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.

The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx.

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.

[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.

Established the first clinical prediction model regarding the risk of hyperuricemia in adult IgA nephropathy.

OBJECTIVE: To construct a novel nomogram model that predicts the risk of hyperuricemia incidence in IgA nephropathy (IgAN). METHODS: Demographic and clinicopathological characteristics of 1184 IgAN patients in the First Affiliated Hospital of Zhengzhou University Hospital were collected. Univariate analysis and multivariate logistic regression were used to screen out hyperuricemia risk factors. The risk factors were used to establish a predictive nomogram model. The performance of the nomogram model was evaluated using an area under the receiver-operating characteristic curve (AUC), calibration plots, and a decision curve analysis. RESULTS: Independent predictors for hyperuricemia incidence risk included sex, hypoalbuminemia, hypertriglyceridemia, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), 24 h urinary protein (24 h TP), gross hematuria and tubular atrophy/interstitial fibrosis (T). The nomogram model exhibited moderate prediction ability with an AUC of 0.834 (95% CI 0.804-0.864). The AUC from validation reached 0.787 (95% CI 0.736-0.839). The decision curve analysis displayed that the hyperuricemia risk nomogram was clinically applicable. CONCLUSION: Our novel and simple nomogram containing 8 factors may be useful in predicting hyperuricemia incidence risk in IgAN.

Effectiveness of shengxuexiaoban capsules combined with glucocorticoid therapy for immune thrombocytopenia: A meta-analysis.

OBJECTIVE: To evaluate the effectiveness of the Shengxuexiaoban Capsules combined with glucocorticoid therapy for immune thrombocytopenia (ITP). METHODS: We collected randomized controlled trials (RCTs) using shengxuexiaoban capsules in combination with glucocorticoid to treat ITP by searching major Chinese and English electronic databases. The outcome indicators were the effective rate, recurrence rate, the number of platelets in the blood, recovery time of platelets, and adverse reactions. We used STATA 16.0 and RevMan 5.3 for meta-analysis and GRADE pro. for evidence quality evaluation. RESULTS: A total of 27 RCTs were included in the meta-analysis, and the results showed a significant difference (all p<0.05) in the effective rate, recurrence rate, the number of platelets, and the recovery time of platelets (≥ 100×109) between ITP patients in the control group (who received glucocorticoid therapy alone) and test group (who received glucocorticoid therapy combined with the Shengxuexiaoban Capsules). And that Shengxuexiaoban capsules combined with glucocorticoid therapy were safe. The funnel plot and Egger's test results indicated no obvious publication bias. The GRADE evidence rating showed an intermediate quality of evidence rating for recurrence rate and overall effectiveness. CONCLUSION: Glucocorticoid therapy combined with the Shengxuexiaoban Capsules showed more effectiveness in the treatment of ITP. It can improve the effective rate, reduce the recurrence rate, increase the number of platelets and shorten the recovery time of platelets, and has a good safety profile.

Potential molecular mechanisms of Ermiao san in the treatment of hyperuricemia and gout based on network pharmacology with molecular docking.

A network pharmacology integrated molecular docking strategy was used to predict the underlying molecular mechanism of Ermiao san in the treatment of hyperuricemia and gout. Traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform were used to screen out the active compounds and their targets of Ermiao san. The disease target genes related to hyperuricemia (HUA) and gout were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, OMIM, TTD, and PharmGKB databases with "Hyperuricemia" and "Gout" as keywords, respectively. The potential targets of Ermiao san in the treatment of HUA and gout were screened through a Venn diagram. The protein-protein interaction network was constructed using Cytoscape software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were then conducted. Finally, some compounds and core targets were selected for molecular docking verification by Autodock Vina and Pymol software. Forty-six active compounds, such as quercetin, wogonin and beta-sitosterol, etc were identified. Ermiao san plays a therapeutic role in HUA and gout regulating various biological processes, cellular compounds, and molecular functions. The core targets of Ermiao san for treating HUA and gout are AT1 (namely Protein Kinase Bα), interleukin-1 beta, prostaglandin-endoperoxide synthase 2, JUN, etc. And the key pathways are nuclear factor-κB, interleukin-17 and tumor necrosis factor. The results of molecular docking analyses suggested that active compounds of Ermiao san could bind well to the core protein receptors. Ermiao san has a synergistic mechanism of multiple compounds, multiple targets, and multiple pathways in the treatment of HUA and gout, which provides a good theoretical basis for the clinical application.

[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.