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Objective To demonstrate the feasibility of oblique lumbar interbody fusion (OLIF) combined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1 (M0) was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the M0 model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models (M2-M4) and one 6-screw fixation model (M5) were established.The segmental and overall range of motion (ROM) and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral (left and right) flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixation can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.
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Parafusos Ósseos , Análise de Elementos Finitos , Vértebras Lombares , Fusão Vertebral , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Humanos , Vértebras Lombares/cirurgiaRESUMO
OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.
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Complemento C1q , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Complemento C1q/imunologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/sangue , Feminino , Criança , Masculino , Lúpus Eritematoso Sistêmico/imunologia , Estudos Retrospectivos , Adolescente , Autoanticorpos/sangue , Pré-Escolar , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologiaRESUMO
OBJECTIVES: To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022. RESULTS: Among the AAV children, there were 5 males and 20 females, with a median age of onset of 11.0 years. Involvement of the urinary system was seen in 18 cases (72%); respiratory system involvement in 10 cases (40%); skin involvement in 6 cases (24%); eye, ear, and nose involvement in 5 cases (20%); joint involvement in 4 cases (16%); digestive system involvement in 2 cases (8%). Eleven cases underwent kidney biopsy, with 5 cases (46%) showing focal type, 2 cases (18%) showing crescentic type, 2 cases (18%) showing mixed type, and 2 cases (18%) showing sclerotic type. Immune complex deposits were present in 5 cases (45%). Seven cases reached chronic kidney disease (CKD) stage V, with 2 cases resulting in death. Two cases underwent kidney transplantation. At the end of the follow-up period, 2 cases were at CKD stage II, and 1 case was at CKD stage III. Of the 16 cases of microscopic polyangiitis (MPA) group, 13 (81%) involved the urinary system. Of the 9 cases of granulomatosis with polyangiitis (GPA), 6 cases (66%) had sinusitis. Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group (P<0.05), while red blood cell count and glomerular filtration rate were lower in the MPA group (P<0.05). CONCLUSIONS: AAV is more common in school-age female children, with MPA being the most common clinical subtype. The onset of AAV in children is mainly characterized by renal involvement, followed by respiratory system involvement. The renal pathology often presents as focal type with possible immune complex deposits. Children with MPA often have renal involvement, while those with GPA commonly have sinusitis. The prognosis of children with AAV is poor, often accompanied by renal insufficiency.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Feminino , Masculino , Criança , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Estudos Retrospectivos , Adolescente , Pré-Escolar , Insuficiência Renal Crônica/etiologiaRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems, presenting a complex and diverse clinical manifestation. The heterogeneous treatment response and prognosis of SLE pose significant challenges to its diagnosis, classification, and homogeneous treatment. The emergence of new technologies and fields, such as synthetic biology, genomics, and proteomics, has contributed to a deeper exploration of the pathogenesis and biomarkers of SLE, facilitating precision diagnosis and treatment. This review summarizes the latest research data and achievements in SLE for the years 2021-2022, providing an overview and summary of relevant studies conducted in the past two years.
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Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , ProteômicaRESUMO
This paper reports the clinical and genetic characteristics of a case of combined pituitary hormone deficiency type I (CPHD1) caused by POU domain, class 1, transcription factor 1 (POU1F1) gene variation. A 2 years and 3 months old girl mainly presented with short stature, special facial features of prominent forehead, enophthalmos, and short mandible, loose skin, central hypothyroidism, complete growth hormone deficiency, and anterior pituitary hypoplasia. Gene analysis identified a novel heterozygous mutation, c.889C>T (p.R297W), in POU1F1 gene, and this locus of her parents was wild-type. This mutation was analyzed as a possible pathogenic variant according to the guidelines of the American College of Medical Genetics and Genomics, which has not been previously reported in the literature and conforms to the autosomal dominant inheritance. This child was diagnosed with CPHD1. Her height increased by 19.8 cm and showed a catch-up growth trend after one year of combined treatment with growth hormone and euthyrox. This study enriches the mutation spectrum of POU1F1 gene and has important significance for the diagnosis and classification of combined pituitary hormone deficiency.
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Hipopituitarismo , Pré-Escolar , Feminino , Humanos , Mutação , Fator de Transcrição Pit-1 , Fatores de TranscriçãoRESUMO
Acute kidney injury (AKI) is characterized by a reversible increase in blood concentration of creatinine and nitrogenous waste products and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. AKI in hospitalized patients is independently associated with increased morbidity and mortality in pediatric and adult populations. Continued reliance on serum creatinine and urine output for the diagnosis of AKI has resulted in an inability to provide successful therapeutic and supportive interventions to prevent and mitigate AKI. Research efforts over the last decade have foused on the discovery and validation of novel biomarkers to detect AKI prior to a change in kidney function and to make a differential diagnosis of AKI.
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Injúria Renal Aguda/classificação , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/prevenção & controle , Biomarcadores , Criança , Creatinina/urina , HumanosRESUMO
BACKGROUND: The incidence of AKI appears to have increasing trend. Up to now, prospective, multi-center, large-sample epidemiological study done on pediatric AKI on aspects of epidemiological characteristics, causes and outcomes have not reported. It is necessary to develop prospective, multi-center, large-sample epidemiological study in our country on pediatric AKI. The aim of this study was to determine the clinical features, etiology, and outcomes of acute kidney injury (AKI) in Chinese children. METHOD: Paediatric patients (≤18 years old) admitted to 27 hospitals (14 children's hospitals and 13 general hospitals) affiliated with the Medical University were investigated. AKI was defined using the 2005 Acute Kidney Injury Network criteria. RESULTS: During the study period, 388,736 paediatric patients were admitted. From this total, AKI was diagnosed in 1,257 patients, 43 of whom died. The incidence and mortality of AKI was 0.32% and 3.4% respectively. The mean (± SD) age of patients was 48.4 ± 50.4 months. Among the 1,257 AKI paediatric patients, 632 were less than one year old. Among the AKI paediatric patients, 615 (48.9%) were in stage 1, 277 (22.0%) in stage 2, and 365 (29.0%) in stage 3. The most common causes of AKI were renal causes (57.52%), whereas postrenal (25.69%) and prerenal (14.96%) causes were the least common. The three most common causes of AKI according to individual etiological disease were urolithiasis (22.35%), of which exposure to melamine-contaminated milk accounted for the highest incidence (63.7%); acute glomerulonephritis (10.10%); and severe dehydration (7.48%). A total of 43 AKI patients (3.4%) died during their hospital stay; 15 (34.9%) of the 43 died as a result of sepsis. CONCLUSION: Primary renal diseases are a major risk factor for paediatric AKI in China. In terms of specific etiological disease, urolithiasis (postrenal disease) was the leading cause of paediatric AKI in 2008, when the disease was linked to exposure to melamine-contaminated milk. Sepsis is the leading cause of death in Chinese paediatric AKI patients. Future studies should focus on effective ways of controlling renal disorders and sepsis to improve the clinical management of paediatric AKI in China.
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Injúria Renal Aguda/mortalidade , Doenças Transmitidas por Alimentos/mortalidade , Nefrite/mortalidade , Sepse/mortalidade , Triazinas/intoxicação , Urolitíase/mortalidade , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Adolescente , Distribuição por Idade , Causalidade , Criança , Pré-Escolar , China/epidemiologia , Comorbidade , Feminino , Doenças Transmitidas por Alimentos/diagnóstico , Doenças Transmitidas por Alimentos/terapia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Nefrite/diagnóstico , Nefrite/terapia , Estudos Prospectivos , Sepse/diagnóstico , Sepse/terapia , Taxa de Sobrevida , Urolitíase/diagnóstico , Urolitíase/terapiaRESUMO
OBJECTIVE: To investigate the clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the Interlaminar Endoscopic Surgical System(iLESSYS) Delta for the treatment of lumbar spinal stenosis (LSS) in the elderly. METHODS: Total of 29 patients with LSS treated with the iLESSYS Delta from December 2018 to January 2021 were retrospectively analyzed, including 12 males and 17 females with an average age of (71.52±10.82) years old ranging from 63 to 83 years old. All patients had definite intermittent claudication, mainly neurogenic symptoms of both lower limbs. All patients had single-level spinal stenosis, including L3,4 5 cases, L4,5 21 cases, and L5S1 3 cases. Visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified Macnab assessment criteria were used to evaluate pain, low back pain dysfunction index and clinical efficacy, respectively. RESULTS: All 29 cases were successfully completed. The operation time was (73.45±5.89) min, the intraoperative blood loss was (9.93±0.83) ml, the hospital stay was (4.03±0.41) days, and the follow-up was more than 12 months. The VAS scores of low back pain before surgery and 1 day, 1 month, 3 months, 1 year after surgery were 2.31±0.88, 1.45±0.62, 1.21±0.61, 1.10±0.55, 1.03±0.49;VAS of leg pain were 6.48±0.49 0.56, 1.97±0.61, 1.31±0.59, 1.17±0.59, 1.10±0.55;ODI scores were 38.41±2.74, 18.14±1.17, 5.17±0.53, 5.07±0.45, 4.90±0.48;low back and leg pain VAS score and ODI score have statistically significant differences between preoperative and postoperative follow-up time points (P<0.05). The MacNab efficacy evaluation at 1-year follow-up:excellent in 22 cases, good in 5 cases and fair in 2 cases. CONCLUSION: The clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the iLESSYS Delta for the treatment of lumbar spinal stenosis in the elderly is satisfactory, with the advantages of less trauma and less bleeding, large microscopic operation space, sufficient decompression, and ideal post-operative recovery, and at the same time, it can minimize the damage to the stable structure of the lumbar spine, which is an ideal surgical method for the treatment of elderly lumbar spinal stenosis.
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Dor Lombar , Estenose Espinal , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estenose Espinal/cirurgia , Estudos Retrospectivos , Canal Medular/cirurgia , Descompressão Cirúrgica/métodos , Resultado do Tratamento , Endoscopia/métodos , Vértebras Lombares/cirurgiaRESUMO
Magnetic order in most materials occurs when magnetic ions with finite moments arrange in a particular pattern below the ordering temperature. Intriguingly, if the crystal electric field (CEF) effect results in a spin-singlet ground state, a magnetic order can still occur due to the exchange interactions between neighboring ions admixing the excited CEF levels. The magnetic excitations in such a state are spin excitons generally dispersionless in reciprocal space. Here we use neutron scattering to study stoichiometric Ni2Mo3O8, where Ni2+ ions form a bipartite honeycomb lattice comprised of two triangular lattices, with ions subject to the tetrahedral and octahedral crystalline environment, respectively. We find that in both types of ions, the CEF excitations have nonmagnetic singlet ground states, yet the material has magnetic order. Furthermore, CEF spin excitons from the tetrahedral sites form a dispersive diffusive pattern around the Brillouin zone boundary, likely due to spin entanglement and geometric frustrations.
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BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The KaplanâMeier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).
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OBJECTIVE: To study the relationship between TAP (transporter associated with antigen processing) gene promoter regional methylation level and cervical lesions with HPV infection in Uyghur women. METHODS: A specialized software was used to design specific primers of CpG island fragments of TAP1 and TAP2 gene promoter for PCR amplification, bisulfitemodified SiHa cancer cell DNA for PCR amplification, cloning and sequencing analysis to obtain the relevant information on the gene base sequence methylation of CpG sites. Seventy-eight fresh cervical tissue samples from Uyghur women with cervicitis (number = 15), cervical intraepithelial neoplasia (CIN, number = 30) and cervical squamous cell carcinoma (number = 33) were collected. The methylation level of TAP1 and TAP2 gene promoter regions was detected using MassArray DNA technology. HPV infection status was determined by HPV gene chips. The relationship between CpG-island methylation of gene promoter regions and HPV infection was then analyzed. RESULTS: Each TAP1 and TAP2 gene corresponding target fragment contained 23 and 8 CpG sites. There were 5 and 8 CpG sites methylation occurred in SiHa cervical cancer cells genomic DNA respectively. The TAP1 methylation level increased steadily with the severity of cervical lesions. The methylation levels in cervical squamous cell carcinoma and CIN (0.048 ± 0.039 and 0.037 ± 0.026, respectively) were higher than that of normal cervical tissue (0.035 ± 0.029, P < 0.05). Although TAP2 gene methylation level also demonstrated similar changes, the difference however was not statistically significant (P > 0.05). HPV gene chip detected 13 HPV genotypes, with HPV16 infection rate being 66.7% (52/78). The methylated proportion of TAP1 positively correlated with HPV16 infection (χ(2) = 6.08, P = 0.039). CONCLUSION: TAP1 methylation is a remarkable phenomenon occurring in a range of cervical lesions and significantly associated with cervical HPV infection.
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Transportadores de Cassetes de Ligação de ATP/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA , Infecções por Papillomavirus , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Adulto , Idoso , Povo Asiático/genética , Carcinoma de Células Escamosas/virologia , Ilhas de CpG/genética , Feminino , Papillomavirus Humano 16 , Humanos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/virologia , Cervicite Uterina/genética , Cervicite Uterina/virologia , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVE: To investigate the changes of blood pressure by 24-hour ambulatory blood pressure (ABP) monitoring in children with primary nephrotic syndrome (PNS) and explore the relationship of the changes in blood pressure with rennin-angiotensin-aldosterone system (RAAS) in these children. METHODS: ABP and casual blood pressure (CBP) monitoring were performed in 114 children with PNS. Plasma levels of rennin activity (PRA), angiotensin II (AngII) and aldosterone (ALD) were measured. The correlation of plasma levels of PRA, AngII and ALD with ABP was evaluated. RESULTS: Of the 114 children with PNS, 101 (88.6%) presented elevated blood pressure. Mild or severe masked hypertension was found in 45 children (39.5%). Eighty (70.2%) children showed non-dipper blood pressure. The index and load of systolic blood pressure were higher than those of diastolic blood pressure. The blood pressure index and blood pressure load during sleep were higher than those during wakefulness. The boy presented higher diastolic blood pressure index and load than girls. Decubitus blood PRA, AngII and ALD levels in children with PNS were significantly higher than normal controls. The group with elevated blood pressure presented significantly higher decubitus blood PRA, AngII and ALD levels than the group with normal blood pressure. AngII level was significantly positively correlated with the index and load of both systolic blood pressure and diastolic blood pressure. CONCLUSIONS: The children with PNS present a high incidence of hypertension, with a large percentage of masked hypertension and non-dipper blood pressure. Systolic blood pressure increases more significantly than diastolic blood pressure. Blood pressure during sleep increases more significantly than that during wakefulness. Diastolic blood pressure increases more significantly in boys than in girls. RAAS activity is elevated and the elevated RAAS activity might increase the blood pressure mainly by AngII in children with PNS.
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Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Síndrome Nefrótica/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
AIM: Our study is aimed at investigating whether Lipopolysaccharide- (LPS-) treated podocytes could polarize naive CD4+ T cells into different subsets in vitro. MATERIALS AND METHODS: Podocytes and mouse bone marrow-derived dendritic cells (BMDCs) were first cultured with 25 µg/ml LPS for 6 hours, respectively. Then, naive CD4+ T cells were cocultured with the LPS-treated podocytes or BMDCs at a ratio of 1 : 1 or 1 : 1 : 1. After 48 hours, we collected the suspended cells and supernatant from all groups to measure T helper (Th)17 cells, regulatory T (Treg) cells, and cytokine concentration. RESULTS: We observed the expression of CD80 and major histocompatibility complex class II molecule (MHC II) in podocytes but did not found the upregulation of them after treating podocytes with LPS. LPS-treated podocytes could induce naive CD4+ T cells to Th17 cells and Treg cells with a higher ratio of Th17/Treg than BMDCs. Possible interaction between podocytes and BMDCs may exist in the induction process of Th17 cells and Treg cells. CONCLUSION: Our study proved that CD80 and MHC II were constitutively expressed in podocytes but not upregulated by LPS. LPS-treated podocytes could polarize naive CD4+ T cells into Th17 and Treg cells and affect the Th17/Treg balance and may incline to cause a Th17 response.
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Linfócitos T CD4-Positivos , Lipopolissacarídeos/farmacologia , Podócitos , Linfócitos T Reguladores , Células Th17 , Animais , Antígeno B7-1/metabolismo , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Camundongos , Podócitos/citologia , Podócitos/efeitos dos fármacos , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/citologia , Células Th17/efeitos dos fármacosRESUMO
BACKGROUND: Tacrolimus, a calcineurin inhibitor, is recommended by the recent guidelines from the Kidney Disease Improving Global Outcomes Group as the first-line treatment for steroid-resistant nephrotic syndrome (SRNS), but its clinical application in China is still limited. We investigated the efficacy and safety of tacrolimus combined with low-dose corticosteroids in a population of Chinese children with SRNS. METHODS: In this prospective non-randomized, non-controlled study, Chinese children with SRNS who failed the previous full-dose prednisone treatment were given tacrolimus (0.1 mg/kg/day) and low-dose prednisone (0.25-0.50 mg/kg/day). We compared the overall remission rate (ORR) and adverse events in the follow-up period with this therapeutic regimen. RESULTS: A total of 76 children were enrolled into the study with an average follow-up period of 18 ± 6 months (maximum 36 months). ORR achieved by the first, third, and sixth months was 94.7%, 94.7%, and 96.0%, respectively. All patients who attained an initial tacrolimus trough concentration (FK506C0) > 6 ng/mL (60.3%) achieved remission. The relative risk of relapse at FK506C0 < 3 ng/mL compared to 3-6 ng/mL, 6-9 ng/mL, and 9-12 ng/mL was 2.3, 3.2, and 16.9, respectively. During the follow-up period, adverse effects that had been previously reported were rare. CONCLUSIONS: Combination of tacrolimus and low-dose prednisone was safe and effective for the treatment of children with SRNS, with high remission rates observed as early as the first month. Relapses were infrequent, but tended to increase significantly with decreases in FK506C0.
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Inibidores de Calcineurina/uso terapêutico , Glucocorticoides/administração & dosagem , Síndrome Nefrótica/tratamento farmacológico , Prednisona/administração & dosagem , Tacrolimo/uso terapêutico , Adolescente , Inibidores de Calcineurina/efeitos adversos , Criança , Pré-Escolar , China , Resistência a Medicamentos , Feminino , Glucocorticoides/efeitos adversos , Humanos , Masculino , Prednisona/efeitos adversos , Estudos Prospectivos , Tacrolimo/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effects of astragalus on tubulointerstitial lesions in rats with IgA nephropathy (IgAN) and to explore the possible mechanism. METHODS: Twenty-eight Sprague-Dawley rats were randomly assigned to three groups. The rat model of IgA nephropathy was induced by intragastric administration of bovine serum albumin and injections of LPS and CC14. Six weeks later, the rats with IgAN were randomly treated with oral astragalus (3 g/kg/d, for 6 weeks) or normal saline. Normal control rats which were not subjected to IgAN were treated with normal saline. The number of urinary erythrocytes and urinary protein and B-D-N-Acetyl glucosaminidase (NAG) contents were determined by Pan-automatic biochemistry analyzing meter. Expression of monocyte chemotactic protein-1 (MCP-1) and nuclear factor-kappa B (NF-kappaB) in tubulointerstitial tissues were analyzed by immunohistochemistry. A semiquantitative score was used to evaluate the degree of renal pathologic lesions. RESULTS: The number of urinary erythrocytes (74.02+/-16.58 / microL vs 383.23+/-4.94 /microL) and urinary protein (13.88+/-4.94 vs 59.82+/-14.73 mg/L) and NAG contents (2.84+/-0.31 vs 5.24+/-0.80 U/L) in the astragalus-treated IgAN rats decreased remarkably compared with those in the IgAN rats without astragalus treatment (P<0.01). Expression of the NF-kappaB and MCP-1 in the renal tissues in the IgAN rats without astragalus treatment was significantly higher than that in the astragalus-treated IgAN rats and normal control rats (P<0.01). There were significant differences in the scores of renal pathologic lesions between the IgAN rats with or without astragalus treatment (6.03+/-0.46 vs 10.57+/-1.23; P<0.01). CONCLUSIONS: Astragalus can decrease the number of urinary erythrocytes and urinary protein and NAG contents, and relieves tubulointerstitial lesions, possibly through the down-regulation of NF-kappaB and MCP-1 expression in rats with IgAN.
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Astrágalo , Quimiocina CCL2/análise , Glomerulonefrite por IGA/tratamento farmacológico , Túbulos Renais/patologia , Fator de Transcrição RelA/análise , Animais , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/patologia , Imuno-Histoquímica , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) plus prednisone on refractory nephrotic syndrome (RNS) in children. METHODS: One hundred and forty-two children with RNS from ten clinical trial centers were divided into two groups: MMF (n=87) and control (n=55). The MMF group patients were administered with oral MMF (30-40 mg/kg daily) for at least 6 months. Afterwards the patients who responded to MMF received another 6 months MMF treatment at a dosage of 10-20 mg/kg daily. The controls were treated with pulse intravenous infusion of cyclophosphamide (CTX) (10 mg/kg daily) for 2 days every 2 weeks for 3 months. Then CTX was administered at a dosage of 500 mg/m2 once a month 4, 7 and 10 months after treatment. While the patients received MMF or CTX treatment, they were treated with oral prednisone (0.5-1 mg/kg daily) for 2 to 3 months, and then the dosage of prednisone was gradually reduced. Urinary protein, liver and renal functions, and side effects of drugs were examined at regular intervals for one year. RESULTS: Of the 87 patients, 58 achieved complete remission, 16 achieved partial remission, 9 achieved early remission and 4 had no response to treatment. In the control group, 35 achieved complete remission, 9 achieved partial remission, 1 achieved early remission and 10 had no response to treatment. The total remission rate in the MMF group (95.4%) was significantly higher than that in the control group (81.8%) (P<0.01). After treatment 67 patients (65.4%) in the MMF group had negative proteinuria compared with 36 patients (65.4%) in the control group (P>0.05). MMF was found to be more effective in reducing proteinuria, and improving hypoproteinemia, oliguria, hyperlipemia, and edema than CTX. MMF was better tolerated with lower incidences of adverse reactions than CTX. CONCLUSIONS: The combined therapy of MMF and prednisone is more effective and tolerable than pulse intravenous infusion of CTX for treatment of RNS in children.
Assuntos
Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Estudos ProspectivosRESUMO
OBJECTIVE: To investigate the efficacy and adverse effect of mycophenolate mofetil (MMF) in the treatment of frequently relapsing nephrotic syndrome in children. METHODS: The study population consisted of 37 children (24 simple nephrotic syndrome and 13 nephritis-type syndrome) suffering from frequently relapsing nephrotic syndrome. Patients received 20-30 mg/(kg d) of MMF in conjunction with 1 mg/(kg d) prednisone for 3-6 months. RESULTS: Out of 24 patients suffered from simple nephrotic syndrome, 17 patients (70.8%) with complete relief, 4 patients (16.7%) with partial relief and 3 patients (12.5%) with non-relief, whereas out of 13 patients suffered from nephritis-type syndrome 6 patients (46.2%) with complete relief, 3 patients (23.1%) with partial relief and 4 patients (30.7%) with non-relief. Eight patients with Minimal Change Disease (MCD) achieved complete relief. Of 23 patients with Mesangial Proliferative Glomerulonephritis (MsPGN) or Membranoproliferative Glomerulonephritis (MPGN), complete relief was observed in 17 patients (73.9%), partial relief in 4 patients (17.4%) and non-relief in 2 patients. CONCLUSION: These Results suggest that MMF has better efficacy against simple renal disease than against nephritis-type syndrome, and MMF may be more suitable for the treatment of frequently relapsing nephrotic syndrome characterized by proliferative lesions.
Assuntos
Ácido Micofenólico/análogos & derivados , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Recidiva , Resultado do TratamentoRESUMO
OBJECTIVE: To construct mesangial cell lines over- or under- expressing glucocorticoid receptor beta (GRbeta), to investigate the effect of GRbeta on glucocorticoid biological function, and to determine whether the overexpression of GRbeta explains the glucocorticoid-resistant in glomerular mesangial cells (GMCs). METHODS: The recombinant human sense or anti-sense gene of GRbeta was transferred into the rat GMCs by retrovirus-mediated stable transfection technique. Expression of hGRbeta mRNA in GMCs was determined by reverse transcription of total RNA followed by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the product of RT-PCR was then analyzed by gene sequencing. The expression of hGRbeta protein in GMCs was tested by Western blot. The inhibitory rate of dexamethasone-mediated cells on lipopolysaccharide (LPS)-stimulated GMC proliferation was detected to assess the effect of GRbeta at different expression levels on the glucocorticoid action. The cell proliferative activity in different cells with different levels of GRbeta was tested by MTT chromatometry. The change of cell cycle was analyzed by flow cytometry. RESULTS: RT-PCR and gene sequencing showed that the recombinant sense and anti-sense genes were correctly integrated into genomic DNA of mesangial cells. The protein expression tested by Western blot showed that GRbeta in cells inserted with the sense hGRbeta gene was higher than those cells inserted with the anti-sense hGRbeta gene (109.74+/-10.63 vs. 19.08+/-1.01, P<0.05). The inhibitory rate of cell proliferation induced by dexamethasone was lower in GMCs transfected with sense hGRbeta gene than those transfected with anti-sense hGRbeta gene (18.47%+/-2.12% vs. 60.33%+/- 5.29%,P<0.05). Under the inhibition of dexamethasone, the decreased cell number of S-stage cells was significantly lower, and the increased cell number of G1- stage cells was significantly higher in GMCs transfected with sense hGRbeta gene than those of non-transfected cells. CONCLUSION: The overexpression of GRbeta may inhibit the glucocorticoid action in GMCs. The GRbeta level in mesangial cells may be an important factor in determining whether they are sensitive or resistant to glucocorticoid.
Assuntos
Glucocorticoides/farmacologia , Células Mesangiais/metabolismo , Receptores de Glucocorticoides/metabolismo , Animais , Linhagem Celular , Dexametasona/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/genética , TransfecçãoRESUMO
OBJECTIVE: To evaluate the benefits and toxicities of different corticosteroid regimes in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). METHODS: MEDLINE (Jan. 1963-Mar. 2007), elsevier (Jan. 1997-Aug. 2006), OVID databank (Jan. 1993-Aug. 2006), Springer databank (Jan. 1994-March 2007), the Cochrane Controlled Trials Register (Cochrane Library, Issue Feb. 2006), Cochrane Renal Group Specialised Register (Jul. 2006), EMBASE (Jan. 1980-Mar. 2007) and CNKI (Jan. 1994-Mar. 2007) etc, were searched by the terms primary nephrotic syndrome, glucocorticoid, corticosteroid, steroid, prednisone, methylprednisolone, dexamethasone and children etc for the human clinical trials about glucocorticoid (GC) administration in primary nephrotic syndrome (PNS) (aged 3 months to 18 years), controlled or semi-controlled ones, including unpublished documents from scientific meetings and theses, and similar documents listed in the references of the above documents were also included. All the studies were evaluated strictly according to Jadad Standard, and the Meta-analysis were adopted. Review manager 4.2 software was used to analyze the data. The odds ratio was calculated for the relapse rate and side effect from the initial episode to the end of follow-up between the patients treated with corticosteroids and the controls. RESULTS: Totally 12 trials with 868 subjects meeting the criteria were included in this review. A Meta-analysis of 7 trials, which compared between 2 months of prednisone and 3 months or more in the first episode, showed that longer treatment duration significantly reduced the risk of relapse at 12-24 months (RR=0.70,95% CI:0.60-0.89),without an increase of side effect. There was a negative linear relationship between the duration of treatment and risk of relapse (r2 =0.66, P=0.05). CONCLUSION: (1) Children in their first episode of SSNS should be treated for at least 3 months of GC. The therapeutic effect of patients in the primary nephrotic syndrome treated with GC for 12 weeks was prior to that for 8 weeks, compared with that in the controls. It could reduce the relapse rate of half year, the longer treatment duration in the NS patients at the first relapse was, the lower relapse risk was.(2) Compared with alternative GC administration, standard GC administration can reduce the side effects; Course more than 1 year of GC administration can reduce the 2-year relapse rate. Hence in children who relapse frequently, multicentre, well-designed experiments should be adopted.
Assuntos
Glucocorticoides/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Criança , Resistência a Medicamentos , Glucocorticoides/farmacologia , HumanosRESUMO
OBJECTIVE: To study the mobilization effects of stem cell factor (SCF) along with granulocyte colony-stimulating factor (G-CSF) on bone marrow stem cells and endothelial progenitor cells in rats with unilateral ureteral obstruction (UUO). METHODS: Fifty-six healthy male Wistar rats were randomly divided into seven groups: control, SCF, G-CSF, SCF+G-SCF, Sham-operated, UUO and UUO+SCF+G-CSF groups (n=8 each). The rats from the control, SCF, G-CSF and SCF+G-CSF groups were hypodermically injected with normal saline (2 mL/kg), SCF (200 microg/kg), G-CSF (200 microg/kg) and SCF along with G-CSF respectively for 5 days. The rats from the UUO and UUO+SCF+G-CSF groups were subjected to the ligation of right ureter and then were hypodermically injected with normal saline (2 mL/kg) and SCF (200 microg/kg)+G-CSF (200 microg/kg) respectively for 5 days. The sham-operated group had the same operative approach as the UUO and the UUO+SCF+G-CSF groups but the right ureter was not ligated. After operation they received a hypodermical injection of 2 mL/kg normal saline for 5 days. Five days later blood samples were collected. The percentages of CD34+ and CD34+/CD133+ cells in intravenous blood mononuclear cells were detected by flow cytometry. Serum contents of glutamate-pyruvate transaminase (GPT), glutamic oxalacetic transaminase (GOT), urea nitrogen and creatinin were measured. RESULTS: Except for the sham-operated group, the other five groups (SCF, G-CSF, SCF+G-SCF, UUO and UUO+ SCF+G-CSF groups) had significantly higher percentage of CD34+ cells and CD34+/CD133+ cells in intravenous blood mononuclear cells than the control group (P < 0.05). There were significant differences in the percentage of CD34+ cells and CD34+/CD133+ cells among the five groups (P < 0.05). The UUO+SCF+G-CSF group showed the highest percentage of CD34+ cells and CD34+/CD133+ cells, followed by the SCF+G-CSF group. There were no significant differences in serum contents of GPT, urea nitrogen and creatinin among the seven groups. Except the UUO group showed higher GOT contents, there were no significant differences in the GOT contents among the other six groups. CONCLUSIONS: The mobilization effects of SCF and G-CSF on bone marrow stem cells and endothelial progenitor cells were not always in paraller. A combination of SCF and G-CSF can effectively mobilize stem cells and endothelial progenitor cells, and side effects were not found in the liver and the kidney.