treatment-naive patients with MDS-EB who underwent next-generation sequencing (NGS) before treatment and completed at least 4 cycles of HMA monotherapy at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, between June 2016 and September 2023, were retrospectively analyzed.Results:① The cohort comprised 47 males and 22 females with a median age of 62 years (range: 41-80). Thirty-nine patients were classified as MDS-EB1 and 30 as MDS-EB2. The median number of treatment cycles was 6 (range: 4-35). The median follow-up duration was 22 months (range: 5-72), and the median overall survival (OS) was 32 months (95% CI: 27-43). ② The presence of DTA (DNMT3A, TET2, or ASXL1) mutations, signaling pathway mutations, transcription factor mutations, or splicing factor mutations before HMA treatment showed no significant association with the best response within 4 treatment cycles, duration of response (DOR), or OS. TP53 mutation status was significantly associated with DOR and shorter OS. The median DOR was 3 months (95% CI: 1-10) for patients with biallelic TP53 mutations, 10 months (95% CI: 3-34) for those with monoallelic TP53 mutations, and 16 months (95% CI: 8-27) in patients without TP53 mutations ( P=0.032). The median OS was 16 months (95% CI: 7-38), 15 months (95% CI: 6-40), and 35 months (95% CI: 14-91), respectively ( P<0.001). ③ Neither the Revised International Prognostic Scoring System (IPSS-R) nor the Molecular International Prognostic Scoring System (IPSS-M) could predict the best response within 4 treatment cycles or DOR in patients receiving HMA therapy. ④ Among patients without TP53 mutations, the median OS was 55 months (95% CI: 9-106) for the major clone significant clearance group ( n=14) and 31 months (95% CI: 16-184) for the major clone non-significant clearance group ( n=10) ( P=0.013). For patients who responded to HMA treatment and had significant major clone clearance, the 3-year OS rate reached (77.8±13.9) %. Conclusion:For MDS-EB patients receiving HMA monotherapy, single gene mutations, IPSS-R, and IPSS-M could not effectively predict treatment outcomes before therapy. However, for patients without TP53 mutations, monitoring the degree of major clone clearance by NGS during treatment may predict the long-term efficacy in MDS patients receiving HMA therapy.

Objective:To analyze the clinical characteristics, therapeutic responses, and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) .Methods:We retrospectively reviewed clinical data from 16 consecutive patients diagnosed with L-HES at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and October 2024. A control group of 65 patients with idiopathic hypereosinophilic syndrome (iHES), diagnosed during the same period, was used for comparison. Clinical and laboratory characteristics, therapeutic responses, and survival outcomes were compared between the two groups.Results:The most frequently involved organs at presentation in patients with L-HES were the skin (75.0%), gastrointestinal tract (25.0%), respiratory tract (18.8%), lymph nodes (18.8%), heart (12.5%), and spleen (6.3%). Compared with iHES patients, patients with L-HES had a significantly higher incidence of skin involvement ( P=0.016), with no statistically significant differences observed in the involvement of other organs. No statistically significant differences were found in complete blood count parameters between the two groups. Multiparameter flow cytometry revealed that the median percentage of CD3 -CD4 + T cells in the peripheral blood of patients with L-HES was 4.08% ( IQR: 1.64%-32.78%), with a median absolute count of 0.10 (0.05-0.55) ×10 9/L. Serum immunoglobulin E (IgE) levels were significantly higher in the L-HES group than in the iHES group ( P<0.001). Clonal rearrangement of T-cell receptor genes was detected in 75.0% of patients with L-HES. After diagnosis, 14 patients with L-HES received glucocorticoids as first-line therapy, yielding an overall response rate of 92.9%. During glucocorticoid tapering, 11 patients experienced recurrent eosinophilia or worsening of clinical symptoms. Three patients received interferon-alpha as a second-line therapy, with two achieving complete remission. After a median follow-up of 16 months ( IQR: 8-28 months), one patient died of cardiac insufficiency 8 months after diagnosis, and no cases of lymphoma transformation were observed. The 2-year overall survival rate was (91.7±8.0) %, which did not significantly differ from that of the iHES group (96.2±2.6) % ( P=0.746) . Conclusions:Patients with L-HES generally have a favorable prognosis and are often characterized by skin involvement and significantly elevated serum IgE levels at diagnosis. They typically respond well to glucocorticoid therapy, although relapse is common during dose tapering. Interferon-alpha may serve as an effective second-line therapeutic option.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

Objective:To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations.Methods:We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024.Results:AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 ( IQR 39–60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 ( IQR 2–4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups ( P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13–25) vs 46 months (95% CI: 38–54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions:MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.

In this paper, two cases of primary familial and congenital polycythemia (PFCP) were reported, and the literature was reviewed. PFCP is a rare autosomal dominant inherited disease caused by a gain-of-function mutation in the EPOR gene, resulting in a loss of negative regulation of erythrocyte proliferation. The two patients were young women with simple polycythemia and clear family history, and identified to carry the truncated mutation c.1316G>A (p.W439*) of EPOR gene. At present, there is no unified treatment plan for PFCP. Currently, there is no standardized treatment for PFCP; management primarily aligns with guidelines for polycythemia vera, focusing on preventing thrombotic complications. This article discusses the clinical features of PFCP, EPOR gene mutations, and their pathogenic mechanisms, while providing diagnostic and therapeutic recommendations based on existing literature.

Objective:to investigate age-related changes in high-sensitivity cardiac troponin T(hs-cTnT)levels among middle-aged and elderly individuals, and to establish reference values for the 99th percentile upper reference limit(99th URL)of hs-cTnT within this demographic.Methods:This research is designed as a cross-sectional study.Hs-cTnT test results were collected from outpatients at Beijing Hospital between January 2018 and December 2023.The final sample included 5, 677 outpatients aged 45 to 85 years(65±10), all of whom were free from cardiovascular diseases and other chronic heart-related conditions.Multiple linear regression was utilized to assess the impact of gender and age group on hs-cTnT concentrations within the middle-aged and elderly populations.Furthermore, a generalized additive model for location, scale, and shape(GAMLSS)was employed to generate percentile curves of hs-cTnT by gender in this cohort, with the aim of determining the 99th URLs for both middle-aged and elderly individuals.Results:Multiple linear regression analyses indicated that both gender and age significantly influenced hs-cTnT levels in middle-aged and elderly populations( β60-69 years=1.399, β≥70 years=5.306, βgender=-2.650, all Pvalues<0.001).The hs-cTnT data for both males and females conformed to Box-Cox-Cole-Green(BCCG)distributions, with percentile curves fitted at the 25th, 50th, 75th, and 99th percentiles according to gender.The percentile values of hs-cTnT in both males and females demonstrated a progressive increase with advancing age.Notably, males exhibited higher 99th percentile values than females across all age groups. Conclusions:The GAMLSS approach is employed to establish continuous reference intervals for hs-cTnT in the middle-aged and elderly population.This effort aims to provide a theoretical foundation for reference values specific to this demographic in China and to offer guidance for clinical diagnosis and treatment.

Objective To assess the application value of mycoplasma pneumonia(MP)real-time fluorescence of RNA simultaneous amplification and testing(SAT)and MP antibody(MP-Ab)in the diagnosis of MP pneumonia(MPP)in children.Methods A total of 242 children with community-acquired pneumonia hospitalized at Beijing Haidian Hospital from September 2023 to October 2024 were enrolled as subjects.The children were divided into MPP group(n=193)and non-MPP group(n=49)based on MPP diagnosis.All children underwent simultaneous MP-SAT testing and initial MP-Ab detection within 24h of admission.MP-SAT results were monitored until they turned negative,with retesting for MP-Ab on 5-7d post-hospitalization in negative cases.The study compared diagnostic accuracy between MP-SAT and MP-Ab methods,while analyzing correlations between MP-SAT negative conversion time and clinical cure duration.Results For children with disease duration ≤ 7 days,MP-SAT demonstrated higher sensitivity than MP-Ab,with statistically significant difference(P＜0.001).The concordance between MP-SAT and initial MP-Ab test results was weak(Kappa=0.072),while the consistency between MP-SAT and follow-up MP-Ab test results was moderate(Kappa=0.614,P＜0.00 1).Both the clinical cure time and SAT seroconversion time were shorter with doxycycline treatment compared to azithromycin therapy.Conclusion The results of MP-SAT can be used to evaluate the condition of MPP children and guide the timely discontinuation of antibiotics.