Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; epidemiology ; Cross-Sectional Studies ; Hepatitis B ; epidemiology ; Humans ; Incidence ; Infant ; Infant, Newborn ; Middle Aged ; Young Adult

Discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas (APAs) with distinct clinical presentations and pathological features. Catenin β1 (CTNNB1) mutation in APAs has been recently described and discussed in the literature. However, significant knowledge gaps still remain regarding the prevalence, clinical characteristics, pathophysiology, and outcomes in APA patients harboring CTNNB1 mutations. Aberrant activation of the Wnt/β-catenin signaling pathway will further modulate tumorigenesis. We also discuss the recent knowledge of CTNNB1 mutation in adrenal adenomas.
Adenoma* ; Aldosterone* ; Carcinogenesis ; Humans ; Prevalence

Objective To simulate the stress generated by contact with the femur during the assembly of novel semi-hip prosthesis, and discuss the operating limits and adaptive prosthesis profile in clinic. Methods CT scans were conducted on the proximal end of the femur in a male volunteer of 60 years old as a physical model. By transferring the CT data to finite element modeling software, the physical model was simplified, meshed, materialized and assembled with the model of prosthesis to establish the three-dimensional finite element model. Surface to surface contact relationship between the femur and the prosthesis was also constructed by utilizing contact elements. Relative sliding distance and stress distribution were solved while simulating the process of assembling the prosthesis. Results Additional stress was generated on the sudden change area of the contact surface when the prosthesis was seated. The greatest contact pressure came from the changing section of the ridge of the prothesis, and the maximum assembly stress and sliding distance range increased nonlinearly along with the pushing distance. The increase rate of additional stress was enhanced significantly while Δz≥0.5 mm. Conclusions Compared with the prosthesis without ridge, the prosthesis with ridge can be easily seated and obtain mechanical stabilization. However, the relevant clinical operating limits should be obeyed to avoid generating excessive additional stress during the implantation of prosthesis, which may cause treatment failure due to the damage in bone cortex.

OBJECTIVETo determine whether an adenoviral construct containing bone morphogenetic protein-4 (BMP-4) gene can be used for lumbar spinal fusion.

METHODSTwelve New Zealand white rabbits were randomly divided into two groups, 8 in the experimental group and 4 in the control group. Recombinant, replication-defective type 5 adenovirus with the cytomegalovirus (CMV) promoter and BMP-4 gene (Ad-BMP-4) was used. Another adenovirus constructed with the CMV promoter and beta-galactosidase gene (Ad-beta-gal) was used as control. Using collagen sponge as a carrier, Ad-BMP-4 (2.9 multiply 10(8) pfu/ml ) was directly implanted on the surface of L(5)-L(6) lamina in the experimental group, while Ad-beta-gal was implanted simultaneously in the control group. X-ray was obtained at 3, 6, and 12 weeks postoperatively to observe new bone formation. When new bone formation was identified, CT scans and three-dimensional reconstruction were obtained. After that, the animals were killed and underwent histological inspection.

RESULTSIn 12 weeks after operation, new bone formation and fusion were observed on CT scans in the experimental group, without the evidence of ectopic calcification in the canal. Negative results were found in the control group. Histological analysis demonstrated endochondral bone formation at the operative site and fusion at early stage was testified.

CONCLUSIONSIn vivo gene therapy using Ad-BMP-4 for lumbar posterolateral spinal fusion is practicable and effective.

Adenoviridae ; genetics ; Animals ; Bone Morphogenetic Protein 4 ; Bone Morphogenetic Proteins ; therapeutic use ; Genetic Therapy ; methods ; Humans ; Lumbar Vertebrae ; surgery ; Rabbits ; Spinal Fusion

OBJECTIVE To investigate the mechanisms of Triptolide in ER(+) human breast cancer MCF-7 cells from CYP19.METHODS The inhibition of the MCF-7 cells influenced by Triptolide and Letrozole was analyzed respectively by MTT assays.The aromatase levels were measured by Western blot.The CYP19 gene was observed by RT-PCR.The MCF-7 cells of high and low expression CYP19 gene were transfacted.It's CYP-19 and downstream channel gene JNK,p-38 and ERK were observed by Western blot.RESULTS Triptolide displayed a dose-and time-dependent inhibition of the MCF-7 cells.It inhibited the aromatase and CYP19.The expression of CYP19 in MCF-7 cells of low expression CYP19 was significantly decreased.Phosphorylation of JNK,p38 and ERK was inhibited too.CONCLUSION Triptolide inhibit MCF-7 cells not only via inhibition aromatase,but also blocking Ras-Raf-MAPK-ERK enzyme.

OBJECTIVETo analyze a Duchenne muscular dystrophy(DMD) patient's muscular regeneration, dystrophin expression and locomotive variation before and after he underwent umbilical cord blood stem cell transplantation in order to assess the therapeutic effect.

METHODSA 12-year-old DMD boy who could not walk for 3 years was confirmed by gene analysis and dystrophin protein immune test on his muscle. He had no other chronic disease. By HLA matching, a piece of umbilical cord blood stem cell with 6 HLA sites matching to the boy was found in Guangdong Umbilical Cord Blood Bank. The number of the nucleated cells of the umbilical cord blood stem cell was 24.08x 10(8). After pretreatment for the DMD boy with busulfan, cyclophosphamide and rabbit anti-human thymocyte globulin, the allergenic cord blood stem cells were transplanted into him by intravenous injection. Cyclosporin A, methylprednisolone, MMF, prostaglandin E1 and ganciclovir were given after the transplantation. At the same time, Gran, the granulocytic cell stimulating factor, and gamma globulin were administered. The biochemistry profile including serum creatine kinase (CK), the reconstruction of blood making, the deletion exon of DMD gene, the regenerating muscles, the dystrophin protein expression, and the locomotive function of the DMD boy were tested regularly.

RESULTS(1) The white blood cells (WBC) of peripheral blood decreased gradually to zero after pretreatment. In a period of 15 days after transplantation, the neutrophil increased to 0.5x 10(9)/L; at 25 days, WBC increased to normal level. Blood platelet was more than 20x 10(9)/L at 22 days. The hemoglobin rose to 85-100 g/L. At 140 days, sternal puncture revealed the rapid growth of neutrophil, blood platelet and hemoglobin. (2)At 140 days, the blood type of the DMD boy transformed from type O to type AB (the donor's blood type being AB). There was no grafe versus host reaction. (3) At 18, 30, 43, 55, 74 and 233 days after transplantation, the PCR-short tandem repeat test of the boy's peripheral blood DNA showed that his genotype was completely the same as the donor's. The results of PCR-short tandem repeat tests of the bone marrow cells DNA by sternal puncture at 140, 183 and 235 days were the same as those of the blood DNA. (4) At 60 days, DMD gene analysis by PCR showed that the defected DMD gene (exon 19 deletion) had been corrected by the umbilical cord stem cells transplantation. (5) At 75 days, the biopsy of calf muscle showed there were myoblast cells and muscular tubes growing. The dystrophin expressions were weak, but a few of them were strong. DNA analysis showed that the donor's gene DNA accounted for 1%-13%. At 126 days, obviously increased dystrophin positive muscular fibers of the boy were found. The donor's fibers rose to 2.5%-25%. (6) The serum CK of the boy declined from 5735 U/L to 274 U/L. (7) At 100 days, physical examination revealed improvement in his arms and legs.

CONCLUSIONThe therapy of Duchenne muscular dystrophy with allogeneic umbilical cord blood hematopoietic stem cell transplantation may reset up the blood-making function, decrease the serum CK level, restore the dystrophin in muscles, and improve the locomotive function of the DMD boy. These data suggest that the allogeneic umbilical cord blood hematopoietic stem cell transplantation may benefit the DMD boys.

Alprostadil ; therapeutic use ; Busulfan ; therapeutic use ; Child ; Combined Modality Therapy ; Cord Blood Stem Cell Transplantation ; methods ; Cyclosporine ; therapeutic use ; Dystrophin ; genetics ; Ganciclovir ; therapeutic use ; Humans ; Male ; Methylprednisolone ; therapeutic use ; Muscular Dystrophy, Duchenne ; genetics ; therapy ; Polymerase Chain Reaction ; Treatment Outcome

The present study was aimed to investigate the role of necroptosis in the pathogenesis of acute respiratory distress syndrome (ARDS). The rat model of ARDS was induced by intravenous injection of oleic acid (OA), and observed for 4 h. The lung injury was evaluated by arterial blood gas, lung wet-dry weight ratio (W/D) and histological analyses. Simultaneously, bronchoalveolar lavage fluid (BALF) was collected for total and differential cell analysis and total protein determination. Tumor necrosis factor alpha (TNF-α) level in BALF was determined with a rat TNF-α ELISA kit. Expressions of receptor interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL) in lung tissue were determined by Western blot and immunohistochemical staining. The interaction between RIPK1 and RIPK3 was explored by immunoprecipitation. The results showed that, compared with those in control group, total white blood cells count (WBC), polymorphonuclear percentage (PMN%), total protein concentration, TNF-α level in BALF, W/D, and the alveolar-arterial oxygen tension difference (P(A-a)O) in OA group were significantly increased at 4 h after OA injection. Western blot and immunostaining further showed remarkably increased expressions of RIPK1, RIPK3 and MLKL in lung tissue from OA group. Additionally, immunoprecipitation results indicated an enforced interaction between RIPK1 and RIPK3 in OA group. Collectively, the TNF-α level in BALF and the RIPK1-RIPK3-MLKL signaling pathway in lung tissue were found to be upregulated and activated with the process of ARDS. These findings implicate that RIPK1/RIPK3-mediated necroptosis plays a possible role in the pathogenesis of ARDS, which may provide a new idea to develop novel drugs for the therapy of ARDS.
Acute Disease ; Animals ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Lung Diseases ; Necrosis ; Oleic Acid ; Rats ; Receptor-Interacting Protein Serine-Threonine Kinases ; Respiration Disorders ; Signal Transduction ; Tumor Necrosis Factor-alpha

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