1.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
2.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
3.SIRT5 Potentiates Hepatocarcinogenesis by Modulating Protein Acylation in Mice
Yu ZHANG ; Feng-Rui REN ; Jia-Yun LI ; Xiang-Yu CHEN ; Zi-Yi WANG ; Qi SUN ; Jun-Cheng ZHAO ; Ye ZHANG ; Zhen HUANG ; Hao HU ; Tao-Tao WEI ; Min XIAO
Progress in Biochemistry and Biophysics 2026;53(6):1712-1722
ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.
4.Inverse Association Between Alcohol Consumption and Parkinson’s Disease Risk and Identification of RIT2 as a Linked Biomarker
Wei LU ; Xiu-Li CHENG ; Xiao-Yun PAN ; Dan-Dan YANG ; Hui-Ling ZOU ; Li-Guo DONG ; Yi-Liang WEI ; Gui-Yun CUI
Progress in Biochemistry and Biophysics 2026;53(6):1723-1733
ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (ORIVW<1) and 9 positive associations (ORIVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (ORIVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (ORIVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.
5.Dingchan Granule (定颤颗粒) for Paroxysmal Atrial Fibrillation with Syndrome of Qi Stagnation and Blood Stasis:A Randomized,Double-Blinded,Placebo-Controlled Clinical Trial
Xiaozhen CHENG ; Xingjuan CHEN ; Weina LI ; Lu XIAO ; Yunhan WANG ; Yun XU ; Yueyue NIU ; Ling FENG
Journal of Traditional Chinese Medicine 2025;66(12):1233-1240
ObjectiveTo observe the clinical effectiveness and safety of Dingchan Granule (定颤颗粒) for paroxysmal atrial fibrillation with syndrome of qi stagnation and blood stasis. MethodsUsing a randomised, double-blind, placebo controlled study method, 90 patients with paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome were divided into 45 cases each in the treatment group and the control group. Both groups were given conventional western medicine treatment, and the treatment group was additionally treated with Dingchan Granule, while the control group was treated with Dingchan Granule placebo, both of which were taken orally for 8 g each time twice a day. Both groups were treated for 8 weeks. We compared the clinical effectiveness, the improvement of traditional Chinese medicine (TCM) symptoms and the recovery rate of atrial fibrillation between the two groups. We compared the number and duration of atrial fibrillation episodes, TCM symptoms score, atrial fibrillation symptom classification, 24-hour average ventricular rate, Pittsburgh Sleep Quality Index (PSQI), anxiety index, depression index before and after treatment, and evaluated the safety of the two groups. ResultsThe total clinical effectiveness rate in the treatment group was 82.22% (37/45), which was better than 60.00% (27/45) in the control group (P<0.05). The total effective rate of TCM syndrome effectiveness in the treatment group was 88.89% (40/45), which was better than 66.67% (30/45) in the control group (P<0.05); and the rate of atrial fibrillation regression in the treatment group was 26.67% (12/45), better than 6.67% (3/45) in the control group (P<0.05). The number and duration of atrial fibrillation episodes in both groups were significantly decreased (P<0.01), and the number and duration of atrial fibrillation episodes in the treatment group were lower than those in the control group (P<0.01). The TCM syndrome scores of both groups after treatment were significantly lower than before treatment (P<0.01), and the scores of the treatment group was lower than those of the control group (P<0.05). The severity of atrial fibrillation symptoms and the grading of atrial fibrillation symptoms in both groups after treatment were improved (P<0.01), and the degree of symptom improvement in the treatment group was better than that in the control group (P<0.01). The 24-hour average ventricular rate of both groups after treatment was significantly lower (P<0.01). The PSQI, anxiety index and depression index of the treatment group were all lower than before treatment (P<0.01), while the PSQI and anxiety index of the control group were both lower than before treatment (P<0.01 or P<0.05), the PSQI, anxiety index and depression index of the treatment group being lower than those of the control group (P<0.05 or P<0.01). No adverse events occurred in both groups, and no abnormalities were observed in blood, urine, stool routine, liver and kidney function, and coagulation function indexes. ConclusionDingchan Granule for paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome can alleviate clinical symptom, improve TCM symptom scores, increase atrial fibrillation recovery rate, stabilise the average ventricular rate, and significantly improve the quality of sleep, alleviate the anxiety and depression, with a good safety profile.
6.Diagnostic value of ultrasonic shear wave elastography for clinically significant prostate cancer
Fang-rui YANG ; Yong-hao JI ; Li-tao RUAN ; Jian-xue LIU ; Yao-ren ZHANG ; Xiao ZHANG ; Qin-yun WAN ; Si-fan REN
National Journal of Andrology 2025;31(6):505-511
Objective:To explore the diagnostic value of shear wave elastography(SWE)for clinically significant prostate cancer(csPCa).Methods:We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer(PCa)in Baoji Central Hospital from June 2017 to July 2023.All the patients underwent the following examinations in the order of serum prostate-spe-cific antigen(PSA)testing,transrectal ultrasonography(TRUS),measurement of the stiffness of the entire prostate gland by SWE,and TRUS-guided prostate puncture biopsy.The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base,middle,and apex of the prostate,including the maximum Young's modulus(Emax),mean Young's modulus(Emean),and minimum Young's modulus(Emin).We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results,focusing on their diagnostic performance for csPCa.Results:Of the 359 cases,189 were diag-nosed by pathological puncture biopsy as BPH,26 as non-csPCa,and 144 as csPCa.The PSA level,Emax,Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups(all P<0.01),but showed no statistically significant difference between the BPH and non-csPCa groups(all P>0.05).The area under the receiver operating characteristic curve(AUC),optimal cut-off value,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accura-cy of Emax in the diagnosis of csPCa were 0.852,143.92 kPa,72.22%,84.65%,75.91%,81.98%and 79.67%;those of Emean were 0.868,82.42 kPa,67.36%,91.16%,83.62%,80.66%and 81.62%;and those of Emin were 0.682,32.73 kPa,47.22%,89.30%,73.91%,71.54%and 72.14%,respectively.In the non-csPCa group,Emax,Emean and Emin were found be-low the optimal cut-off value in 73.08%(19/26),92.31%(24/26)and 88.46%(23/26),respectively.Conclusion:The stiff-ness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa,reduces unnecessary detection of non-csPCa,and provides some reference for its active surveillance.
7.Predictive model for colorectal cancer transformation diagnosis based on multimodal ultrasound parameters and clinical indicators
Xiang-an MENG ; Yong-xin HAO ; Yun LUO ; Yang LI ; Xiao-lin HAN
Chinese Journal of Current Advances in General Surgery 2025;28(1):17-22
Objective:To construct a predictive model for benign and malignant colorectal lesions based on modal ultrasound parameters and clinical indicators,and evaluate the effectiveness of the predictive model.Methods:Clinical data of 198 patients with colorectal lesions treated in Hebei Petro China Central Hospital from March 2020 to March 2024 were recorded.According to pathological diagnosis,they were grouped into a benign lesion group of 102 cases and a malignant lesion group of 96 cases.All patients underwent multimodal ultrasound examination.Multivariate Logistic re-gression analysis was applied to screen the influencing factors of colorectal cancer progression.R software package was applied to build a nomogram prediction model.Hosmer-Lemeshow test,calibration curve,ROC curve,and clinical deci-sion curve were used for validation.Results:There were statistically obvious differences in internal echo,morphology,blood flow signal,rise time(RT),contrast agent of"fast in and fast out",mean Young's modulus(Emean),age,positive fecal occult blood,and polyps between the benign and malignant lesion groups(P<0.05).Uneven internal echoes,irregu-lar shapes,abundant blood flow signals,contrast agent of"fast in and fast out",age ≥ 60 years,positive fecal occult blood,and polyps ≥ 2 were independent risk factors for colorectal cancer(P<0.05),while RT is a protective factor for colorectal cancer(P<0.05).The internal validation results of the nomogram prediction model showed that the Hosmer-Lemeshow test showed x2=3.661 and P=0.886.The calibration curve showed that the actual probability was basically consistent with the predicted probability,and the AUC of the ROC curve was 0.802(95%CI:0.732-0.871),indicating that the calibration and discrimination of the column chart prediction model were good.Within the high-risk threshold range of 0.28-0.98,the decision curve was above the All line and None line,indicating a high net benefit and clinical practicality.Conclusion:Internal echo,morphology,blood flow signal,contrast agent of"fast in and fast out",age,positive fecal occult blood,polyps,and RT are influencing factors for the occurrence of colorectal cancer.The column chart prediction model constructed based on this has good predictive performance and provides reference for early inter-vention by clinical physicians.
8.Correlation between Serum Ferritin Levels and the Efficacy of Platelet Transfusion in Patients with Malignant Hematological Diseases
Yi-Yao LI ; Xiao-Yun GAO ; Hang GUAN ; Yu BAI ; Jun-Hui JIA ; Wei BAI ; Yan-Hui DI ; Hua TIAN ; Li-Duo KOU ; Xin-Hua WANG
Journal of Experimental Hematology 2025;33(6):1779-1783
Objective:To explore the correlation between serum ferritin(SF)levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Methods:Patients with malignant hematological diseases who received repeated transfusions of apheresis platelets in Department of Hematology of Aerospace Center Hospital in 2023 were selected.The platelet corrected count increment(CCI)was used to evaluate the efficacy of platelet transfusion.The correlations between sex,age,disease type,transplantation history,red blood cell transfusion history,and SF level and the efficacy of platelet transfusion were analyzed.Results:A total of 87 patients were included,with a cumulative 326 person-times platelet transfusions.As suggested by one-way analysis of variance,compared with the patients in the age groups of 24-45 years old and 46-66 years old,the patients in the age group of 2-23 years old had a better efficacy of platelet transfusion(P=0.004,P=0.004).There was no significant difference in the efficacy of platelet transfusion between the patients in the age group of 24-45 years old and those in the age group of 46-66 years old(P=0.876).Compared with the patients who had a history of red blood cell transfusion within 3 days,the patients without a history of red blood cell transfusion within 3 days had a better efficacy of platelet transfusion(P<0.001).Compared with the groups with SF levels of 1.44-2.78 ng/L and>2.78 ng/L,the group with SF levels<1.44 ng/L had a better efficacy of platelet transfusion(P=0.028,P<0.001).Compared with the group with SF levels>2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).After adjusting for age and the history of red blood cell transfusion,the transfusion efficacy of the group with SF levels<1.44 ng/L was better than that of the groups with SF levels of 1.44-2.78 ng/L and>2.78 ng/L(P=0.021,P<0.001);Compared with the group with SF levels>2.78 ng/L,the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion(P=0.001).Both univariate and multivariate linear regression models showed that SF levels were negatively correlated with the efficacy of platelet transfusion(P<0.001).Conclusion:There is a negative correlation between SF levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.Detection of SF levels may provide guidance for predicting the efficacy of platelet transfusion.
9.Prognostic Value of Dynamic Monitoring of WT1 Expression Levels for Relapse and Overall Survival in AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation During First Complete Remission
Xiao-Ya HE ; Han-Yun REN ; Yu-Jun DONG ; Li JI ; Qing-Yun WANG ; Yuan LI ; Yue YIN ; Ze-Yin LIANG ; Qian WANG ; Wei-Lin XU ; Jin-Ping OU ; Bing-Jie WANG ; Wei LIU
Journal of Experimental Hematology 2025;33(6):1790-1796
Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0%.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1%.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26%(range:0%-23.64%),with an upper quartile value of 0.74%.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels>0.74%at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P<0.001)compared to patients with WT1 levels ≤0.74%.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level>0.74%at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95%CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95%CI:0.749-16.100,P=0.037).Only WT1 level>0.74%at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95%CI:2.402-19.738,P<0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.
10.Predictive value of Padua score combined with novel thrombotic biomarkers for risk of venous thrombo-embolism in the patients with chronic heart failure
Dan RAN ; Li-ping WU ; Jia ZHAO ; Hong CHEN ; Xiao-yun ZHANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(5):617-623
Objective:This study aims to investigate the risk factors of venous thromboembolism(VTE)in patients with chronic heart failure(CHF),and establish a model for predicting the risk of VTE.Methods:A nested case-control study was conducted on CHF patients admitted in Pengzhou People's Hospital between June 2022 and June 2023.A total of 66 patients were diagnosed with VTE among the 960 CHF patients.Then another 66 patients paired by age and gender to those with VTE were selected from the remaining non-VTE patients as control group.Gener-al data,D dimer(D-D),thrombin-antithrombin complex(TAT),plasmin-α2-antiplasmin complex(PIC),tissue plasminogen activator-inhibitor complex(t-PAIC),thrombomodulin(TM)and Padua score were compared between two groups.Multivariate Logistic regression analysis was used to screen the independent risk factors of VTE in CHF patients.The receiver operating characteristic(ROC)curve analysis was applied to assess the efficacy of each indicator in predicting the risk of VTE in CHF patients.Results:Compared to patients in the non-VTE group,those in the VTE group had significantly higher D-D[3.26(1.87,6.19)mg/L vs.0.81(0.56,1.26)mg/L],TAT[5.60(4.90,8.80)ng/ml vs.2.60(1.70,3.30)ng/ml],TM[16.40(13.50,20.03)TU/ml vs.9.65(7.60,11.20)TU/ml],PIC[1.24(0.94,1.68)μg/ml vs.0.84(0.65,1.22)μg/ml],t-PAIC[12.60(9.38,17.05)ng/ml vs.7.70(5.53,9.70)ng/ml],proportion of atrial fibrillation/flutter(54.5%vs.22.7%)and Padua score[4(3,4)points vs.3(2,3)points](P<0.001 all),and significantly lower lymphocyte count[0.99(0.60,1.38)×109/Lvs.1.20(0.76,1.67)×109/L,P=0.020].Multivariate Logistic regression analysis indicated that after adjusting confounders,TM(OR=2.456,95%CI 1.389~14.296,P=0.012)and Padua score(OR=3.257,95%CI 1.270~13.073,P=0.037)were independent risk factors for VTE in CHF patients.A predictive model was constructed using above-mentioned two indexes.The area under the ROC curve(AUC)of the combined prediction was 0.941(95%CI 0.901~0.980),which was significantly higher than those of TM(AUC=0.889,95%CI 0.833~0.945)and Padua score(AUC=0.801,95%CI 0.731~0.871)alone(Z=2.672,4.063,P=0.008,<0.001).Conclusion:Padua score and TM were independent risk factors for VTE in CHF patients,and their combined detec-tion could better predict the risk of VTE in these patients.

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