Tag: statistics

J Am Stat Assoc. 2025 Apr 4. doi: 10.1080/01621459.2025.2460231. Online ahead of print.

ABSTRACT

Epidemiological approaches for examining human health responses to environmental exposures in observational studies often control for confounding by implementing clever matching schemes and using statistical methods based on conditional likelihood. Nonparametric regression models have surged in popularity in recent years as a tool for estimating individual-level heterogeneous effects, which provide a more detailed picture of the exposure-response relationship but can also be aggregated to obtain improved marginal estimates at the population level. In this work we incorporate Bayesian additive regression trees (BART) into the conditional logistic regression model to identify heterogeneous exposure effects in a case-crossover design. Conditional logistic BART (CL-BART) utilizes reversible jump Markov chain Monte Carlo to bypass the conditional conjugacy requirement of the original BART algorithm. Our work is motivated by the growing interest in identifying subpopulations more vulnerable to environmental exposures. We apply CL-BART to a study of the impact of heat waves on people with Alzheimer’s disease in California and effect modification by other chronic conditions. Through this application, we also describe strategies to examine heterogeneous odds ratios through variable importance, partial dependence, and lower-dimensional summaries.

PMID:40937338 | PMC:PMC12422705 | DOI:10.1080/01621459.2025.2460231

Environ Epigenet. 2025 Sep 4;11(1):dvaf021. doi: 10.1093/eep/dvaf021. eCollection 2025.

ABSTRACT

The increasing incidence of opioid use during pregnancy has led to a rise in the number of infants exposed to opioids in utero. Prenatal opioid exposure may have consequences for health and (neuro)development, including neonatal opioid withdrawal syndrome (NOWS). It is unknown which infants are at greatest risk for NOWS. DNA methylation (DNAm) is an epigenetic mark reflecting both allelic variation and environmental exposures, which may provide biomarkers for prenatal opioid exposure and infant NOWS. The placenta is an accessible, biologically relevant tissue in which to directly investigate the epigenetic effects of prenatal opioid exposure. Therefore, the aims of this study were to examine whether prenatal opioid exposure is associated with differential DNAm, including epigenetic age acceleration (EAA) in the placenta. We performed an epigenome-wide association study based on co-methylated regions and single CpG sites in placental samples from in utero opioid-exposed (n = 19) and nonexposed infants (n = 143), correcting for potential confounders. We did not identify statistically significant differential DNAm profiles, but the strongest associations were found for cg06621211; cg18688392 (ZMIZ1, adjusted P = .068) and cg04460738 (KCNMA1, adjusted P = .068), although effect sizes were very small. One of these DNAm patterns (cg06621211) was in part under control of genetic variants through methylation quantitative trait loci. The involved single nucleotide polymorphism did not show significant associations in recent genome-wide association studies for phenotypes related to substance use, and the finding was not driven by potential co-occurring substance use based on sensitivity analyses. There was also no association between placental EAA and in utero opioid exposure. In conclusion, placental DNAm showed limited associations with in utero opioid exposure and NOWS diagnosis.

PMID:40937335 | PMC:PMC12422002 | DOI:10.1093/eep/dvaf021

Clin Kidney J. 2025 Aug 13;18(9):sfaf263. doi: 10.1093/ckj/sfaf263. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: Short calciprotein crystallization time (low T50) is directly associated with an increased risk of cardiovascular events and mortality. Here, we investigated whether increases in dialysate bicarbonate concentrations increase T50 times in dialysis patients.

METHODS: In a prospective, single-center, single-arm, interventional trial in hemodialysis patients (N = 29), dialysate bicarbonate was decreased from baseline settings to 27 mmol/L (D-Bic 27) followed by an increase to 37 mmol/L (D-Bic 37), over the course of 6 weeks. The primary endpoint was the change in T50 time between the D-Bic 27 and D-Bic 37 phases. Measurements of endogenous calciprotein monomers (CPM), primary (CPP-1) and secondary (CPP-2) calciprotein particles were pre-specified secondary outcomes.

RESULTS: Twenty-four patients completed the study per protocol. T50 time increased significantly from 246 ± 77 to 282 ± 81 min from the D-Bic 27 to the D-Bic 37 phase (P < .0001). The hydrodynamic radius (size) of secondary calciprotein particles generated in the T50 test (CPP-2_Rh) did not differ significantly between study phases (251 ± 75 vs 240 ± 78 nm, P = .27). Comparing the D-Bic 27 with the D-Bic 37 phase, CPM (16.8 × 10³ vs 16.2 × 10³ AU/µL, P = .9) and CPP-1 (4.6 × 105 vs 4.5 × 10⁵ counts/mL, P = .7) did not change significantly, but there was a significant decrease in CPP-2 levels (5.9 × 10⁴ vs 3.2 × 10⁴ counts/mL, P < .0003). Intradialytically, T50 increased, CPM and CPP-1 decreased, while CPP-2 remained stable.

CONCLUSIONS: Raising dialysate bicarbonate resulted in a significant increase in T50 time and a reduction of CPP-2 levels.

PMID:40937333 | PMC:PMC12421725 | DOI:10.1093/ckj/sfaf263

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1155-1160. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.034.

ABSTRACT

OBJECTIVE: To analyze the positive rate and distribution of anti-M unexpected antibody in pediatric inpatients aged 0 to 14 years in central China.

METHODS: A total of 30 049 pediatric inpatients admitted to the Second Xiangya Hospital of Central South University, Wuhan Children’s Hospital and Children’s Hospital Affiliated of Zhengzhou University from May 2020 to August 2022 were enrolled in this study, and relevant clinical data were collected. Blood samples from the patients were tested for blood typing and screened for unexpected antibodies. For samples that screened positive for unexpected antibodies, identification was conducted using the identification panel to determine the specificity of the antibodies. The distribution and differences of anti-M antibodies in pediatric patients of different sexes, ages, blood groups, disease types, with or without a history of blood transfusion, and across different regions were analyzed.

RESULTS: Among 30 049 inpatients, the positive rate of unexpected antibodies was 0.91% (273/30 049), of which the positive rate of anti-M antibodies was 0.44% (131/30 049). The positive rate of anti-M antibodies in the neonates aged 0 to < 1 month was 0.10% (5/4 881), and all of them were IgG antibodies from their mothers; The positive rate of anti-M antibodies for the group aged from 1 month to < 1 year old was 0.23% (7/3 108), with no anti-M antibodies detected in patients aged 1-6 months; The positive rates of anti-M antibodies in the 1-4 years old group, 5-9 years old group, and 10-14 years old group were 0.87% (88/10 064), 0.38% (27/7 190), and 0.08% (4/4 806), respectively. The positive rate of anti-M antibodies in the 1-4 years old group was significantly higher than that of the other groups ( P <0.001), and there were also statistical differences in the positive rate between the 5-9 years old group and the 0-< 1 month and 10-14 years old groups ( P <0.001). The prevalences of anti-M antibodies in ABO blood group A, B, O and AB were 0.32% (30/9 482), 0.70% (58/8 293), 0.32% (31/9 595) and 0.45% (12/2 679), respectively. The prevalence of anti-M antibodies in patients with blood group B was significantly higher than that in patients with blood groups A and O ( P <0.05). The prevalences of anti-M antibodies in Hunan, Hubei and Henan was 0.18%, 0.32% and 0.71%, respectively. The prevalence of anti-M antibodies in Henan was significantly higher than that in Hunan and Hubei ( P <0.05), and the distribution showed obvious regional differences between the north and the south. There were no significant differences in the positive rate of anti-M antibodies between the children with different sexes, disease types, and with or without a history of blood transfusion (P >0.05).

CONCLUSION: This study reveals the distribution pattern of anti-M antibodies in pediatric inpatients aged 0-14 years in central China, which has reference value for the research on unexpected red blood cell antibodies in Chinese children.

PMID:40936145 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.034

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1131-1137. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.030.

ABSTRACT

OBJECTIVE: To investigate the expression of CSF-1 and CSF-1R in the peripheral blood of children with immune thrombocytopenia (ITP) and its clinical significance.

METHODS: Forty-four children with ITP treated in our hospital from February 2023 to January 2024 were selected as the observation group, and 40 healthy children were selected as the control group during the same period, and relevant clinical data were collected. Peripheral blood mononuclear cells (PBMC) of children with ITP and healthy children were separated, and the plasma levels of M1 macrophage-associated cytokines (TNF-α, IL-6), M2 macrophage-associated cytokines (IL-10, TGF-β), and CSF-1 were detected by ELISA in the children of both groups. The mRNA levels of M1 macrophage surface markers (CD86, iNOS), M2 macrophage surface markers (CD206, Arg-1) and CSF-1R were detected by RT-PCR in PBMC of children in both groups. Western blot was used to detect the expression of CSF-1R protein in PBMC of the two groups of children. The correlation between platelet count and CSF-1R mRNA expression in PBMC, TNF-α, IL-6, IL-10, TGF-β and CSF-1 in plasma was analyzed.

RESULTS: Compared with the control group, the levels of IL-10, TGF-β, CSF-1 and platelet count in plasma of children with ITP were significantly decreased (P < 0.01), and the levels of TNF-α and IL-6 were significantly increased (P < 0.01); the mRNA levels of the M1 macrophage surface markers (CD86, iNOS) in PBMC of children with ITP were significantly increased (P < 0.05), mRNA levels of M2 macrophage surface marker CD206 in PBMC of children with ITP were decreased compared with controls but the difference was not statistically significant ( P >0.05), mRNA levels of Arg-1 were decreased, the difference was statistically significant (P < 0.05). The mRNA and protein levels of CSF-1R in PBMC of ITP children were higher than that in controls. CSF-1R expression in PBMC of ITP was positively correlated with platelet count, IL-10, CSF-1 were positively correlated (r =0.822,0.481,0.405).

CONCLUSION: CSF-1 is significantly reduced in the plasma of ITP, and CSF-1R mRNA and protein expression is significantly elevated in PBMC of ITP, which are involved in the regulation of macrophage M1/M2 imbalance, and could serve as a potential therapeutic target for ITP.

PMID:40936141 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.030

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1127-1130. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.029.

ABSTRACT

OBJECTIVE: To investigate the efficacy and safety of stanozolol combined with avatrombopag in the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with relapsed/refractory tumors.

METHODS: Twenty-five patients with relapsed/refractory CIT admitted to the Hematology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences between March 2023 to December 2023 were enrolled. These patients received a combined therapy of stanozolol and avatrombopag. The clinical efficacy, onset time, changes in platelet levels and blood cell counts before and after treatment, and adverse reactions of patients were evaluated.

RESULTS: The combination therapy demonstrated remarkable efficacy with a total effective rate of 100%. Among the 25 patients, 19 achieved complete remission and 6 achieved partial remission. The median onset time was 42.5（range: 35-48）days. The average platelet count of the 25 patients increased from (25.73±17.75)×10⁹/L before treatment to (146.4±49.59)×10⁹/L after 3 months of treatment, with a statistically significant difference ( P < 0.05). 18 patients who previously required platelet transfusion were all weaned off platelet transfusion after 3 months of treatment, with a median time to be free from platelet transfusion was 26 (range: 18-51) days. During the treatment, both neutrophils and hemoglobin exhibited various degrees of elevation. Two patients experienced a slight increase in alanine aminotransferase(ALT) levels, which normalized after treatment with oral hepatoprotective drug. One patient had a PLT increase exceeding 350×10⁹/L, and the treatment with avatrombopag was suspended, and aspirin and other drugs were given to prevent thrombosis. No thrombose events or CIT-related bleeding events were observed in all patients.

CONCLUSION: The combination therapy of stanozolol and avatrombopag is significantly effective for treating relapsed/refractory CIT patients, with a high response rate and good safety, making it a suitable clinical treatment option.

PMID:40936140 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.029

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1098-1103. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.025.

ABSTRACT

OBJECTIVE: To retrospectively analyze the genetic differences of thalassemia gene mutations among ethnic groups in Hechi, Guangxi.

METHODS: A total of 15 595 whole blood samples of residents of Hechi from January 1, 2020 to June 30, 2023 were screened for thalassemia, and the Gap-PCR method and RDB-PCR method were used to perform genetic testing on the positive samples. Gene sequencing was performed on the samples with positive screening results but negative genotyping results.

RESULTS: Among the 15 595 samples, 10 501 cases were screened positively, and 8 506 cases were thalassemia gene carriers among the positive samples, with a positive coincidence rate of 81.00%. Among them, there were 5 374 cases of α-thalassemia, 2 531 cases of β-thalassemia, and 601 cases of α+β compound thalassemia. A total of 13 mutant types were detected in α-thalassemia, including —^SEA (48.57%), –α ^3.7 (31.31%), α ^CS (8.57%) and –α ^4.2 (8.07%). A total of 17 mutant types were detected in β-thalassemia, mainly CD17 (48.27%) and CD41-42 (41.24%). The thalassemia gene carriers were mainly from the Zhuang (6 106 cases), Han (969 cases), Yao (793 cases), Mulam (275 cases), and Maonan (228 cases) ethnic groups. The comparison of constituent ratios within the above five ethnic groups demonstrated that there were differences in the proportions of — ^SEA, –α ^3.7, α ^CS , and –α ^4.2 among the Zhuang, Han, and Yao ethnic groups (P < 0.005). The proportion of α ^CS in the Mulam ethnic group was not significantly different from –α ^3.7 and –α ^4.2. The proportions of — ^SEA, -α^3.7, and α ^CS in the Maonan ethnic group were not significantly different. There were no significant differences in the proportion of CD17 and CD41-42 among the Han, Yao, Mulam and Maonan ethnic groups. The proportion of —^SEA was the highest in the Mulam ethnic group (56.68%), which was statistically different from 35.92% in the Maonan ethnic group. The proportion of –α ^3.7 was the highest in the Zhuang ethnic group (33.25%), and the difference was statistically significant compared to the Mulam ethnic group which had the lowest proportion (18.72%). The proportion of α ^CS was the highest in the Maonan ethnic group (27.46%), and the differences were statistically significant compared with other ethnic groups. The proportions of CD17 in the Zhuang and Maonan ethnic groups (50.79%, 55.68%) were higher than those in the Han (39.12%), Yao (39.63%) and Mulam (30.00%), and the differences were statistically significant. There was no significant difference in the proportion of CD41-42 among the above five ethnic groups.

CONCLUSIONS: The mutation type and distribution differences of genes causing thalassemia among main ethnic groups in the minority inhabited areas of Hechi, Guangxi, show the characteristics of ethnic differentiation. The result is helpful to develop a special prevention and control plan for thalassemia in line with the population distribution characteristics, and provide reference for revealing the genetic background and geographical distribution of thalassemia in this area.

PMID:40936136 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.025

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1086-1093. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.023.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with hemophagocytic lymphohistiocytosis (HLH).

METHODS: Clinical data of 78 patients with HLH admitted to Gansu Provincial People’s Hospital from January 2014 to May 2023 were collected, and the correlation between relevant indicators and patient prognosis was analyzed.

RESULTS: Among the 78 HLH patients, there were 48 males and 30 females, with a median age of onset of 48 (1-84) years old; 26 patients were treated with chemotherapy, 44 patients were treated with glucocorticoids, immunoglobulin or cyclosporine, 5 patients received symptomatic treatment, 1 patient received plasma exchange, and 2 patients refused treatment. By the end of the follow-up, there were 39 survivors, 35 deaths, and 4 patients lost to follow-up. There was no significant correlation between sex, ferritin, triglycerides, hemophagocytosis, bone marrow cellularity, Epstein-Barr virus (EBV) infection, SUV value of PET-CT, alanine aminotransferase (ALT), interleukin-6 (IL-6), platelet-to-lymphocyte ratio (PLR) and overall survival (OS) of the patients (P >0.05). Patients with age≥60 years, neutrophil-to-lymphocyte ratio (NLR) >0.59, red cell distribution width-to-platelet ratio (RPR) >0.30, lymphocyte-to-monocyte ratio (LMR)≤2.74, red blood cell distribution width (RDW)>16.45%, tumor-associated HLH, aspartate aminotransferase (AST)≥148 U/L, procalcitonin (PCT)≥0.66 ng/ml, neutrophils (NEU) <2×10⁹/L, fibrinogen (FIB)<1.85 g/L, lactate dehydrogenase (LDH)≥1 740 U/L, hemoglobin (Hb)<85 g/L, platelet (PLT)<57×10⁹/L had significantly shorter OS, with statistical significance (P < 0.05). Multivariate analysis showed that LMR≤2.74, RDW>16.45%, LDH≥1 740 U/L, and NEU<2×10⁹/L were independent risk factors affecting OS in HLH patients (P < 0.05).

CONCLUSION: Some blood-based inflammatory markers are significantly associated with OS in patients with HLH. NLR, RPR, LMR, RDW and PCT can be used to assess the prognosis of HLH patients, and RDW and LMR are independent factors affecting OS of HLH patients, which provide greater predictive value for prognosis. Hypercellular bone marrow in HLH patients may indicate a poor prognosis.

PMID:40936134 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.023

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1069-1078. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.021.

ABSTRACT

OBJECTIVE: To construct the inflammation score (IS) and nutrition-immunity score (NIS) for patients with multiple myeloma (MM), and to verify their prognostic stratification effects and significance.

METHODS: The clinical data of 129 newly diagnosed MM patients admitted to our hospital from August 2011 to September 2022 were retrospectively analyzed. Univariate and multivariate Cox regression analysis of overall survival (OS) were comducted on clinical parameters, including inflammatory indicators such as red blood cell volume distribution width (RDW) and platelet count (PLT), nutritional-immune indicators such as albumin (ALB), absolute lymphocyte count (ALC), and suppressed immunoglobulin count (S-Ig count). To construct IS and NIS for prognosis, X-tile software and multivariate Cox regression analysis were used to verify the prognostic stratification role and significance of IS and NIS. The time-dependent receiver operating characteristic (ROC) curve, C-index curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical net benefit of IS and NIS in predicting overall survival(OS), and compared to the international staging system (ISS).

RESULTS: IS was constructed based on the scores of RDW and PLT, and NIS was constructed based on the scores of ALB, ALC, and S-Ig count. According to X-tile analysis and multivariate Cox regression analysis, IS and NIS can divide the patients into three risk strata respectively: low, medium and high IS and NIS groups. The differences in OS and hazard ratio (HR) between the low, medium, and high strata were statistically significant (P < 0.05). IS and NIS are both independent prognostic predictors for MM. The area under the ROC curve (AUC) and C index of IS and NIS for predicting 1- to 7-year OS were greater than those of ISS, and both were greater than 0.7. The prediction results of IS and NIS for 1-, 3-, and 5-year OS rates were well consistent with the actual observed results. The DCA curves of IS and NIS for predicting 1-, 3-, and 5-year OS were higher than that of ISS in a wide range of threshold probability intervals.

CONCLUSION: IS and NIS have independent predictive significance for OS in MM patients. Their predictive discrimination, accuracy, and clinical net benefit are higher and better than ISS, and they may have potential application value in MM prognosis.

PMID:40936132 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.021

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Aug;33(4):1036-1041. doi: 10.19746/j.cnki.issn.1009-2137.2025.04.015.

ABSTRACT

OBJECTIVE: To investigate the relationship between Ig class switch recombination (CSR) and mismatch repair (MMR) protein, microsatellite phenotype in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

METHODS: Forty cases of MALT lymphoma archived in the Department of Pathology, Jiading District Central Hospital, Shanghai University of Medicine & Health Sciences were selected as the observation group, and twenty cases of benign lymphoid tissue hyperplasia were as the control group. The expressions of IgG, IgM, IgD, and IgA in both groups were detected by immunohistochemical double staining, and MMR proteins including MLH1, MSH2, MSH6, and PMS2 in both groups were detected by immunohistochemistry. Multiplex fluorescence PCR capillary electrophoresis was used to detect microsatellite phenotype in tumor and adjacent tissues of the experimental group.

RESULTS: In the observation group, the proportions of single Ig heavy chain expression (modeⅠ), negative expression (modeⅡ), and multiple expression (mode Ⅲ) were 65% (26/40), 27.5% (11/40), and 7.5% (3/40), respectively, while in the control group were 0 (0/20), 5% (1/20), and 95% (19/20). The proportion of Ig heavy chain expression mode Ⅰ+Ⅱ in the observation group was 92.5%, which was significantly higher than 5% in the control group (P < 0.01). In the observation group, partial deletion of MMR protein was observed in 3 cases (7.5%), including 2 cases of MSH6 deletion and 1 case of both MSH6 and PMS2 deletion. In the control group, there was 1 case (5%) with PMS2 deletion. There was no significant difference in the deletion rate of MMR protein between the two groups ( P >0.05). A total of 5 cases of microsatellite instability (MSI) were detected in the observation group, including 1 case of low-frequency MSI (MSI-L), 4 cases of high-frequency MSI (MSI-H), and 2 cases of MSI-H with MSH6 deletion. When the loss expression of MSI-H or MMR protein was counted as a positive result, the MSI-H rate detected by PCR capillary electrophoresis was 10% (4/40), which was slightly higher than the MMR protein deletion rate detected by immunohistochemistry (7.5%, 3/40), but there was no statistically significant difference between the two groups (P >0.05). The MMR protein deletion rates among the Ig heavy chain protein expression mode Ⅰ, mode Ⅱ, and mode Ⅲ groups were 0 (0/26), 18.2% (2/11), and 33.3% (1/3), respectively. There was a statistically significant difference in the constituent ratios among the three groups (P < 0.05). The MMR protein deletion rates among the MSS, MSI-L, and MSI-H groups were 2.9% (1/35), 0 (0/1), and 50% (2/4), respectively. There was a statistically significant difference in the constituent ratios among the three groups (P < 0.05). MMR protein deficiency was positively correlated with Ig heavy chain expression pattern and MSI ( r =0.41, P < 0.05; r =0.48, P < 0.05), but Ig heavy chain expression pattern was not correlated with MSI ( r =0.02, P >0.05).

CONCLUSION: Ig heavy chain CSR detection is helpful for the differential diagnosis of MALT lymphoma. Low frequency MMR protein deletion and MSI-H phenotype exist in MALT lymphoma, which may be of certain value for the study of its occurrence, development and clinical treatment.

PMID:40936126 | DOI:10.19746/j.cnki.issn.1009-2137.2025.04.015