Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective:To investigate mevalonic acid(MEV)on reversing the antitumor effects of fluvastatin sodium(FS)on tongue squamous cell carcinoma(TSCC)cells.Methods:TSCC HSC-4 cells were treated with different concentrations of FS and MEV re-spectively or in combination.Cell counting kit-8,flow cytometry,wound healing,immunofluorescence and western blotting assays were conducted to examine cell proliferation,apoptosis and migration capacities,as well as the expression levels of Ras homolog family member A(RHOA),tissue factor(TF)and B-cell lymphoma-2-associated X(BAX)proteins,respectively.Results:FS inhibited HSC-4 cell proliferation and migration,decreased the expression of RHOA and TF,and increased BAX expression.MEV reversed the above antitumor effects of FS and promoted intracellular RHOA and TF expression.Conclusion:MEV reverses the antitumor effects of FS on HSC-4 cells in vitro.

Objective:To evaluate the curative effect, safety and feasibility of percutaneous transhepatic cholangio drainage(PTCD) combined with balloon dilatation in treating benign biliary-enteric anastomosis stricture(BBES).Methods:The clinical data of 33 patients with benign biliary-enteric anastomosis stricture, who were admitted to the First Affiliated Hospital of Zhengzhou University during the period from January 2013 to May 2019, were retrospectively analyzed. There were 23 cases of benign etiology and 10 cases of malignant etiology, benign strictures of which 15 cases were located in the hepatic hilum and of which 18 cases outside of it. All patients were considered as benign stenosis by at least two imaging examinations of magnetic resonance imaging of pancreatic or enhanced MRI or enhanced CT, laboratory examinations of tumor markers and other clinical data before operation. 10 cases of malignant etiology were confirmed by intraoperative biopsy and pathology. All patients were treated with balloon dilatation at an interval of 1 to 4 weeks after PTCD. The changes of clinical symptoms, bilirubin and liver function before and after operation were compared and analyzed, and the postoperative complications and anastomotic patency rate were followed up.Results:PTCD combined with balloon dilatation was performed successfully in all patients, and the success rate was 100%. After operation, the benign biliary-enteric anastomosis stricture was significantly improved in all patients, and the clinical symptoms were improved obviously. The liver function and bilirubin decreased significantly in all patients after operation, and there was significant statistical significance ( P<0.05). There is no serious complications such as biliary bleeding and biliary fistula were found after operation. At 3 months, 6 months, 12 months, 24 months and 36 months after operation, the anastomotic patency rates of all patients were 90.9%(30/33), 72.7%(24/33), 63.6%(21/33), 63.6%(21/33), 60.6%(20/33), respectively. During the whole follow-up period, anastomotic restenosis happened in 13 patients, of which 9 cases with restenosis, the benign stenosis site of the anastomosis was the hepatic hilum and of which 4 cases located on the outside of the hepatic hilum. After treatment, the incidence of benign restenosis of the anastomosis at the hepatic hilum (60.0%, 9/15) was higher than that at outside of the hepatic hilum (22.2%, 4/18) and it's statistically significant ( P<0.05). Among the 13 patients with recurrence of BBES, 4 cases underwent choledochojejunostomy for malignant causes and 9 cases with benign causes. The recurrence rates after the first balloon dilatation were 40.0% (4/10) and 39.1% (9/23), respectively, and the average recurrence time was 5.8 months and 6.8 months respectively, the difference was not statistically significant( P>0.05). Conclusion:For the treatment of benign biliary-enteric anastomosis stricture, percutaneous transhepatic cholangio drainage combined with balloon dilatation with reliable curative effect, with high safety and less trauma, with less operative complications, and with repeatability, so it is worth applying in clinic.

To investigate the efficacy of manipulation combined with electrical stimulation and biofeedback on the treatment of female sexual dysfunction. 
 Methods: Seventy-two female patients with sexual dysfunction were recruited from the Third Xiangya Hospital of Central South University from January 2014 to December 2015. Subjects were randomly divided into three groups (A, B, and C). Patients in group A and group B received manipulation therapy and electrical stimulation biofeedback therapy, respectively, while patients in group C received manipulation combined with biofeedback electrical stimulation treatment for 30 days. The strength and fatigue degree of the type I and the type II muscle fiber of the pelvic muscles in all groups were evaluated before and one month after the treatment for further comparison. Questionnaire survey was used to investigate the frequency of sexual life and orgasm before and after treatment.
 Results: The strength and fatigue degree of patients in group C was significantly better than those of the other two groups (P<0.05).
 Conclusion: Manipulation therapy combined with electrical stimulation and biofeedback can effectively enhance the recovery of sexual dysfunction in postpartum women and improve the quality of sexual life for patients with postpartum sexual dysfunction. It therefore can be spread in clinical practice.
Biofeedback, Psychology ; Electric Stimulation ; Female ; Humans ; Physical Therapy Modalities ; Quality of Life ; Random Allocation ; Sexual Dysfunction, Physiological ; therapy ; Surveys and Questionnaires

Objective To study the effects of PVA-H coating thickness and tip angle on the tissue injury caused by the implantation of neural electrodes. Methods Simulated implantation experiments were conducted based on a tissue injury evaluation system to evaluate the tissue injury caused by electrode implantation. The coating thicknesses were controlled by the number of dip coating times (0, 1, 2, and 3), whereas the tip angles were set as 30°, 40°, and 50°. The maximum tissue strain and insertion force were selected as the measurement of the tissue injury. Results thicker hydrogel coating and larger tip angle would cause more serious tissue injury. Simultaneously, reducing the tip angle of the neural electrode could reduce the degree of the hydrogel coating effect on the tissue injury. When the tip angle was 30°, the maximum strain and the peak insertion force increased by 3.4% and 3.8%, respectively, whereas when the wedge angle was 60°, the maximum strain and maximum insertion force increased by 11.3% and 18.1%, respectively. Conclusions The hydrogel coating of the neural electrode increased the injury of biological tissues caused by the implantation of the neural electrode. However, the method of decreasing the tip angle of the electrode could reduce the degree of the negative effects of the hydrogel coating thickness on the implantation injury.

Objective To evaluate and verify the preventive and therapeutic effects of electroacupuncture (EA) plus pelvic floor muscle training (PFMT) in treating mild-moderate female stress urinary incontinence (SUI). Method By adopting a single-blind randomized controlled design, eighty-two SUI patients were randomized into an observation group of 40 cases and a control group of 42 cases. The observation group was intervened by EA plus PFMT, while the control group only received PFMT. Before the treatment and after 4-week treatment, the 1 h urine leakage amount, Incontinence Questionnaire Short Form (ICI-Q-SF) and improvement rate were evaluated in the two groups, to analyze the effects of the two methods in improving mild-moderate SUI. Result For mild SUI patients, the 1 h urine leakage amount and ICI-Q-SF score dropped significantly after the treatment in the observation group (P<0.05), and the observation group was significantly lower than the control group (P<0.05). For moderate SUI patients, the 1 h urine leakage amount and ICI-QSF score dropped significantly in both groups after the intervention (P<0.05), the observation group was significantly lower than the control group (P<0.05), and the improvement rate in the observation group was markedly higher than that in the control group (P<0.01). Conclusion EA plus PFMT caneffectively improve the urine leakage and urination in mild-moderate SUI patients. EA plus PFMT can effectively prevent the aggravation of moderate female SUI, and its effect is better than PFMT alone.

Objective To observe the therapeutic effects of different opportune time and hyperbaric oxygen (HBO) courses in adjunctive therapy of comminuted tibial fracture.Methods In accordance with different treatment methods, 49 cases of comminuted tibial fracture were divided into the HBO group (n =27) and the conventional therapy group (n =22).Cure rates, as well as different opportune time and HBO courses were compared between the 2 groups.Results The cure rate of the HBO group (81.5％) was obviously higher than that of the conventional therapy group (54.5％), and statistical significance could be noted, when comparisons were made between the 2 groups (P ＜ 0.05).Cure rates for those patients who received HBO therapy 3 days, 3-7 days or over 7 days after surgery, were respectively 92.3％ , 88.9％ and 40.0％.There was statistical significance, when the cure rate of the 3-day after surgery subgroup was compared with that of the 7-day after surgery subgroup (P ＜ O.05).The cure rates for the patients who underwent less than 5 sessions,5-10 sessions or over 10 sessions of HBO therapy were respectively 75.0％, 78.6％ and 88.9％, with statistical significance (P ＜ 0.05).Conclusions Adjunctive HBO therapy could increase the cure rate of comminuted tibial fracture, and the earlier HBO therapy was implemented, the better results could be achieved.

Objective To observe the therapeutic effects of different opportune time and hyperbaric oxygen (HBO) courses in adjunctive therapy of comminuted tibial fracture.Methods In accordance with different treatment methods, 49 cases of comminuted tibial fracture were divided into the HBO group (n =27) and the conventional therapy group (n =22).Cure rates, as well as different opportune time and HBO courses were compared between the 2 groups.Results The cure rate of the HBO group (81.5％) was obviously higher than that of the conventional therapy group (54.5％), and statistical significance could be noted, when comparisons were made between the 2 groups (P ＜ 0.05).Cure rates for those patients who received HBO therapy 3 days, 3-7 days or over 7 days after surgery, were respectively 92.3％ , 88.9％ and 40.0％.There was statistical significance, when the cure rate of the 3-day after surgery subgroup was compared with that of the 7-day after surgery subgroup (P ＜ O.05).The cure rates for the patients who underwent less than 5 sessions,5-10 sessions or over 10 sessions of HBO therapy were respectively 75.0％, 78.6％ and 88.9％, with statistical significance (P ＜ 0.05).Conclusions Adjunctive HBO therapy could increase the cure rate of comminuted tibial fracture, and the earlier HBO therapy was implemented, the better results could be achieved.