Objective To investigate the effect of orphan nuclear receptor NR4A1 expression on oxygenglucose deprivation (OGD)-induced apoptosis in cultured rat cerebellar granule neurons and its possible mechanisms.Methods Primary rat cerebellar granule neurons were cultured for 7 to 8 days,and then treated with OGD.The activity of cultured rat cerebellar granule neurons was assessed by methyl thiazolyl tetrazolium (MTT) assay,apoptosis was detected with flow cytometry,the expressions of NR4A1,caspase-3 and cytochrome c were determined by Western blot analysis,NR4A1 mRNA expression was detected with real-time polymerase chain reaction.The rat cerebellar granule neurons were transfected with lentiviral vector-encoding rat NR4A1.The apoptotic rates and expressions of caspase-3 and cytochrome c in rat cerebellar granule neurons transfected with NR4A1 were detected after OGD.Results The activity of rat cerebellar granule neurons decreased significantly,the apoptotic rate increased significantly,the expressions of NR4A1 mRNA and protein as well as caspase-3 and cytochrome c incrased significantly along with the OGD time.NR4A1 was overexpressed,apoptosis rate was significantly reduced in rat cerebellar granule neurons transfected with NR4A1.The expressions of caspase-3 and cytochrome c were significantly reduced in the rat cerebellar granule neurons transfected with NR4A1 after OGD.Conclusions NR4A1 overexpression may reduce OGD-induced apoptosis in rat cerebellar granule neurons by downregulating the expressions of caspase-3 and cytochrome c.

Vascular endothelial growth factor (VEGF) is a powerful angiogeuetic factor. In recent years, it has been found that it has a powerful capacity to promote nerve regeneration, and has potential value in the treatment of ischemic cerebrovascular disease. Newborn endothelial celts can form "vascular niche", and promote neurogenesis by releasing an array of neurotrophic factors. Also, newborn neuronal cells can enhance angiogenesis. There is a "cross-talk" between angiogenesis and neurogenesis, and VEGF plays a very important intermediary role in it. This article reviews the studies of VEGF in promoting angiogenesis and neurogenesis after cerebral ischemia.

Objective: To summarize the clinical features and genetic analysis results of 10 children with Dent disease. Methods: The clinical data and gene test results of 10 boys aged from 8 months to 12 years with Dent disease diagnosed in Children's Hospital of Nanjing Medical University from January 2014 to July 2017 were analyzed retrospectively. Results: All patients had insidious onset, 5 cases were found to have proteinuria on routine urine examination after hospitalization duo to other diseases, 4 cases were admitted to hospital because increased foams in the urine, and 1 case was found to have proteinuria on health checkup. All cases presented with low molecular weight proteinuria, urine protein electrophoresis showed that the proportion of low molecular weight protein was greater than 50%, 7 cases had nephrotic-range proteinuria, but none had hypoproteinemia. Six cases had hypercalciuria, 3 cases had nephrocalcinosis, 1 case had nephrolithiasis, 2 cases had glomerular microscopic hematuria, in 1 case urine glucose wa weakly positive but blood glucose was normal. All patients had normal renal function, normal serum calcium, no hypophosphoremia and none had rickets. Genetic analysis results showed that 7 patients with variants in the CLCN5 gene, including 2 nonsense variants (p.R637X, p.Y143X), 3 missense variants (p.A540D, p.G135E, p.G703V), 1 deletion variant (exons 9, 10, 11, 12, 13, 1 missing), and 1 frameshift variant (p.T260Tfs*10). Three cases had missense variants of OCRL gene (p.I274T, p.I371T, p.F399S). Except for p.R637X and p.I274T, the other 8 cases had newly discovered variants. Five patients underwent a renal biopsy, the biopsy revealed focal global glomerulosclerosis in 3 patients, mild mesangial proliferative glomerulonephritis in 1 patient and renal minimal change in 1 patient. Mild focal tubular atrophy and interstitial fibrosis were noted in three cases. Mild segmental foot process effacement was noted under electron microscope in all five cases. Conclusions All the children with Dent disease had insidious onset, low molecular weight proteinuria is the main clinical manifestation, most cases presented with nephrotic-range proteinuria, but there was no hypoalbuminemia, some cases were not associated with hypercalciuria. The pathogenic genes in most cases were CLCN5 and a few were OCRL. The types of genetic variation include missense variant, nonsense variant, deletion variant and frameshift variant. Although Dent disease is a renal tubular disease, renal biopsy suggests that most cases are associated with glomerular lesions.

Objective:To analyze the clinical data of corona virus disease 2019 (COVID-19) in pregnant women, and to study the characteristics of disease onset, diagnosis and treatment in pregnant women complicated with COVID-19.Methods:The clinical data of 29 pregnant women with COVID-19 hospitalized in Renmin Hospital of Wuhan University from January 30 to February 23, 2020 were retrospectively analyzed. The disease characteristics and experiences of diagnosis and treatment were concluded. The first day of onset was defined as the day when respiratory symptoms such as fever, cough, fatigue, and chest tightness occurred. Group one was admitted to the hospital within the first week of onset, and group two was hospitalized during the second week of onset. Statistical analysis was conducted by t test and Mann-Whitney U test. Results:The age of 29 patients ranged from 24 to 40 years old, with fever, cough and fatigue as the initial symptoms. There were five cases in the first trimester of pregnancy, five cases in the second trimester and 19 cases in the third trimester of pregnancy. There were 28 ordinary patients and one severe patient. Among the 29 patients, 14 were hospitalized in the first week of onset (group one), nine in the second week of onset (group two), and the remaining six were asymptomatic. On the day of admission, 22 patients showed lymphocytopenia in complete blood count and all the indicators of cellular immunity (CD3 + , CD4 + , CD8 + , CD19 + , CD16 + CD56 + T lymphocytes) were reduced in two patients. There were no significant differences between patients in group one and group two (all P>0.05). The levels of IgE and complement 3 were 28.45(18.30, 51.70) IU/mL and (1.219±0.320) g/L in group one, and 20.30(18.30, 75.80) IU/mL and (1.170±0.147) g/L in group two. The differences were statistical significance ( U=67 222.000, t=0.442, P=0.024、0.028). Primary chest computed tomography revealed ground-glass opacity in all 29 cases, which was considered as the diagnostic marker of viral pneumonia. Conventional therapy such as oxygen inhalation, antiviral, anti-infection was the main regimen for COVID-19 in pregnant women. Methylprednisolone and gamma globulin could be used for severe patients or ordinary patients with disease progression and slow recovery. No abortion or premature delivery occurred in patients in the first and second trimester of pregnancy. But in the third trimester of pregnancy patients, three cases of preterm labor and 13 cases of full-term pregnancy were all given emergency cesarean section after admission. One patient admitted to the hospital at gestation of 35 weeks underwent expectant management and then was given cesarean section at 37 weeks + 6 gestation. 2019 novel coronavirus nucleic acid detection in 17 neonatal nasal and pharyngeal swabs were all negative. Nineteen patients were cured and discharged, and the course of the patients was (19.60±5.38) days. The remaining 10 patients in hospital were mild. Conclusions:The COVID-19 patients with pregnancy generally exhibit mild symptoms and a favorable recovery. Concurrent damages to heart, liver and kidney and vertical transmission rarely occur. Most of the patients could be cured under routine treatment.

Objective:To investigate the clinical manifestations, pathological characteristics, treatment and prognosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in 13 children.Methods:The clinical and pathological data of 13 cases of AAV in children′s Hospital of Nanjing Medical University from June 2000 to December 2021 were retrospectively analyzed.Results:Among the 13 cases, 12 cases were diagnosed with microscopic polyangiitis (MPA) and 1 case was granulomatosis with polyangiitis (GPA), including 10 females and 3 males. The onset age ranged from 3 years and 11 months to 13 years and 10 months. The most frequently involved organ was the kidney (12 cases, 92.3%), followed by respiratory system (7 cases, 53.8%), skin (5 cases, 38.5%), digestive system (4 cases, 30.8%), nervous system (4 cases, 30.8%) and cardiovascular system (3 cases, 23.1%). There were 10 cases with orthotic anemia, 7 cases with positive antinuclear antibody, and 3 cases with mildly decreased complement C3. Among the 12 children with renal impairment, 9 cases were accompanied by abnormal renal function at the beginning of the disease. Renal biopsy was classified according to the Berden as follows: sclerotic in 5 cases, crescentic 3 cases, focal in 2 cases and mixed in 2 cases. All children were treated with glucocorticoid combined with immunosuppressant. During the follow-up time from 8 months to 128 months, 4 cases acquired complete remission, 8 cases achieved partial remission and 1 case recurred after complete remission, and 7 cases progressed to chronic kidney disease stage 5. Three children with complete remission underwent repeated renal biopsy, including 2 cases of mixed type and 1 case of crescent type initially, and all changed to focal type.Conclusions:AAV in children occurs mainly in school-age female, and most of AAV in children is MPA. The clinical manifestations are various. Most of them have renal damage and anemia, and lung damage is also common. Patients with skin purpura onset may be misdiagnosed as Henoch-Schonlein purpura, and AAV with ANA positive or complement reduction should exclude systemic lupus erythematosus. Once the renal function is abnormal in AAV, especially estimated glomerular filtration rate<60 ml·min -1·(1.73 m 2) -1 and the pathological classification is sclerotic type or crescent type, it is difficult to reverse even after active treatment. Early diagnosis and treatment are very important for AAV.

Objective:To analyze the clinical and pathological features of adolescent- onset primary nephrotic syndrome (PNS) in children (10 years≤age≤18 years), so as to explore the renal biopsy indications in adolescent-onset PNS.Methods:It was a single-center retrospective observational study. The clinical and pathological data of adolescent-onset PNS (age≥10 years) who underwent renal biopsy in Children's Hospital Affiliated to Nanjing Medical University from December 2004 to June 2022 were analyzed retrospectively.Results:A total of 110 children were included in the study, including 76 males (69.1%) and 34 females (30.9%), with the onset age ranging from 10 years to 14 years and 9 months. Forty-nine cases (44.5%) were accompanied by hematuria, including 14 cases (12.7%) of gross hematuria and 35 cases (31.8%) of microscopic hematuria. Twenty-five cases (22.7%) had hypertension, 19 cases (17.3%) had renal insufficiency, and 4 cases (3.6%) had low complement C3 at the onset. Fifty-two cases (47.3%) were steroid sensitive nephrotic syndrome and 58 cases (52.7%) were steroid resistant nephrotic syndrome. Biopsy results showed that minimal change disease(MCD) was the most common histopathological subtype (47.3%, 52 case), followed by focal segmental glomerulosclerosis (FSGS) in 22 cases (20.0%), IgA nephropathy (IgAN) in 17 cases (15.5%), membranous nephropathy (MN) in 7 cases (6.4%), mesangial proliferative glomerulonephritis in 5 cases (4.5%), IgM nephropathy in 4 cases (3.6%), membranous proliferative glomerulonephritis in 2 cases (1.8%), and C1q nephropathy in 1 case (0.9%). Among 44 children with simple type nephrotic syndrome, the pathological type was mainly MCD (77.3%), and 66 children with nephritic type nephrotic syndrome were mostly non-MCD (72.7%), such as IgAN, FSGS, MN, etc. If there are two or more clinical manifestations of persistent hematuria, hypertension, renal insufficiency or low C3 levels, the proportion of non-MCD would further increase to 92.0%(23/25). The pathological type of patient with gross hematuria or low C3-emia was non-MCD. The frequency of hematuria (69.0% vs. 17.3%, χ2=29.619, P<0.001), hypertension (31.0% vs. 13.5%, χ2=4.821, P=0.028) and renal insufficiency (24.1% vs. 9.6%, χ2=4.047, P=0.044) in non-MCD group was significantly higher than those in MCD group. Conclusions:If the clinical manifestation of PNS in adolescent over 10 years old is simple type nephrotic syndrome, the histopathological lesion is mostly MCD, and most of them are steroid sensitive. It is recommended to give hormone treatment first, and then perform renal biopsy if steroid resistance occurs; If the clinical manifestation is nephritic type nephrotic syndrome, the histopathological lesion is mostly non-MCD, especially those with gross hematuria or low C3-emia, or those have two or more clinical manifestations of persistent hematuria, hypertension, renal insufficiency and hypocomplement C3-emia, a kidney biopsy should be performed at onset.