Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb / 中华儿科杂志

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

Efficacy and Safety of the Safe Triangular Working Zone Approach in Percutaneous Vertebroplasty for Spinal Metastasis

Objective@#This study aimed to assess the technical feasibility, efficacy, and safety of the safe triangular working zone (STWZ) approach applied in percutaneous vertebroplasty (PV) for spinal metastases involving the posterior part of the vertebral body. @*Materials and Methods@#We prospectively enrolled 87 patients who underwent PV for spinal metastasis involving the posterior part of the vertebral body, with or without the STWZ approach, from January 2019 to April 2022. Forty-nine patients (27 females and 22 males; mean age ± standard deviation [SD], 57.2 ± 11.6 years; age range, 31–76 years) were included in group A (with STWZ approach), accounting for 54 vertebrae. Thirty-eight patients (18 females and 20 males; 59.1 ± 10.9 years; 29–81 years) were included in group B (without STWZ approach), accounting for 57 vertebrae. Patient demographics, procedure-related variables, and pain relief as assessed using the visual analog scale (VAS) were collected at different time points. Tumor recurrence in the vertebrae after PV was analyzed using Kaplan–Meier curves. @*Results@#The STWZ approach was successful from T1 to L5 without severe complications. Cement filling was satisfactory in 47/54 (87.0%) and 25/57 (43.9%) vertebrae in groups A and B, respectively (v< 0.001). Cement leakage was not significantly different between groups A and B (p= 1.000). Mean VAS score ± SD before and 1 week and 1, 3, 6, 9, and 12 months after PV were 7.6 ± 1.8, 4.2 ± 2.0, 2.7 ± 1.9, 1.9 ± 1.5, 1.7 ± 1.4, 1.7 ± 1.1, and 1.6 ± 1.3, respectively, in group A and 7.2 ± 1.7, 4.0 ± 1.3, 3.4 ± 1.6, 2.4 ± 1.2, 1.8 ± 1.0, 1.4 ± 0.5, and 1.7 ± 0.9, respectively, in group B. Kaplan–Meier analysis showed a lower tumor recurrence rate in group A than in group B (p = 0.001). @*Conclusion@#The STWZ approach may represent a new, safe, alternative/auxiliary approach to target the posterior part of the vertebral body in the PV for spinal metastases.

Analysis of clinical characteristics of 35 inflammasomopathies cases / 中华儿科杂志

Objective: To summarize the clinical characteristics of inflammasomopathies, enhance the recognition of those diseases, and help to establish the early diagnosis. Methods: The clinical manifestations including fever, rash, systems involvement as well as laboratory results and genotypic characteristics of 35 children with inflammasomopathies diagnosed by the Department of Pediatrics, Peking Union Medical College Hospital, from January 1, 2008 to December 31, 2020 were analyzed retrospectively. Results: A total of 35 cases of inflammasomopathies were diagnosed, and 20 of them were boys while 15 were girls. Inflammasomopathies patients have early onset, the age of onset as well as diagnostic age were 1 (0,7) and 7 (3,12), respectively. Among those patients, 10 had familial mediterranean fever, 3 had mevalonate kinase deficiency, 15 cases had NLRP3 gene associated autoinflammatory disease, 4 cases had NLRP12-associated autoinflammatory disease, 2 cases had familial cold autoinflammatory syndrome 3, and 1 case had familial cold autoinflammatory syndrome 4. A total of 34 cases (97%) showed recurrent fever, 27 cases (77%) had skin rashes, while 11 cases (31%), 10 cases (29%), and 8 cases (23%) were presented with lymphadenopathy, hepatosplenomegaly and growth retardation, respectively. In terms of systemic involvement, there were 18 cases (51%), 12 cases (34%), 8 cases (23%), and 5 cases (14%) with skeletal, neurological, auditory, and renal involvement, respectively. Central nervous system involvement was seen only in NLRP3 gene associtated autoinflammatory diseases (12 cases), sensorineural deafness was seen in NLRP3 gene associtated autoinflammatory diseases (6 cases) and NLRP12 gene associated autoinflammatory diseases (2 cases), and abdominal pain was observed in familial Mediterranean fever (5 cases), mevalonate kinase deficiency (1 case) and NLRP12 gene related autoinflammatory diseases (1 case). In the acute inflammatory phase, the acute phase reactants (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) of 35 cases (100%) were significantly increased. There were 21 cases received ferritin examination, and only 4 cases (19%) showed an increase of it. In terms of autoantibodies, among all 35 patients, 4 cases (11%) were positive for antinuclear antibodies (ANA). Conclusions: Fever, skin rash, and skeletal manifestations are the most common clinical features, accompanied with increased CRP and ESR, and negative results of autoantibodies such as ANA. The clinical manifestations of those diseases are complex and diverse, and it is prone to delayed diagnosis and treatment.

Efficacy of Wenyangbushen Formula on mRNA Expression of Osteoprotegerin, Receptor Activator of Nuclear Factor-kappa B and Its Ligand in Rabbits with Steroid-induced Avascular Necrosis of Femoral Head / 中国康复理论与实践

Objective:To observe the effect of Wenyangbushen formula on mRNA expression of osteoprotegerin (OPG), receptor activator of nuclear factor- kappa B (RANK) and receptor activator of nuclear factor- kappa B ligand (RANKL) in rabbits with steroid-induced avascular necrosis of femoral head (SANFH). Methods:A total of 46 healthy conventional New Zealand white rabbits were randomly divided into normal group (n = 10) and model building group (n = 36). The modified method of horse serum plus methylprednisolone was used to establish the SANFH model. Two rabbits from the normal group and four from the model building group were used for HE staining. Then the other models were randomly divided into model group, and low-dose, medium-dose and high-dose treatment groups, with eight rabbits in each group. The normal group was given normal saline 10 ml/d, and the treatment groups were given Wenyangbushen formula 6.44 g/(kg·d), 9.66 g/(kg·d) and 12.88 g/(kg·d), respectively, for eight weeks. The mRNA expression of OPG, RANK and RANKL was detected by reverse transcription- polymerase chain reaction. Results:The empty lacuna rate was significantly higher in the model group than in the normal group (t = 17.085, P < 0.001). Compared with the model group, the mRNA expression of OPG increased (P < 0.01), and the mRNA expression of RANK and RANKL decreased (P < 0.01), in the treatment groups. Compared with the low-dose treatment group, the mRNA expression of OPG increased (P < 0.01), and the mRNA expression of RANK and RANKL decreased (P < 0.01), in the medium-dose and high-dose treatment groups. There was no significant difference in the mRNA expression of OPG, RANK and RANKL between the low-dose treatment group and the high-dose treatment group (P > 0.05). Conclusion:Wenyangbushen formula could increase the mRNA expression of OPG and inhibit the mRNA expression of RANK and RANKL in the femoral head tissue of the rabbits with SANFH.

Clinical features and TTC21B genotype of a child with nephronophthisis type 12 / 中国当代儿科杂志

Nephronophthisis (NPHP) is a group of autosomal recessive tubulointerstitial cystic kidney disorders. This article reports a case of NPHP type 12 caused by TTC21B mutations. The girl had an insidious onset, with moderate proteinuria, renal dysfunction, stage 2 hypertension, situs inversus, and short phalanges when she visited the hospital for the first time at the age of 3 years and 6 months. The renal lesions progressed to end-stage renal disease (ESRD) before she was 4 years old. Urine protein electrophoresis showed glomerular proteinuria. There were significant increases in urinary β2-microglobulin and α1-microglobulin. Gene detection revealed two compound heterozygous mutations, c.1552T>C (p.C518R) and c.752T>G (p.M251R), in the TTC21B gene, which came from her father and mother respectively. The c.752T>G mutation was a novel mutation. It is concluded that besides typical tubular changes of NPHP, marked glomerular damage is also observed in patients with TTC21B gene mutations.

A timeliness comparison of catheter in interval and screw-type catheters for enteral nutrition of patients with severe craniocerebral injury / 中国医学装备

Objective: To compare the timeliness of catheter in interval and screw-type catheters for enteral nutrition of patients with severe craniocerebral injury. Methods: 120 patients with severe craniocerebral injury were divided into observation group and control group as different catheter method. Patients of observation group received catheter in interval and that of control group received screw-type catheter. The success rate of catheterization, complication and beginning time of enteral nutrition between the two groups were compared. Results: The waiting time of observation group was significantly lower than that of control group (x2=94.925, P<0.05). During intubation, the difference of incidence of mild bleeding of nasal mucosa between the two groups was no significant. The respiratory tract ectopic or digestive tract perforation and other complications didn't appear in the two groups. Besides, the success rate of catheterization in 48h of observation group was significantly higher than that of control group (x2=40.752, P<0.05). Conclusion: The new method has higher timeliness for implementing enteral nutrition of patients with severe craniocerebral injury. And it is safe and effective.

Practical exploration of multi-teaching model in pediatric teaching among undergraduate medical students / 基础医学与临床

Objective To compare the effectiveness of implementation of multi-teaching model ( MT) and case based teaching ( CBT) in pediatric teaching among undergraduate medical students. Methods Eighty one trainee students were divided into CBT and MT groups. Scenario based teaching ( SBT) , sandwich teaching ( ST) and CBT were given to students of MT group. Results The self evaluation scores of " how much have you grasp before the class"by students after class in MT group were higher than those of CBT group[5.0(2.5,7,5) vs 4.0(3.0,5.0), Z=2.011,P＜0.05]. The scores of obstructive structured clinical examination after training of MT group were higher than those of CBT group[ 93.0(90.3,97.0) vs 83.25(78.3,86.4),Z=7.752,P＜0.001]. Conclusions MT is better than CBT in pediatric training among undergraduate medical students.

A clinical analysis of 15 children with systemic lupus erythematosus accompanied by pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical features, laboratory findings, diagnosis and treatment, and prognosis of children with systemic lupus erythematosus (SLE) accompanied by pulmonary hypertension (PH).</p><p><b>METHODS</b>The clinical symptoms, laboratory findings, echocardiographic features, SLE disease activity index, and treatment outcome of 15 hospitalized children with SLE accompanied by PH were retrospectively analyzed.</p><p><b>RESULTS</b>Among the 15 patients, the median interval from diagnosis of SLE to diagnosis of PH was 0.1 year (range: 0-6.5 years). Aside from PH-related symptoms, Raynaud's phenomenon was observed in 6 (40%) of the 15 patients. There was no significant difference in SLE disease activity (evaluated by complements 3 and 4 levels, erythrocyte sedimentation rate, and positive rate of anti-double-stranded DNA) between patients with mild-to-moderate PH and those with severe PH (P<0.05). As for treatment, 13 patients received immunosuppressive therapy with glucocorticoids, and among them 2 patients received PH-targeted therapy. During a median follow-up of 8.0 years (range: 0.5-18.1 years) since the diagnosis of PH, 2 deaths were noted with class III or IV cardiac function (World Health Organization), while the other patients were in a stable condition.</p><p><b>CONCLUSIONS</b>Raynaud's phenomenon is a common clinical manifestation in children with SLE accompanied by pulmonary hypertension (PH). PH severity is not significantly associated with SLE disease activity, and thus greater focus should be placed upon early screening of pulmonary arterial pressure in SLE patients. Early diagnosis and early treatment can improve the prognosis of children with SLE.</p>

SLC2A2 gene analysis in three Chinese children with Fanconi-Bickel syndrome / 中国当代儿科杂志

Fanconi-Bickel syndrome (FBS, OMIM 227810), a rare autosomal recessive disorder of carbohydrate metabolism, is caused by SLC2A2 (GLUT2) mutations. The study reported 3 cases of FBS who were confirmly diagnosed by SLC2A2 gene analysis. The three patients showed typical features like glycogen storage disease and proximal renal tubular nephropathy. Homozygous splice-site mutation IVS8+5G>C (c.1068+5 G>C) was found in patient A and homozygous nonsense mutation c.1194T>A (p.Tyr398X) in patient B. Patient C harboured a missense mutation c.380C>A (p.Ala127Asp) and a de novo insertion c.970dupT (p.324TyrfsX392) which was not inherited from her parents. Four mutations were identified in the 3 Chinese FBS patients. Except IVS8+5G>C mutation, the other 3 mutations were novel in Chinese population. To the best of our knowledge, patient C may be the first FBS case worldwide with de novo mutation.

Application of plasma clearance of iohexol in evaluating renal function in chinese children with chronic kidney disease / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the accuracy of plasma clearance of iohexol (PCio) for glomerular filtration rate (GFR) measurement in Chinese children with chronic kidney disease (CKD) and assess the feasibility of single-blood-sample method or dried capillary blood spots in determining the PCio.</p><p><b>METHODS</b>Totally 45 CKD children were included,in whom the (99m) Technetium-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) plasma clearance and iohexol plasma clearance were simultaneously determined. Blood samples were obtained 2,4,and 5 hours after injection. In addition, we also evaluated the efficacy of single blood sample method and dried blood spots method in iohexol plasma clearance.</p><p><b>RESULTS</b>Forty-five CKD children completed the iohexol plasma clearance and thirty-six children completed the (99m)Tc-DTPA plasma clearance at the same time among them. Thirteen children finished the iohexol dried blood spot clearance. The correlation coefficient between (99m)Tc-DTPA plasma clearance and iohexol plasma clearance was 0.941 and the bias was (6.53 ± 11.6) ml/ (min·1.73 m²), and the intraclass correlation coefficient (ICC) was high (ICC=0.947). The correlation between iohexol single-sample plasma clearance and double samples was also strong (r=0.958), with the bias being (4.26 ± 9.06)ml/(min·1.73 m²) and the ICC being 0.970. The iohexol clearance by dried blood spots showed a good correlation with the serum iohexol clearance (r=0.950), with the bias still being small [(0.48 ± 10.89)ml/(min·1.73 m²)].</p><p><b>CONCLUSIONS</b>Iohexol plasma clearance has satisfactory agreement with (99m)Tc-DTPA plasma clearance and can be used as an ideal method to measure GFR in CKD children. The single-sample method and dried blood spots method make iohexol plasma clearance more convenient and practical.</p>

A splicing mutation of EXT1 in a Chinese pedigree with hereditary multiple exostoses / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Hereditary multiple exostoses (HME) is an autosomal dominant monogenic disorder of paraplasia ossium. Mutations in EXT1 and EXT2 have been suggested to be responsible for over 70% of HME cases. This study aimed to analyze the clinical features and pathogenic mutations in a Chinese family with HME (6 patients in 24 members of 3 generations) and to review the relative literature regarding mutations in EXT1 and EXT2 in the Chinese population.</p><p><b>METHODS</b>Clinical pedigree dada from a Chinese family of HME were collected and analysed. EXT gene mutations in this pedigree assessed by PCR and sequencing. Pubmed and Wanfang (a Chinese database) were searched for the literature related to gene mutations in Chinese HME patients.</p><p><b>RESULTS</b>In the pedigree analyzed, the age of onset of HME was becoming younger, the disease was becoming more severe, and the number of osteochondromas was increasing, in successive generations. A splicing mutation IVS5+1G>A, first identified in Chinese population, was found in all diseased members of this pedigree. According the currently available literature, EXT1 and EXT2 mutations have been detected in 29% (26/90) and 43% (39/90) Chinese families with HME.</p><p><b>CONCLUSIONS</b>HME starts earlier and becomes more severe and extensive with each successive generation in members of the pedigree analyzed. A splicing mutation, IVS5+1G>A, of EXT1, first identified in Chinese population, may be responsible for HME in the studied pedigree. EXT1 and EXT2 mutation rates may be different between the Chinese and Western populations.</p>

Clinical characteristics of Pneumocystis carinii pneumonia in children with systemic lupus erythematosus / 中华儿科杂志

<p><b>OBJECTIVE</b>To identify the risk factors which will indicate the Pneumocystis carinii (Pc) infection in children with systemic lupus erythematosus (SLE) and investigate the clinical features and to elevate the level to find out the high-risk patients and make early diagnosis and treatment.</p><p><b>METHOD</b>The characteristics, clinical features, laboratory examinations, treatment and prognosis of Pneumocystis carinii pneumonia (PCP) in children with SLE under 18 years of age treated in our hospital between January 2000 and January 2013 were prospectively reviewed. A comparison was made with the 26 cases of SLE children without PCP who were matched for gender, age and course, and a literature review was made.</p><p><b>RESULTS</b>(1) Five cases were enrolled, 3 were male and 2 female. Their age range was 13-17 (14.0 ± 1.6) years. All the children had kidney involvement. The courses were from 3 months to 4.5 years. All patients were receiving daily glucocorticoid therapy and immunosuppressive drugs before the diagnosis of PCP.Four patients were in the inactive phase of SLE (SLEDAI 2-4 points), and the fifth case was in active phase (SLEDAI 8, low complement 2 points, anti-dsDNA antibody positive 2 points, urine-protein 4 points). (2) Besides the clinical manifestations of SLE, most patients had progressive dyspnea, fever and dry cough at onset of PCP. Two children accepted mechanical ventilation because of respiratory failure. The mean duration of the symptoms to diagnosis was 10-30 (17.6 ± 7.8) days. Lactose dehydrogenase (LDH) was elevated more or less, median was (700 ± 263) U/L. Lymphocyte count were (0.3-1.4)×10(9)/L (median 0.5×10(9)/L), and three children had CD4 T lymphocyte count <0.3×10(9)/L. Arterial blood gas analyses showed severe hypoxemia. Chest radiographs showed in all cases diffuse interstitial infiltration. Pc was positive in the sputum. All patients were treated with trimethoprim-sulfamethoxazole and corticosteroids.</p><p><b>CONCLUSION</b>When SLE children are treated with corticosteroids and immunosuppressive drugs, low lymphocyte count is the risk factor for Pc infection.It is essential to monitor lymphocyte count.We should pay more attention to fever, dry cough and hypoxemia. Chest radiologic examination may help diagnose the PCP in SLE children.It may be helpful for SLE children whose CD4T lymphocyte was below 0.3×10(9)/L to take trimethoprim-sulfamethoxazole for PCP prophylaxis.</p>

Significance of detecting the EBV-DNA level in peripheral blood mononuclear cells and the EBV-infected cell type in patients with chronic active EBV infection / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the difference in the EBV-DNA level in peripheral blood mononuclear cells (PBMC) and the type of Epstein-Barr virus (EBV)-infected cells in pediatric patients with chronic active EBV (CAEBV) infection, acute EBV infection (AEBV) and healthy children, and to analyze the relationship between the above difference and the clinical manifestation of CAEBV.</p><p><b>METHOD</b>Real-time fluorescent quantitative polymerase chain reaction (PCR) was used to detect the EBV-DNA levels in peripheral blood mononuclear cells (PBMC) in 12 normal children, 10 pediatric patients with CAEBV infection and 13 pediatric patients with AEBV infection in our hospital between March 2004 and April 2008. Immunomagnetic bead cell fractionation and fluorescent in situ hybridization (FISH) by EBV encoding RNA-1 ( EBER-1) probe were used in the healthy children, EBV-DNA positive CAEBV patients and AEBV patients to detect the type of EBV-infected cells.</p><p><b>RESULT</b>The average EBV-DNA level in CAEBV patients' PBMC was (6.8 x 10(7) +/- 1.1 x 10(8)) copies/ml, while the average EBV-DNA level of AEBV patients' PBMC was (1.3 x 10(6) +/- 1.6 x 10(6)) copies/ml. The average EBV-DNA level of CAEBV infected patients' PBMC was significantly higher than that of AEBV infected patients' PBMC (P<0.01). The cell fractionation and FISH in seven CAEBV patients showed that EBV in CAEBV patients infected not only B cells, but NK cells and CD4+ and CD8+ T cells to different degree, and these patients presented recurrent and persistent infectious mononucleosis (IM)-like symptoms. In 6 CAEBV patients infection mainly occurred to T cells, in one case, infection occurred mainly in CD8+ T cells, and the patient died from fulminant and deadly T lymphocytes proliferative syndrome except presenting firstly high fever, enlargment of the liver, spleen, lymphnode and the severe decrease of one or three kinds of blood cells. In 1 CAEBV patient the infection was mainly found in NK cells, who presented with hypersensitivity to mosquito biting and high IgE level (2500 U/ml). But EBV in seven AEBV patients infection was found only in B cells who presented with only IM for one time and no EBV-infected PBMC were found in the remaining 6 healthy children.</p><p><b>CONCLUSION</b>There are much more EBV replications and different EBV-infected cell types in CAEBV patients. Detection of EBV-DNA level by real-time fluorescent quantitative PCR and the detection of the type of EBV-infected cells may help in diagnosis, treatment and development evaluation of children with CAEBV infection.</p>

Stimulatory effect of TNF-α on differentiation and maturation of dendritic cells / 中国实验血液学杂志

The study was aimed to explore the stimulatory effect of tumor necrosis factorα (TNF-α) on differentiation and maturation of human peripheral blood mononuclear cell-derived dendritic cells (PBMNCDC). 30 ml of peripheral blood from healthy volunteers were collected, the PBMNC were isolated according to Thomas' method and were cultured with incubation of granulocyte/macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) for 8 day, and TNF-α was added on day 5. The expression of HLA-DR, CD83 and CD1a on surface of DC were detected by flow cytometry, the ability of DC to stimulate the proliferation of allogenic T cells was evaluated by MTT assay. The results showed that the TNF-α could up-regulate the expression of HLA-DR, CD83 and CD1a and activated DC could enhance the proliferation of allogenic T cells. Furthermore, the TNF-α at the concentration of 20 ng/ml was more effective. It is concluded that the TNF-α can effectively enhance the functional differentiation and maturation of the PBMNCDC and TNF-α at the concentration of 20 ng/ml is most effective to enhance differentiation and maturation of DC.

Differential effect of three mitogen-activated protein kinases on lipoprotein (a)-induced human mesangial cell proliferation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mesangial hypercellularity is a critical early histopathological finding in human and experimental glomerular diseases. Hyperlipidemia and the glomerular deposition of lipoproteins are commonly associated with mesangial hypercellularity and play an important pathobiological role in the development of glomerular diseases. The activated cytoplasmic mitogen-activated protein kinase (MAPK), including mainly extracellular-signal regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38, has been thought to translocate into the nucleus and activate various transcription factors and protooncogenes associated with cell growth and proliferation. Lipoprotein (a) (Lp(a)) has been shown to stimulate proliferation of mesangial cells, but the events of Lp(a) signaling have not yet been characterized. The purpose of this study was to investigate the signal transduction pathways involved in Lp(a)-induced cell proliferation and provide an evidence for the participation of Lp(a) in intracellular signaling pathways for mesangial cell proliferation.</p><p><b>METHODS</b>Lp(a) was isolated from a patient who was being treated with low density lipoprotein (LDL)-apheresis by density gradient ultracentrifugation and then chromatography. Human mesangial cells (HMCs) were isolated by the sequential sieving technique and stimulated with Lp(a) in different concentration and time course. The DNA synthesis of the cells was measured by [3H] thymidine incorporation for detecting the proliferation. The expression of all the three members of MAPK family, including ERK1/ERK2, JNK, and p38, and their phosphorylation were detected by Western blotting.</p><p><b>RESULTS</b>Lp(a) could induce a significant dose-dependent proliferation of HMCs. The 3H-TdR incorporation was 1.64+/-0.31, 1.69+/-0.48, 3.59+/-0.68 (P<0.01), 4.14+/-0.78 (P<0.01), and 4.05+/-0.55 (P<0.01) (10(3) cpm) at the Lp(a) concentration of 0, 5, 10, 25, and 50 microg/ml, respectively. Lp(a) induced an increase in ERK1/ERK2 phosphorylation between 5 and 60 minutes, and in JNK phosphorylation between 15 and 30 minutes after incubating with HMCs, whereas the level of p38 and its phosphorylation was not changed.</p><p><b>CONCLUSIONS</b>Lp(a) could stimulate the proliferation of HMCs by activiating the phosphorylation of ERK1/ERK2 and JNK MAPK signaling pathway, whereas p38 pathway had no effect on the Lp(a)-induced HMC proliferation, which indicated that three MAPKs seem to be distinctly involved in the effect. In particular, it also provides the evidence that Lp(a) may act as one of the major endogenous modulators for mitogenic signaling response and cell proliferation within the glomerulus.</p>

Clinical manifestations, laboratory test, treatment and outcome of neuropsychiatric involvement in pediatric systemic lupus erythematosus patients / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical manifestations, laboratory test, treatment and outcome of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (SLE) patients.</p><p><b>METHODS</b>Seventy-seven patients with NP syndromes of SLE (NPSLE) seen from 1987 to 2007 were retrospectively reviewed. The relationship between the relative factors and the relapse of NPSLE was analyzed with logistic regression model.</p><p><b>RESULTS</b>NPSLE was found in 17.3% of the SLE patients and 75% of the NPSLE patients the NP involvements occurred in the first 2 years of the onset of SLE. The most frequent NP manifestations were headache (31.8%) and seizure disorder (29.1%). In the active phases, the levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores of the 92.2% patients were higher than 15 and belonged to severe lupus. The patients were accompanied frequently with fever (88.3%) and rash (84.4%). The most frequently involved organs were kidney (76.6%) and blood system (67.5%). In the active phases, the ANA was positive (98.7%), the level of ESR increased (86.3%), the level of complement profile decreased (72.7%). The cerebrospinal fluid (CSF) study, the CT, the MRI and the EEG were abnormal (90.1%, 60.7%, 54.8%, 73.9%, respectively). All the patients received glucocorticoids and immunodepressant treatment in which 79.2% received IV high-dose methylprednisolone (MP), 51.9% received intrathecal (IT) methotrexate (MTX) and dexamethasone (DXM), 26.0% received IVIG, 2 patients received autologous peripheral blood stem cell transplantation. The mortality was 9.0%. The rate of relapse was 22.0% and in 75.0% of relapsed patients the relapse occurred within 24 months from the onset of NPSLE. The SLEDAI scores related to the relapse of the NPSLE (chi(2) = 3.987, P = 0.0459, OR = 1.172, 95% CI 1.003 and 1.370).</p><p><b>CONCLUSION</b>SLEDAI scores were significantly helpful in predicting recurrence of NPSLE.</p>

Characteristics of peripheral blood lymphocyte immune subsets in patients with chronic active Epstein-Barr virus infection / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the characteristics of the peripheral blood lymphocyte subsets in pediatric patients with chronic active EBV (CAEBV) infection.</p><p><b>METHOD</b>Flow cytometry was used to detect the peripheral blood NK, B, T lymphocyte subsets and the functional, regulatory, naïve, memory and activatory subsets of T lymphocytes in 10 pediatric patients with CAEBV infection, 13 pediatric patients with acute Epstein-Barr virus infection (AEBV) and 12 healthy children in our hospital between March 2004 and April 2008.</p><p><b>RESULT</b>Compared with AEBV group, the number of white blood cells [3325 x 10(6)/L (median, just the same as the following)], lymphocytes (1078 x 10(6)/L), NK cells (68 x 10(6)/L), B cells (84 x 10(6)/L), total T cells (684 x 10(6)/L), CD4+ T cells (406 x 10(6)/L) and CD8+ T cells (295 x 10(6)/L) in CAEBV patients were lower (P<0.05). The functional subset of the CD4+ T cells in CAEBV group (94.5%) was lower than those of the healthy control group (98.7%) (P<0.05), but was still higher than those of AEBV group (74.0%) (P<0.05). While the functional subset of the CD8+ T cells in CAEBV (40.7%) was not dramatically different from the healthy control group (48.3%), but was still higher than that of AEBV group (21.0%) (P<0.05). Although the regulatory subset in CAEBV group (5.0%) was higher than the health control group (4.6%) (P<0.05), but lower than AEBV group (5.8%) (P<0.05). In CAEBV, the proportion of CD4+/CD8+ naïve T cells (32.3%/37.5%) was lower than that of normal group (58.3%/56.6%) (P<0.05), but the proportion of CD4+/CD8+ effective memory T cells in CAEBV group (23.9%/15.1%) was lower than that in AEBV group (36.5%/69.8%) (P<0.05), while the proportion of CD8+ fake naïve T cells in CAEBV (17.5%) was higher than the other 2 groups (P<0.05). The CD8+ activatory subset in CAEBV group (84.4%/34.0%) was higher than that of the healthy control group (44.1%/16.7%) (P<0.05), but still lower than AEBV group (96%/95%) (P<0.05).</p><p><b>CONCLUSION</b>There is an imbalance in lymphocyte subsets and disturbance in cellular immunity in CAEBV patients, which may be associated with EBV chronic active infection. Detecting the peripheral haematologic parameters and lymphocyte subsets may be helpful in the diagnosis and the differential diagnosis of CAEBV.</p>

Diagnosis of glycogen storage disease type IIIA by detecting glycogen debranching enzyme activity, glycogen content and structure in muscle / 中华儿科杂志

<p><b>OBJECTIVE</b>Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by glycogen debranching enzyme (GDE) gene (AGL gene) mutation resulting in hepatomegaly, hypoglycemia, short stature and hyperlipidemia. GSD IIIA, involves both liver and muscle, and accounts for up to 80% of GSD III. The definitive diagnosis depends on either mutation analysis or liver and muscle glycogen debranching enzyme activity tests. This study aimed to establish enzymologic diagnostic method for GSD IIIA firstly in China by detecting muscular GDE activity, glycogen content and structure and to determine the normal range of muscular GDE activity, glycogen content and structure in Chinese children.</p><p><b>METHOD</b>Muscle samples were collected from normal controls (male 15, female 20; 12-78 years old), molecularly confirmed GSD III A patients (male 8, female 4, 2-27 years old) and other myopathy patients (male 9, 2-19 years old). Glycogen in the muscle homogenate was degraded into glucose by amyloglucosidase and phosphorylase respectively. The glycogen content and structure were identified by glucose yield determination. The debranching enzyme activity was determined using limit dextrin as substrate. Independent samples Kruskal-Wallis H test, Nemenyi-Wilcoxson-Wilcox test, and Chi-square test were used for statistical analyses by SPSS 11.5.</p><p><b>RESULT</b>(1) GSD III A patients' glycogen content were higher, but G1P/G ratio and GDE activity were lower than those of the other two groups (P < 0.01). In all of the three parameters, there were no significant difference between normal controls and other myopathy patients. (2) The range of normal values: glycogen content 0.31%-0.43%, G1P/G ratio 22.37%- 26.43%, GDE activity 0.234-0.284 micromol/(g. min). (3) Enzymologic diagnostic method had a power similar to that of gene analysis in diagnosis of GSD-IIIA patients. The sensitivity and specificity of enzymologic diagnostic method and mutation detection were 91.7% and 100% respectively.</p><p><b>CONCLUSION</b>Enzymologic diagnostic method of GSD IIIA was firstly established in China. The range of normal values was determined. This method could be used in diagnosing suspected GSD IIIA patients in the clinic.</p>

Clinical characteristics and follow-up of 12 cases with severe chronic active Epstein-Barr virus infection / 中华儿科杂志

<p><b>OBJECTIVE</b>There are two different types of chronic active Epstein-Barr virus (CAEBV) infection: chronic EBV (CEBV) having persistent infectious mononucleosis (IM)-like illness with relatively good prognosis, and severe CAEBV (SCAEBV)infection that has rather severe manifestations and generally poor prognosis with many life-threatening complications, such as EBV-associated malignant lymphoma and hemophagocytic syndrome (HPS). The purpose of this study was to clarify the clinical and prognostic characteristics in 12 cases with SCAEBV infection.</p><p><b>METHOD</b>Data of 12 cases with SCAEBV infection were analyzed retrospectively, which included clinical and auxiliary examination, pathological data, especially EB virus (EBV)-antibodies and DNA in peripheral blood mononuclear cells (PBMC) and infected tissue, and follow-up information.</p><p><b>RESULT</b>Of the 12 cases, 7 were male and 5 were female. The age at the onset of diseases ranged from 35 months to 14 years (median, 11 years). The major manifestations were fever (100%), splenomegaly (91.7%), hepatomegaly (83.3%), lymphadenopathy (75.0%), and others, including skin rash, development retardation, jaundice, ascites, pulmonary hypertension, oral ulcer, cholecystitis and pleural effusion. The abnormalities of auxiliary examination were as follows: elevated LDH level (91.7%), liver dysfunction (83.3%), anemia (75.0%), leukopenia (58.3%), neutropenia (50.0%), thrombocytopenia (25.0%) and abnormal chest X-ray findings. At the time of onset, 58.3% of the patients had an IM-like illness. In all of the 12 cases, EBV serologic tests revealed high IgG antibody levels against EB viral capsid antigen (VCA). The patients often had positive IgM and IgA antibodies against VCA (33.3% and 66.7%) as well. Elevated IgG antibody level to early antigen (EA) (100.0%), occasionally positive IgA antibody (40.0%) were also seen. The mean load of EBV-DNA detected by real-time polymerase chain reaction (PCR) in the PBMC was (8.12 x 10(6), median)copies/ml. Four of 12 cases presented a poor clinical course, two of whom died from EBV-associated HPS, 1 from severe multiple pathogens infection, and 1 from multiple organ failure. In addition, 1 case developed Hodgkin's T cell lymphoma and another case showed hepatopulmonary syndrome in 2 years after splenectomy.</p><p><b>CONCLUSIONS</b>The clinical feature of SCAEBV infection varied exceedingly. EBV-DNA load in PBMC of SCAEBV infected patients was significantly increased. More attention should be paid to the disease because of its severe complications, poor prognosis and high mortality.</p>

Relapsing polychondritis in childhood: report of three cases and review of the literature / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical features, diagnosis, treatment and prognosis of relapsing polychondritis (RP) in childhood.</p><p><b>METHODS</b>A retrospective analysis of three cases of childhood RP from our hospital on clinical features, diagnosis and treatment was performed, data of the other sixteen cases from MEDLINE were also reviewed. Clinical features of all nineteen children with RP were compared with adults with RP.</p><p><b>RESULTS</b>The age of the three cases at the time of diagnosis ranged from 10 years to 15 years (the minimum age was 2 years in the literature). The course from onset of clinical symptom to making definite diagnosis varied from 3 months to 9 months (from 3 months to 2 years in the literature). In the three cases, childhood RP affected multiple system/organs, and produced diverse clinical manifestations such as arthritis, auricular chondritis, nasal chondritis (leading to a saddle nose deformity), conjunctivitis and so on. Also, tracheostomy was performed because of severe difficulty in breathing for all the 3 cases. Compared with adult RP, involvement of respiratory system existed in 78.9% of childhood patients, which was more frequent and serious than that of adult cases with RP (35.2%); arthritis was the most common clinical manifestation and first symptoms; Fewer children with RP were associated with other autoimmune diseases than adults. Although both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) blood levels were high in the three cases, anti-nuclear antibody (ANA), double stranded DNA (dsDNA) and extractable nuclear antigen (ENA) were all negative, it was difficult to define the diagnosis of RP because there were no specific laboratory indicators for diagnosis. The confirmation of diagnosis of two cases was relied on clinical criteria, while another case got pathological material for diagnostic support. CT images with three-dimensional reconstruction of the respiratory tract were helpful for early diagnosis of childhood RP. All the three patients were responsive to glucocorticoid, especially to methylprednisolone, however, recurrence of RP was frequent. Treatment with etanercept was successful in one case with refractory RP.</p><p><b>CONCLUSIONS</b>It is very important to obtain detailed medical history, complete physical examination and do necessary laboratory and imaging tests (e.g. CT images with three-dimensional reconstruction of the airways, pulmonary function tests and so on) for reducing misdiagnosis or missed diagnosis. Glucocorticoid and immunosuppressants are usually effective for childhood RP, but the effects may not be lasting. Etanercept may be a new option to treat refractory RP in childhood.</p>