Objective: To study the influence of steroid withdrawal protection strategy on height growth in pediatric patients after kidney transplantation. Methods: The prospective cohort study enrolled 40 stage 5 chronic kidney disease children receiving kidney transplantation from July 2017 to September 2022 at Guangzhou Women and Children's Medical Center. Based on the primary preoperative disease, patients with immune abnormality-associated glomerular diseases or unknown causes were assigned to the steroid maintenance group, in which patients received steroid tapering within 3 months after surgery to a maintenance dose of 2.5 to 5.0 mg/d. While patients with hereditary kidney disease or congenital urinary malformations were assigned to the steroid withdrawal group, in which patients had steroids tapered off within 3 months. The characteristics of height catch-up growth and clinical data were compared between the 2 groups at baseline, 6, 12, 18 and 24 months after kidney transplantation. T-test, repeated measurement of variance analysis, Mann-Whitney U test, and Fisher exact test were used for the comparison between the 2 groups. Results: Among the 40 children, 17 were males, 23 were females, 25 were in the steroid withdraw group ((7.8±2.8) years old when receiving kidney transplantation) and 15 cases were in the steroid maintenance group ((7.6±3.5) years old when receiving kidney transplantation). The study population was followed up for (26±12) months. The total dose per unit body weight of steroids in the steroid withdrawal group was lower than that in the steroid maintenance group ((0.13±0.06) vs. (0.36±0.19) mg/(kg·d), t=5.83, P<0.001). The height catch-up rate (ΔHtSDS) in the first year after kidney transplantation in the steroid withdraw and steroid maintenance groups was 1.0 (0.7, 1.4) and 0.4 (0.1, 1.0), respectively; in the second year, the ΔHtSDS in the steroid withdraw group was significantly higher than that in the steroid maintenance group (1.1 (0.2, 1.7) vs. 0.3 (0, 0.8), U=28.00, P=0.039). The HtSDS in the steroid withdrawal group at the five follow-up time points was -2.5±0.8, -2.0±0.8, -1.5±0.8, -1.3±0.9 and -0.5±0.3, respectively, while in the steroid maintenance was -2.4±1.3, -2.2±1.1, -2.0±1.0, -1.8±1.0 and -1.6±1.0, respectively. There were statistically significant differences in HtSDS at different follow-up time points in both 2 groups (F=19.81, P<0.01), but no statistical differences in overall impact between the 2 groups (F=1.13, P=0.204). The steroid treatment was interaction with the increase of follow-up time (F=3.62, P=0.009). At the 24^th month after transplantation, the HtSDS in the steroid withdrawal group was significantly higher than that in the steroid maintenance group (P=0.047). Six patients in the steroid withdrawal group experienced antibody-mediated immune rejection (AMR), while 3 did in the steroid maintenance group. Moreover, there was no significant difference in AMR between the two groups (χ²=0.06, P=0.814). Conclusion: The steroid withdrawal protection strategy favors the height catch-up growth in pediatric patients after kidney transplantation and does not increase the risk of postoperative antibody-mediated immune rejection.
Male ; Humans ; Child ; Female ; Child, Preschool ; Kidney Transplantation ; Prospective Studies ; Steroids/therapeutic use* ; Antibodies ; Body Weight

Aim To establish human U87-MG glioma model in nude mice brain and to observe the characteristics of the tumor growth. Methods Human U87-MG glioma cells were cultured in vitro. 5 μL of cell suspension containing 3.0 ×1010·L-1, 4.0×1010·L-1and 5.0×1010·L-1respectively was inocula-ted into the right caudate nucleus of 18 male nude mice brain un-der the guidance of stereotaxic apparatus, separately, whereas another 6 nude mice as the control group, were inoculated into the same volume of Hanks solution. The moving and survival state of rats with gliomas were observed. The examinations of the tumors formation, volumes, metastasis and histopathology were performed and the obtained brain samples were stained with HE and immunohistochemistry. Results All the tested rats of dif-ferent inoculation doses developed brain tumors without extracra-nial metastasis. The mean survival time of three groups was (46.50 ± 3.27) d,(38.50 ± 3.28) d and (30.67 ± 3.51) d,respectively. The tumors showed the similar morphological fea-tures and immunophenotype to human glioma. There was positive expression of GFAP and S-100 in the tumors. Conclusions The orthotopic implantation model of human U87-MG glioma, by in-oculating quantitative U87-MG cells stereotaxically into the brains of the nude mice, is successfully established with 100 yield of intracranial tumor and no extracranial growth extension. It resembles the histopathological and morphological features of human glioma,which can be used as a reliable animal model for the study of the tumorigenesis, pathogenesis, biological charac-teristics and therapy of glioma.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

BACKGROUNDA multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.

METHODSAdult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.

RESULTSChanges of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.

CONCLUSIONSThe domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.

Adolescent ; Adult ; Aged ; Dialysis Solutions ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Dialysis ; methods ; Young Adult

Objective To explore the causes and preventive measures of missed diagnosis of motor system's fiactures following traumatic brain injury.Methods Retrospective analysis was performed on 52 patients suffering from severe traumatic brain injury and motor system's fractures from January 1995 to December 2009. Statistical analysis was performed to demonstrate the relation between doctors' seniority and the missed diagnosis on fracture, and different results between the patients with missed diagnosis and correct diagnosis were compared. Results 56 fractures, including fractures spinal in 18, pelvic fractures in 11 and fractures of the extremities in 23, were noted in 52 patients. The doctors' seniority was closely correlated to the missed diagnosis rate; the residents had a significantly higher missed diagnosis rate than the attending physicians (P＜0.05). Patients with fractures of the extremities showed obviously low efficacy than those with correct diagnosis (P＜0.05). Conclusion strict and regulated medical examinations and timely X-ray photographs or CT examination can help to make correct diagnosis; choosing the proper operation time on the fractures can effectively reduce the morbidity rate.

OBJECTIVETo explore the efficacy and toxicity of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for relapsed/refractory acute lymphocytic leukemia (ALL).

METHODSForty-seven patients with relapsed/refractory ALL received allo-HSCT, which containing 19/47 from HLA-identical sibling donors (sib-HSCT), 18/47 from HLA-identical unrelated donors (URD-HSCT) and 10/47 from haplo-identical donors (Hi-HSCT). Conditioning regimens included "TBI plus Cyclophosphamide (Cy) (42/ 47)" or "busulfan (Bu) plus Cy (5/47)". Cyclosporine (CsA) combined with a short-course Methotrexate (MTX) were used for graft versus host disease (GVHD) prophylaxis. In addition, patients receiving URD-HSCT or Hi-HSCT were given mycophenolate mofetil (MMF) and anti-thymocyte immunoglobulin (ATG). Patients with molecular or cytogenetic relapse tendency on minimal residual disease (MRD) monitoring received donor lymphocyte infusion (DLI).

RESULTSAll patients tolerated the therapy well except for mucositis. Renal dysfunction occurred in 2 patients on CsA therapy. Epilepsy occurred in 1 patient, fatal infectious complications in 9 (including 3 interstitial pneumonia), grade III-IV acute GVHD (aGVHD) in 7, chronic GVHD (cGVHD) in 22 and hemorrhagic cystitis (HC) in 4 patients. Thirteen patients relapsed after transplantation. The median time of hematopoietic reconstitution was + 17 ds. Nineteen patients received DLI, and 6 of them had no disease progression. With a median follow-up duration of 43 (10-77) months, the estimated 5-year overall survival (OS) and disease free survival (DFS) rates were 49.65% and 46.55%, respectively.

CONCLUSIONAllo-HSCT is an effective therapy for relapsed/refractory ALL. Relapse after transplantation, fatal infection, and severe acute GVHD are the main causes for failure. DLI might decrease the relapse rate after transplantation.

Adolescent ; Adult ; Child ; Female ; Follow-Up Studies ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Lymphocyte Transfusion ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Survival Rate ; Transplantation Conditioning ; Transplantation, Homologous ; adverse effects ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the activation status of signal pathway of mTOR/S6 in bone marrow (BM) T lymphocytes of refractory/relapsed aplastic anemia patients (AA), and the effects of rapamycin (RAPA) and CTLA-4 immunoglobulin (CTLA-4Ig) on this pathway.

METHODSBM was collected from 13 refractory/relapsed AA patients, 8 newly diagnosed severe AA (SAA) patients and 10 iron deficiency anemia (IDA) (as controls) patients, and cocultured with RAPA and CTLA-4 Ig. The expression of p-mTOR, p-S6 and Interferon gamma (IFN-gamma) in CD3(+)T cells was measured by flow cytometry (FCM).

RESULTS(1) The expression of p-mTOR, p-S6 and IFN-gamma in CD3(+)T cells in refractory/relapsed AA group were significantly higher than those in controls (P < 0.01). (2) The expression of p-mTOR and p-S6 in T cells in newly diagnosed SAA group, was similar to those in controls (P > 0.05), but significantly lower than those in refractory/relapsed AA group (P < 0.01). The expression level of IFN-gamma in T cells were significantly higher than that in controls (P < 0.01). (3) On exposure to RAPA, the levels of p-mTOR, p-S6 and IFN-gamma in T cells in refractory/relapsed AA patients were significantly lower than those before the exposure (all P < 0.05). And so were when exposed to CTLA-4 Ig (all P < 0.01).

CONCLUSION(1) The mTOR/S6 signal pathway is activated in refractory/relapsed AA. (2) The expression of p-mTOR, p-S6 and IFN-gamma in refractory/relapsed AA can be suppressed by RAPA or CTLA-4Ig. (3) The signal pathway of CD28/mTOR/S6/IFN-gamma might take part in immune pathogenesis of refractory/relapsed AA.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; immunology ; metabolism ; Antigens, CD ; pharmacology ; CTLA-4 Antigen ; Child ; Female ; Humans ; Interferon-gamma ; metabolism ; Male ; Middle Aged ; Ribosomal Protein S6 ; metabolism ; Signal Transduction ; drug effects ; Sirolimus ; pharmacology ; T-Lymphocytes ; immunology ; metabolism ; TOR Serine-Threonine Kinases ; metabolism ; Young Adult

OBJECTIVETo compare the clinical outcomes between unrelated donor hematopoietic stem cell transplantation (URD-HSCT) and HLA-haploidentical (Hi)-HSCT.

METHODSTwenty-five patients with hematologic malignancies received URD-HSCT and thirty patients received Hi-HSCT. The conditioning regimen consisted of modified BUCY or modified total body irradiation (TBI) plus CY. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of cyclosporin ( CsA), short-term methotrexate (MTX), mycophenolate mofetil (MMF), or the combination of CsA, MTX and MMF plus antithymocyte globulin (ATG) or antilymphocyte globulin (ALG), or the combination of CsA, MTX, MMF, ATG/ ALG and CD25 monoclonal antibody.

RESULTSAll patients in the URD-HSCT group and 29 patients in the Hi-HSCT group were engrafted successfully. The median follow-up duration was 7 (2 -59) months for URD-HSCT group and 7.3 (1 - 35) months for Hi-HSCT group. The 3-year probabilities of disease-free survival (DFS) for URD-HSCT and Hi-HSCT group were (54.1 +/- 11.9)% and (43.1 +/- 9.1)%, respectively (P =0.13). Grade III - IV aGVHD occurred in 10 patients in URD-HSCT group and 11 in Hi-HSCT group (the cumulative incidence 40.0% vs 37.9%, P > 0.05), respectively. Ten patients (40.0%) died of transplantation-related mortality (TRM) in URD-HSCT group and 17 (56.7%) in Hi-HSCT group (P >0. 5). Two patients relapsed in each group (the rate of relapse 8.0% vs 6.0%, P >0.05). The primary causes of death included severe aGVHD with infection,severe pulmonary infection and relapse.

CONCLUSIONBoth URD-HSCT and Hi-HSCT are effective and curable treatment for refractory or high-risk hematologic malignancies. The optimal donor should be chose individually. The severe aGVHD and consequent infection are still the main cause of TRM.

Adolescent ; Adult ; Child ; Female ; Follow-Up Studies ; Graft vs Host Disease ; prevention & control ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Middle Aged ; Tissue Donors ; Transplantation Conditioning ; Treatment Outcome ; Young Adult

AIMTo explore the effect of Simvastatin on the regeneration of sciatic nerve with crush injury in rats.

METHODSAnimals were randomized into the following experimental groups: Simvastatin-treated, vehicle and sham-operated groups. Sciatic nerves with crush injury were performed. After surgery, the functional evaluation of nerve recovery, electrophysiologic assessment, histological assessment, serum IL-6 and lipid were performed.

RESULTSThe toe spread index of Simvastatin-treated rats after operation was higher significantly than vehicle rats at 5 d and 8 d (P<0.05). CMAP was higher and NCV was faster (P < 0.05). The serum IL-6 at 5 d of post-operation was significant lower (P < 0.05). Total serum cholesterol of Simvastatin-treated animals was higher than that of other animals (P < 0.05) at 2 weeks of post-operation. The histological analysis showed that the numbers of myelinated axons and the thickness of myelin sheath of Simvastatin-treated crush injury animals at 4 weeks of post-operation were more than that of vehicle animals.

CONCLUSIONThe present study showed that Simvastatin could promote the regeneration of the sciatic nerve after crush injury in rats, partly through inhibiting immune and inflammatory responses and making the balance of serum cholesterol during these processes.

Animals ; Female ; Nerve Crush ; Nerve Regeneration ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; drug effects ; injuries ; physiology ; Simvastatin ; pharmacology

OBJECTIVETo explore the possible role of CD28/CTLA-4 co-stimulators in immune pathophysiology of acquired aplastic anemia(AA).

METHODSBy FACS, the percentages of CD28, CTLA-4 expressing CD3+ CD4+ T cells and the level of Th1, Th2 in bone marrow were detected in 23 AA patients at active phase, 10 at recovery phase and 15 normal controls. The relationship between the co-stimulators, Th1, Th2, and absolute neutrophil counts (ANC) was evaluated.

RESULTS(1) The percentage of CD28 and CTLA-4 expressing CD3+ CD4+ T cells in bone marrow, and CD28+/CTLA-4+ ratios were (31.40 +/- 10.83)%, (2.45 +/- 1.30)% , and 17.02 +/- 13.44 in normal controls respectively, (39.84 +/- 10.89)%, (1.43 +/- 0.67)%, and 43.04 +/- 37.61 in AA at active phase, respectively, (22 +/- 9.08)%, (3.46 +/- 2.26)%, and 10.49 +/- 7.8 in AA at recovery phase, respectively. The percentage of CD28 and CD28+/CTLA-4+ ratio were significantly higher, while CTLA-4 were lower in active phase AA patients than in normal controls (P < 0.05). These values in recovery phase AA were comparable to those in normal controls. (The Th1, Th2, and Th1/Th2 in bone marrow were (4.21 +/- 2.11)%, (1.99 +/- 1.27)%, and 2.46 +/- 1.28 in normal controls respectively, (11.13 +/- 4. 96)%, (2.46 +/- 1.65)%, and 5.20 +/- 1.98 in active phase AA and (5.39 +/- 4.2)9%, (2.53 +/- 2.41)%, and 2.87 +/- 1.43 in recovery phase AA, respectively. The percentage of Th1 and Th1/Th2 ratio were significantly higher in AA patients at active phase than in normal controls (P < 0.05). (3) The CD28+/CTLA-4+ ratio was positively related to the Th1+ /Th2+ ratio (P < 0.05). ANC was negatively related to CD3+ CD4+ CD28+ T cells (P < 0.01), and positively to CD3 + CD4 ' CTLA-4' T cells (P < 0.01) respectively.

CONCLUSION(1) The expression of CD28 was increased while CTLA-4 decreased on the membranes of CD3+ CD4+ T cells in bone marrow of AA patients. (2) The abnormal expression of CD28 costimulator promoted the shift of immune balance to Thl type. (3) The unbalance of CD28+ / CTLA-4+ is important for the immune pathophysiology of AA.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; immunology ; metabolism ; Antigens, CD ; immunology ; metabolism ; CD28 Antigens ; immunology ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; CTLA-4 Antigen ; Child ; Female ; Humans ; Male ; Middle Aged ; Th1 Cells ; immunology ; Th2 Cells ; immunology