Exploring the pathways of drug repurposing and Panax ginseng treatment mechanisms in chronic heart failure: a disease module analysis perspective.

Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein-protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.

The efficacy and safety of Longmu Tang granule for the treatment of atopic dermatitis: study protocol for a single-centred, double-blinded, randomised, placebo-controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing skin disease that has long-term physical and mental health impacts on children with this condition. Current treatments mainly include anti-inflammatory, antibacterial, and anti-allergic interventions, systemic therapy, and recently emerging target-focused agents. However, these treatments have limited effectiveness and unwanted side effects. The use of traditional Chinese medicine (TCM) in the treatment of AD has a long history, with promising efficacies, low toxicity, and improvements in the quality of life of patients with AD. Longmu Tang granule, a TCM, has been used to effectively treat AD since 2008 through doctors' prescriptions. To scientifically evaluate the clinical efficacy and safety of Longmu Tang granule, we proposed to launch a single-centred, double-blinded, randomised, placebo-controlled trial. METHODS: In this single-centred, double-blinded, randomised, placebo-controlled clinical trial conducted at Xiyuan Hospital of China Academy of Chinese Medical Sciences, a total of 60 participants will be randomly assigned (1:1) to receive the Longmu Tang granule or placebo granule for 8 weeks. The primary outcome will be evaluated using the index of Scoring Atopic Dermatitis. The secondary outcomes will be evaluated using the Children's Dermatology Life Quality Index and the number cancellation test. The mechanistic evidence will be the serum levels of inflammatory cytokines, including immunoglobulin E, tumour necrosis factor-α, interleukin-1, and interleukin-6. DISCUSSION: The results of this trial will provide evidence of the efficacy and safety of the Longmu Tang granule and prove its anti-inflammatory action in patients with AD. TRIAL REGISTRATION: Chinese Clinical Trial Registry Chictr.org ID: ChiCTR2100041591 . Registered on 1 January 2021.

Effectiveness of flesh-moistening paste in psoriasis vulgaris patients with symptom pattern of blood stasis: a randomized and parallel-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of flesh-moistening paste for treating psoriasis vulgaris in patients with blood stasis pattern in terms of Traditional Chinese Medicine (TCM). METHODS: Eudipleural rashes on both the left and right side of the same patients with psoriasis vulgaris, diagnosed via TCM as blood stasis pattern, were selected as the targeted skin lesions. A randomized, double-blind, parallel-controlled, multicenter controlled trial was conducted. The targeted skin lesions were categorized into either the treatment or control group. The treatment group used the flesh-moistening paste; the control group used a placebo. Both the paste and the placebo were topically applied twice daily for eight weeks. The patients were examined biweekly to evaluate the effects. The two groups were compared in terms of the psoriasis area and severity index (PASI) of the targeted skin lesions, which is scored according to erythema, desquamation, infiltration, area, pruritus, and improvement of skin barrier function. Adverse events were recorded during the study period. SPSS 21.0 was used to analyze the data. RESULTS: Fifty-six patients were enrolled between February 2016 and October 2017. Two were complicated by cardio-cerebrovascular disease and were excluded; thus, 54 outpatients were finally enrolled in the study. Four dropped out during the study period: three failed to complete their follow-up visits for unknown reasons, and one exited due to an adverse event. The final trial comprised 50 of the 56 originally selected patients, with a 92.6% completion rate. After 8 weeks of treatment, the targeted skin lesion scores differed significantly (P < 0.05). The PASI scores of the targeted skin lesions differed significantly beginning at week 6 (P < 0.05). The treatment group presented better results than those of the control group. Only one patient had an adverse reaction associated with the treatment. Improvements in skin barrier function differed significantly (P < 0.05). CONCLUSION: The flesh-moistening paste demonstrated a reliable curative effect and safety for treating psoriasis vulgaris in patients with blood stasis patterns. The topical paste improved the barrier function of the skin lesions.

Somatic variants in new candidate genes identified in focal cortical dysplasia type II.

OBJECTIVE: Focal cortical dysplasia type II (FCDII) is a malformation of cortex development commonly found in children with drug-resistant epilepsy. FCDII has been associated with somatic mutations in mammalian target of rapamycin (mTOR)-related pathway genes and an upregulation of mTOR. Somatic mutations were found in 10%-63% of FCDII samples; the frequency of the mutant allele was 0.93%-33.5%. This study aimed to find new candidate genes involved in FCDII. METHODS: We collected resected FCD lesions, perilesional brain tissues, and peripheral blood from 17 children with pathologically confirmed FCDII. We performed whole exome sequencing and followed a set of screening and analysis strategies to identify potentially deleterious somatic variants (PDSVs) in brain-expressed genes. We performed site-specific amplicon sequencing to validate the results. We also performed an in vitro functional study on an IRS1 variant. RESULTS: In six of 17 samples, we identified seven PDSVs in seven genes, including two frameshift variants and five missense variants. The frequencies of the variant allele were 1.29%-5.50%. The genes were MTOR, TSC2, IRS1, RAB6B, RALA, HTR6, and ZNF337. PDSVs in IRS1, RAB6B, ZNF337, RALA, and HTR6 had not been previously associated with FCD. In one lesion, two PDSVs were found in two genes. In a transfected cell line, we demonstrated that the c.1791dupG (identified in FCDII from Patient 1) led to a truncated IRS1 and significant mTOR hyperactivation compared to cells that carried wild-type IRS1. mTOR was also activated in FCDII tissue from Patient 1. SIGNIFICANCE: Seven PDSVs were identified in FCDII lesions in six of 17 children. Five variant genes had not been previously associated with cortical malformations. We demonstrated that the IRS1 variant led to mTOR hyperactivation in vitro. Although functional experiments are needed, the results provide evidence for novel candidate genes in the pathogenesis of FCDII.

[Effect on chronic urticaria and serum IL-4 and IgE in the patients treated with moving cupping therapy and autohemotherapy with acupoint inection].

OBJECTIVE: To explore the clinical efficacy and effect mechanism on chronic urticaria treated with moving cupping therapy combined with autohemotherapy with acupaint injection for desensitization at acupoints. METHODS: One hundred and four patients of chronic urticaria were randomized into a comprehensive therapy group and a medication group, 52 cases in each one. In the comprehensive therapy group, the moving cupping therapy along the governor vessel and bladder meridian of foot-taiyang was applied combined with autohemotherapy with acupaint injection for desensitization at acupoints. The self-venous blood was injected at bilateral Quchi (LI 11) and Zusanli (ST 36), 1 mL at each acupoint, once every 3 days. In the medication group, cetirizine tablets, 10 mg were prescribed for oral administration, once every day, and the compound dexamethasone acetate cream was used externally, once to twice a day. The clinical efficacy: was observed in 30 days of treatment in the two groups. The changes of serum interleukin 4 (IL-4) and immunoglobulin E (Ig E) before and after treatment were observed. The recurrence rate was compared between the two groups in 3 months after treatment. RESULTS: The cured and markedly effective rate was 90.4% (47/52) in the comprehensive therapy group, which was higher obviously than 78.8% (41/52, P < 0.05) in the medication group. The levels of serum IL-4 and IgE were reduced in the patients of the two groups, indicating the significant difference in comparison before and after treatment (all P < 0.01) and the reducing degree in the comprehensive therapy group was much more significant than that in the medicine group (both P < 0.01). The recurrence rate was 19. 1% (9/47) in the comprehensive therapy group in the 3-month follow-up after treatment, and apparently lower than 51.2% (21/41, P < 0.01). CONCLUSION: The moving cupping therapy combined with autohemotherapy with acupaint injection for desensitization at acupoints achieves the better efficacy on chronic urticaria compared with the routine western medicine treatment and the recurrence rate is low. The effect mechanism is possibly related to the down-regulation of serum IL-4 and IgE in the patients.