[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.

Sophora flavescens Alkaloids and Corticosteroid Synergistically Augment IL-10/IL-5 Ratio with Foxp3-Gene-Epigenetic Modification in Asthma PBMCs.

BACKGROUND: It has been demonstrated that ASHMI (antiasthma-simplified herbal medicine intervention) can improve airway function and reduce inflammation in human asthmatic patients with high safety and tolerability. In addition, ASHMI significantly suppresses Th2 cytokine production and increases Th1 cytokine production in treating asthma. OBJECTIVE: Allergic asthma is associated with dysregulation of cytokines. We focused on IL-5 and IL-10 as signature Th2 and Treg cytokines to characterize ASHMI immunomodulatory components. METHODS: The effects of ASHMI and individual herbal constituents on IL-5 and IL-10 production by PBMCs from asthmatic subjects were determined ex vivo. Sophora flavescens (SF)-F2, containing alkaloid compounds, effects on PBMC IL-10 and IL-5 production in the presence or absence of dexamethasone (Dex), and on DNA methylation levels at the foxp3 gene promoter were determined. RESULTS: The ratio of anti-CD3/CD28 stimulated IL-10/IL-5 production by PBMCs from asthmatic subjects was significantly reduced compared to healthy subjects. In PBMCs from asthmatic subjects, ASHMI significantly reduced IL-5 production and increased IL-10 secretion in a dose-dependent manner (p < 0.05-0.01). SF-F2 was most effective in increasing IL-10, whereas SF-F4 (flavonoid compounds) was most effective in suppressing IL-5 production. Dex-treated PBMCs from asthma subjects showed a trend of increasing ratio of IL-10/IL-5 while demonstrating reduced levels in both IL-5 and IL-10 (p < 0.05). Co-culture with Dex and SF-F2 significantly prevented Dex suppression of IL-10, while retained Dex-suppression of IL-5 production, and increased IL-10/IL-5 ratio by Dex. Co-culture with SF-F2 and Dex significantly reduced DNA methylation levels at the foxp3 gene promoter at CpG-126. CONCLUSION: The SF alkaloid-rich fraction may be responsible for ASHMI induction of IL-10 production by PBMCs and plays a synergistic effect with Dex for augmenting IL-10/IL-5 ratio.

[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.

Traditional Chinese medicine versus regular therapy in Henoch-Schönlein purpura nephritis in children: study protocol for a randomized controlled trial.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is the most common secondary glomerular disease in children. Currently, the treatment for HSPN is always selected based on the Kidney Disease Improving Global Outcomes guidelines; however, this approach may lead to undertreatment, especially in patients with persistent proteinuria that does not reach nephrotic levels and/or hematuria and those with a pathological classification between grades 1 and 3 according to the International Study of Kidney Disease in Children. This study was performed to evaluate the curative effect and safety of a traditional Chinese medicine (TCM) integrated treatment program in this type of HSPN. METHODS: This multicenter, open-label, large-sample, randomized controlled trial was performed in China and included 500 children with HSPN exhibiting mild pathological patterns. The treatment group to control group ratio was 2:1, and each group was further stratified into two types, light and heavy, according to urinary protein quantification and pathological type. The treatment group received tripterygium glycosides (TGs), tanshinone IIa sodium sulfonate injection, and Chinese herbs selected based on syndrome differentiation in TCM. The heavy and light subgroups received treatment courses and dosages of TG. In the control groups, the light group received benazepril hydrochloride tablets, low molecular weight heparin calcium injection, dipyridamole tablets, and a Chinese medicine placebo, while the heavy group received the same treatment plus prednisone. All groups were treated for 3 months and then followed up for 9 months. The efficacy and safety of the treatments were then evaluated among the groups. DISCUSSION: Currently, few treatments are available for HSPN patients with mild pathological patterns indicating light to moderate proteinuria and/or hematuresis. In this large-sample study, we provide a new approach for HSPN that includes an integrated treatment program that incorporates TCM. TRIAL REGISTRATION: Clinical Trials.gov, NCT03591471 . Re-registered on 19 July 2018.

Clinical practices s of Traditional Chinese Medicine for acute upper respiratory tract infection in children.

OBJECTIVE: To develop Clinical practice s of Traditional Chinese Medicine (TCM) for acute upper respiratory tract infection (AURI) in children; TCM is used alone or administered together with antibiotics. METHODS: Under the guidance of evidence-based medicine concept, in strict accordance with the rules of international s development, as well as on the basis of evidence of clinical research of TCM, the s solicited opinions from clinical experts and methodologists in TCM and Western Medicine. GRADE standard was applied to form experts' consensus. RESULTS: The s standardized classification of TCM patterns and TCM treatments in children with AURI, including prescription, Chinese patent medicine, non-drug treatment and prevention. CONCLUSION: Follows the principle of ""evidence based, consensus supplemented, and experience referred"", these s were formulated, but the quality of evidence of included studies were relatively low. Further refinement of the s should be needed as deeper clinical studies as available in future.

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+).

A case of anaphylactoid purpura nephritis accompanied by pulmonary hemorrhage and review of the literature.

Cases of Henoch-Schönlein purpura and purpura nephritis accompanied by pulmonary hemorrhage are rare. Mild cases are easily ignored due to a lack of evident bleeding, and severe cases may be fatal. We have only treated one patient with Henoch-Schönlein nephritis (HSPN), a female child. The clinical manifestations were not evident, however, the imaging manifestations were clear. Finally, the patient was definitively diagnosed with HSPN accompanied by pulmonary hemorrhage. Following treatment with antiinflammatory and steroidal agents, tripterygium glycosides and traditional Chinese medicine, the patient recovered. In the present study, we report the diagnosis and treatment of this disease, with a review of the literature.