Investigation into molecular mechanisms and high-frequency core TCM for pulmonary fibrosis secondary to COVID-19 based on network pharmacology and data mining.

BACKGROUND: The complication, pulmonary fibrosis (PF) secondary to COVID-19, may have a second wave of late mortality, given the huge number of individuals infected by COVID-19. However, the molecular mechanisms of PF secondary to COVID-19 haven't been fully elucidated, making the identification of novel strategies for targeted therapy challenging. This study aimed to systematically identify the molecular mechanisms and high-frequency core traditional Chinese medicine (TCM) targeting PF secondary to COVID-19 through network pharmacology and data mining. METHODS: The molecular mechanisms of PF secondary to COVID-19 were identified by mapping the COVID-19 differentially expressed gene and known targets associated with PF, protein-protein interactions network analysis, and enrichment pathway analysis; then the high-frequency core TCM targeting PF secondary to COVID-19 were identified by data mining and "Key targets related to PF secondary to COVID-19 - Ingredients" and "Key ingredients-key herbs" network analysis; and last we validated the interaction between the key ingredients and key targets by molecular docking. RESULTS: The molecular mechanisms of PF secondary to COVID-19 were mainly related to tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction pathway, and NF-κB signaling pathway. Among these, cytokines interleukin 6 (IL-6), TNF, and IL-1ß were identified as the key targets associated with PF secondary to COVID-19. The high-frequency core TCM targeting these key targets were identified, including ingredients of quercetin, epigallocatechin-3-gallate, emodin, triptolide, resveratrol, and herb of Polygonum cuspidatum. Finally, our results were validated by quercetin and resveratrol both well docked to IL-6, TNF, and IL-1ß protein, with the estimated docking energy <0 kcal/mol. CONCLUSIONS: This study identified the cytokines-related molecular mechanisms of PF secondary to COVID-19, and the high-frequency core TCM against PF by targeting IL-6, TNF, and IL-1ß. Which provides new ideas for the discovery of small molecular compounds with potential therapeutic effects on PF secondary to COVID-19.

Compound XiongShao Capsule ameliorates streptozotocin-induced diabetic peripheral neuropathy in rats via inhibiting apoptosis, oxidative - nitrosative stress and advanced glycation end products.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound XiongShao Capsule (CXSC), a traditional herb formula, has been approved for using to treat diabetic peripheral neuropathy (DPN) by the Shanghai Food and Drug Administration, with significant efficacy in clinic. AIM OF THE STUDY: This study aimed to investigate the multidimensional pharmacological mechanisms and synergism of CXSC against DPN in rats. METHODS: The quality analysis of CXSC was performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography. Rats with DPNinduced by streptozotocin/high-fat diet for 4 weeks were treated with CXSC at three doses (1.2 g/kg, 0.36 g/kg, and 0.12 g/kg), or epalrestat (15 mg/kg) daily for 8 weeks continuously. During the treatment period, body weight, serum glucose levels, and nerve function, including nerve conduction velocity (NCV), and mechanical and thermal hyperalgesia were tested and assessed every 4 weeks. In the 13th week, the histopathological examination in the sciatic nerve was performed using a transmission electron microscope. The expression of apoptosis-related proteins of BAX, BCL2, and caspase-3 in the sciatic nerve was examined using hematoxylin and eosin staining. The serum levels of advanced glycation end products (AGEs), oxidative-nitrosative stress biomarkers of superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured using a rat-specific ELISA kit. RESULTS: CXSC had no significant effect on body weight or serum glucose levels (P > 0.05), but it significantly improved mechanical hyperalgesia (F5,36 = 18.24, P < 0.0001), thermal hyperalgesia (F5,36 = 8.45, P < 0.0001), and NCV (motor NCV: F5,36 = 7.644, P < 0.0001, sensory NCV: F5,36 = 12.83, P < 0.0001). Besides, it maintained myelin and axonal structure integrity, downregulated the expression of apoptosis-related proteins in the sciatic nerve tissue, reduced AGEs and NOS levels, and enhanced antioxidant enzyme SOD activities in the serum. CONCLUSION: CXSC exerted neuroprotective effects against rats with DPN through multidimensional pharmacological mechanisms including antiapoptotic activity in the sciatic nerve and downregulation of the level of serum NOS, SOD and AGEs.

Repair of circular scar in the forearm by expanded double-pedicle omega-shaped flap at the rear flank of bottom-waist / 中华整形外科杂志

<p><b>OBJECTIVE</b>To discuss the method for repairing the circular scar in the forearm.</p><p><b>METHODS</b>Large expander (400-600 ml) were implanted subcutaneously at the rear flank of bottom-waist in the way of overlapping or continued expansion. After expansion was completed, the horizontal opened omega-shaped flap was formed by advancement of expanded skin with the two pedicles at the two sides. Then the forearm was tunneled under flap with the wound covered by flap. The pedicles were cut off at the third stage.</p><p><b>RESULTS</b>From April 1998 to June 2009, 8 cases were treated with no flap necrosis. The patients were followed up for 1 to 3 years with good flap color and thickness. Flap sensory was partially recovered. Linear atrophic scar was left in the donor sites.</p><p><b>CONCLUSIONS</b>It is feasible to repair forearm circular scar by expanded double-pedicle omega-shaped flap at the rear flank of bottom-waist.</p>

Reconstruction of skin defect at frontal hair line with mastoid fasciocutaneous island flap / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the reconstruction of skin defect at frontal and temporal hair line.</p><p><b>METHODS</b>5 cases with skin defect at frontal and temporal hair line were treated with mastoid fasciocutaneous island flap pedicled with parietal branch of superficial temporal artery.</p><p><b>RESULTS</b>All the flaps survived completely. Hair grew up 5 - 7 days after operation, showing good reconstructed hair line.</p><p><b>CONCLUSIONS</b>Mastoid fasciocutaneous island flap is a reliable method for reconstruction of skin defect at frontal and temporal hair line.</p>

The expanded cross-leg flap for repairing the soft tissue defects of the instep / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the clinical application of the expanded cross-leg flap for repairing instep soft tissue defects with bone exposure.</p><p><b>METHODS</b>The expanded cross-leg flap was used to repair instep defects in 10 patients. After flap transferring the donor site was closed directly without skin grafting.</p><p><b>RESULTS</b>Satisfactory results were achieved in all the cases. The flaps survived well. The donor site had less scar and kept good appearance.</p><p><b>CONCLUSIONS</b>The expanded cross-leg flap is a better choice for repairing the soft tissue defects of the instep. It is simple and easy with less trauma to the donor site. After the operation, both the recipient and the donor areas had good appearance.</p>