ObjectiveTo investigate the risk factors and construct a predictive model for severe myelosuppression due to chemotherapy in triple negative breast cancer （TNBC）. MethodsPatients with TNBC who received anthracycline combined with cyclophosphamide sequential paclitaxel chemotherapy regimen at the Second Affiliated Hospital of Nanchang University from September 2， 2016 to September 2， 2021 were selected and assigned to severe myelosuppression group and no/mild myelosuppression group. The χ² test and binary logistic regression were used to analyze the risk factors for severe myelosuppression due to chemotherapy and to develop a prediction model. Hosmer-Lemeshow test and receiver operating characteristic （ROC） curve were used to evaluate the predictive efficiency of the regression model. Kappa consistency test was used to verify the regression model externally. ResultsA total of 207 patients who met the inclusion were enrolled and 106 patients （51%） had severe myelosuppression. Binary logistic regression multivariate analysis showed that age 40 to 60 years （OR = 3.463， 95% CI： 1.144 to 10.486， P = 0.028）， age >60 years （OR = 3.474， 95% CI： 1.004 to 12.020， P = 0.049）， body mass index （BMI） 18.5 to 24.0 （OR = 1.445， 95% CI： 0.686 to 3.087， P = 0.328）， BMI <18.5 （OR = 3.582， 95% CI： 1.260 to 10.182， P = 0.017）， tumor TNM stage Ⅱ （OR = 1.698， 95% CI： 0.831 to 3.468， P = 0.146）， tumor TNM stage Ⅲ （OR = 2.943， 95% CI： 1.199 to 7.227， P = 0.019）， previous diabetes （OR = 2.441， 95% CI： 1.076 to 5.539， P = 0.033）， low pre-treatment albumin level （OR = 2.759， 95% CI： 1.141 to 6.669， P = 0.024） and low pre-treatment lymphocytes （OR = 3.428， 95% CI： 1.689 to 6.958， P = 0.001） were independent risk factors for severe myelosuppression due to chemotherapy. The χ² value for the logistic regression model Hosmer-Lemeshow test was 11.507， P= 0.175， the area under the ROC curve was 0.763， standard error 0.033， 95% CI： 0.698-0.828， P=0.000. External validation showed that the prediction model had a specificity of 88% and a sensitivity of 80%； the kappa value was 0.679， standard error 0.081， P=0.000. conclusionThis logistic regression model had high predictive efficacy and is useful for clinicians to predict whether patients with TNBC develop severe myelosuppression.

OBJECTIVE: Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis (AR). However, the results are inconclusive. We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR. METHODS: A total of 2,348 pregnant women from Ma'anshan, Anhui Province, China, who were screened before antenatal visits and met the inclusion criteria, were included in the present study. We assessed AR in their offspring aged 36 months with a questionnaire. Quantitative PCR was performed to measure placental inflammatory factor mRNAs. The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates. RESULTS: Childhood AR may be related to education and family monthly income ( P = 0.01). The phthalate metabolites, mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyl) phthalate (MEHHP), in pregnant women were associated with a significantly increased risk for infant AR in males [ P < 0.05; odds ratio ( OR): 1.285; 95% confidence interval ( CI): 1.037-1.591, and OR: 1.232, 95% CI: 1.008-1.507, respectively], but not females. Additionally, irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants ( OR: 1.175; 95% CI: 1.038-1.329 and OR: 1.181; 95% CI: 1.056-1.322, respectively). The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis. CONCLUSION The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant. Placental HO-1 was a fractional mediator in the associations between MEHHP and AR. Thus, the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.
Biomarkers ; Child, Preschool ; Cohort Studies ; Diethylhexyl Phthalate/analogs & derivatives* ; Female ; Humans ; Interleukin-4/pharmacology* ; Male ; Maternal Exposure/adverse effects* ; Phthalic Acids/adverse effects* ; Placenta ; Pregnancy ; Rhinitis, Allergic/epidemiology*

OBJECTIVE: To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period. METHODS: A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated. RESULTS: After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%. CONCLUSION The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.
Acupuncture Points ; Acupuncture Therapy ; COVID-19/therapy* ; Humans ; Lung ; Vascular Surgical Procedures

Objective: To investigate risk factors for the long-term prognosis of primary focal segmental glomerulosclerosis (FSGS) and associated with renal prognosis in children. Methods: A retrospective study was conducted by collecting clinical data including general information, clinical features and renal pathological findings of 124 children with primary FSGS in Department of Pediatrics of Jinling Hospital from January 2003 to December 2019. The cumulative renal survival rate was calculated by Kaplan-Meier survival analysis. The risk factors related to renal prognosis were identified by Cox regression risk model analysis and receiver operating characteristic (ROC) curve. Results: Among 124 children, 94 were males (75.8%) and 30 were females (24.2%). The children were 16 (14, 17) years of age at the time of kidney biopsies. There were 102 cases (82.3%) aged from 13 to 18 years. The period of follow-up was 64.8 (32.1, 86.0) months. There were 49 cases (39.5%) with nonspecific variant, 33 cases (26.6%) with tip variant, 22 cases (17.7%) with collapsing variant, 14 cases (11.3%) with cellular variant and 6 cases (4.8%) with periportal variant. The data of Kaplan-Meier survival analysis showed that cumulative renal survival rates of end-stage kidney disease (ESKD) or ≥50% decline in estimated glomerular filtration rate (eGFR) from baseline at the year of 5, 10 and 15 after renal biopsies were 66.9%, 51.4% and 21.0% respectively. Multivariate Cox regression analysis showed that hypertension, glomerular segmental sclerosis ratio, moderate to severe chronic tubulointerstitial lesions were independent risk factors for progressing to ESKD or ≥50% reduction in eGFR from baseline in pediatric FSGS (HR=5.28, 1.03, 7.81, 95%CI 2.77-10.05, 1.01-1.04, 4.08-14.98, all P<0.01). ROC curve analysis showed glomerular segmental sclerosis ratio (AUC=0.734, P<0.05, optimal cut-off value=25.4%, sensitivity=50.0%, specificity=88.6%), moderate and severe chronic renal tubulointerstitial lesions (AUC=0.724, P<0.05, sensitivity=46.3%, specificity=98.6%) had good efficacy in evaluating renal outcomes of FSGS. Conclusions: The long-term prognosis of FSGS in children is poor. The risk factors of poor prognosis in children with FSGS are hypertension, moderate to severe chronic renal tubulointerstitial lesions and glomerular segmental sclerosis (≥25.4%).
Adolescent ; Child ; Female ; Glomerulosclerosis, Focal Segmental/complications* ; Humans ; Hypertension ; Kidney Failure, Chronic/etiology* ; Male ; Prognosis ; Retrospective Studies ; Sclerosis

Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) manipulation for pediatric adenoid hypertrophy (AH). Methods: A total of 60 children with AH were randomized into an observation group and a medication group, with 30 cases in each group. The observation group was treated with pediatric Tuina treatment, and the medication group was treated with 0.05％ mometasone furoate nasal spray. The changes of main clinical symptom score, quality of life (QOL) score and X-ray nasopharynx lateral film were observed, and the clinical efficacy was evaluated. Results: The total effective rate of the observation group was 90.0％, and that of the medication group was 66.7％. The difference between the two groups was statistically significant (P<0.05). After treatment, the A/N value [ratio of adenoid thickness (A) and nasopharyngeal cavity width (N)] of posterior nasopharyngeal lateral film did not show significant change in either group (P>0.05). After treatment, the clinical symptom scores in both groups decreased, and the intra-group differences were statistically significant (P<0.001), but there was no statistical difference between the two groups (P>0.05). After treatment, the QOL scores of children in both groups decreased, and the intra-group differences were statistically significant (P<0.001), and the difference between the two groups was statistically significant (P<0.001). Conclusion: Tuina manipulation is effective in treating pediatric AH, and produces a better effect in improving traditional Chinese medicine symptoms and QOL than 0.05％ mometasone furoate nasal spray.

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

BACKGROUND: The low accuracy of equations predicting 24-h urinary sodium excretion using a single spot urine sample contributed to the misclassification of individual sodium intake levels. The application of single spot urine sample is limited by a lack of representativity of urinary sodium excretion, possibly due to the circadian rhythm in urinary excretion. This study aimed to explore the circadian rhythm, characteristics, and parameters in a healthy young adult Chinese population as a theoretical foundation for developing new approaches. METHODS: Eighty-five participants (mean age 32.4 years) completed the 24-h urine collection by successively collecting each of the single-voided specimens within 24 h. The concentrations of the urinary sodium, potassium, and creatinine for each voided specimen were measured. Cosinor analysis was applied to explore the circadian rhythm of the urinary sodium, potassium, and creatinine excretion. The excretion per hour was computed for analyzing the change over time with repeated-measures analysis of variance and a cubic spline model. RESULTS: The metabolism of urinary sodium, potassium, and creatinine showed different patterns of circadian rhythm, although the urinary sodium excretion showed non-significant parameters in the cosinor model. A significant circadian rhythm of urinary creatinine excretion was observed, while the circadian rhythm of sodium was less significant than that of potassium. The circadian rhythm of urinary sodium and creatinine excretion showed synchronization to some extent, which had a nocturnal peak and fell to the lowest around noon to afternoon. In contrast, the peak of potassium was observed in the morning and dropped to the lowest point in the evening. The hourly urinary excretion followed a similar circadian rhythm. CONCLUSION It is necessary to consider the circadian rhythm of urinary sodium, potassium, and creatinine excretion in adults while exploring the estimation model for 24-h urinary sodium excretion using spot urine.
Adult ; China ; Circadian Rhythm ; Creatinine ; Humans ; Potassium ; Sodium ; Urine Specimen Collection ; Young Adult

OBJECTIVE: To compare the therapeutic effect of electroacupuncture (EA) combined with donepezil hydrochloride and donepezil hydrochloride alone on improving learning-memory ability in patients with Alzheimer's disease (AD), and to explore its action mechanism. METHODS: Sixty patients of AD were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the observation group were treated with EA at governor vessel (GV) combined with donepezil hydrochloride. EA was applied at Baihui (GV 20) and Fengfu (GV 16) with dilatational wave (10 Hz/50 Hz of frequency, 0.5 to 5.0 mA of intensity), and the needles were kept for 40 min, EA was given once a day; the donepezil hydrochloride tablet was taken orally, 5 mg, once a day, and after 4 weeks the dosage might be increased to 10 mg per day according to the specific situation. All the treatment was given for 8 weeks. The patients in the control group were only treated with donepezil hydrochloride with the identical procedure as the observation group. The Montreal cognitive assessment (MoCA) and Alzheimer's disease assessment scale cognitive part (ADAS-Cog) were evaluated before and after treatment; P300 (latency and amplitude of N2 and P3) was detected by EEG/ERP system brain event related potential instrument, and amyloid precursor protein (APP) and β-amyloid protein 1-42 (Aβ) were detected by ELISA. RESULTS: Compared before treatment, the MoCA scores were increased after treatment in the two groups (<0.05), and the MoCA score in the observation group was higher than that in the control group (<0.05). Compared before treatment, the ADAS-Cog scores were decreased after treatment in the two groups (<0.05), and the ADAS-Cog score in the observation group was lower than that in the control group (<0.05). Compared before treatment, the latency of N2 and P3 was shortened and the amplitude was increased after treatment in the two groups (<0.05); after treatment, the latency of N2 and P3 in the observation group was shorter than that in the control group and the amplitude was higher than that in the control group (<0.05). Compared before treatment, the serum levels of APP and Aβ were lower after treatment in the two groups (<0.05), and the serum levels of APP and Aβ in the observation group were lower than those in the control group (<0.05). CONCLUSION EA at Baihui (GV 20) and Fengfu (GV 6) combined with donepezil hydrochloride can effectively reduce the serum levels of APP and Aβ and improve the scores of MoCA and ADAS-Cog and the levels of N2 and P3 of P300 in AD patients, which has superior effect to donepezil hydrochloride alone in improving the learning-memory of AD patients.
Alzheimer Disease ; blood ; therapy ; Amyloid beta-Peptides ; blood ; Amyloid beta-Protein Precursor ; blood ; Cognition ; Donepezil ; therapeutic use ; Electroacupuncture ; Humans ; Learning ; Memory ; Peptide Fragments ; blood

BACKGROUND: Total and differential white blood cell counts are important for the diagnostic evaluation of suspected diseases. To facilitate the interpretation of total and differential white blood cell counts in pediatric patients, the present study investigated age-dependent changes in total and differential white blood cell counts in healthy reference children. METHODS: Data were obtained from the Pediatric Reference Intervals in China study (PRINCE), which aims to establish and verify pediatric reference intervals for Chinese children based on a nationwide multicenter cross-sectional study from January 2017 to December 2018. Quantile curves were calculated using the generalized additive models for location, shape, and scale method. The 2.5th, 50th, and 97.5th quantile curves were calculated for both total and differential white blood counts. Percents of stacked area charts were used to demonstrate the proportions of differential white blood cells. All statistical analyses were performed using R software. RESULTS: Both 50th and 97.5th quantiles of total white blood cell count and monocyte count were highest at birth, then rapidly decreased in the first 6 months of life; relatively slow reduction continued until 2 years of age. The lymphocyte count was low during infancy and increased to its highest level at 6 months of age; it then exhibited moderate and continuous reduction until approximately 9 years of age. The pattern of neutrophil count changed with age in a manner opposite to that of lymphocyte count. Besides, there were two inter-sections of lymphocyte count and neutrophil count during infancy and at approximately 5 years of age, based on locally weighted regression (LOESS) analysis. There were no apparent age-related changes in eosinophil or basophil counts. CONCLUSION These data regarding age-related changes in total and differential white blood cell counts can be used to assess the health of pediatric patients and guide clinical decisions.