1.Effects of human umbilical cord blood platelet-rich plasma,mononuclear cells,and mesenchymal stem cells in repairing thin endometrium in rats
Yanli MU ; Anchun HU ; Wenchi XU ; Panpan CHEN ; Hao CHEN ; Shuyun ZHAO ; Guanyou HUANG ; Xiaojuan CHEN
Chinese Journal of Tissue Engineering Research 2026;30(1):78-92
BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95%ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P<0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P<0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P<0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P<0.001),and their expression levels decreased after treatment(all P<0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P<0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P<0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P<0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.
2.Effects of human umbilical cord blood platelet-rich plasma,mononuclear cells,and mesenchymal stem cells in repairing thin endometrium in rats
Yanli MU ; Anchun HU ; Wenchi XU ; Panpan CHEN ; Hao CHEN ; Shuyun ZHAO ; Guanyou HUANG ; Xiaojuan CHEN
Chinese Journal of Tissue Engineering Research 2026;30(1):78-92
BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95%ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P<0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P<0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P<0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P<0.001),and their expression levels decreased after treatment(all P<0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P<0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P<0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P<0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.
3.Clinical efficacy of caragliflozin and empagliflozin in obese patients with type 2 diabetes mellitus
Limei HU ; Huiying LIU ; Yaru CHEN ; Panpan ZHAO ; Jun GU ; Weidong REN
Tianjin Medical Journal 2025;53(10):1071-1076
Objective To analyze effects of caragliflozin and empagliflozin on inflammatory markers,glucose and lipid metabolism and miR-144 expression in obese patients with type 2 diabetes mellitus(T2DM).Methods A total of 148 obese T2DM patients admitted to our hospital from June 2021 to May 2024 were selected and divided into the caragliflozin group and the empagliflozin group by random number table method.The two groups were treated with canagliflozin and empagliflozin on the basis of conventional treatment for 6 months.The inflammatory indicators,glucose metabolism indicators,lipid metabolism indicators,microRNA-144(miR-144)expression,body mass index(BMI),clinical efficacy and incidence of adverse reactions were compared between the two groups.Results After a total of 7 cases were excluded during the treatment period,there were 71 cases in the caragliflozin group and 70 cases in the empagliflozin group.After treatment,the levels of tumor necrosis factor-α,interleukin-6,C-reactive protein,fasting blood glucose(FBG),2 h postprandial blood glucose(2 h-PPG),glycosylated hemoglobin(HbA1c),triglyceride(TG),total cholesterol,low density lipoprotein cholesterol,BMI and miR-144 expression were lower than those before treatment in two groups of patients(P<0.05),and the levels of FBG,2 h-PPG,HbA1c,TG and miR-144 expression were lower in the caragliflozin group than those of the empagliflozin group(P<0.05).After treatment,high density lipoprotein cholesterol was higher than that before treatment in the two groups(P<0.05),and that in the canagliflozin group was higher than the empagliflozin group(P<0.05).There were no significant differences in the clinical efficacy and incidence of adverse reactions between the two groups after treatment(P>0.05).Conclusion Both caragliflozin and empagliflozin have certain therapeutic efficacy and good safety for obese T2DM patients,and caragliflozin is more effective in improving glucose and lipid metabolism.
4.Development of a 5-year mortality risk prediction model for patients with small cell neuroendocrine carcinoma of the cervix based on the SEER database
Haiban LI ; Xiaomeng SHI ; Panpan LI ; Yu HU ; Lu DING ; Feiyun JIANG
Journal of Shenyang Medical College 2025;27(3):261-269
Objective:To develop a 5-year mortality risk prediction model for patients with small cell neuroendocrine carcinoma of the cervix(SCNEC).Methods:Based on the Surveillance,Epidemiology,and End Results(SEER)database and R software version 4.3.3,variables were screened via Lasso regression,followed by multivariable logistic regression and stepwise regression to develop a 5-year mortality risk prediction model for SCNEC patients.The Akaike Information Criterion(AIC),C-index,receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test,and calibration curve were employed to evaluate the model.Results:Age,M stage,surgical status,and lymph node metastasis were ultimately selected as variables to construct the 5-year mortality risk prediction model for SCNEC patients.The model demonstrated superior predictive performance compared to FIGO staging(P<0.01).The Hosmer-Lemeshow test yielded a P-value>0.05.The C-index values for the training and validation sets were 0.808 and 0.755,respectively,with the areas under the ROC curves of 0.826 and 0.744.The calibration curves of the model fluctuated near the diagonal line,indicating good agreement between predicted and observed outcomes.The decision curve analysis demonstrated significant clinical net benefit.Results showed that higher mortality risk was associated with advanced age,M1 status,lymph node metastasis,and lack of surgical opportunity.Conclusions:The model exhibits good discriminatory power and accuracy,providing significant benefits to patients.Enhanced management should be implemented for patients with advanced age,distant metastasis,lymph node metastasis,or ineligibility for surgery.Lymph node metastasis is an independent risk factor for 5-year mortality in patients with SCNEC.
5.Development and psychometric evaluation of a long-term care needs assessment questionnaire for community-dwelling older adults
Hengyu HU ; Panpan CUI ; Lu CHANG ; Junmei ZHANG ; Hui FENG
Chinese Journal of Modern Nursing 2025;31(25):3409-3416
Objective:To develop and evaluate the reliability and validity of a questionnaire for assessing long-term care needs among community-dwelling older adults.Methods:Guided by the International Classification of Functioning, Disability and Health (ICF), an initial item pool for the questionnaire was constructed based on literature review, descriptive qualitative research, and expert consultations. The draft questionnaire was formulated by transforming the established indicator system for long-term care needs into survey items. Using stratified sampling, a total of 622 older adults from community settings in Changsha were surveyed between June and August 2021. Item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and reliability testing were conducted.Results:The final questionnaire consists of three subscales (mental function, physical function, and activity and participation), comprising a total of 47 items. The item-level content validity index ( I- CVI) ranged from 0.830 to 1.000, and the scale-level content validity index ( S- CVI) was 0.915. EFA results showed that the extracted factors aligned well with the predefined dimensions after adjustment, with factor loadings exceeding 0.600 and cumulative variance contributions exceeding 70.000% for all subscales. CFA results indicated good model fit across all subscales and the overall questionnaire, confirming stable structural validity. The Cronbach's α coefficients ranged from 0.877 to 0.970, and test-retest reliability coefficients ranged from 0.901 to 0.957. Conclusions:The long-term care needs assessment questionnaire for community-dwelling older adults demonstrates strong reliability and validity, and can serve as a reliable tool for evaluating long-term care needs in this population.
6.WNK1 Alleviates Chloride Efflux-Induced NLRP3 Inflammasome Activation and Subsequent Neuroinflammation in Early Brain Injury Following Subarachnoid Hemorrhage.
Panpan ZHAO ; Huimiao FENG ; Xinyu ZHOU ; Jingyuan ZHOU ; Fangbo HU ; Taotao HU ; Yong SUN
Neuroscience Bulletin 2025;41(9):1570-1588
The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1's inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.
Animals
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Subarachnoid Hemorrhage/complications*
;
Inflammasomes/metabolism*
;
Rats
;
Mice
;
Neuroinflammatory Diseases/metabolism*
;
WNK Lysine-Deficient Protein Kinase 1/genetics*
;
Male
;
Humans
;
Chlorides/metabolism*
;
Mice, Inbred C57BL
;
Rats, Sprague-Dawley
;
Brain Injuries/metabolism*
;
Microglia/metabolism*
;
Protein Serine-Threonine Kinases
7.Analyses of clinical characteristics and prognostic factors of newly-treated elderly acute myeloid leukemia patients with intermediate-risk karyotype
Qingyun PENG ; Hao LI ; Zhiwei WU ; Xiao XIAO ; Xinchen FANG ; Panpan HUANG ; Chaojie HU
Journal of Leukemia & Lymphoma 2025;34(7):403-407
Objective:To investigate the clinical features and prognostic factors of newly-treated elderly acute myeloid leukemia (AML) patients with intermediate-risk karyotype.Methods:A retrospective case series study was conducted. A total of 87 newly-treated elderly AML patients with intermediate-risk karyotype in the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2013 to December 2023 were selected. The clinical characteristics were summarized. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was used to make univariate and multivariate analyses of prognostic factors.Results:The median age [ M ( Q1, Q3)] of 87 patients was 69 (60, 87) years. The patients with normal karyotype and abnormal karyotype accounted for 77.1% (67/87), 22.9% (20/87), respectively. A total of 74 patients (85.1%) had 1 or more gene mutations, of which FLT3-ITD, NPM1 mutation, CEBPA mutation and WT1 high expression accounted for 29.9% (26/87), 26.4% (23/87), 19.5% (17/87), and 65.5% (57/87), respectively; additionally, 44.7% (39/87) of patients had 2 or more gene mutations. The objective response rate of patients after induction therapy was 47.7% (41/87), while the relapse rate was 73.2% (30/41). The median progression-free survival (PFS) time was 7.8 months, and the median overall survival (OS) time was 12.1 months. Univariate analysis result revealed that age, FLT3-ITD, hypomethylating agents, and minimal residual disease complete remission (MDR-CR) were factors influencing the OS of newly-treated elderly AML patients with intermediate-risk karyotype (all P < 0.05). Multivariate analysis indicated that MDR-CR was an independent risk factor for OS (yes vs. no: HR = 0.27, 95% CI: 0.14-0.51, P < 0.001). Conclusions:Newly-treated elderly AML patients with intermediate-risk karyotype have a high relapse rate and poor prognosis, and MDR-CR is identified as an independent influencing factor for the prognosis of these patients.
8.Research progress on the mechanism and intervention of behavioral and psychological symptoms in Alzheimer′s disease
Xuerui PANG ; Miao FANG ; Xingqi WU ; Guixian XIAO ; Yulong DAI ; Shanshan ZHOU ; Panpan HU ; Kai WANG
Chinese Journal of Neurology 2025;58(5):546-552
Alzheimer′s disease is a serious neurodegenerative disorder. Approximately 80% to 90% of patients are accompanied by behavioral and psychological symptoms of dementia (BPSD), which manifest as a series of behavioral, psychological and mental abnormalities. These abnormalities can accelerate the cognitive deterioration and premature death of patients, and thus are regarded as important clinical symptoms. However, the pathogenesis of BPSD is still unknown, and treatment methods are limited. The pathogenesis of BPSD from the perspective of neuroimaging and pathophysiology, and possible treatment measures were analyzed in this article, in order to provide references for the early diagnosis and treatment of BPSD.
9.Application of superficial ultrasonography in diagnosing and guiding management of a refractory scalp wound complicated by epidural abscess.
Yu LING ; Hongyang HU ; Gang XIANG ; Panpan LYU
Journal of Zhejiang University. Medical sciences 2025;54(5):637-640
A middle-aged patient presented with persistent purulent discharge from a scalp incision five years after undergoing craniotomy with artificial dura mater implantation. The wound showed no significant improvement despite a month of systemic antibiotic therapy and local debridement. Subsequent superficial ultrasonography revealed complete separation of the artificial dura mater implant area from the surrounding flap tissue, with a loss of local blood supply. Based on these findings, the artificial dura mater was surgically removed, and a free skin flap transplantation was performed to successfully cover the wound. The wound was well-healed at the 10-month postoperative follow-up.
Humans
;
Scalp/diagnostic imaging*
;
Middle Aged
;
Male
;
Epidural Abscess/etiology*
;
Ultrasonography
;
Surgical Flaps
;
Surgical Wound Infection/surgery*
;
Dura Mater/surgery*
10.Comorbidity features and related factors of restless legs syndrome in patients with obstructive sleep apnea
Qin GUO ; Panpan LU ; Hongqiang SUN ; Sifan HU
Chinese Journal of Psychiatry 2025;58(8):603-611
Objective:To investigate the clinical characteristics and associated factors of comorbid obstructive sleep apnea (OSA) coexisting with restless legs syndrome (RLS).Methods:A retrospective case-control study was conducted, enrolling hospitalized patients diagnosed with OSA or RLS at Peking University Sixth Hospital from June 2015 to May 2023. Participants were divided into three groups: OSA with RLS (comorbid group, n=26), OSA alone ( n=60, RLS-excluding), and RLS alone ( n=45, OSA-excluding). Demographic characteristics, clinical data, laboratory indicators (i.e., hemoglobin, ferritin, serum iron, folate, vitamin B 12, calcium, phosphorus, magnesium, fasting glucose), and polysomnography (PSG) parameters were collected. Group differences were analyzed using ANOVA, chi-square tests, and non-parametric tests. Multivariate logistic regression was performed to identify factors associated with OSA comorbid RLS. Results:Laboratory analyses revealed that patients in the comorbid group had significantly lower hemoglobin ( P=0.046) and ferritin levels ( P=0.024) than the OSA-alone group. Conversely, serum phosphorus was markedly elevated in the comorbid group compared to both control groups ( F=2.23, P<0.01). Polysomnography test found significantly higher periodic limb movement during sleep index (PLMSI) in the comorbid group vs. OSA-alone group (Dunn-Bonferroni correction P=0.001), reduced minimum oxygen saturation in the comorbid group vs. RLS-alone group (Dunn-Bonferroni correction P<0.001), and increased respiratory-related microarousals in the comorbid group vs. RLS-alone group (Dunn-Bonferroni correction P<0.001). Multivariate analysis adjusted for covariates confirmed that periodic limb movement during sleep index (PLMSI) ( OR=1.04, 95% CI=1.02-1.07, P=0.001) and serum phosphorus ( OR=6.51, 95% CI=1.86-27.40, P=0.003) independently contributed to OSA-RLS comorbidity. Conclusion:The coexistence of OSA and RLS manifests as dual dysregulation in iron-phosphorus metabolism and synchronized respiratory-motor dysfunction. Mechanistically, hypoxia-induced systemic inflammation may serve as a nexus linking metabolic perturbations and sleep fragmentation in this clinical subpopulation, highlighting potential biomarkers for targeted management.

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