Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

Objective:To evaluate the effects of fine particle matter(PM2.5)and ozone(O3)com-bined exposure on adenosine triphosphate(ATP)amount and ATPase activities in nasal mucosa of Spra-gue Dawley(SD)rats.Methods:Twenty male SD rats were divided into control group(n=10)and exposure group(n=10)by random number table method.The rats were fed in the conventional clean environment and the air pollutant exposure system established by our team,respectively,and exposed for 208 d.During the exposure period,the concentrations of PM2 5 and O3 in the exposure system were moni-tored,and a comprehensive assessment of PM2 5 and O3 in the exposure system was conducted by combi-ning self-measurement and site data.On the 208 d of exposure,the core,liver,spleen,kidney,testis and other major organs and nasal mucosal tissues of the rats were harvested.Each organ was weighed and the organ coefficient calculated.The total amount of ATP was measured by bioluminescence,and the ac-tivities of Na+-K+-ATPase and Ca2+-ATPase were detected by spectrophotometry.The t test of two inde-pendent samples was used to compare the differences among the indicator groups.Results:From the 3rd week to the end of exposure duration,the body weight of the rats in the exposure group was higher than that in the control group(P＜0.05),and there was no significant difference in organ coefficients be-tween the two groups.The average daily PM2 5 concentration in the exposure group was(30.68±19.23)μg/m3,and the maximum 8 h ozone concentration(O3-8 h)was(82.45±35.81)μg/m3.The chemi-luminescence value(792.4±274.1)IU/L of ATP in nasal mucosa of the rats in the exposure group was lower than that in the control group(1 126.8±218.1)IU/L.The Na+-K+-ATPase activity(1.53±0.85)U/mg in nasal mucosa of the rats in the exposure group was lower than that in the control group(4.31±1.60)U/mg(P＜0.05).The protein content of nasal mucosa in the control group and the exposure group were(302.14±52.51)mg/L and(234.58±53.49)mg/L,respectively,and the ac-tivity of Ca2+-ATPase was(0.81±0.27)U/mg and(0.99±0.73)U/mg,respectively.There was no significant difference between the groups.Conclusion:The ability of power capacity decreased in the rat nasal mucossa under the sub-chronic low-concentration exposure of PM2 5 and O3.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Objective:To investigate the effect of pre-treatment plasma Epstein-Barr virus(EBV)DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).Methods:The clinical characteristics,survival rate,and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study.Patients were divided into three groups,including the EBV DNA-negative group(＜5.0 × 102 copies/ml),lower EBV-DNA loads group(5.0 × 102-8.51 × 104 copies/ml),and higher EBV-DNA loads group(＞8.51 × 104 copies/ml),according to pre-treatment plasma EBV-DNA copy number.Cox regression model was established for screening prognostic factors.Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index(C-index)and calibration curves were calculated to verify model predictive and discriminatory capacity.Results:Among 171 adult sHLH patients,84 patients were not infected with EBV(EBV DNA-negative group),and 87 with EBV(EBV DNA-positive group,48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group).Consistent elevations in the levels of liver enzymes(ALT and AST),LDH,TG,β2-microglobulin and ferritin across the increasing of EBV-DNA load(all P＜0.05),while the levels of fibrinogen decrease(P＜0.001).The median follow-up time was 52 days(range 20-230 days),and 123 patients died.The overall survival(OS)rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group(median OS:40 days vs 118 days,P＜0.001).Higher EBV-DNA loads had worse OS(median OS:24 days vs 45 days vs 118 days,P＜0.0001 for trend)compared to lower EBV-DNA loads and EBV DNA-negative group.Multivariate Cox analysis revealed that higher EBV-DNA loads(P=0.005),fibrinogen≤ 1.5 g/L(P=0.012),ferritin(P=0.041),associated lymphoma(P=0.002),and anti-tumor based strategy(P=0.001)were independent prognostic factors for OS.The C-indexes of 30 day,90 days,365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability.Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women,ferritin＞5 000 μg/L,β2-microglobulin＞7.4 mmol/L and regardless of age,etiologies,HScore points.Conclusion:The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH.The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.

Aim To explore the differences in sedative and hypnotic effects of Semen Ziziphi Spinosae(SZS)before and after processing based on network pharma-cology and animal experiments.Methods The chemi-cal components and corresponding targets of SZS were collected through relevant platforms and databases,the insomnia and sleep disorder targets were retrieved,and the intersection targets of drugs and diseases were ob-tained.The protein interaction relationships were con-structed,and the Chinese medicinal herb-component-target-pathway network was drawn.Then database was used to analyze pathway enrichment.Based on the pre-dicted results,the effects of different SZS products on Kunming mice were evaluated through pentobarbital in-duced sleep test,behavioral analysis,brain tissue relat-ed gene mRNA levels,and plasma neurotransmitters.Results The target genes related to SZS and insomnia were acetylcholinesterase(ACHE),alpha-1B adrener-gic receptor(ADRA1B),solute carrier family 6(neu-rotransmitter transporter,serotonin),member 4(SLC6 A4),which might play a role through 9 related pathways and 69 biological processes such as calcium signaling pathway,salivary secretion,and so on.In vi-vo experiments found that SZS could reduce mouse ac-tivity,enhance the hypnotic effect of pentobarbital sodi-um,lower the levels of ACEE,ADRA1B,and SLC6A4 mRNA in cortex and hippocampus,and regulate the levels of acetylcholine,adrenaline,and other substances in plasma,all of which could be used in combination with raw and fried methods.The effect was proportion-al to the dosage of the drug.Conclusions SZS has sedative and hypnotic effects,and high doses of crude and parched SZS combined decoction have better effects.This effect may be caused by affecting the lev-els of neurotransmitters and their related receptors,me-diating the central nervous system.

This study systematically retrieved the clinical studies in the treatment of idiopathic pulmonary fibrosis(IPF) with traditional Chinese medicine(TCM) and employed evidence mapping to summarize the overall research status and deficiencies of TCM in treating IPF. CNKI, VIP, SinoMed, Wanfang, PubMed, Web of Science, Cochrane Library, and EMbase were searched for the relevant studies published from inception to February 20, 2024. The distribution characteristics of the evidence were analyzed and presented through charts combined with words. A total of 323 studies were included, including 295 randomized controlled trials(RCTs) and 28 Meta-analysis. The number of publications in this field rose with fluctuations, yet the proportion of core papers was low, and the research lacked the attention of foreign researchers. There were scant cross-regional collaboration between researchers and insufficient attention from relevant departments. The included RCT generally had low quality, with small sample sizes, short treatment courses, and insufficient attention to acute exacerbation and complications of IPF. In addition, few studies employed TCM alone, and the TCM syndromes remained to be standardized. A considerable number of outcome indicators were involved in the publications, while the majority of them failed to emphasize the disparity between primary and secondary outcome indicators. There were diverse reference standards for the comprehensive indicators among the outcome indicators, and insufficient attention was paid to long-term prognosis and health economic indicators. The included Meta-analysis concluded that TCM had potential clinical efficacy in treating IPF. However, the methodological credibility grading and the GRADE grading results of outcome indicators were low. The results suggested that TCM demonstrated certain advantages in the treatment of IPF, while the quality of the included studies was not high. In the future, clinical research protocols should be standardized and registered. Multicenter, large-sample, and follow-up clinical studies should be conducted. The research reports should refer to relevant reporting standards to improve the quality and generate high-level evidence, thus providing a reference for the clinical application of TCM in the treatment of IPF.
Humans ; Idiopathic Pulmonary Fibrosis/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

Chinese patent medicines(CPMs) are unique therapeutic drugs in China. Establishing and improving the evaluation criteria is an important measure to promote the high-quality development of CPMs. Based on the "evaluation criteria of high-grade CPMs with quality as the core index" established by our group in 2018, the "high-quality evaluation criteria for CPMs based on whole process control" was proposed in the present study in 2022. The scope of application and basic principles of the new criteria were clarified. A quality evaluation scoring table was established in the new criteria, including five parts: raw material selection, production process, quality control, efficacy evaluation, and brand building. The technical evaluation indexes involved have increased from 20% in the original criteria to 70% in the new criteria, and efficacy evaluation has been added in the new criteria. The subjective evaluation indicators account for a large proportion in the original criteria, which is prone to bias. The improved criteria overcome this shortcoming. It is expected that the new criteria as a basis can play a better role in the selection of high-quality products of CPMs, guide enterprises and institutions to participate actively in the evaluation and research of high-quality CPMs, and promote the high-quality development of CPMs.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Nonprescription Drugs ; Chlorobenzenes ; China

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Anemia, Iron-Deficiency/epidemiology* ; Sucrose/therapeutic use* ; Ferric Compounds/therapeutic use* ; Retrospective Studies ; Iron/therapeutic use* ; Hemoglobins/therapeutic use*