Successful treatment with oseltamivir phosphate in children with ITP who failed first-line therapy: a case series report.

Immune thrombocytopenia (ITP) is a common bleeding disorder in children. First-line medicines (glucocorticoids and immunoglobulin) may not be effective for some children, endangering their lives, posing challenges for healthcare facilities, and leading to an unfavorable prognosis. As a sialidase inhibitor, oseltamivir phosphate can reduce the destruction of platelets in liver macrophages by inhibiting the sialylation of platelets, and finally achieve the purpose of increasing platelet count. In this paper, three cases of children with ITP who failed first-line therapy and were cured by oral administration of oseltamivir phosphate granules were reported. The mechanism of action of oseltamivir phosphate granules was clarified.

[Comparison of distribution of eight components from Liangxue Tuizi Mixture between normal and Henoch-Schonlein purpura rats].

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.

[Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics].

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.

[Effect of multi-glycosides of Tripterygium wilfordii on renal injury in diabetic kidney disease rats through NLRP3/caspase-1/GSDMD pyroptosis pathway].

This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1ß(IL-1ß) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1ß and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1ß and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.

[Clinical features of children with coronavirus disease 2019 caused by Delta variant infection in different age groups]. / 不同年龄段儿童Deltaå˜å¼‚æ ªæ„ŸæŸ“æ‰€è‡´æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with coronavirus disease 2019 (COVID-19) caused by Delta variant infection in different ages groups. METHODS: A total of 45 children with COVID-19 caused by Delta variant infection who were hospitalized in the designated hospital in Henan Province, China, from November 17 to December 17, 2021, were included. They were divided into three groups: <6 years group (n=16), 6-13 years group (n=16), and >13 years group (n=13). The three groups were compared in clinical features and laboratory examination data. RESULTS: COVID-19 in all age groups was mainly mild. Main manifestations included cough and expectoration in the three groups, and fever was only observed in the 6-13 years group. The <6 years group had significantly higher serum levels of aspartate aminotransferase, lactate dehydrogenase, and creatine kinase isoenzymes than the other two groups (P<0.05). The 6-13 years group had the highest proportion of children with elevated serum creatinine levels (50%). Among the three groups, only 4 children in the >13 years group had an increase in serum C-reactive protein levels. The 6-13 years group had the lowest counts of CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, and natural killer cells in the peripheral blood among the three groups. The >13 years group had a significantly higher positive rate of SARS-CoV-2 IgG on admission than the other two groups (P<0.05). There was no significant difference in the imaging findings on chest CT among the three groups (P>0.05). CONCLUSIONS: The clinical features of COVID-19 caused by Delta variant infection in children of different age groups may be different: children aged <6 years tend to develop myocardial injury, and those aged 6-13 years have fever except cough and expectoration and tend to develop renal and immune dysfunction.

[Clinical features of children with coronavirus disease 2019 Delta variant infection after vaccination with inactivated SARS-CoV-2 vaccine]. / æŽ¥ç§æ–°åž‹å† çŠ¶ç— æ¯’ç­æ´»ç–«è‹—åŽæ„ŸæŸ“Deltaå˜å¼‚æ ªçš„æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæ‚£å„¿ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with coronavirus disease 2019 (COVID-19) Delta variant infection vaccinated or not vaccinated with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. METHODS: A total of 11 children with COVID-19 Delta variant infection who were vaccinated with inactivated SARS-CoV-2 vaccine and were hospitalized in the designated hospital in Henan Province, China, from November 3 to December 17, 2021 were enrolled as the vaccinated group. Thirty-one children with COVID-19 Delta variant infection who were not vaccinated and were hospitalized during the same period were enrolled as the unvaccinated group. A retrospective analysis was performed on their epidemiological data, clinical features, and laboratory examination results. RESULTS: There was no significant difference in gender composition and disease classification between the two groups (P>0.05), and there was also no significant difference in the incidence rates of the clinical symptoms such as cough, expectoration, and fever between the two groups (P>0.05). No significant difference was found between the two groups in leukocyte count, lymphocyte percentage, alanine aminotransferase, and serum creatinine (P>0.05). Compared with the unvaccinated group, the vaccinated group had significantly lower levels of aspartate aminotransferase, lactate dehydrogenase, and creatine kinase-MB (P<0.05). There was no significant difference between the two groups in the proportion of children with elevated C-reactive protein or procalcitonin and the levels of peripheral blood cytokines (P>0.05). The vaccinated group had significantly lower counts of B lymphocytes and total T lymphocytes (CD3+) than the unvaccinated group (P<0.05). Compared with the unvaccinated group, the vaccinated group had a significantly higher positive rate of IgG on admission and at week 2 of the course of disease (P<0.05), as well as a significantly higher Ct value of nucleic acid at weeks 1 and 2 of the course of disease (P<0.05). CONCLUSIONS: Vaccination with inactivated SARS-CoV-2 vaccine may reduce myocardial injury caused by SARS-CoV-2 Delta variant. For children with SARS-CoV-2 Delta variant infection after the vaccination, more attention should be paid to their immune function.

Correlation between endocapillary proliferative and nephrotic-range proteinuria in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: The endocapillary proliferative (EP) lesion is not included in the International Study of Kidney Disease in Children (ISKDC) pathological classification of Henoch-Schönlein purpura nephritis (HSPN). The main objective of the study was to determine the pathological importance of EP in the development of proteinuria in children with Henoch-Schönlein purpura nephritis (HSPN). METHODS: The pathological features of 148 HSPN children with nephrotic-range proteinuria were investigated retrospectively. Urinary IgG, transferrin, and albumin levels were measured by immunonephelometry. The correlations between EP lesion and 24-h proteinuria, urinary IgG, urinary transferrin, and urinary albumin were analyzed. Renal biopsy specimens were immunohistochemically stained for nephrin and podocalyxin. RESULTS: Of the total 581 cases of children with HSPN who underwent renal biopsy, 148 cases (25.5%) presented with nephrotic-range proteinuria. The pathological types of HSPN with nephrotic-range proteinuria were categorized as IIb, IIIa, IIIb, IIIb with diffuse EP, IVb, pure focal EP type, and pure diffuse EP type. Among these types, pure diffuse EP type accounted for 7.4%. The levels of 24-h proteinuria and urinary albumin were the highest in pure diffuse EP type among all pathological types, and the percentage of EP correlated with 24-h proteinuria and urinary albumin levels. 24-h proteinuria was significantly higher in pure diffuse EP type relative to HSPN IIb type, and significantly higher in IIIb with EP, compared with HSPN IIIb. Nephrin, but not podocalyxin, was downregulated in EP segment. CONCLUSIONS: EP is an independent pathogenic factor in HSPN with nephrotic-range proteinuria. Downregulation of nephrin in EP segment is a potential molecular mechanism of nephrotic-range proteinuria. Albumin is the major urinary protein component in HSPN with EP.

[Study on mechanism of Cuscutae Semen flavonoids in improving reproductive damage of Tripterygium Glycosides Tablets in rats based on high-throughput transcriptome sequencing].

Tripterygium Glycosides Tablets has good anti-inflammatory and immunomodulatory activities,but its reproductive damage is significant. Previous studies of the research group have found that Cuscutae Semen flavonoids can improve spermatogenic cell damage caused by Tripterygium Glycosides Tablets by regulating spermatogenic cell cycle,apoptosis and related protein expression,but the mechanism of action at the gene level is still unclear. In this study,Illumina high-throughput sequencing platform was applied in transcriptional sequencing of spermatogenic cells of rats after the intervention of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets. Differentially expressed genes were screened out and the GO enrichment and KEGG pathway analysis of differentially expressed genes were conducted to explore the mechanism of Cuscutae Semen flavonoids in improving reproductive injury caused by Tripterygium Glycosides Tablets. The results showed that 794 up-regulated genes and 491 down-regulated genes were screened in Tripterygium Glycosides Tablets group compared with the blank group. Compared with Tripterygium Glycosides Tablets,440 up-regulated genes and 784 down-regulated genes were screened in the Cuscutae Semen flavonoids+Tripterygium Glycosides Tablets group. Among them,the gene closely related to reproductive function is DNMT3 L. Analysis of GO function and KEGG signaling pathway enrichment showed that the above differentially expressed genes were mainly enriched in cell,cell process,catalytic activity,binding,ovarian steroid synthesis,thyroid hormone and other functions and pathways. The thyroid hormone signaling pathway was the common enrichment pathway of the two control groups. In a word,Cuscutae Semen flavonoids has a good treatment effect on male reproductive damage caused by Tripterygium Glycosides Tablets. The mechanism may be closely related to up-regulation of DNMT3 L genes and intervention of thyroid hormone signaling pathway. At the same time,the discovery of many different genes provides valuable information for study on the mechanism of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets compatibility decreasing toxicity and increasing efficiency.

[Long-term effect of Tripterygium Glycosides Tablets combined with traditional Chinese medicine on adulthood fertility].

To preliminarily investigate the effect of Tripterygium Glycosides Tablets( TGT) combined with traditional Chinese medicine( TCM) on the fertility and female menstruation on persons who have took during childhood. The children with henoch-schonlein purpura( HSP) or henoch-schonlein purpura nephritis( HSPN) who treated with TGT under 18 years old and now older than 18 years old( including 18 years old) during January 1998 to December 2010 were selected in our research. The content of follow-up visit included marriage,marriage age,fertility and child health; and unmarried female patients were asked whether they had menstrual abnormalities. The data of the unmarried female patients,including age,clinical classification,TCM syndrome type,initial dose and other related factors that may affect menstrual cycle,was analyzed by using binary logistic regression analysis. A total of 195 patients who met the criteria were followed up in this study,and 26 patients married for more than 1 year. Among the 26 married patients,1 HSP patient had no birth planning due to rheumatoid arthritis,and the remaining 25 patients all had given birth or were pregnant. The 169 unmarried patients included 89 female patients. Among the 89 female patients,4 cases refused to tell the menstrual situations,72 cases had normal menstruation( 84. 7%),13 cases had abnormal menstruation( 15. 3%),and there was no case of amenorrhea. Logistic regression analysis results showed that the age,clinical classification,TCM syndrome type and initial dose had no correlation with abnormal menstruation. Our results demonstrated that TGT has no effect on adulthood fertility among patients who took TGT combined with traditional Chinese medicine during childhood.

Steroids combined with levothyroxine to treat children with idiopathic nephrotic syndrome: a retrospective single-center study.

BACKGROUND: The clinical efficacy and safety of low-dose levothyroxine in the treatment of idiopathic nephritic syndrome accompanied by thyroid dysfunction have not been established. METHODS: One hundred and sixty-four patients were divided into three groups according to the levels of thyroid hormone and treatment. The thyroid status, efficacy and adverse reactions of thyroid treatment were observed in each group. RESULTS: Thyroid dysfunction was found in 73 patients. 40 cases were treated with steroids combined with levothyroxine. Proteinuria, cholesterol and thyroid-stimulating hormone (TSH) levels were significantly higher in patients with thyroid dysfunction, whereas serum albumin and free and total T3 and T4 levels were lower than those of euthyroid patients. The time for proteinuria remission in patients receiving levothyroxine therapy was shorter and their serum albumin higher than for patients without levothyroxine treatment. CONCLUSIONS: Thyroid hormonal changes are related to the degree of both proteinuria and serum albumin in patients with INS. Combined treatment with low-dose levothyroxine supplementation and steroids in children with INS and thyroid dysfunction is associated with reduced proteinuria and increased plasma albumin compared with patients treated with steroids only.

HIF­1α promotes the stemness of oesophageal squamous cell carcinoma by activating the Wnt/ß­catenin pathway.

Hypoxia­inducible­factor 1α (HIF­1α) is a marker for poor prognosis in the majority of the cancer types, and it has been revealed to be essential for maintaining cancer stem cells (CSCs). In the present study, it was determined that the expression of HIF­1α and CSC­related genes under hypoxic conditions was upregulated. Stable knockdown of HIF­1α significantly inhibited cell proliferation, migration and tumour growth in vivo in oesophageal squamous cell carcinoma (ESCC). A previous study revealed that the Wnt/ß­catenin pathway may play a key role in maintenance and progression of CSCs. Therefore, it was also revealed that stable knockdown of HIF­1α reduced the formation of spheroid body cells, the expression of CSC­related genes and Wnt/ß­catenin pathway­related target genes, as well as the activity of the Wnt/ß­catenin pathway. Collectively, the present results indicated that HIF­1α may regulate the stemness of ESCC by activating the Wnt/ß­catenin pathway.

Kangxian capsules: Effects on convulsive injuries, N-methyl-d-aspartate (NMDA) receptor subunit expression, and free Ca(2+) concentration in a rat hippocampal neuron epileptic discharge model.

PURPOSE: To investigate the effects and mechanisms of Kangxian (KX) capsules on hippocampal neuron convulsive injuries. METHODS: An epileptic discharge model was prepared with hippocampal neurons and divided into groups that were subjected to control, Mg-free, MK801, or anti-epilepsy (KX) interventions for 6 or 24h. The N-methyl-d-aspartate (NMDA) receptor channel current was recorded with a whole-cell patch-clamp technique, and the decay tau was determined from the receptor channel attenuation. The NMDA receptor subunits (NR1, NR2A, and NR2B) were detected by immunoblot assays, and intracellular free Ca(2+) was detected by laser confocal microscopy. RESULTS: The discharge times (6h: 100.66±36.51min, 24h: 134.42±86.43min) and tau values (6h: 934.0±564.9s, 24h: 846.6±488.0) of the Mg-free group were significantly increased (P<0.05) compared to the control group. All of the groups had similar levels of NR1 expression. NR2A and NR2B expression was significantly decreased in the Mg-free group and significantly increased most in the MK801 group, which was followed by the KX group (P<0.01). The free Ca(2+) concentrations in the control group were lower than those in the MK-801 and KX groups, the concentrations of which were significantly lower than those in the Mg-free group and which decreased with time. CONCLUSION: Kangxian capsules played its antiepileptic and neuroprotective roles via multiple targets and the underlying mechanisms included acceleration of the attenuation time course of NMDA receptor channels, alterations in the expression of NMDA receptor subunits, and reductions in the concentration of intraneuronal Ca(2+).

Clinicopathological features and prognosis of membranoproliferative-like Henoch-Schönlein purpura nephritis in children.

BACKGROUND: The aim of this retrospective study was to define the clinical manifestations, pathological features and prognosis of children with membranoproliferative-like Henoch-Schönlein purpura nephritis (HSPN), representing International Study of Kidney Disease in Children (ISKDC) grade VI. METHODS: Among 245 patients with HSPN treated in our hospital between 2008 and 2010, nine patients (3.7%) were diagnosed with HSPN of ISKDC grade VI (males = 5, females = 4, age: 9.5 ± 2.03 years, mean ± SD). The clinical features, laboratory and pathological findings, treatment and outcome of the 9 patients were retrospectively analyzed. RESULTS: Of the 9 patients, 7 (78%) presented with hematuria and nephrotic syndrome, and were treated with steroids (oral prednisone or intravenous methylprednisolone pulse therapy) and immunosuppressants (oral tripterygium glycosides or intravenous cyclophosphamide pulse therapy). One (11%) patient had hematuria and nephrotic range proteinuria (> 50 mg/kg per 24 hours) and was treated with oral prednisone and tripterygium glycosides. Another (11%) patient presented with hematuria and moderate proteinuria (25-50 mg/kg per 24 hours) and was treated with oral tripterygium glycoside only. Histopathological examination showed diffuse glomerular mesangial and endocapillary proliferation, mesangial interposition, double-contour formation, podocyte hypertrophy, shedding, and cytoplasmic absorption droplets. The percentages of glomeruli with small cellular crescents varied from 4%-25% in 6 of 9 patients. Follow-up for 2 to 4 years showed excellent recovery in all patients. CONCLUSIONS: The main clinical feature of ISKDC grade VI HSPN in children is a nephrotic syndrome with hematuria. The excellent prognosis of the disease was probably related to early diagnosis and treatment with steroids and/or immunosuppressants, and mild degree of glomerulosclerosis and tubulointerstitial damage.