OBJECTIVE: To analyze the molecular genetic spectrum of children with acute myeloid leukemia (AML), and explore its correlation with clinical characteristics and prognosis. METHODS: The clinical and molecular genetic data of 116 children with newly diagnosed AML in Wuhan Children's Hospital from September 2015 to August 2022 were retrospectively analyzed. The Fisher's exact test was used to analyze the correlation of gene mutations with clinical features, and Kaplan-Meier curve was used to analyze the influences of gene mutations on the prognosis. RESULTS: NRAS (22%), KRAS (14.9%), and KIT (14.7%) mutations were the most common genetic abnormalities in 116 children with AML. Children with KIT, CEBPA and GATA2 mutations showed a higher median onset-age than those without mutations (all P < 0.05). Children with FLT3-ITD mutation exhibited a higher white blood cell count at initial diagnosis compared to those without mutations (P < 0.05). Children with ASXL2 mutation had lower platelet count and hemoglobin at initial diagnosis than those without mutations (both P < 0.05). KIT mutations were often co-occurred with t(8;21)(q22;q22). There was no significant relationship between gene mutation and minimal residual disease (MRD) remission rate after the first and second induction therapy (P >0.05). KIT and NRAS mutations were not associated with prognosis significantly (P >0.05). The overall survival (OS) rates of children with CEBPA and FLT3-ITD mutations were superior to those without mutations, but the differences were not statistically significant (P >0.05). The 3-year OS rate of 61 children treated by allogeneic hematopoietic stem cell transplantation was 89.8%, which was significantly higher than 55.2% of those only treated by chemotherapy (P < 0.001). CONCLUSIONS Gene mutations are common in children with AML, and next-generation sequencing can significantly improve the detection rate of gene mutations, which can guide the risk stratification therapy. In addition, FLT3-ITD and KIT mutations may no longer be poor prognostic factors.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Retrospective Studies ; fms-Like Tyrosine Kinase 3/genetics* ; Child ; Proto-Oncogene Proteins c-kit/genetics* ; Male ; Female ; CCAAT-Enhancer-Binding Proteins/genetics* ; Membrane Proteins/genetics* ; Child, Preschool ; Adolescent ; GATA2 Transcription Factor/genetics* ; GTP Phosphohydrolases/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics*

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:To investigate the causal relationship between trimethylamine N-oxide (TMAO) and its precursors (betaine, carnitine, and choline) and pancreatic diseases based on the Mendelian randomization (MR) method.Methods:Genome-wide association study data of TMAO, betaine, carnitine, choline, acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC), and circulating immune cell characteristics (white blood cell, lymphocyte, monocyte, neutrophil, eosinophil and basophil) were collected. According to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines, the available genetic variants [single nucleotide polymorphism (SNP)] were strictly screened. The causal relationship between exposure (TMAO and its precursors) and outcomes (pancreatic diseases and circulating immune cell characteristics) was evaluated using inverse variance weighting (IVW), MR-Egger regression and weighted median. The reliability of the results was evaluated by sensitivity analysis based on MR-Egger regression, MR-PRESSO, Cochrane's Q test and leave-one-out method. Results:A total of 36 SNP associated with TMAO and its precursors were included. Five of these were associated with TMAO, 13 with betaine, 12 with carnitine, and 6 with choline. ① MR analysis showed that TMAO may increase the risk of AP [odds ratio ( OR) = 1.100, 95% confidence interval (95% CI) was 1.008-1.200, P = 0.032], and choline may reduce the risk of alcoholic acute pancreatitis (AAP; OR = 0.743, 95% CI was 0.585-0.944, P = 0.015). The analysis results of MR-Egger regression and weighted median were consistent with the IVW results. There is no evidence to support a causal relationship between TMAO and its precursors and the risk of CP and PC. Sensitivity analysis indicated that SNP analyzed by MR showed no heterogeneity and low pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. ② There was a positive causal relationship between plasma TMAO level and circulating monocyte count ( OR = 1.017, 95% CI was 1.000*-1.034, P = 0.048, * represented that the data was obtained by correcting to 3 decimal places from 1.000 1). The causal effect obtained by MR-Egger regression and weighted median analysis was consistent with the results of IVW. Sensitivity analysis illustrated SNP analyzed by MR showed no heterogeneity and pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. Conclusion:TMAO and choline may change the risk of AP, and TMAO may contribute to the increase of circulating monocyte count in AP.

Objective: To investigate the association of sleep quality, depressive symptoms and their interaction with non suicidal self injury (NSSI) among rural middle school students, so as to provide a reference for early prevention and control of NSSI among rural middle school students. Methods: A multi stage cluster sampling method was used to randomly select four rural middle schools in Xuzhou, Jiangsu Province. A total of 1 723 middle school students were investigated according to the principle of grade stratification and class random selection. Paper questionnaires (including demographic factors, Non Suicidal Self Injury Short Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnare-9) were used to conduct the questionnaire survey. Logistic regression model was used to analyze the association of sleep quality, depressive symptoms and their interaction with NSSI among rural middle school students. Results: Totally 30.5% of middle school students had NSSI. Univariate results showed that girls (33.0%) had a higher incidence of NSSI than boys(27.3%), and those with sleep disorders and depressive symptoms had a higher incidence of NSSI, which was 46.8%, 43.6%. The results of multivariate Logistic regression showed that the risk of NSSI in students with sleep disorder was 1.80 times that in those without sleep disorder( OR 95%CI=1.42-2.28, P <0.01). The risk of NSSI in students with depressive symptoms was 3.32 times higher than that in those without depressive symptoms( OR 95%CI=2.60-4.24, P <0.01). The interaction results showed that there was additive interaction between sleep disturbance and depressive symptoms on the occurrence of NSSI behavior in rural middle school students, and the relative excess risk, attributable proportion and synergy index were 1.80, 0.30 and 1.57, respectively. Conclusion Sleep disorder and depressive symptoms are risk factors for NSSI among rural middle school students, and there is additive interaction between them.

Adult ; Humans ; Acute Disease ; Leukemia

BACKGROUND: There has been minimal research on the role of benevolent childhood experiences (BCEs) and how such events may offer protection from the insidious effects of adverse childhood experiences (ACEs) or later in life. OBJECTIVES: This research aims to learn how BCEs and ACEs interact to affect adolescents' psychological distress. METHODS: Cross-sectional survey was conducted in three cities (Xuzhou, Nanjing, and Wuhan) in China from March 2021 to May 2021. Latent class analysis (LCA) was used to classify the patterns of ACEs and BCEs. We adopted hierarchical multivariable regression to examine the influences of ACEs and BCEs on depression and suicidal ideation. RESULTS: To explore the relationship between childhood experience and suicidal ideation and depression, LCA revealed three patterns of ACEs: (1) emotional abuse (10.57%); (2) high ACEs (0.55%); and (3) low ACEs classes (88.88%). Adolescents with emotional abuse (depression: OR = 3.82, 95%CI = 2.80-5.22, P < 0.001; suicidal ideation: OR = 5.766, 95%CI = 3.97-8.38, P < 0.001) and high ACEs class (suicidal ideation: OR = 5.93, 95%CI = 1.19-29.66, P < 0.05) had an increased risk of psychological distress (reference: low ACEs). LCA revealed four patterns of BCEs: (1) relationship support (14.54%); (2) low BCEs (4.85%); (3) high BCEs (55.34%); and (4) high quality of life classes (25.28%). Adolescents with a high quality of life (depression: OR = 0.09, 95%CI = 0.05-0.16, P < 0.001; suicidal ideation: OR = 0.22, 95%CI = 0.12-0.40, P < 0.001) and high BCEs (depression: OR = 0.05, 95%CI = 0.03-0.09, P < 0.001; suicidal ideation: OR = 0.15, 95%CI = 0.09-0.26, P < 0.001) protected the mental health of adolescents (reference: low BCEs). CONCLUSIONS High ACEs and emotional abuse classes were significantly associated with poorer mental health symptoms, including suicidal ideation and depression. In contrast, high BCEs and high quality of life classes were associated with better mental health. These findings point out that it is more necessary to identify and support victims of ACEs, and it is urgent to increase BCEs in early childhood.
Adolescent ; Humans ; Cross-Sectional Studies ; Depression ; East Asian People ; Latent Class Analysis ; Quality of Life ; Suicidal Ideation ; Adverse Childhood Experiences

Objective:To provide a basis for selecting the optimization method for intracavitary/interstitial brachytherapy (IC/ISBT) of cervical cancer by comparing graphical optimization (GO), inverse planning simulated annealing (IPSA), and hybrid inverse planning optimization (HIPO) using dosimetric and radiobiological models.Methods:This study selected 65 patients with cervical cancer who were treated with image-guided IC/ISBT. The afterloading therapy plans for these patients were optimized using GO, IPSA, and HIPO individually, with a prescription dose high-risk clinical target volume (HRCTV) D90 of 6 Gy. The non-parametric Friedman test and the non-parametric Wilcoxon rank test were employed to analyze the differences in duration, dose-volume parameters, and radiobiology between the three types of optimized plans. Results:Inverse planning optimization (IPSA: 46.53 s; HIPO: 98.36 s) took less time than GO (135.03 s). In terms of gross target volume (GTV) dose, the high-dose irradiation V150% (53.66%) was slightly higher in the HIPO-optimized plans, while the V200% (30.29%) was higher in the GO-optimized plans. The GO-optimized plans had a higher conformity index (CI; 0.91) than other plans, showing statistically significant differences. Compared with other plans, the HIPO-optimized plans showed the lowest doses of D1 cm 3 and D2 cm 3 at bladders and rectums and non-statistically significant doses at small intestines ( P > 0.05). In terms of the equivalent uniform biologically effective dose (EUBED) for HRCTV, the HIPO-optimized plans showed a higher value (12.35 Gy) than the GO-optimized plans (12.23 Gy) and the IPSA-optimized plans (12.13 Gy). Moreover, the EUBED at bladders was the lowest (2.38 Gy) in the GO-optimized plans, the EUBED at rectums was the lowest (3.74 Gy) in the HIPO-optimized plans, and the EUBED at small intestines was non-significantly different among the three types of optimized plans ( P = 0.055). There was no significant difference in the tumor control probability (TCP) predicted using the three types of optimized plans ( P > 0.05). The normal tissue complication probabilities (NTCPs) of bladders and rectums predicted using the HIPO-optimized plans were lower than those predicted using the GO- and IPSA-optimized plans( χ2 = 12.95-38.43, P < 0.01), and the NTCP of small intestines did not show significant differences ( P > 0.05). Conclusions:Among the three types of optimization algorithms, inverse optimization takes less time than GO. GO-optimized plans are more conformal than IPSA- and HIPO-optimized plans. HIPO-optimized plans can increase the biological coverage dose of the target volume and reduce the maximum physical/biological exposure and NTCP at bladders and rectums. Therefore, HIPO is recommended preferentially as an optimization algorithm for IC/ISBT for cervical cancer.

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.
Humans ; Nomograms ; Retrospective Studies ; Carcinoma, Renal Cell/pathology* ; Prognosis ; Risk Factors ; Nephrectomy ; Kidney Neoplasms/pathology* ; Necrosis