OBJECTIVE: To retrospectively analyze the clinical characteristics of 15 children with B-cell acute lymphoblastic leukemia (B-ALL) treated with blinatumomab, and summarize the efficacy and safety of blinatumomab in the treatment of pediatric B-ALL. METHODS: Fifteen children who received treatment with blinatumomab from February 2022 to January 2023 were enrolled in this study. One course (28 days) of blinatumomab concurrent with intrathecal chemotherapy was given according to the standard regimen, except for 2 cases who had shortened course of treatment due to hematopoietic stem cell transplantation (HSCT) and did not receive combined intrathecal chemotherapy, and 1 case had a shortened course of treatment due to economic problems. The efficacy and safety of the treatment were evaluated. RESULTS: In terms of efficacy, for the children who had achieved complete molecular remission (CMR) before treatment, blinatumomab treatment could effectively maintain CMR status; For the children who did not achieve CMR, the CMR rate after one standard course of treatment with blinatumomab reached 66.7%(4/6); For the children with relapsed/refractory ALL (R/R ALL) who had minimal residual disease (MRD), the MRD clearance rate reached 75.0%(3/4). The statistical results of the incidence of adverse events showed that 13.3%(2/15) of the children did not experience any adverse events. The most common adverse events were cytokine release syndrome (CRS) (73.3%, 11/15) and transaminase elevation (26.7%, 4/15); 33.3%(5/15) of the children experienced grade 3 or higher adverse events. All the adverse events were resolved after symptomatic treatment.The level of IgG decreased significantly after 4-7 weeks of treatment with blinatumomab, and gradually recovered after 8 weeks of treatment. CONCLUSION Blinatumomab can be used as a safe and effective treatment for inducing deep remission in pediatric R/R-ALL patients and as a bridge therapy for the pediatric ALL patients who are intolerant to chemotherapy.
Humans ; Antibodies, Bispecific/therapeutic use* ; Child ; Retrospective Studies ; Female ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Remission Induction ; Treatment Outcome ; Child, Preschool ; Adolescent ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

Objective:To compare the characteristics of four commonly adopted animal models of hyperuricemia （HUA） for traditional Chinese medicine （TCM） screening， so as to choose the adequate model for screening Chinese herbs and herbal compounds capable of lowering the uric acid. Method:Fifty-four male SD rats were randomly divided into nine groups， namely the normal group， hypoxanthine （HX） + oxonic acid potassium salt （OAPS） model group， yeast extract （YE） + OAPS model group， low-dose adenine （AD） + ethambutol （EMB） model group， high-dose AD + EMB model group， and four positive drug allopurinol （Allo） groups. The modeling lasted for 14 d. The levels of serum uric acid （SUA）， urinary uric acid （UUA）， serum creatinine （SCr）， urea nitrogen （BUN）， kidney injury molecule 1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL） were detected on the 3rd， 7th， and 14th days. Urine was collected on the 7th and 14th days to investigate changes in urine volume， and the crystals in the residual urine were observed under a polarizing microscope. After the modeling， the kidney was harvested and weighed， followed by pathological examination. Result:The urine volumes in the HX + OAPS model group and high-dose AD + EMB model group were significantly reduced （P<0.05）. The renal indexes of each model group， except for the YE + OAPS model group， were significantly elevated （P<0.05， P<0.01）. The increase in SUA of the HX + OAPS model group and YE + OAPS model group started later （P<0.05）. The KIM-1 and NGAL levels of the HX + OAPS model group rose significantly from the 7th day （P<0.05， P<0.01）， and the BUN increased significantly on the 14th day （P<0.05）. There was no significant difference in the above-mentioned indicators in the YE + OAPS model group. The SUA levels of the low- and high-dose AD + EMB model groups increased significantly on the 3rd day （P<0.05， P<0.01）， with a persistent increase found in the low-dose AD + EMB model group. Besides， the increase in BUN， KIM-1， and NGAL occurred later （P<0.05， P<0.01）. By contrast， the high-dose AD + EMB model group exhibited a transient increase in SUA. Moreover， the SCr， BUN， KIM-1， and NGAL elevation occurred earlier and were more obvious than those in the low-dose AD + EMB model group （P<0.01）. Remarkable histomorphological abnormalities were detected in the kidney of all model groups， except for the YE+OAPS model group， with the most severe injury present in the high-dose AD+EMB model group. Conclusion:The four models commonly used to screen TCM have their own characteristics. In the four models， the SUA elevation in the HX + OAPS model group and YE + OAPS model group started later， with the mild renal injury observed in the HX + OAPS model group instead of the YE + OAPS model group. The SUA of the low-dose AD + EMB model group increased rapidly and lasted for a long time， accompanied by mild renal injury. The SUA of the high-dose AD + EMB model group only showed a transient increase， accompanied by severe renal injury. The investigation on the characteristics and application of different models and the evaluation of these models based on sensitive and objective indicators are helpful for determining the suitable model for the screening of TCM targeting HUA in the future.

OBJECTIVE: To explore the effect of posaconazole in the primary prevention of invasive fungal disease (IFD) in the induction therapy of childhood acute lymphoblastic leukemia (ALL). METHODS: From August 2018 to November 2020, 144 pediatric patients with ALL treated in Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University were selected, 88 cases received fluconazole as IFD prophylaxis (fluconazole prophylaxis group), 56 cases received posaconazole as IFD prophylaxis (posaconazole prophylaxis group). The incidence of IFD and treatment-related adverse reactions between the two groups were compared, and the safety of posaconazole was evaluated. RESULTS: The incidence of IFD in the fluconazole prophylaxis group was 20.4% (18/88), and in the posaconazole prophylaxis group was 7.1% (4/56). The incidence of IFD between the two groups was statistically significant different(P=0.030). There was no serious adverse reactions in the two groups. The incidence of mild adverse reactions in the posaconazole prophylaxis group (23.2%) was lower than that in the fluconazole prophylaxis group(39.8%), and the difference was statistically significant (P=0.039). There were 12 cases died in the fluconazole prophylaxis group and 4 in the posaconazole prophylaxis group, while no significant difference in the overall survival rate between the two groups (P=0.281). CONCLUSION The effect of posaconazole in the primary prophylaxis of IFD is better and incidence of adverse reactions is lower than fluconazole. Posaconazole can be tolerated, and expected to become the first-line primary prophylaxis drug for IFD during the induction remission therapy of childhood ALL.
Antifungal Agents/therapeutic use* ; Child ; Humans ; Induction Chemotherapy ; Mycoses/drug therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Primary Prevention ; Triazoles

Objective:To evaluate the effects of aquatic exercise on lower-limb motor function and activities of daily living for patients with stroke. Methods:The randomized controlled trials (RCTs) about effects of aquatic therapeutic exercise on stroke patients were recalled from the databases of Cochrane Library, PEDro, PubMed, EMBASE, Web of Knowledge, Web of Science, OVID, EBSCO, CMCI, CNKI, Wanfang and VIP. The methodological quality of the included RCTs was evaluated. The data were extracted, and analysed with RevMan 5.3. Results:A total of 23 RCTs that represented 861 participants were evaluated. Compared with the control group, aquatic exercise significantly improved the performance of Berg Balance Scale (WMD = 2.69, 95%CI 1.21 to 4.16,P < 0.001), Timed Up and Go Test (WMD = -1.56, 95%CI -3.07 to -0.05,P < 0.05), Functional Reach Test (WMD = 2.69, 95%CI 1.21 to 4.16,P < 0.001), sway velocity of center of pressure (SVCOP) (left/right) (WMD = -1.38, 95%CI -2.72 to -0.05,P < 0.05), SVCOP (anteroposterior) (WMD = -1.64, 95%CI -3.10 to 　-0.18,P < 0.05), walking speed (SMD = 0.33, 95%CI 0.07 to 0.58,P < 0.05), Two Minute Walk Test (WMD = 12.75, 95%CI 4.17 to 21.34,P < 0.01), Functional Ambulation Category (WMD = 0.94, 95%CI 0.67 to 1.20,P < 0.001), muscle strength of knee extensor (WMD = 4.30, 95%CI 1.53 to 7.07,P < 0.01), muscle strength of knee flexor (WMD = 4.80, 95%CI 0.29 to 9.32,P < 0.05), and Functional Independence Measurement (WMD = 6.12, 95%CI 3.98 to 8.27,P < 0.001), but not significantly in the score of modified Barthel Index (WMD = 2.92, 95%CI -6.74 to 12.58,P = 0.55). Conclusion:Aquatic exercise can improve balance, walking and muscle strength of lower extremities of stroke patients, but do not for activities of daily living.

Objective:To explore the application of mobile medical technology in aquatic rehabilitation assessment for patients with spinal cord injury. Methods:From November, 2017 to April, 2018, 72 patients with spinal cord injury accepted aquatic exercise were randomly divided into control group (n = 36) and experimental group (n = 36). All the patients were assessed with Water Orientation Assessment of Alyn (WOTA), using paper scale for the control group, mobile scale for the experimental group, twice. The time for assessment and for recall was recorded. The accuracy of results and variety between assessment was compared. Results:The time for assessment and for recall was less in the experimental group than in the control group (t > 10.492, P < 0.001), with more accuracy of standard total score, the variety of total score and standard total score (χ² > 4.545, P < 0.05). Conclusion:Compared with the paper-based assessment, the assessment based on mobile technology may improve work efficiency.

BACKGROUND/AIMS: Increasing evidence shows involvement of psychological disorders in functional dyspepsia (FD), but how psychological factors exert their influences upon FD remains largely unclear. The purpose of the present study was to explore the brain-based correlations of psychological factors and FD. METHODS: Based on Fluorine-18-deoxyglucose positron emission tomography-computed tomography, the altered cerebral glycometabolism was investigated in 40 FD patients compared with 20 healthy controls during resting state using statistical parametric mapping software. RESULTS: FD patients exhibited increased glucose metabolism in multiple regions relative to controls (P < 0.001, family-wise error corrected). After controlling for the dyspeptic symptoms, increased aberrations persisted within the insula, anterior cingulate cortex (ACC), middle cingulate cortex (MCC) and middle frontal cortex (midFC), which was related to anxiety and depression score. Interestingly, FD patients without anxiety/depression symptoms also showed increased glycometabolism within the insula, ACC, MCC and midFC. Moreover, FD patients with anxiety/depression symptoms exhibited more significant hypermetabolism within the above 4 sites compared with patients without anxiety/depression symptoms. CONCLUSIONS: Our results suggested that the altered cerebral glycometabolism may be in a vicious cycle of psychological vulnerabilities and increased gastrointestinal symptoms.
Anxiety ; Cerebral Cortex ; Depression ; Dyspepsia* ; Electrons ; Glucose ; Gyrus Cinguli ; Humans ; Metabolism ; Psychology*

The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system, focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system.
Epithelium ; immunology ; Humans ; Immunity, Cellular ; Immunity, Mucosal ; immunology ; Mouth Diseases ; immunology ; Mouth Mucosa ; immunology ; Pharynx ; immunology ; T-Lymphocyte Subsets ; classification ; immunology

OBJECTIVETo explore the protective effects of danshen (Salvia Miltiorrhiza) on vascular endothelial cells in hypertension patients in the gestation period.

METHODSThe umbilical vein endothelial cells pre-incubated with Danshen solution at different concentrations (0, 100, 200, and 300 mg/L) were randomly divided into 3 groups, i.e., the blank control group (8 cases), the normal control group (14 cases, cultured in the serum from 14 normal pregnant women), and the observation group (14 cases, cultured in the serum from 14 pregnant women with severe pre-eclampsia). The levels of nitric oxide (NO) and endothelin-1 (ET-1) in each culture supernatant were detected respectively.

RESULTSThe ET-1 level was higher in 300 mg/L Danshen solution group than in 0 mg/L and 100 mg/L Danshen solution groups (P <0.05). The NO level was lower in the observation group than in the blank control group and the normal control group (P <0. 05). The NO level was higher in 200 mg/L Danshen solution group than in 0 mg/L Danshen solution group (P <0.05). The NO level was higher in 300 mg/L Danshen solution group than in 0 mg/L, 100 mg/L, and 200 mg/L Danshen solution groups (P <0.05).

CONCLUSIONDanshen could increase the secretion of NO from in vitro umbilical vein endothelial cells cultured in the serum from patients with pre-eclampsia, and reduce the secretion of ET-1.

Cells, Cultured ; Culture Media ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; cytology ; drug effects ; secretion ; Endothelin-1 ; metabolism ; Female ; Humans ; Nitric Oxide ; metabolism ; Phenanthrolines ; pharmacology ; Pre-Eclampsia ; blood ; metabolism ; Pregnancy ; Salvia miltiorrhiza ; chemistry ; Serum ; chemistry ; Umbilical Veins ; cytology

OBJECTIVETo explore the effect of Salvia miltiorrhiza monomer IH764-3 on apoptosis in hydrogen peroxide (H2O2)-stimulated hepatic stellate cells (HSCs).

METHODSHSCs were cultured in medium with different IH764-3 doses (10 mg/L, 20 mg/L, 30 mg/L, 40 mg/L) and without IH764-3. Direct cell count, 3H-thymidine incorporation, Annexin-V/Propidium Iodide double-labeled flow cytometry, TUNEL and transmission electron microscopy were employed to estimate the influence of IH764-3 on proliferation and apoptosis of HSCs. The expression of extracellular signal-regulated kinase 1 (ERK1) mRNA and protein in HSCs were detected using RT-PCR and Western blot respectively.

RESULTSIt was showed that H2O2 could promote HSC proliferation. In contrast, IH764-3 at concentrations of 10 mg/L, 20 mg/L, 30 mg/L and 40 mg/L inhibited its proliferation. The inhibition rates were 7.13%, 28.36%, 53.80% and 73.10% (P < 0.01). And the inhibition rates of IH764-3 at concentrations of 30 mg/L at 12 h, 24 h and 48 h were 22.24%, 40.51% and 61.65%. Furthermore, IH764-3 could also induce the HSC apoptosis in dose-dependent an dtime-dependent manners (P < 0.01). In addition, after exposed of HSCs to IH764-3 for 24 h, ERK production decreased and ERK1 mRNA was down-regulated earlier about 2 h after exposure to IH764-3.

CONCLUSIONIH764-3 may inhibit the proliferation and induce apoptosis of HSCs in both dose-dependent and time-dependent manners, which may be related to down-regulation of ERK expression.

Apoptosis ; drug effects ; physiology ; Cell Line ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Hepatic Stellate Cells ; cytology ; Humans ; Hydrogen Peroxide ; pharmacology ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry

BACKGROUNDIt is generally accepted that spleen plays a complex role in the tumor immunity, which would change in the different periods of cancer. In this study, we investigated the changes in the function of splenic macrophage (Mphi) in different stages of liver cancer induced by diethylnitrosamine (DEN) in rats. The aim was to support the characteristics of "two-way" and "phase" of spleen in tumor immunity.

METHODSThe model of pulmonary metastasis of liver cancer was established in forty male SD rats by DEN. In the 8th, 13th and 16th week, 10 rats were randomly chosen and sacrificed, and divided into cirrhosis, liver cancer and pulmonary metastasis groups depending on the pathological result, respectively. The other 10 rats were taken as control group. The Mphi was isolated by anchoring cultivation. The changes in ultrastructure, phagocytosis, cytokine secretion, antigen processing and presenting, and viability of splenic Mphi were detected by transmission electron microscopy, Vybrant(TM) Phagocytosis Assay, DQ(TM) Ovalbumin, and rat TNF-alpha ELISpot kits.

RESULTSUnder the electron microscope, the Mphi in the control group had some pseudopodium-like prominences, and mitochondria, ribosome, rough endoplasmic reticulum, lysosome can be found in the cytoplasm, and phagocytized RBC. In the liver cirrhosis and liver cancer group, Mphi had more prominences, meanwhile much more mitochondria, ribosome, rough endoplasmic reticulum, lysosome can be found in the cytoplasm, especially in the liver cancer group. In the pulmonary metastasis group, the Mphi was swelling, with few organelle. As compared to the control group, the function of splenic Mphi increased in cirrhosis and cancer groups, but decreased in metastasis group (phagocytosis rate: (84.7 +/- 1.9)%, (89.5 +/- 3.1)%, and (36.0 +/- 2.6)% vs (75.6 +/- 1.7)%, P < 0.05, P < 0.01; viability: (1.53 +/- 0.15)%, (1. +/- 0.14)%, and (1.12 +/- 0.29)% vs (1.48 +/- 0.17)%, P < 0.05, P < 0.01; TNF-alpha secretion: (741.0 +/- 52.9)%, (1126.2 +/- 174.5)%, and (313.8 +/- 50.8)% vs (626.6 +/- 24.6)%, P < 0.05, P < 0.01; positive cell rate of antigen processing and presenting: (24.03 +/- 1.87)%, (27.95 +/- 2.63)%, and (10.46 +/- 2.16)% vs (16.45 +/- 1.86)%, P < 0.01).

CONCLUSIONSIn the stage of cirrhosis and early cancer, the immune functions of splenic Mphi were reinforced. It may promote the non-specificity tumor immunity. On opposite, in the stage of pulmonary metastasis, the immune functions of splenic Mphi were impaired. It may lead to the decrease of tumor immunity.

Animals ; Cells, Cultured ; Diethylnitrosamine ; toxicity ; Disease Models, Animal ; Liver Cirrhosis ; immunology ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; complications ; immunology ; ultrastructure ; Lung Neoplasms ; immunology ; secondary ; ultrastructure ; Macrophages ; pathology ; ultrastructure ; Male ; Microscopy, Electron, Transmission ; Rats ; Rats, Sprague-Dawley ; Spleen ; pathology ; ultrastructure