[Incidence of hypogammaglobulinaemia in children with steroid-dependent/frequently relapsing nephrotic syndrome treated with rituximab and its association with severe infections].

Objective: To investigate the incidence and influencing factors of hypogammaglobulinemia (HGG) in children with steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with rituximab (RTX), and its relationship with the risk of severe infections. Methods: The clinical data of children with SDNS/FRNS treated with RTX at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University from December 2020 to January 2023 were retrospectively analyzed. RTX treatment was performed using a B-cell-guided regimen (a single dose of 375 mg/m2, a maximum of 500 mg/dose, and an additional one dose when reassessment of peripheral blood CD19+B cells≥1%). Patients were divided into HGG and non-HGG groups according to the presence or absence of HGG during the follow-up period. A multivariate logistic regression model was used to analyze the influencing factors of HGG, and the predictive value of each influencing factor on HGG was assessed by plotting the receiver operating characteristic (ROC) curve. Results: A total of 59 SDNS/FRNS children (48 males and 11 females) were included, and aged [M (Q1, Q3)] 9.4 (6.5, 12.2) years at the time of the first RTX treatment, with a median application of 3 (2, 4) doses of RTX. During the follow-up period of 15.5 (9.9, 22.8) months, the HGG was present in 16 (27.1%) children, of which seven persisted for more than 1 year. Compared with non-HGG group, HGG group had a shorter duration of the disease [3.3 (2.1, 3.6) vs 4.6 (2.4, 8.0) years, P=0.030], younger age at the time of the first RTX treatment [6.2 (5.6, 7.4) vs 11.3 (8.8, 13.3) years, P<0.001], and lower serum IgG levels [5.9 (4.9, 6.4) vs 7.5 (6.1, 8.2) g/L, P<0.001]. Multivariate logistic regression analysis showed that young age at the time of the first RTX treatment (OR=0.52, 95%CI: 0.35-0.78, P=0.002) was an influencing factor of HGG. The area under the curve (AUC) for age at first RTX treatment to predict HGG was 0.887 (95%CI: 0.778-0.955, P<0.001), with an optimal cut-off value of 8.3 years. During the follow-up period, six children (10.2%) developed severe infectious, and there was no statistically significant difference in the incidence of serious infections between the HGG and non-HGG groups [12.5% (2/16) vs 9.3% (4/43), P=1.000]. Conclusions: HGG is frequent in children with SDNS/FRNS treated with RTX, and nearly half of HGG persists for more than 1 year. The possibility of HGG is greater in those≤8.3 years at the first RTX treatment, but HGG does not increase the risk of severe infections in children.

[Long-term outcomes of childhood steroid-sensitive nephrotic syndrome].

Objective: To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome (SSNS). Methods: A retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included. Clinical data including general characteristics, clinical manifestation, laboratory tests, treatment and prognosis. The primary outcome was the clinical cure, and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up. According to the primary outcome, the patients were divided into clinical cured group and uncured group. Categorical variables were compared between 2 groups using the χ2 or Fisher exact test, and continuous variables by t or Mann-Whitney U test. Multiple Logistic regression models were used for multivariate analysis. Results: Of the 105 children with SSNS, the age of onset was 3.0 (2.1, 5.0) years, and 82 (78.1%) were boys, 23(21.9%) were girls. The follow-up time was (13.1±1.4) years; 38 patients (36.2%) had frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS) and no death or progression to end-stage kidney disease. Eighty-eight patients (83.8%) were clinically cured. Seventeen patients (16.2%) did not reach the clinical cure criteria, and 14 patients (13.3%) had relapsed or ongoing immunosuppressive treatment within the last year of follow-up. The proportion of FRNS or SDNS (12/17 vs. 29.5% (26/88), χ2=10.39), the proportion of treatment with second-line immunosuppressive therapy (13/17 vs. 18.2% (16/88), χ2=21.39), and the level of apolipoprotein A1 at onset ((2.0±0.5) vs. (1.7±0.6) g/L, t=2.02) in the uncured group were higher than those in the clinical cured group (all P<0.05). Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term (OR=14.63, 95%CI 4.21-50.78, P<0.001). Of the 55 clinically cured patients who had relapsed, 48 patients (87.3%) did not relapse after 12 years of age. The age at last follow-up was 16.4 (14.6, 18.9) years, and 34 patients (32.4%) were ≥18 years of age. Among the 34 patients who had reached adulthood, 5 patients (14.7%) still relapsed or ongoing immunosuppressive treatment within the last year of follow-up. At the last follow-up, among the 105 patients, 13 still had long-term complications, and 8 patients were FRNS or SDNS. The proportion of FRNS or SDNS patients with short stature, obesity, cataracts, and osteoporotic bone fracture was 10.5% (4/38), 7.9% (3/38), 5.3% (2/38), and 2.6% (1/38), respectively. Conclusions: The majority of SSNS children were clinically cured, indicating a favorable long-term prognosis. History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term. While it is not uncommon for children with SSNS to persist into adulthood. The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.

Protein transduction domain-hA20 fusion protein protects endothelial cells against high glucose-induced injury.

We constructed a plasmid containing a protein transduction domain (PTD) and a human A20 (hA20) gene fragment; the fusion protein was obtained by highly expressing this plasmid in the yeast Pichia pastoris GS115. The plasmid was obtained by adding 9xArg and EcoRІ recognition sites to the end of the primer, and 6xHis-Tag and NotІ recognition sites to its end. After sequencing, the hA20 gene fragment was inserted into plasmid pPIC9k to construct expression vector pPIC9k-PTD-hA20; then, we transfected GS115 with the vector and induced PTD-hA20 protein expression. We purified protein from the yeast fermentation supernatant using a nickel column. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose medium (30 mM glucose) and in high glucose medium containing different concentrations of protein. Apoptosis of HUVECs was assayed by TUNEL 72 h later. The biological activity tests indicated that the fusion protein not only passed through the cell membrane freely, but also inhibited apoptosis of HUVECs induced by high glucose levels. We conclude that the fusion protein PTD-hA20 has potential for clinical use.

Zinc finger protein A20 overexpression inhibits monocyte homing and protects endothelial cells from injury induced by high glucose.

Diabetes mellitus causes vascular lesions and may ultimately lead to atherosclerosis. One of the earliest steps in the development of atherosclerotic lesions is the adhesion of monocytes to endothelial cells of the vessel wall. It is currently unknown whether zinc finger protein A20 is able to protect endothelial cells from injury caused by high levels of glucose and monocyte homing. In our study, adhesion of monocytes to the vessel wall endothelium was detected by measuring the rolling velocity of monocytes along human umbilical vein endothelial cells (HUVECs). Activation of NF-κB was analyzed through Western blot. HUVEC apoptosis was monitored by TUNEL in situ end-labeling and flow cytometry. High glucose concentrations (25 mM) stimulated monocytes, reducing the velocity at which they roll along HUVECs. Stimulation of monocytes with high levels of glucose also induced HUVEC apoptosis. Overexpression of the zinc finger protein A20 inhibited monocyte recruitment, NF-κB activation, P-selectin expression, and HUVEC apoptosis induced by high glucose levels. We conclude that zinc finger protein A20 can protect HUVECs from injury induced by high levels of glucose and potentially could be used to develop treatments against diabetic vascular lesions.

A PstI restriction fragment length polymorphism in the 5' untranslated region of DRD4 is not associated with schizophrenia.

We detected a PstI restriction fragment length polymorphism in the 5'-non-coding region of the dopamine D4 receptor gene (DRD4), making it the seventh known polymorphism for DRD4. DNA polymorphisms in the putative regulatory region of DRD4 are of interest because of the reported six-fold increase in D4 receptors in post-mortem schizophrenic brain tissue [Seeman P, Guan HC, Van Tol HHM (1993) Nature, 365, 441-445]. We found no difference in the PstI allele frequencies between DSM-III-R schizophrenia patients (0.76 and 0.24, n = 41), and matched control Caucasians (0.77 and 0.23, n = 46). The PstI DRD4 polymorphism has potential use in linkage and association studies with neuropsychiatric and cardiovascular disorders.

Wnt/beta-catenin is involved in the proliferation of hippocampal neural stem cells induced by hypoxia.

BACKGROUND AND AIM: Beta-catenin, as a major effector molecule in the canonical Wnt signaling pathway, could regulate adult neurogenesis. Here, the role of Wnt/ß-catenin signaling pathway in the proliferation of hippocampal neural stem cells (NSCs) induced by hypoxia was investigated. METHODS: The hippocampal NSCs of neonatal green fluorescent protein transgenic mice on day 0 were cultured in hypoxia (5% O(2)) and traditional O(2) (20% O(2)). The expression of ß-catenin, p-GSK-3ß, and cyclinD1 in NSCs was measured under hypoxia or traditional O(2) by western blotting. NSCs were electroporated with pTOPFLASH reporter in different conditions and the LEF/TCF-dependent luciferase activity was assayed. RESULTS: Hypoxia increased the proliferation and reduced the apoptosis of hippocampal NSCs. NSCs proliferation was inhibited by transfecting with pAxin, whereas promoted by transfecting with pß-catenin. CONCLUSION: Hypoxia could enhance the proliferation of hippocampal NSCs and ß-catenin contributed to this action.

Mathematical representation with graphic reconstruction on a microcomputer for an arterial tree.

The branching arterial tree is considered as a collection of numerous points and lines. When treated with vertex analysis, it can be expressed with a new mathematical representation, and graphical reconstruction can be carried out on a microcomputer. This new method is useful for recording an arterial tree precisely on anatomical books or comparing arteries under hypertension with those under normotension in order that the early morphological changes of hypertensive vascular disease can be revealed.

Anatomic bases of the vascularized hepatic teres ligament flap.

The hepatic ligamentum teres was investigated in 30 adult specimens. The ligament represents a fibrous remnant of the umbilical v. and a small irregular lumen still exists in the ligament in adult life. The ligament is supplied by one set of independent round ligament a. and paraumbilical vv. Since the proximal segment of the ligament is easily mobilised and since the ligamentous a. originates from the right hepatic a. near the hilum, a proximal vascularized pedicle flap of the ligamentum teres has been recommended. Surgical repair of the extrahepatic bile duct using a vascularized pedicle flap of the ligamentum teres has been carried out successfully in 12 patients.

Analysis of the arterial supply of the extrahepatic bile ducts and its clinical significance.

The purpose of this study is to describe the arterial supply of the entire extrahepatic bile duct system. The cross-sectional area of all arteries that supply the ducts is measured under an operating microscope in 50 adult cadavers injected with red latex through the aorta. The extrahepatic bile duct system is divided into four topographic portions: cystic duct and gallbladder, right and left hepatic ducts, bile (common) duct and including its supra-retroduodenal parts, and the pancreatic and intraduodenal portions. The arterial supply to each portion is carefully detailed. The ducts are supplied by more than seven arteries, of which the major arteries are the cystic artery, posterior superior pancreaticoduodenal artery, right hepatic artery, and retroportal artery. Collectively they provide 94.5% of the blood supply to the ducts. Arteries form three types of anastomotic patterns on the walls of the ducts, suggesting that ductal incisions can be made in ways that least disturb the blood supply. The patterns are: a network, a longitudinal anastomotic chain, and an arterial circle. These data emphasize the importance of the arterial supply in biliary surgery and especially the treatment of hemobilia.

Search for unstable DNA in schizophrenia families with evidence for genetic anticipation.

Evidence for genetic anticipation has recently become an important subject of research in clinical psychiatric genetics. Renewed interest in anticipation was evoked by molecular genetic findings of a novel type of mutation termed "unstable DNA." The unstable DNA model can be construed as the "best fit" for schizophrenia twin and family epidemiological data. We have performed a large-scale Southern blot hybridization, asymmetrical PCR-based, and repeat expansion-detection screening for (CAG)n/(CTG)n and (CCG)n/(CGG)n expansions in eastern Canadian schizophrenia multiplex families demonstrating genetic anticipation. There were no differences in (CAG)n/(CTG)n and (CCG)n/(CGG)n pattern distribution either between affected and unaffected individuals or across generations. Our findings do not support the hypothesis that large (CAG)n/(CTG)n or (CCG)n/(CGG)n expansions are the major etiologic factor in schizophrenia. A separate set of experiments directed to the analysis of small (30-130 trinucleotides), Huntington disease-type expansions in individual genes is required in order to fully exclude the presence of (CAG)n/(CTG)n- or (CCG)n/(CGG)n-type unstable mutation.