Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

Purpose To investigate the expression of POLR2M in colorectal cancer(CRC)and its effects on cell growth,apoptosis and invasion.Methods GEPIA2.0,TCGA and Kaplan-Meier Plotter databases were used to ana-lyze the differential expression of POLR2M in CRC tissues and normal adjacent tissues,and to evaluate its prognostic significance using the Log-rank test.Quantitative real-time PCR(qRT-PCR)was used to detect the expression of POLR2M in human colorectal cancer cell lines SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116,SW620 and human normal colorectal cell line FHC.DLD-1 and RKO cells were stably transfected with lentivirus,and the POLR2M groups were up-regulated into the control group(LV-NC)and experimental group(LV-POLR2M),and the transient transfec-tion of SW620 and SW480 cells with interfering fragments of SiRNA was used to down-regulate the POLR2M groups into the control group(Si-NC)and experimental group(Si-POLR2M),and the transfection efficiency of each group was verified.CCK-8,plate cloning,Transwell and scratch healing assays were used to detect cell proliferation,invasion and migration.Flow cytometry was used to detect the effects of POLR2M on cell cycle and apoptosis.Results GE-PIA2.0,TCGA and Kaplan-Meier Plotter database analysis showed that the expression of POLR2M in colorectal cancer was significantly higher than in normal adjacent tissues(P＜0.05),and the expression of POLR2M was closely associ-ated with the histological type of colorectal cancer and lymph node metastasis(P＜0.05),but not with the age,gen-der,tumor grade and vascular invasion of patients(P＞0.05).The prognosis of patients with POLR2M overexpression was poor(P＜0.05).The results of qRT-PCR showed that compared with FHC cells,the mRNA expression of POLR2M in SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116 and SW620 cell lines was increased(F=97.7,P＜0.05),and POLR2M stable overexpression and interference cell lines were successfully constructed.Compared with the LV-NC group,the viability,colony number,number of cells passing through the chamber and cell mobility of DLD-1 and RKO cells in the LV-POLR2M group were significantly increased(P＜0.05).Compared with the Si-NC group,the viability,colony number,number of cells passing through the chamber,and cell mobility of SW620 and SW480 cells in the Si-POLR2M group were significantly decreased(P＜0.05).Downregulation of POLR2M induced cell cycle arrest in G1 phase and promotes apoptosis(P＜0.05).Conclusion POLR2M may play a role as a pro-tumor gene in CRC,and its high expression can significantly promote the proliferation and invasion of CRC cells.

Objective:To explore the mediating effect of frailty between stress perception and kinesiophobia in elderly patients after temporary cardiac pacemaker implantation.Methods:A total of 129 elderly patients who underwent temporary cardiac pacemaker implantation surgery in the Department of Cardiovascular Medicine of the First Affiliated Hospital of Zhengzhou University from February 2023 to April 2024 were selected by convenience sampling method, and were surveyed by the general information questionnaire, the exercise fear scale, the perceived stress scale and the Chinese Tilburg frailty scale.The t test, one-way ANOVA and non parametric test were used to analyze the data by SPSS 29.0 software.The macro program PROCESS was used to construct and test the mediation model. Results:The total score of kinesiophobia was (41.08±2.77), the total score of stress perception was (36.22±3.07), and the total score of frailty was (11.19±1.53) in elderly patients after temporary cardiac pacemaker implantation. The total score of kinesiophobia was positively correlated with the total score of stress perception ( r=0.383, P<0.01), the total score of kinesiophobia was positively correlated with the total score of frailty ( r=0.451, P<0.01), and the total score of stress perception was positively correlated with the total score of frailty ( r=0.289, P<0.01).The total effect of stress perception on motor fear was 0.359 ( P<0.01) and the direct effect was 0.226 ( P<0.01).Frailty played a partial mediating role between stress perception and kinesiophbia in elderly patients after temporary pacemaker implantation, with an indirect effect of 0.133 (95% CI=0.062-0.243), accounting for 37.05% of the total effect. Conclusion:Stress perception not only directly affects kinesiophobia in elderly patients with temporary cardiac pacemaker implantation, but also indirectly affects kinesiophobia through frailty.

Objective:To explore the mediating effect of frailty between stress perception and kinesiophobia in elderly patients after temporary cardiac pacemaker implantation.Methods:A total of 129 elderly patients who underwent temporary cardiac pacemaker implantation surgery in the Department of Cardiovascular Medicine of the First Affiliated Hospital of Zhengzhou University from February 2023 to April 2024 were selected by convenience sampling method, and were surveyed by the general information questionnaire, the exercise fear scale, the perceived stress scale and the Chinese Tilburg frailty scale.The t test, one-way ANOVA and non parametric test were used to analyze the data by SPSS 29.0 software.The macro program PROCESS was used to construct and test the mediation model. Results:The total score of kinesiophobia was (41.08±2.77), the total score of stress perception was (36.22±3.07), and the total score of frailty was (11.19±1.53) in elderly patients after temporary cardiac pacemaker implantation. The total score of kinesiophobia was positively correlated with the total score of stress perception ( r=0.383, P<0.01), the total score of kinesiophobia was positively correlated with the total score of frailty ( r=0.451, P<0.01), and the total score of stress perception was positively correlated with the total score of frailty ( r=0.289, P<0.01).The total effect of stress perception on motor fear was 0.359 ( P<0.01) and the direct effect was 0.226 ( P<0.01).Frailty played a partial mediating role between stress perception and kinesiophbia in elderly patients after temporary pacemaker implantation, with an indirect effect of 0.133 (95% CI=0.062-0.243), accounting for 37.05% of the total effect. Conclusion:Stress perception not only directly affects kinesiophobia in elderly patients with temporary cardiac pacemaker implantation, but also indirectly affects kinesiophobia through frailty.

Purpose To investigate the expression of POLR2M in colorectal cancer(CRC)and its effects on cell growth,apoptosis and invasion.Methods GEPIA2.0,TCGA and Kaplan-Meier Plotter databases were used to ana-lyze the differential expression of POLR2M in CRC tissues and normal adjacent tissues,and to evaluate its prognostic significance using the Log-rank test.Quantitative real-time PCR(qRT-PCR)was used to detect the expression of POLR2M in human colorectal cancer cell lines SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116,SW620 and human normal colorectal cell line FHC.DLD-1 and RKO cells were stably transfected with lentivirus,and the POLR2M groups were up-regulated into the control group(LV-NC)and experimental group(LV-POLR2M),and the transient transfec-tion of SW620 and SW480 cells with interfering fragments of SiRNA was used to down-regulate the POLR2M groups into the control group(Si-NC)and experimental group(Si-POLR2M),and the transfection efficiency of each group was verified.CCK-8,plate cloning,Transwell and scratch healing assays were used to detect cell proliferation,invasion and migration.Flow cytometry was used to detect the effects of POLR2M on cell cycle and apoptosis.Results GE-PIA2.0,TCGA and Kaplan-Meier Plotter database analysis showed that the expression of POLR2M in colorectal cancer was significantly higher than in normal adjacent tissues(P＜0.05),and the expression of POLR2M was closely associ-ated with the histological type of colorectal cancer and lymph node metastasis(P＜0.05),but not with the age,gen-der,tumor grade and vascular invasion of patients(P＞0.05).The prognosis of patients with POLR2M overexpression was poor(P＜0.05).The results of qRT-PCR showed that compared with FHC cells,the mRNA expression of POLR2M in SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116 and SW620 cell lines was increased(F=97.7,P＜0.05),and POLR2M stable overexpression and interference cell lines were successfully constructed.Compared with the LV-NC group,the viability,colony number,number of cells passing through the chamber and cell mobility of DLD-1 and RKO cells in the LV-POLR2M group were significantly increased(P＜0.05).Compared with the Si-NC group,the viability,colony number,number of cells passing through the chamber,and cell mobility of SW620 and SW480 cells in the Si-POLR2M group were significantly decreased(P＜0.05).Downregulation of POLR2M induced cell cycle arrest in G1 phase and promotes apoptosis(P＜0.05).Conclusion POLR2M may play a role as a pro-tumor gene in CRC,and its high expression can significantly promote the proliferation and invasion of CRC cells.

Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Objective To determine the effects of continuous θ burst stimulation of contralateral premotor areas on post-stroke spasticity gait in patients with severe hemiplegia.Methods A pro-spective trial was conducted on 186 stroke patients with severe hemiplegia admitted to our depart-ment from January 2019 to January 2024.They were randomly into control group(93 cases,con-ventional rehabilitation training)and observation group(93 cases,continuous θ burst transcranial stimulation).In 4 weeks after treatment,gait parameters,Fugl-Meyer assessment of lower ex-tremity(FMA-LE)score,Berg balance scale(BSS)score,clinic spasticity index(CSI)score,lower limb sensation,spasticity improvement,and total effective rate were compared between the two groups.Results After treatment,both the 2 groups had significantly higher hip flexion,knee flex-ion,stride length,step frequency,step speed,FMA-LE score,BSS score,CSI score,and H wave latency,and lower two-point discrimination perception and H/M ratio when compared with the levels before treatment(P＜0.01).What's more,all above indicators were obviously better in the observation group than the control group(P＜0.01).The observation group had 1(1.1％),11(11.8％),48(51.6％),31(33.3％)and 2 cases(2.2％),respectively,of spasticity improvement grades 1,1+,2,3,and 4,and the control group had 0,7(7.5％),29(31.2％),44(47.3％),and 13 cases(14.0％),respectively,with statistical differences between the two group(P＜0.01).The total effective rate was notably higher in the observation group than the control group(96.8％vs 77.4％,x2=15.500,P＜0.01).Conclusion For severe hemiplegia patients,continuous θ burst stimulation can improve muscle spasm,restore gait,and better improve lower limb sensory and motor function.

In various types of inspections and self-inspections, it was found that compliance and rationalization in diagnosis and charging were the more common problems in hospital, leading to refusal of medical insurance payment. In 2022, the failure mode and effect analysis was conducted in a Grade-A tertiary hospital in Jinhua to identify the high-risk points in the process of diagnosis and treatment and charging, and building six major information technology transformation scenarios and formulating specific transformation measures, to avoid or reduce the refusal of medical insurance payment in advance. Through the digital transformation of medical insurance supervision system, a whole process intelligent supervision has been implemented, including pre event review, mid event reminder and intelligent correction, and post event big data precise analysis. It promoted compliant diagnosis and treatment of medical personnel and accurate charging, which could provide reference for other medical institutions to use medical insurance funds reasonably.

AIM: To explore the clinicopathological and immunohistochemistry(IHC)characteristics of meibomian gland carcinoma(MGC).METHODS: Patients who were pathologically diagnosed as MGC from January 1, 2015 to December 31, 2020 in our hospital were enrolled, and their clinicopathological information was retrospectively analyzed. Cancer tissues from all the cases were IHC stained. En Vision two-step method, DAB staining, as well as hematoxylin re-staining were applied in the IHC assay.RESULTS: A total of 50 patients with 21 males and 29 females(1:1.38)were enrolled in the study, ranging from 26 to 80 years old, with a median age of 60 years. The upper eyelid, which was the predilection site, accounting for 66%(33/50). Histopathologically, moderately or poorly differentiated was in the majority(35/50, 70%). The expression rates of IHC parameters of MGC patients were as follows: GATA-3(49/50, 98%), EMA(49/50, 98%), CAM5.2(42/50, 84%), AR(41/50, 82%), MSH2(50/50, 100%), MSH6(50/50, 100%), MLH1(50/50, 100%), PMS2(50/50, 100%), Ki67(positive, 50%-90%). All the patients were followed up for 12 to 72 mo, with 5 cases of recurrence and 0 deaths.CONCLUSION: Pathological diagnosis of MGC should focus on observing cancer cells' cytoplasm to find relevant clues for cortical gland differentiation. Comprehensive analysis of multiple indicators is required when using IHC to assist diagnosis. For most MGC cancer cells, positive expressions of GATA-3, EMA, AR, CAM5.2 and a high Ki67 proliferation index could be always found. In addition, screening for Muir-Torre syndrome related IHC indicators could be also performed in diagnosing MGC simultaneously.