OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
Caspofungin/therapeutic use* ; Child ; Child, Preschool ; Dyspnea ; Female ; Humans ; Male ; Pneumonia, Pneumocystis/therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Respiratory Sounds ; Retrospective Studies

OBJECTIVE: To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC. METHODS: 17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs. RESULTS: The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 10/kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P＞0.05). CONCLUSION The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.

OBJECTIVE: To investigate the clinical characteristics, prevention and treatment of invasive fungal disease (IFD). METHODS: The clinical data of 164 patients who met the diagnostic criteria of IFD in our center from January 2012 to January 2015 were retrospectively analyzed. The incidence, clinical characteristics, related factors, treatment methods and prognosis were analyzed. RESULTS: Among 1289 cases of blood diseases, 164 cases suffered from IFD with inciduce of 12.7%. The main infection sites were as followed: lung, blood and gastrointestinal tract, with incidence of 84.2%, 5.5% and 3% respectively. The funge was found in 35 cases by detection; among fungi, the detected rate of candida albicans. aspergillus and candida glabrata was more high with 51.5%, 20% and 14.3% respectively. Among 164 childen with blood deseases complicated by IFD, 36 cases gained complete remission, 97 cases gained partial remission, 10 cases were stable, 11 cases were progressive and 10 cases died, the overall effective rate reached 81.1%. The univariate analysis showed that the gramulopenia, granulocyte recovery, long-term use of corticosteroid and immuno-suppressive agents, as well as different grades of diagnosis were significant factors affecting the efficacy of antifungal therapy for blood disease children with IFD, the multivariate analysis further showed that the granulocyte recovery and diagnosis grades were independent prognostic factors affecting the therapeutic efficacy for IFD children. The overall survival rate of IFD children with 12 weeks of antifungal treatnment was 81.7%, out of which the survival rate of IFD children at 12 weeks of treatment with itraconazole, voriconazole, amphotericin B and caspofungin was 81.4%, 80%, 69.4% and 97.1% respectively, there were significant differences in survival rate between each other by long rank test. In addition of caspofungin, the other 3 kinds of drugs had toxic side effects of different degrees, but IFD children could tolerated these effects after symptomatic treatment. CONCLUSION The incidence of IFD in children with blood deseases in our hospital is 12.7%, the lung is most common infective site, moreover patogens of IFD mainly is candida. The promotion of granulocyte recovery and early stratified diagnosis can contribule to the treatment of IFD. For the IFD children with better economic condition, the caspofungin is a potent antifungal agent with high efficacy, low toxicity and better prognosis.
Amphotericin B ; Antifungal Agents ; Child ; Hematologic Diseases ; etiology ; Humans ; Invasive Fungal Infections ; complications ; Retrospective Studies

OBJECTIVETo prospectively study the correlation BKV with the occurrence and development of late onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT).

METHODSThe clinical data of a total of 276 patients with allo-HSCT in our department between January 1998 and March 2016 were analyzed ratrospectvely. Quantitative Real-time PCR assay was used to prospectively monitor the BKV DNA load of the urine and plasma for 23 patients accepting allo-HSCT from August 2015 to March 2016.

RESULTSLOHC(24.28%) occurred in 67 of 276 cases with allo-HSCT. Univariate analysis showed that age older than 6 years, different diseases, unrelated donor, pretreatment with BU, Ⅲ-Ⅳ aGVHD significantly correlated with LOHC. Multivariate analysis demonstrated that age older than 6 years (P<0.01), pretreatment with BU(P<0.05), and aGVHD of grade Ⅲ-Ⅳ （P= 0.011） were the independent risk factors for LOHC. Among 23 patients after allo-HSTC, 10 of which were positive of urine BKV, and LOHC occurred in 6 cases. The positive rate of urine BKV (85.7%)in group LOHC was significantly higher than that in the group LOHC(25.0%）(χ=5.043, P<0.01). The incidence of LOHC positively correlated with the positive rate of BKV (r=0.564, P<0.01), and the severity of LOHC positively correlated with urinary BKV load (r = 0.502, P<0.01). And 5 of 6 petriatic patients with LOHC had aGVHD. All of them were subject to the strengthened antiviral treatment, and 4 of them accepted intensive immunosuppression therapy.

CONCLUSIONAge ≥6 years old, precenditioning regieme with BU and aGVHD of grade Ⅲ-Ⅳ are independent risk factors for LOHC after allo-HSCT, the positive rate of urine BKV load positively correlates with the severity of LOHC after allo-HSCT.

Child ; Cystitis ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hemorrhage ; Humans ; Incidence ; Risk Factors ; Transplantation, Homologous

OBJECTIVETo study the curative effect and safety of menchymal stem cell infusion in treatment of children with refractory late-onset hemorrhagic cystitis(LOHC) after allogeneic HSCT.

METHODSThirty cases of children with refractory LOHC after allo-HSCT in our department between December 2010 and July 2016 were analyzed retrospectively, out of 30 cases 7 received MSC treatment. The used MSC of all were four-to-five generation MSC from bone marrows of third party donors, and were infused into patients with (1.87±0.456)×10/kg MSCs once a week (1-4 times in total) until the hematuria and odynuria symptoms being improved. To observe whether unfavorable reactions occurred after MSC treatment, the patients accepted daily physical examination and regular assistant examination. The cytokine levels were also measured and dynamically detected in 2 cases before and after MSC treatment.

RESULTSIn 30 children with refractory LOHC, the hematuria difficultly reached the remission after routine hydration, alkalizing and antiviral therapy, Among 25 cases who were received methylprednisolone, MTX and CTX therapy, 7 cases received MSC infusion for 1-4 times with dose of (1.87±0.456)×10/(kg·time) as a result, 7 cases of LOHC were cured. The TNF-α and IL-2R levels in 2 cases progressively decreased after MSC infusion, no occurence of fever, rash, embolism and so on were found in 7 cases received MSC infusion; the BKV detection showed that the viral load did not increase; the leukemia relapse or secondary cancer did not occure.

CONCLUSIONThe MSC treatment is safe and effective for refractory LOHC after allo-HSCT.

Child ; Cystitis ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Mesenchymal Stem Cell Transplantation ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo investigate the efficacy and safety of NOPHO-AML 2004 chemotherapy regimen for treatment of children with acute myelocytic leukemia(non-M3).

METHODSThirty-three patients aged 1-13 with acute myelocytic leukemia (non-M3) were diagnosed from January 2013 to June 2017. FAB typing showed that 1 case in M0, 4 cases in M1, 12 cases in M2, 5 cases in M4, 8 cases in M5, 1 case in M6, and 2 cases in M7; Risk stratification showed that: 19 cases in standard risk, and 14 cases in high risk. All patients were treated with NOPHO-AML 2004 chemotherapy regimen. SPSS 22.0 software was used, the Kaplan-Meier survival analysis method and Cox regression model were used for statistical analysis.

RESULTSIn the first course of treatment (AIET), among 33 child patients there were 27 cases with complete remission, and 5 cases with non-remission, thus the remission rate was 81.8%. Out of the 5 child patients without remission, 4 cases reached to the complete remission after the second course (AM), and 1 case did not remission, thus the total remission rate was 96.9%.9 cases (27.3%) underwent bone marrow recurrence and the median recurrence time was 30 months after complete continuous remission. Univariate analysis showed that age and erythrocyte transfusion frequency were significant factors to affect the early treatment response; the multiple Cox regression analysis showed that: age >7, MRD positive, erythrocyte transfusion >4 times and poor response to early treatment were independent risk factors for recurrence; Allogeneic hematopoietic stem cell transplantation(HSCT) in 8 high-risk children received enhanced chemotherapy had better efficacy as compared with the chemotherapy alone. The 3-year event-free survival rate was 59.9%, and 3-year overall survival rate was 69.2%. 33 children patients experienced varying degrees of infection and myelosuppression, or drug-related gastrointestinal reactions and allergic reactions, patients were tolerable to these side reactions after active symptomatic treatment.

CONCLUSIONNOPHO-AML 2004 chemotherapy regimen has high response rate and good tolerance, early treatment response is an important factor influencing prognosis. Age and repeated red blood cell infusions are the important factors influencing the prognosis, which promote bone marrow recurrence in AML children. For the children suffered from clinical high-risk AML, the NOPHO-AML 2004 chemotherapy regimen combined with HSCT can improve the prognosis of patients.

Adolescent ; Child ; Child, Preschool ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Leukemia, Myeloid, Acute ; Prognosis ; Remission Induction ; Treatment Outcome

OBJECTIVE: To analyze the clinical features and prognosis of 28 children with myelodysplastic syndrome (MDS) and to screen the high risk factors affecting the prognosis so as to provide the new ideas for standard of clinical diagnosis and therapy. METHODS: The clinical data of 28 children with newly diagnosed MDS treated in our hospital from March 1994 to July 2016 were analyzed retrospectively, the features of disease onset and the results of laboratory examination were summarized, all MDS children were followed up, the prognosis and the high risk factors affecting the prognosis were evaluated. RESULTS: In all 28 MDS children, the ratio of male to female was 1.8∶1, the incidence of MDS was observed in boys, while the low incidence of MDS was found in older children. The clinical manifestations were mainly the decrease of three series blood cells in 16 cases (57.14%), other cases presented simple anemia (7.1%), simple thrombocytopenia (7.1%), neutropenia with anemia (14.29%), and anemia with thrombocytopenia (14.28%).The bone marrow image showed mainly hyperplasia (82.14%), and the pathological hematopoiesis, moreover the manifistation of pathological hematopoiesis was different in forma and degree; the bone marrow biopsy showed the typical abnormal localization of immature precursor(ALIP) accepted for 33.33%; the chromosome karyotype detection showed the detected rate of chronosome abnormality was 41.18%. The median follow-up time was 1.75 years. 5 children with MDS received the hematopoietic stem cell transplantation (HSCT), among them 1 dead and 4 maintained CCR; Out of other 23 patients no-received HSCT, 7 cases given up treatment after confirmed diagnosis, 16 cases received the chemotherapy (2 cases given up treatment after CR, 5 cases transformed into AML, 3 cases relapsed, 3 cases maintained CCR), 11 cases dead, 9 cases failed to be followed up. The 5-years OS rate and EFS rate in all patients were predicted as (38.2±11.3)% and (35.3±11.3)%,respectively, among them, the OS and EFS rates of patients received the HSCT allo superior to those of patients did not received HSCT ［(80.0±17.9）% vs.(22.8±11.5）%］ (P<0.05) and ［(80.0±17.9)% vs (17.5±11.1)%］(P<0.05). Analysis showed that in addition to receiving the HSCT(P<0.05), platelet decrease in peripheral blood(P<0.01), the age, sex, existance of micromegakaryocytes in bone marrow and progressive MDS or no influenced not on the prognosis(P>0.05). CONCLUSION The children MDS is rare and easy to be misdiagnosis, moreover displays more high heterogeneity and poor prognosis, thereby the early diagnosis is crucial, in addition, the system of prognosis evaluation is imperative to be perfected. The HSCT may be the effective method for curative treatment of childhood MDS.
Child ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Karyotyping ; Male ; Myelodysplastic Syndromes ; Prognosis ; Retrospective Studies

Objective To investigate the clinical effectiveness of disease-syndrome combination therapy for anovulatory infertility through randomized controlled trial, thus to provide high-level evidence-based medical reference for the diagnosis and treatment of WHO typeⅡovulation disorder infertility. Methods Eighty-six patients with WHO typeⅡovulation disorder infertility were randomized into treatment group and control group , 43 cases in each group. Both groups were given the treatment for correcting endocrinic disorder if necessary. Additionally, by following the principle of combination of disease differentiation and syndrome differentiation , Zhuyun Recipe 1, Zhuyun Recipe 2, and Zhuyun Recipe 3 were separately given orally to the patients with kidney-yang deficiency (WHO type Ⅱ ovulation disorder without PCOS), patients with liver-kidney insufficiency(WHO typeⅡovulation disorder complicated with hyperandrogenitic lean-PCOS),and patients with kidney-deficiency complicated with phl egm-dampness (WHO type Ⅱ ovulation disorder complicated with insulin-resistant obesity-PCOS) in the treatment group respectively. The patients in the control group was given oral use of the first-rate ovulation induction drug Clomiphene. The treatment covered 3 menstruation cycles. Ovulation rate,pregnancy rate and alive fetus rate were used as the indicators for evaluating the effectiveness,and the safety was also monitored. Results(1)Of the 86 cases,5 cases dropped out(loss to follow-up or being excluded),with the drop-out rate being 6%. Of the 5 drop-out cases,3 were from the control group,and 2 were from the treatment group. (2)Ovulation rate of the treatment group was 70.7%,and that of the control group was 85.0%. The ovulation rate of the two groups was enhanced,but the difference between the two groups was insignificant(P > 0.05).(3)Pregnancy rate of the treatment group was 51.2%,and that of the control group was 30.0%, the differen ce being significant between the two groups(P < 0.05).(4)Alive fetus rate of the treatment group was 45.2%,and that of the control group was 22.5%,the difference being significant between the two groups(P < 0.05).(5)No adverse reaction was found in the two groups during the treatment. Conclusion The disease-syndrome combination therapy for WHO type Ⅱanovulatory infertility shows the advantages of higher pregnancy rate and alive fetus rate, which makes up for the disadvantages of low pregnancy rate and high abortion rate of Clomiphene.

Objective To apply barcode technology to the patient information management in the hyperbaric medicine unit to sim plify the workflow of outpatient registration and facilitate access to patient's information.Methods The barcode designed by some hospital and its use were introduced,and then compared with the traditional way on time consuming,patient satisfaction and etc.Results Barcode technology enhanced the nurse's efficiency and the patient's satisfaction.Conclusion Barcode technology simplifies the working flow in the hyperbaric oxygen outpatient,increases medical service quality,decreases medical disputes and meets the requirements for appointment treatment,and thus is worthy promoting practically.

OBJECTIVEThe aim of this study is to investigate hepatic and renal toxicity of acrylamide (ACR) , the antagonistic effect and possible mechanism of N-acetylcysteine (NAC) on the toxicity.

METHODSForty female SD rats were randomly divided into four groups. All the rats were administrated by intraperitoneal(i.p.) injection and 1.5 hours later by gavage. The control group was administrated with 0.9% NaCl by i.p. injection and gavaged with 0.9% NaCl. The NAC group was administrated with 200 mg/kg NAC by injection and gavaged with 0.9% NaCl. The ACR group was administrated with 0.9% NaCl by injection and gavaged with 40 mg/kg ACR. The combined treatment group was administrated with 200 mg/kg NAC by i.p. injection and gavaged with 40 mg/kg ACR. The rats were administrated once a day for 2 weeks. After 24 hours of the last administration, the rats were decapitated. The blood was collected, the liver and kidney were separated. The body weight, organ coefficient and serum biochemical parameters were measured, and the pathological changes of the tissues were examined with a microscope. Then the expression of NF-κB p65, IκB-α and COX-2 were detected by Western blot.

RESULTSFrom the second day to the end of the exposure, the body weight of rats in the ACR group was statistically lower than that in the control group (P<0.05) . Compared with the combined treatment group, the body weight in the ACR group statistically decreased in the second and third days (P < 0.05) . The liver and kidney organ coefficients in the ACR group were (4.159%±.371%) and (0.764%±0.068%) respectively, which increased statistically when compared with the control group (P < 0.05) . The contents of ALT, AST and Cr in the serum in the ACR group were (77.370±16.397) U/L、(379.410±57.817) U/L and (77.812±6.391) μmol/L respectively, which were not significantly different with those in the control group and the combined treatment group (P>0.05) . The content of BUN in the serum in the ACR group was (7.005±1.009) mmol/L, which was statistically higher than that in the control group (P<0.05) . Histopathology results showed unclear boundary and nucleus pyknosis in hepatocytes, loose and disordered structures of hepatic cords in the ACR group, but no obvious pathology changes were observed in the kidneys of each group. In the Western blot results, the expression of nuclear NF-κB p65 and COX-2 in the liver in the ACR group was statistically higher than that in the control group and the combined treatment group (P<0.05) , and the expression of IκB-α in the liver in the ACR group statistically decreased compared with the control group and the combined treatment group (P<0.05) . The expression of total NF-κB p65 in the liver in the ACR group was statistically higher than that in the control group (P<0.05) .

CONCLUSIONUnder the conditions of this experiment, ACR may induce hepatic toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the hepatic toxicity of ACR by inhibiting the NF-κB signaling pathway, whereas the toxic effect of ACR on kidney needs to be further studied.

Acetylcysteine ; pharmacology ; Acrylamide ; toxicity ; Animals ; Cyclooxygenase 2 ; metabolism ; Female ; I-kappa B Proteins ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; NF-KappaB Inhibitor alpha ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transcription Factor RelA ; metabolism