IgA nephropathy and kidney transplantation according to the Oxford classification / Nefropatia por IgA e transplante renal segundo a classificação de Oxford

Abstract Introduction: IgA nephropathy (IgAN) is the most common glomerular disease globally, and its susceptibility and the risk for the development of end-stage kidney disease are related to genetic and environmental factors. IgAN recurrence after kidney transplantation is relatively common, impacting graft function and survival. This study evaluated the risk factors and the clinical, laboratory, and histological characteristics of post-transplant IgAN recurrence based on the Oxford classification. Material and methods: Retrospective single-center cohort study including kidney transplant recipients with biopsy-proven pre-transplantation IgAN, with analysis of risk factors and clinical, laboratory, and histological characteristics of the IgAN recurrence cases. Results: 53 patients fulfilled the inclusion criteria and were included in the study. The majority was male, white, eutrophic, with a mean age of 27 ± 9 years at IgAN diagnosis. Systemic arterial hypertension and proteinuria were frequent in the pretransplant period. Four recipients (7.5%) presented IgAN recurrence in a period of 6 to 122 months post-transplant. According to the Oxford classification, they had high scores of mesangial hypercellularity and segmental glomerulosclerosis in the native kidney biopsies and there was mesangial hypercellularity in all analyzed graft biopsies. None of these patients had received induction immunosuppression and all of them presented graft failure in the follow-up. Conclusions: In this series, there was a high prevalence of mesangial hypercellularity and segmental glomerulosclerosis on native kidney biopsies, and mesangial hypercellularity occurred in all IgAN recurrence graft biopsies. Despite the lower incidence of recurrence of IgAN post-transplant compared to previous reports, progression to graft loss was of 100%.

Resumo Introdução: Nefropatia por IgA (NIgA) é a doença glomerular mais comum mundialmente. Sua suscetibilidade e risco para desenvolvimento de doença renal em fase terminal estão relacionados a fatores genéticos e ambientais. A recidiva de NIgA pós-transplante é relativamente comum, impactando na função e sobrevida do enxerto. Este estudo avaliou fatores de risco e características clínicas, laboratoriais e histológicas da recidiva de NIgA pós-transplante, com base na classificação de Oxford. Material e métodos: Estudo de coorte retrospectivo de centro único, incluindo receptores de transplante renal com NIgA pré-transplante comprovada por biópsia, com análise dos fatores de risco e características clínicas, laboratoriais e histológicas dos casos de recidiva de NIgA. Resultados: 53 pacientes preencheram critérios de inclusão e foram incluídos no estudo. A maioria era homem, branco, eutrófico, com idade média de 27 ± 9 anos no diagnóstico de NIgA. Hipertensão arterial sistêmica e proteinúria foram frequentes no período pré-transplante. Quatro receptores (7,5%) apresentaram recidiva de NIgA entre 6-122 meses pós-transplante. Segundo a classificação de Oxford, eles apresentaram altos escores de hipercelularidade mesangial e glomeruloesclerose segmentar nas biópsias de rins nativos. Houve hipercelularidade mesangial em todas as biópsias de enxerto analisadas. Nenhum destes pacientes recebeu imunossupressão de indução. Todos apresentaram falência do enxerto no acompanhamento. Conclusões: Nesta série, houve alta prevalência de hipercelularidade mesangial e glomeruloesclerose segmentar em biópsias de rins nativos, e hipercelularidade mesangial ocorreu em todas as biópsias do enxerto de recidiva da NIgA. Apesar da menor incidência de recidiva de NIgA pós-transplante comparada a relatos anteriores, a progressão para perda do enxerto foi de 100%.

Schõnlein-Henoch purpura in adults: Report of four cases

Schoenlein-Henoch purpura is a systemic small vessel vasculitis mediated by IgA-1 deposition in organs such as the skin, kidney, and gastrointestinal tract; it has been mainly described in children where it has a favourable prognosis. Although much rarer in adulthood it is associated with an increased risk of severe kidney involvement, gastrointestinal com-plications, and prolonged hospital stay. The therapeutic options are wide and vary according to the degree of involvement of the patient and the organ mainly affected.

La púrpura de Schönlein-Henoch es una vasculitis sistêmica de pequeno vaso mediada por depósito de IgA en órganos como la piel, el riñón y el tracto gastrointestinal. Se ha descrito principalmente en niños, grupo de población en el que tiene un pronóstico favorable. Si bien en la edad adulta es mucho menos frecuente, se asocia con un mayor riesgo de compromiso renal severo, complicaciones gastrointestinales y estancia hospitalaria prolongada. Las opciones terapêuticas son amplias y varían según el grado de compromiso del paciente y el órgano más afectado.

Changes of gut microflora in newly diagnosed IgA nephropathy patients and its correlation with clinical risk factors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the gut microbiota in newly diagnosed IgA nephropathy patients with chronic kidney disease (CKD) stages 1-2 and the association between the gut microbiota and the clinical risk factors of IgA nephropathy.@*METHODS@#Fresh fecal samples were collected from nineteen newly diagnosed IgA nephropathy patients with CKD stages 1-2 and fifteen age- and sex-matched healthy controls. Fecal bacterial DNA was extracted and microbiota composition were characterized using 16S ribosomal RNA (16S rRNA) high-throughput sequencing for the V3-V4 region. The Illumina Miseq platform was used to analyze the results of 16S rRNA high-throughput sequencing of fecal flora. At the same time, the clinical risk factors of IgA nephropathy patients were collected to investigate the association between the gut microbiota and the clinical risk factors.@*RESULTS@#(1) At the phylum level, the abundance of Bacteroidetes was significantly reduced (P=0.046), and the abundance of Actinobacteria was significantly increased (P=0.001). At the genus level, the abundance of Escherichia-Shigella, Bifidobacte-rium, Dorea and others were significantly increased (P < 0.05). The abundance of Lachnospira, Coprococcus_2 and Sutterella was significantly reduced (P < 0.05). (2) There was no significant difference in the abundance of gut microbiota between the newly diagnosed IgA nephropathy patients and the healthy control group (P>0.05), but there were differences in the structure of the gut microbiota between the two groups. The results of LEfSe analysis showed that there were 16 differential bacteria in the newly diagnosed IgA nephropathy patients and healthy controls. Among them, the abundance of the newly diagnosed IgA nephropathy patients was increased in Enterobacteriales, Actinobacteria, Escherichia-Shigella, etc. The healthy control group was increased in Bacteroidetes and Lachnospira. (3) The result of redundancy analysis (RDA) showed that Bifidobacterium was positively correlated with serum IgA levels, 24-hour urinary protein levels and the presence of hypertension. Lachnoclostridium was positively correlated with the presence of hypertension. Escherichia-Shigella was positively correlated with urine red blood cells account. Bifidobacterium was positively correlated with the proliferation of capillaries. Faecalibacterium was positively correlated with cell/fibrocytic crescents. Ruminococcus_2 was positively correlated with mesangial cell proliferation, glomerular segmental sclerosis and renal tubular atrophy/interstitial fibrosis.@*CONCLUSION@#The gut microbiota in the newly diagnosed IgA nephropathy patients with CKD stages 1-2 is different from that of the healthy controls. Most importantly, some gut bacteria are related to the clinical risk factors of IgA nephropathy. Further research is needed to understand the potential role of these bacteria in IgA nephropathy.

Reference intervals for serum immunoglobulin A levels in Brazilian children aged 1 to 10 years: a population-based study

Abstract Objective: To determine reference intervals (Rl) for serum immunoglobulin A (IgA) levels in healthy children aged 1 to 1 0 years residing in the central region of Brazil. Methods: This cross-sectional study was conducted on 1,743 healthy children randomly selected from kindergartens and public schools in Cuiabá, MT, Brazil. The IgA RIs were defined using the statistical methods postulated by the guidelines of the United States Clinical and Laboratory Standards Institute, the nonparametric bootstrap method, and Horn's robust method after the correction of discrepancies by Tukey's, Dixon's, and Horn's methods, respectively. The results were defined based on the values contained between the 2.5th and 97.5th percentiles and their respective 95% confidence intervals. Results: Partition by sex was not necessary to determine the IgA Rl of the studied children. Homogeneous subgroups were identified among children aged 1-<2, 2-<5, and 5-<11 years, whose IgA-specific RIs were determined. Conclusion: The serum IgA RIs were established for three groups of Brazilian children aged 1-11 years, which differed from those currently applied in Brazilian pediatric practice and from those defined by international studies. This definition will help Brazilian pediatricians formulate an accurate diagnosis and facilitate decision-making.

Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bushen Jianpi Jiedu Liyan formula on the expression of integrin alpha 4 beta 1 （α4 β1）， vascular cell adhesion molecule-1 （VCAM-1）， stromal-derived factor-1 （SDF-1）， and chemokine receptor-4 （CXCR4） in the small intestine and bone marrow of the rat model of immunoglobulin A（IgA） nephropathy. MethodA total of 120 male SD rats were used to establish the IgA nephropathy model by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of CCl4， and tail vein injection of lipopolysaccharide （LPS）. The successfully modeled rats were randomized into blank， model， lotensin （63 mg·kg-1）， and low-， medium-， and high-dose （10.4， 20.81， 41.62 g·kg-1， respectively） Bushen Jianpi Jiedu Liyan formula groups （n=16）. The rats were treated with corresponding drugs according to their body weight. After 7 weeks of administration， the rats were sacrificed for the collection of samples， and the protein and mRNA levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the small intestine and bone marrow were determined by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed increased red blood cell count in the urine at the 10th， 12th， 14th， 16th weeks （P<0.01）， and such increases were reduced in the drug intervention groups （P<0.05）， especially in the medium-dose Bushen Jianpi Jiedu Liyan formula group （P<0.05）. Compared with those in the blank group， the protein levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria in the model group were up-regulated （P<0.05）， and such un-regulations were inhibited in the drug intervention groups （P<0.05）. Compared with the model group， medium-dose Bushen Jianpi Jiedu Liyan formula down-regulated the protein levels of SDF-1 and CXCR4 in the intestinal lamina propria （P<0.05）. Compared with the blank group， the model group showed down-regulated mRNA levels of α4 β1 and SDF-1 and up-regulated mRNA levels of VCAM-1 and CXCR4 （P<0.05）. Compared with the model group， the drug intervention groups showed down-regulated mRNA levels of SDF-1 and CXCR4 （P<0.05）. ConclusionBushen Jianpi Jiedu Liyan formula regulates the expression of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria to inhibit the homing effect of plasma cells， which may be associated with the Toll-like receptor-mediated activation of immune response. Bushen Jianpi Jiedu Liyan formula can down-regulate the expression of adhesion molecules to inhibit the proliferation of plasmocytes in circulation， so as to reduce the renal injury of IgA nephropathy.

Effect of Dahuang Xiezhuo Prescription on Renal Tubular Function in Patients with IgA Nephropathy Complicated with Hyperuricemia / 中国实验方剂学杂志

ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the clinical symptoms， blood uric acid， and renal tubular function of patients with immunoglobulin A （IgA） nephropathy in stages 1-2 of chronic kidney disease （CKD） complicated with hyperuricemia （HUA）. MethodSixty patients with IgA nephropathy in stages 1-2 of CKD complicated with HUA of spleen and kidney deficiency and combined turbidity and blood stasis syndromes were randomly divided into an observation group and a control group， with 30 cases in each group. The patients in the control group received basic treatment， i.e.， losartan potassium tablets 50-100 mg/time， once per day， and sodium bicarbonate tablets 0.5 g/time， three times per day by oral administration， combined with low-salt， low-fat， and low-purine diet. The patients in the observation group received Dahuang Xiezhuo prescription on the basis of basic treatment， one dose per day， twice a day in the morning and evening with warm water. Both groups were treated for two months. The total scores of traditional Chinese medicine（TCM）syndrome， blood pressure， 24 h urinary protein （24 h UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr） ［glomerular filtration rate （eGFR） was calculated by CKD-epidemiology collaboration （CKD-EPI） formula］， serum uric acid （SUA）， and renal tubular function indexes ［urinary α1-microglobulin （α1-MG）， urinary β2-microglobulin （β2-MG）， urinary kidney injury molecule-1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL）］ of the two groups before treatment and two months after treatment were recorded. The clinical efficacy of the two groups was evaluated two months after treatment. ResultAfter 2 months of treatment，the total effective rate in the observation group was 81.48%（22/27），higher than 50.00%（14/28） in the control group（χ2 =6.661，P<0.05）. The total scores of TCM syndrome， 24 h UTP， and SUA in the observation group and the observation group were lower than those before treatment （P<0.05）， and compared with the control group after treatment， the observation group decreased more significantly （P<0.05）. After treatment， the blood pressure in the observation group and the observation group was lower than that before treatment （P<0.05）， and there was no significant difference in blood pressure between the two groups after treatment. After treatment， the levels of urinary α1-MG， β2-MG， KIM-1， and NGAL in the two groups were lower than those before treatment （P<0.05）， and the observation group was lower than the control group after treatment （P<0.05）. There were no significant inter-group and intra-group differences in BUN， SCr， and eGFR levels before and after treatment. There were no obvious abnormalities in blood routine， liver function， and electrolytes before and after treatment in the two groups， and no adverse reactions such as allergies occurred. ConclusionDahuang Xiezhuo prescription can effectively improve the clinical symptoms of IgA nephropathy with HUA （CKD1-2） patients with spleen and kidney deficiency and combined turbidity and blood stasis syndromes， reduce blood uric acid level， alleviate renal tubular injury， and protect the kidney. The curative effect is better than that of basic treatment.

Stability of human immunoglobulin(pH 4) for intravenous injection after process optimization / 中国生物制品学杂志

@#Objective To evaluate the stability of human immunoglobulin(pH 4)for intravenous injection(IGIV)after process optimization.Methods A filter plate and B filter membrane were used to filter the protein components in different separation stages to reduce the residue of immunoglobulin A(IgA)in the product in multi-batch large-scale production. The finished product was examined for the physical properties(appearance,visible foreign body,insoluble particle examination and thermal stability test)and the chemical properties[protein content,purity,molecular size distribution,titers of antiHBs,diphtheria antibody,prokallikrein activator(PKA),anti-complement activity(ACA),anti-A and anti-B hemagglutinin,and IgA residue]. The accelerated and long-term stability tests were performed.Results There was no significant difference in the key quality indicators between IGIV batches produced by the optimized process and the normal process,while the IgA residue decreased significantly(t = 3. 992 and 11. 215 respectively,each P < 0. 05). In the accelerated stability and long-term stability tests,all the test results of IGIV after process optimization were qualified,which met the relevant regulations in the third part of Chinese Pharmacopoeia(2020 edition).Conclusion IGIV after process optimization can effectively reduce IgA residue with good stability,which is of great significance for blood product manufacturers to improve the quality of IGIV products.

Effects of timing of chemotherapy after breast cancer surgery on patient's immune function and quality of life / 中国基层医药

Objective:To investigate the effects of the timing of chemotherapy after breast cancer surgery on patient's immune function and quality of life.Methods:A total of 100 patients who underwent modified radical mastectomy for breast cancer from January 2017 to January 2019 in Jining No. 1 People's Hospital were included in this study. These patients were randomly divided into a control group and an early chemotherapy group ( n = 50/group). Patients in the control group underwent chemotherapy 4-6 weeks after surgery. Patients in the early chemotherapy group received chemotherapy 2 weeks after surgery. The chemotherapy regimens were the same in the two groups. The levels of CD 4+, CD 8+, CD 4+/CD 8+, immunoglobulin A (IgA), and immunoglobulin G (IgG) were measured before and after chemotherapy in each group. Chemotherapy-related reverse reactions and infections were recorded. The quality of life was evaluated in each group at the last follow-up. Results:Before chemotherapy, there were no significant differences in CD 4+, CD 8+, CD 4+/CD 8+, IgA, and IgG levels between the two groups (all P > 0.05). After chemotherapy, CD 4+ and CD 4+/CD 8+ levels in the early chemotherapy group were (51.76 ± 5.21)% and (2.00 ± 0.25), respectively, which were significantly higher than (48.21 ± 4.78)% and (1.70 ± 0.21) in the control group ( t = 3.55, 4.98, both P < 0.05). After chemotherapy, the CD 8+ level in the early chemotherapy group was (25.93±2.43)%, which was significantly lower than (28.29 ± 2.31)% in the control group ( t = 6.50, P < 0.05). Serum IgA and IgG levels in the early chemotherapy group were (3.24 ± 0.38) g/L and (9.27 ± 1.04) g/L, respectively, which were significantly higher than (2.75 ± 0.37) g/L and (8.43 ± 0.97) g/L in the control group ( t = 6.53, 4.18, both P < 0.05). During chemotherapy, there was no significant difference in the incidence of reverse reactions between the two groups (all P > 0.05). The incidence of infections was significantly lower in the early chemotherapy group than the control group ( P < 0.05). At the last follow-up, generic quality of life inventory-74 scores in the early chemotherapy group were significantly higher than those in the control group (all P < 0.05). Conclusion:Early chemotherapy can markedly reduce the effects of chemotherapy on the immune function of patients after breast cancer surgery, decrease the incidence of infections, and improve quality of life.

Study on improvement effects and mechanism of rhein on immunoglobulin A nephropathy / 中国药房

OBJECTIVE To study the improvement effects and mechanism of rhein on immunoglobulin A nephropathy （IgAN） model rat based on signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS Rats were randomly divided into normal control group， IgAN model group and rhein treatment group， with 10 rats in each group. IgAN model group and rhein treatment group were given combination of bovine serum albumin+lipopolysaccharide+carbon tetrachloride to induce IgAN model. Since the 7th week， rhein treatment group rats were intragastrically given relevant medicine， and normal control group and model group rats were given equal amount of normal saline intragastrically， for consecutive 4 weeks. After the last administration， the count of urine sediment erythrocyte， 24 h-urine total protein （UTP）， the levels of immunoglobulin A （IgA） in serum and secretory immunoglobulin A （sIgA） in intestinal mucosa were detected. The pathological changes of Peyer’s patch in renal cortex and intestinal mucosa and IgA deposition in renal cortex were observed. The expressions of interleukin-17 （IL-17）， IL- 6 and transforming growth factor β （TGF-β） in Peyer’s patch of intestinal mucosa in rats were detected. The expressions of STAT3 and related orphan receptor γt （RORγt） mRNA in Peyer’s patch were detected. The expressions of p-STAT3 and RORγt proteins in Peyer’s patch were detected. RESULTS Compared with normal control group， the count of urine sediment erythrocyte， 24 h-UTP， the levels of IgA in serum and sIgA in intestinal mucosa were increased significantly in IgAN model group （P＜0.01）； enlarged renal corpuscles， dilated renal sacs， obvious intratubular mesangial hyperplasia and fibrosis were observed in renal cortex； the volume and germinal center of Peyer’s patch in intestinal mucosa increased； IgA deposition of renal cortex zxyylxk20220103） was obvious； the expressions of IL-17， IL-6 and TGF-β in Peyer’s patch， mRNA expressions of STAT3 and RORγt， protein expressions of p-STAT3 and RORγt were increased significantly （P＜0.01）. Compared with IgAN model group，above indexes were decreased significantly in rhein treatment group （P＜0.01）， pathological damage of renal cortex was improved， the volume of Peyer’s patch and germinal center of intestinal mucosa were reduced， and IgA deposition in renal cortex was weakened. CONCLUSIONS Rhein can improve IgAN model rats， the mechanism of which may be associated with inhibiting STAT3 signaling pathway and regulating immune function of Peyer’s patch in intestinal mucosa.

Dermatosis ampollar por IgA lineal inducida por Vancomicina: reporte de un caso / Vancomycin-induced linear igabollous dermatosis: a case report

RESUMEN La dermatosis ampollar por IgA lineal del adulto (DLA) es una enfermedad autoinmune adquirida infrecuente, caracterizada por el depósito lineal de anticuerpos IgA en la membrana basal. La mayoría de los casos reportados son de causa idiopática, pero esta entidad también se ha visto asociada a ciertos fármacos, siendo la vancomicina el más frecuente. Se presenta un caso de DLA asociada a vancomicina, con extensa afectación cutánea y compromiso mucoso, tratado con dapsona y corticoides sistémicos con buena respuesta.

ABSTRACT Adult linear IgA bollous dermatosis (LABD) is a rare acquired autoimmune disease characterized by linear deposition of IgA antibodies on the basement membrane. Most of the reported cases are of idiopathic cause, but this entity has also been associated with certain drugs, vancomycin being the most frequent. We present a case of LABD associated with vancomycine, with extensive skin and mucosal involvement, treated with dapsone and systemic corticosteroids with a good response.

Central Retinal Vein Occlusion as a Presenting Feature Caused by Hypertensive Crisis Secondary to IgA Nephropathy

We present a case of Ischemic Central retinal vein occlusion (CRVO) caused by hypertension secondary to renal failure in IgA nephropathy. A 17 year old male came with chief complaints of sudden painless diminution of vision in RE since 15 days. On examination the Right eye showed multiple superficial retinal haemorrhages in all 4 quadrents with dilated veins and cystoid macular edema suggestive of CRVO and Left eye showed superficial flame shaped haemorrhage suggestive of grade 3 hypertensive changes.

Algoritmo para el diagnóstico y tratamiento de la hipoplasia del timo pediátrica, asociada o no a inmunodeficiencia / Algorithm for diagnosis and treatment of thymus hypoplasia in childhood, associated or not with immune deficiency

Hace aproximadamente 20 años un grupo de médicos investigadores de Cuba reportaron el empleo de las mediciones del timo por ultrasonografía, como un arma valedera en la evaluación inmunológica de los niños menores de 7 años con cuadros de infecciones frecuentes, fundamentalmente respiratorias. El rango de normalidad propuesto del área de la silueta tímica, es entre 1010,6 - 1425,4 mm2, o sea, 1 218 ± 207,4 mm2. Por debajo y por encima de estos valores se hablaría de hipoplasia e hiperplasia, respectivamente. Se considera hipoplasia grave cuando el área tímica es menor de 500 mm2; moderada cuando se encuentra entre 500 y 799 mm2 y leve cuando se halla entre 800 y 999 mm2. Se propone un algoritmo de diagnóstico y tratamiento que engloba la experiencia clínica de 12 años de trabajo en inmunología clínica pediátrica en el Instituto de Hematología e Inmunología. Este puede constituir una herramienta útil en las manos de los inmunólogos clínicos pediátricos que adecuarían el tratamiento idóneo para llevar el órgano a su tamaño estándar con la consecuente disminución de los procesos infecciosos y la elevación de los niveles de inmunoglobulina A en los pacientes(AU)

About 20 years ago, a group of Cuban medical researchers reported to the literature the use of measurements of the thymus by ultrasonography, as a valid weapon in the immunological evaluation of children under 7 years of age with frequent infections, mainly respiratory. The range of normality proposed for the area of the thymic silhouette is between 1010.6 - 1425.4 mm2, that is, 1 218 ± 207.4 mm2. Below and above these values, we would speak of hypoplasia and hyperplasia, respectively. Severe hypoplasia is considered when the thymic area is less than 500 mm2; moderate when it is between 500 and 799 mm2 and mild when it is between 800 and 999 mm2. A diagnosis and treatment algorithm is proposed that encompasses the clinical experience of 12 years of work in pediatric clinical immunology at the Institute of Hematology and Immunology. It can be a useful tool in the hands of pediatric clinical immunologists who would adapt the ideal treatment to bring the organ to its standard size with the consequent decrease in infectious processes and the elevation of immunoglobulin A levels in patients(AU)

Effect of oropharyngeal colostrum administration on salivary secretory IgA levels in extremely/very low birth weight infants fed by gastric tube / 中国新生儿科杂志

Objective:To study the effect of oropharyngeal colostrum administration on salivary secretory IgA (sIgA) levels in extremely/very low birth weight preterm infants fed by gastric tube.Methods:Preterm infants with birth weight <1 500 g ( n=90) hospitalized in neonatal intensive care unit of the Affiliated Shenzhen Maternity & Child Healthcare Hospital of Southern Medical University from August 2020 to January 2021 were enrolled as research subjects. They were assigned into observation group and control group. The observation group accepted oropharyngeal administration of colostrum before being fed by gastric tube once every 3 hours for 7 days. The control group was given normal saline before each feeding. Other nursing interventions were consistent with the observation group. Saliva samples were collected at the 2 hour and 7 day after birth and the levels of slgA were tested. SPSS 26.0 statistical software was applied to analyse the data. Results:A total of 81 preterm infants completed this study. The content of salivary sIgA in observation group (42 cases) on 7 day after birth were significantly higher than those on the 2 hour after birth [15.4 (0.6, 106.7) μg/ml vs. 0.6 (0.0, 5.3) μg/ml] ( P<0.05). There was no statistically significant difference between the sIgA levels in the saliva of the control group (39 cases) at the 7 postnatal day and 2 hour after birth [0.0 (0.0, 1.4) μg/ml vs. 0.0 (0.0, 5.2) μg/ml] ( P>0.05). The content of salivary sIgA in observation group were significantly higher than those in control group on the 7 day after birth, the difference was statistically significant ( P<0.05). The salivary sIgA levels in the observation group were negatively correlated with the starting time of oropharyngeal administration of colostrum ( r=-0.330, P<0.05), and positively correlated with the total number of oropharyngeal administration of colostrum ( r=0.388, P<0.05). Conclusions:Oropharyngeal colostrum administration can improve the levels of salivary sIgA of extremely/very low birth weight preterm infants fed by gastric tube.

Progress of IgA antibody class switch in the pathogenesis of IgA nephropathy / 国际儿科学杂志

IgA nephropathy(IgAN)is a common primary glomerular disease.The abnormal increase of IgA molecules in serum can be regarded as the initiation stage of IgAN development, and the abnormal IgA antibody class switch process in B cells leads to the overproduction of IgA.In order to provide new ideas for the prevention and treatment of IgAN, this paper reviews the role of IgA antibody class switch in the pathogenesis of IgAN from the aspects of mucosal immunity, T cells, cytokines and signaling pathways, as well as possible therapeutic targets.

Clinical significance of combined detection of serum immunoglobulin and interleukin-18 in patients with viral hepatitis B / 中国基层医药

Objective:To detect serum immunoglobulin and interleukin-18 (IL-18) levels in patients with viral hepatitis B and investigate the clinical significance of combined detection of serum immunoglobulin and IL-18 levels.Methods:A total of 102 patients with viral hepatitis B who received treatment in Jinan 2 nd People's Hospital from September 2019 to September 2020 were included in the observation group. An additional 99 patients who concurrently underwent physical examination were included in the control group. Serum immunoglobulin and IL-18 levels were detected in each group and they were compared between the two groups. Changes in serum immunoglobulin and IL-18 levels detected after treatment relative to before treatment were analyzed in the observation group. Results:Serum levels of immunoglobulin A, immunoglobulin G, immunoglobulin M, and IL-18 in the observation group were (2.68 ± 0.74) g/L, (15.24 ± 4.17) g/L, (2.59 ± 1.03) g/L, (2.53 ± 0.21) ng/mL, respectively, which were significantly higher than those in the control group [(1.76 ± 0.63) g/L, (11.58 ± 3.46) g/L, (1.38 ± 0.49) g/L, (1.68 ± 0.34) g/L, respectively, t = 9.45, 6.74, 10.54, 21.36, all P < 0.01). In the observation group, serum levels of immunoglobulin A, immunoglobulin G, immunoglobulin M, and IL-18 were (2.03 ± 0.51) g/L, (13.12 ± 3.25) g/L, (1.93 ± 0.47) g/L, (1.74 ± 0.15) μg/L after treatment, which were significantly lower than those before the treatment [(2.68 ± 0.74) g/L, (15.24 ± 4.17) g/L, (2.59 ± 1.03) g/L, (2.53 ± 0.21) μg/L , t = 7.26, 4.02, 10.54, 5.87, all P < 0.01). Conclusion:Serum immunoglobulin and IL-18 levels in combination can reflect the condition of viral hepatitis B patients and provide scientific reference for clinical treatment. The research results are scientific and innovative and are worthy of promotion.

Effect of Modified Shengjiangsan on Gd-IgA1 in IgA Nephropathy Rats： Based on C1GALT1/C1GALT1C1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveThe effect of modified Shengjiangsan on immunoglobulin A （IgA） nephropathy was observed. The microRNA-148b （miRNA-148b）， interleukin 6 （IL-6）， core 1 beta 1，3-galactosyltransferase （C1GALT1）， molecular chaperone Cosmc （core1β3-Gal-T-specific molecular chaperone C1GALT1C1）， and galactose-deficient IgA1 （Gd-IGA1） in serum and kidney tissues of IgA nephropathy rats were detected to explore the underlying mechanism. The result is expected to lay a scientific basis for clinical application of modified Shengjiangsan in the treatment of IgA nephropathy. MethodA total of 42 SPF male SD rats were randomized into the normal group （8rats） and modeling group （34 rats） with the random number table method. After one week of adaptive feeding， rats for modeling were given bovine serum albumin （BSA， gavage）， lipopolysaccharide （LPS， injection into tail vein）， carbon tetrachloride （CCl4， subcutaneous injection）， and castor oil to induce IgA nephropathy. After modeling， two rats were randomly selected to test the modeling outcome. Then the model rats were classified into the model group， low-dose Chinese medicine group （modified Shengjiangsan，6.27 g·kg-1）， high-dose Chinese medicine group （modified Shengjiangsan，12.54 g·kg-1）， and benazepril group （10 mg·kg-1） with the random number table method， 8 in each group. The administration （gavage， once a day） lasted 4 weeks. The 24-h urinary total protein （24 h-UTP） was detected at the end of the 1st， 9th， and 13th week of the experiment. At the 14th week， after anesthesia， femoral artery blood was collected and centrifugated. The supernatant was collected to detect albumin （ALB）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The expression levels of IL-6 and Gd-IGA1 were determined by enzyme-linked immunosorbent assay （ELISA）. Based on hematoxylin-eosin （HE）/Masson/periodic Schiff-methenamine silver （PASM） staining， the pathological changes of renal tissues were observed. Ultrastructural changes of glomeruli were observed by transmission electron microscopy. The expression of miRNA-148b， IL-6， C1GALT1， and C1GALT1C1 was detected by immunohistochemistry. The mesangial area of the glomeruli was observed by immunofluorescence. Real-time polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of mirNA-148b， IL-6， C1GALT1， and C1GALT1C1， and Western blot was used to detect the protein levels of IL-6， C1GALT1， and C1GALT1C1. ResultCompared with normal group， the model group showed increase in the content of 24 h-UTP， SCr， ALT， IL-6， and GD-IGA1 （P<0.05）， decrease in ALB content （P<0.05）. Moreover， rats in the model group demonstrated hyperplasia of glomerular mesangial cells， thickening of mesangial area， podocyte foot process effacement， and a large number of granular IgA immune complex in the mesangial area. In addition， the model group showed increase in the expression of IL-6 in mesangial area and podocytes， decrease in the expression of C1GALT1 and C1GALT1C1 in mesangial area and podocytes， enhanced expression of IL-6 mRNA and miRNA-148b （P<0.01）， weakened expression of C1GALT1 mRNA and C1GALT1C1 mRNA （P<0.01）， rise of IL-6 protein expression （P<0.01）， and reduction in the protein expression of C1GALT1 and C1GALT1C1 （P<0.01）. Compared with the model group， modified Shengjiangsan decreased the content of 24 h-UTP， SCr， ALT， IL-6， and Gd-IGA1 （P<0.05） and increased the content of ALB （P<0.05， P<0.01）. Moreover， with the treatment of this Chinese medicine， the pathological damage was significantly alleviated and the deposition of IgA immune complex in basement membrane was reduced. The expression of IL-6 in the mesangial area and podocytes of rats was decreased， and the expression of C1GALT1 and C1GALT1C1 in the mesangial area and podocytes of rats was increased. Moreover， the expression of IL-6 mRNA and miRNA-148b was decreased （P<0.01）， and the expression of C1GALT1 mRNA and C1GALT1C1 mRNA was increased （P<0.01）. The protein expression of IL-6 was decreased （P<0.05， P<0.01）， and the protein expression of C1GALT1 and C1GALT1C1 was enhanced （P<0.05， P<0.01）. The Chinese medicine group showed obvious dose-effect trend. ConclusionModified Shengjiangsan may reduce the expression of miRNA-148b and IL-6 in serum and kidney tissue of IgA nephropathy rats， restore the expression of C1GALT1 and C1GALT1C1， and decrease the generation of Gd-IGA1， so as to reduce renal pathological damage and proteinuria， protect the kidney protection， and finally delay the disease progression. Moreover， the effect is enhanced with the rise of dose.

Mechanism of Modified Shengjiangsan in Treatment of IgA Nephropathy Based on Network Pharmacology， Molecular Docking， and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active components， targets， and signaling pathways of modified Shengjiangsan in the treatment of immunoglobulin A nephropathy （IgAN） based on network pharmacology， and to explore its underlying mechanism through molecular docking and experimental verification on animals. MethodThe active ingredients and related targets of modified Shengjiangsan were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）， UniProt， SwissTargetPrediction， and literature review. IgAN-related targets were obtained from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Cytoscape 3.9.0 was used to construct the regulation network of the related targets of Shengjiangsan and IgAN， and the protein-protein interaction （PPI） network was plotted by STRING. The common genes were analyzed for gene ontology （GO） functional annotation and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment by Metascape. Key targets and main active ingredients were selected for molecular docking by AutoDockTools 1.5.6. The experimental model of IgAN was induced by bovine serum albumin（BSA， ig） combined with lipopolysaccharide （LPS， iv） and the complex of CCl4 and castor oil （sc） in rats. The model rats were treated with modified Shengjiangsan and benazepril hydrochloride for four weeks. The rats were sacrificed after drug administration. The levels of transforming growth factor-β1 （TGF-β1） and interleukin-6 （IL-6） in the serum and kidney tissues were detected by enzyme-linked immunosorbent assay（ELISA）， immunohistochemistry， Real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot. ResultA total of 105 active ingredients were obtained according to oral bioavailability（OB）， drug-likeness（DL）， and literature screening. There were 124 common genes and 59 core targets. Neurotrophic tyrosine receptor kinase 1 （NTRK1）， cullin-3 （CUL3）， tumor protein 53 （TP53）， epidermal growth factor receptor （EGFR）， exportin 1 （XPO1）， and other targets might be closely related to IgAN. As predicted by KEGG enrichment analysis， the treatment of IgAN with modified Shengjiangsan mainly involved the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， nuclear transcription factor-kappa B （NF-κB） signaling pathway， and cytokine-cytokine receptor interaction signaling pathway. As revealed by molecular docking， the main active ingredients in modified Shengjiangsan showed stable binding activities with NTRK1， CUL3， TP53， EGFR， and XPO1 in the core targets， indicating that it presumedly regulated inflammatory responses by affecting NTRK1， CUL3， TP53， EGFR， and XPO1 target proteins. The results of experimental verification on animals showed that the expression levels of cytokines TGF-β1 and IL-6 in the serum and kidney tissues of IgAN rats were significantly decreased by modified Shengjiangsan， suggesting that Shengjiangsan might inhibit excessive fibrosis， and inflammatory and immune responses by regulating signaling pathways such as cytokine-cytokine receptor interaction， PI3K/Akt， and NF-κB. ConclusionModified Shengjiangsan may treat IgAN through multiple targets and pathways. Its mechanism may be related to the inhibition of excessive fibrosis， and inflammatory and immune responses by affecting the expression of NTRK1， CUL3， TP53， EGFR， and XPO1 and the regulation of the cytokine-cytokine receptor interaction， PI3K/Akt， NF-κB， and other signaling pathways.

Clinical Efficacy of Maxingshigantang Enema in Treating Infants with Pneumonia and Asthma and Intervention Mechanism of Lung-intestine Microenvironment / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Maxingshigantang enema in the treatment of infant viral pneumonia by comparing related indicators， and comprehensively evaluate the effect of traditional Chinese medicine （TCM） enema on the intestinal microenvironment. MethodSixty infants with viral pneumonia were selected and randomly divided into 3 groups. The dosage of enema drugs in high- （0.117 g·mL-1） and low-concentration （0.07 g·mL-1） TCM enema groups was same （3.5 g per time）， and the control group received normal saline enema， once a day for 7 days. Finally， the curative effect， total symptom score， salivary secretory immunoglobulin A （sIgA）， human beta defensin 2 （hBD2） and fecal calprotectin （CALP） of each group were statistically analyzed by SPSS 21.0， and the clinical efficacy of TCM enema in treating children with pneumonia and asthma was comprehensively evaluated. ResultThe curative effect of high-concentration TCM enema group （total effective rate 100%， χ2=7.059） was equivalent to that of low-concentration TCM enema group （total effective rate 95%， χ2=4.329）， higher than that of control group （total effective rate 70%） （P<0.017）. After treatment， compared with control group and low-concentration TCM enema group， high-concentration TCM enema group had higher total symptom score of children （P<0.05， P<0.01）. The proportion of coccobacillus was reduced in three groups， with high- and low-concentration TCM enema groups lower than control group （P<0.05）. The salivary sIgA concentration was increased in three groups （P<0.05）， with high-concentration TCM enema group higher than the other groups （P<0.01）. The hBD2 concentration was decreased in three groups， with high- and low-concentration TCM enema groups lower than control group （P<0.05）. The three groups reduced the fecal CALP concentration， and high-concentration TCM enema group had the highest reduction， followed by low-concentration TCM enema group （P<0.01）. ConclusionTCM enema outweighs western medicine in improving clinical symptoms， intestinal flora， and mucosal immune function， and reducing inflammation in children， and the high-concentration TCM enema group has better curative effect. Therefore， with easiness to operate， high compliance， and significant therapeutic effect， TCM enema is worthy of clinical promotion.

The correlation between diamine oxidase and T helper cells 17/regulatory T cell immune balance in rheumatoid arthritis / 中华风湿病学杂志

Objective:To investigate the changes of intestinal mucosal barrier function related indexes [diamine oxidase and secretory immunoglobulin A (sIgA)] in peripheral blood of patients with rheumatoid arthritis (RA) and their correlation with peripheral immune function.Methods:A total of 40 patients with RA who admitted to the Rheumatology and Immunology department of the Second Hospital of the Shanxi Medical University were enrolled. We collected their clinical and laboratory data, and selected 20 age and gender matched people as the control group. Enzyme-linked immunosorbnent assay (ELISA) was used to detect the level of DAO and sIgA in the peripheral blood, the lymphocytes and CD4 + T subsets were detected by flow cytometry. Then t-test, rank sum test and correlation analysis were conducted for statistical analysis. Results:① The level of DAO in patients with RA was higher than that of healthy controls [205(164, 251) ng/ml vs 364 (276, 483) ng/ml, Z=-4.48, P<0.001], while the level of sIgA was decreased [3.64 (2.76, 4.83)×10 5 ng/ml vs 6.83 (4.80, 9.44)×10 5, Z=-3.84, P<0.001]. ② The absolute number of B and CD4 + T cells were increased in RA, the difference were statistically significant, but the absolute number of T, natural killer cells (NK) and CD8 + T cells were not significantly different between the two groups. For CD4 + T subsets, the absolute number of T helper cells (Th)1 and Treg cells in RA group were significantly decreased than healthy controls, but there were no statistical significant difference in the number of Th2 and Th17 cells. ③ The level of DAO was positively correlated with absolute number of Th17 cells in patients with RA ( r=0.36 P=0.038), and positively correlated with age and white blood cell count ( r=0.40, P=0.021; r=0.40, P=0.020), but no significant correlation among other indicators were found. ④ The serum sIgA level of RA patients in antimutated citrullinated vimentin antibody (MCV), antiperinuclear factor (APF) and antikeratin antibody (AKA) positive group were higher than those in the negative group [3.99(2.99, 5.58)×10 5 ng/ml vs 2.73(2.29, 3.05)×10 5 ng/ml, Z=-2.55, P=0.011; 5.49 (3.26, 5.70)×10 5 ng/ml vs 3.12 (2.29, 4.04)×10 5 ng/ml, Z=-2.28, P=0.023; 4.07 (3.19, 5.65)×10 5 ng/ml vs 2.88 (2.24, 3.86)×10 5 ng/ml, Z=-2.42, P=0.016], while there was no significant difference in DAO level between groups. ⑤ The DAO level of RA patients with pulmonary interstitial fibrosis was significantly higher than that in the group without pulmonary interstitial fibrosis [421 (216, 528) ng/ml vs 191 (150, 223) ng/ml, Z=-2.81, P=0.005], while there were no significant differences in DAO and sIgA levels among other groups. Conclusion:In RA patients with inte-stinal mucosal barrier impairment, the DAO level is increased, while the sIgA is decreased, and in addition, elevated peripheral blood Th17 may be involved in the process of intestinal mucosal barrier impairment.

Nefropatía por inmunoglobulina A en pediatría, desenlaces clínicos con diferentes esquemas de manejo / IgA nephropathy in pediatric patients, clinical outcomes with three types of management

Resumen Introducción: la nefropatía por inmunoglobulina A (NIgA) es la enfermedad glomerular más común en el mundo. En Colombia, el 11-22 % de las glomerulonefritis primarias en niños corresponden a NIgA y de estos casos, el 30 % progresa a enfermedad renal terminal. Objetivo: describir las características paraclínicas e histopatológicas de la NIgA, así como los resultados clínicos según tres tipos de tratamiento en pacientes pediátricos con esta enfermedad atendidos en un hospital de alta complejidad del suroccidente colombiano. Materiales y métodos: estudio retrospectivo realizado en pacientes pediátricos de entre 1 mes y 18 años de edad con diagnóstico de NIgA. Las variables categóricas se presentaron como proporciones y las continuas con medianas y rango intercuartílico. Se usó la prueba de Fisher para comparar los tres esquemas de tratamiento. Resultados: se incluyeron 58 pacientes pediátricos atendidos entre 1996 y 2013. La media de edad al inicio de síntomas fue 7,5±4,2 años y al momento de la biopsia renal, 10±3,8 años. El 77,6 % de los pacientes presentó hematuria microscópica y el 27,6 %, macroscópica. Además, el 81 % tuvo proteinuria, siendo severa el 29 %. Histológicamente, el 10 % se clasificó como grado I, el 62 % como grado II, el 21 % como grado III y el 7 % como grado IV. Tres pacientes requirieron diálisis y dos, trasplante renal. Los esquemas terapéuticos evaluados fueron: solo prednisona (n=20, 34,5 %), prednisona y mofetil micofenolato (MMF) (n=13, 22,4 %) y sin prednisona ni MMF (n=25, 43,1 %). La diferencia en la presencia de hematuria entre los grupos fue significativa (p>0,001), siendo más frecuente en el grupo sin prednisona ni MMF (68 %). No hubo diferencia entre los grupos de proteinuria, hipertensión arterial y valor de creatinina. La mediana de años entre la biopsia renal y el ultimo control fue de 4 años (RIC 1-7). La supervivencia de la función renal fue del 89,1 % a los 5 años. Conclusión: la NIgA amerita reconocimiento temprano y seguimiento estricto, ya que puede tener desenlaces ominosos como enfermedad renal crónica.

Abstract Introduction: IgA nephropathy (IgAN) is the most common glomerular disease in the world, in Colombia belongs to 11-22 % of primary glomerulonephritis in pediatric patients. Of these, 30 % progress to chronic kidney disease. Materials and methods : It is a retrospective descriptive study. We used median and IRQ for continuous variables, and proportions for categorical variables, Fisher test to compare clinical outcomes. Results: Between 1996 to 2013 58 patients were diagnosed. The mean age at symptoms onset was 7.5 years (SD±4.2) and at the time of renal biopsy was 10 years (SD±3.8). At diagnosis, 77.6 % of the patients showed microscopic hematuria, 27.6 % gross hematuria and 81 % proteinuria, classified as severe in 29 %. Three patients required dialysis and two needed kidney transplant. Three groups with different therapeutic regimens were evaluated: first group only prednisone 34.5 % (n = 20), second group prednisone and mycophenolate mofetil (MMF) 22.4 % (n = 13) and third group without prednisone neither MMF 43.1 % (n = 25). The difference in the presence of hematuria among the groups was significant (p> 0.001), being more frequent in the group without prednisone neither MMF (68 %). There were no significant differences in proteinuria, hypertension or creatinine among the groups. The median of years between the renal biopsy and the last control was 4 years RI 1-7. At five years, the renal function survival probability (GFR >90 ml/min/1.73m2) was 89.1 %. Conclusion: IgAN needs early recognition and strict follow-up, since it may have ominous outcomes.