1.Predicting Survival in Patients with Neuroendocrine Prostate Cancer: A SEER-Based Comprehensive Study
Tianlong LUO ; Jintao HU ; Bisheng CHENG ; Peixian CHEN ; Jianhan FU ; Haitao ZHONG ; Jinli HAN ; Hai HUANG
The World Journal of Men's Health 2025;43(2):415-427
Purpose:
Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC.
Materials and Methods:
Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses.
Results:
The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses.
Conclusions
The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.
2.Predicting Survival in Patients with Neuroendocrine Prostate Cancer: A SEER-Based Comprehensive Study
Tianlong LUO ; Jintao HU ; Bisheng CHENG ; Peixian CHEN ; Jianhan FU ; Haitao ZHONG ; Jinli HAN ; Hai HUANG
The World Journal of Men's Health 2025;43(2):415-427
Purpose:
Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC.
Materials and Methods:
Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses.
Results:
The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses.
Conclusions
The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.
3.Mechanism of vanillic acid against cardiac fibrosis induced by isoproterenol in mice based on Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways.
Hai-Bo HE ; Mian WU ; Jie XU ; Qian-Qian XU ; Fang-Zhu WAN ; Hua-Qiao ZHONG ; Ji-Hong ZHANG ; Gang ZHOU ; Hui-Lin QIN ; Hao-Ran LI ; Hai-Ming TANG
China Journal of Chinese Materia Medica 2025;50(8):2193-2208
This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals
;
Isoproterenol/adverse effects*
;
Male
;
Mice
;
Signal Transduction/drug effects*
;
Vanillic Acid/administration & dosage*
;
Dynamins/genetics*
;
Mice, Inbred C57BL
;
Fibrosis/genetics*
;
Apoptosis/drug effects*
;
Mitochondria/metabolism*
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Myocardium/metabolism*
;
Humans
4.Identification of critical quality attributes related to property and flavor of Jianwei Xiaoshi Tablets based on T1R2/T1R3/TRPV1-HEMT biosensor.
Dong-Hong LIU ; Yan-Yu HAN ; Jing WANG ; Hai-Yang LI ; Xin-Yu GUO ; Hui-Min FENG ; Han HE ; Shuo-Shuo XU ; Zhi-Jian ZHONG ; Zhi-Sheng WU
China Journal of Chinese Materia Medica 2025;50(14):3930-3937
The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry*
;
Biosensing Techniques/methods*
;
TRPV Cation Channels/chemistry*
;
Tablets/chemistry*
;
Receptors, G-Protein-Coupled/genetics*
;
Quality Control
;
Taste
;
Humans
;
Mass Spectrometry
5.Comparison of short-term clinical efficacy between CO external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures.
Min-Rui FU ; Chang-Long SHI ; Yong-Zhong CHENG ; Ming-Ming MA ; Zheng-Lin NIU ; Hai-Xiang SUN ; Jing-Hua GAO ; Zhong-Kai WU ; Yi-Ming XU
China Journal of Orthopaedics and Traumatology 2025;38(1):10-17
OBJECTIVE:
To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO).
METHODS:
Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications.
RESULTS:
The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05).
CONCLUSION
Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans
;
Male
;
Female
;
Middle Aged
;
Radius Fractures/physiopathology*
;
Adult
;
Bone Plates
;
Fracture Fixation, Internal/methods*
;
External Fixators
;
Retrospective Studies
;
Fracture Fixation/methods*
;
Wrist Fractures
6.Clinical efficacy of open reduction and internal fixation with plates versus minimally invasive Kirschner wire fixation for osteoporotic Colles' fractures.
Jun-Wei ZHANG ; Jin-Yong HOU ; Zhao-Hui LI ; Zhen-Yuan MA ; Xiang GAO ; Hong-Zheng BI ; Ling-Ling CHEN ; Hai-Tao WANG ; Wei-Zhi NIE ; Yong-Zhong CHENG ; Xiao-Bing XI
China Journal of Orthopaedics and Traumatology 2025;38(1):18-24
OBJECTIVE:
To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients.
METHODS:
Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores.
RESULTS:
The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05).
CONCLUSION
Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans
;
Female
;
Male
;
Middle Aged
;
Aged
;
Fracture Fixation, Internal/instrumentation*
;
Bone Wires
;
Bone Plates
;
Retrospective Studies
;
Colles' Fracture/surgery*
;
Minimally Invasive Surgical Procedures/methods*
;
Open Fracture Reduction/methods*
;
Osteoporotic Fractures/surgery*
7.Two cases of creatine deficiency syndrome caused by GAMT gene mutations and literature review.
Ting-Ting ZHAO ; Zou PAN ; Jian-Min ZHONG ; Hai-Yun TANG ; Fei YIN ; Jing PENG ; Chen CHEN
Chinese Journal of Contemporary Pediatrics 2025;27(3):340-346
OBJECTIVES:
To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations.
METHODS:
A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024.
RESULTS:
The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial.
CONCLUSIONS
GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
Child
;
Female
;
Humans
;
Male
;
Creatine/deficiency*
;
Guanidinoacetate N-Methyltransferase/deficiency*
;
Intellectual Disability/genetics*
;
Mutation
;
Retrospective Studies
;
Rhabdomyolysis/genetics*
;
Language Development Disorders
;
Movement Disorders/congenital*
8.Case Analysis of MYH9 Related Disease with Non-Hodgkin Lymphoma Caused by Rare Mutations.
Xue-Ting KONG ; Dan-Yu WANG ; Ze-Lin LIU ; Zhao-Gui ZHOU ; Nan ZHONG ; Lei LIU ; Meng-Di JIN ; Hai-Yan CUI
Journal of Experimental Hematology 2025;33(4):1145-1149
OBJECTIVE:
To analyze the MYH9 gene sequence of a patient with hereditary thrombocytopenia and diffuse large B-cell lymphoma and his family members, and to explore the relationship between MYH9 gene and tumors.
METHODS:
Peripheral blood samples were collected from the patients and their family members for complete blood count analysis. The platelet morphology was observed under microscope. The MYH9 gene sequence was analyzed by Whole Exon Sequencing and Sanger Sequencing.
RESULTS:
The mutation site c.279C>A:p.(Asn93Lys) in exon 2 of the MYH9 gene were found in patient and his family members, both presenting as thrombocytopenia. The platelet count was significantly increased after the administration of Avatrombopag.
CONCLUSION
A novel mutation of MYH9 was found in this study, and the case was sensitive to Avatrombopag, by exploring the relationship between the MYH9 gene and tumors, suggesting that the MYH9 gene may be associated with the development of diffuse large B-cell lymphoma.
Humans
;
Myosin Heavy Chains/genetics*
;
Thrombocytopenia/genetics*
;
Mutation
;
Male
;
Lymphoma, Non-Hodgkin/genetics*
;
Lymphoma, Large B-Cell, Diffuse/genetics*
;
Molecular Motor Proteins/genetics*
;
Pedigree
9.Clinical Characteristics of Adult Acute Myeloid Leukemia Patients with NUP98::HOXA9 Fusion Gene.
Hai-Xia CAO ; Ya-Min WU ; Shu-Juan WANG ; Zhi-Dan CHEN ; Jing-Han HU ; Xiao-Qian GENG ; Fang WANG ; Ling SUN ; Zhong-Xing JIANG ; Zhi-Lei BIAN
Journal of Experimental Hematology 2025;33(5):1241-1247
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*
10.Analysis of Hormone Levels in Patients with Hematological Diseases Before and After Hematopoietic Stem Cell Tansplantation.
Fen LI ; Yu-Jin LI ; Jie ZHAO ; Zhi-Xiang LU ; Xiao-Li GAO ; Hai-Tao HE ; Xue-Zhong GU ; Feng-Yu CHEN ; Hui-Yuan LI ; Qi SA ; Lin ZHANG ; Peng HU
Journal of Experimental Hematology 2025;33(5):1443-1452
OBJECTIVE:
By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage.
METHODS:
The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed.
RESULTS:
After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same.
CONCLUSION
HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans
;
Hematopoietic Stem Cell Transplantation
;
Female
;
Male
;
Hematologic Diseases/blood*
;
Follicle Stimulating Hormone/blood*
;
Triiodothyronine/blood*
;
Luteinizing Hormone/blood*
;
Thyroid Gland/metabolism*
;
Estradiol/blood*
;
Thyrotropin/blood*
;
Gonads/metabolism*
;
Adult
;
Middle Aged
;
Adrenocorticotropic Hormone/blood*
;
Hormones/metabolism*
;
Adrenal Cortex/metabolism*
;
Prolactin

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