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Background: AURKA, Aurora kinase A encoding gene, is an important signaling hub gene for mitosis. In recent years, AURKA has been implicated in the occurrence and development of several cancers. However, its relationship with the tumor microenvironment in skin cutaneous melanoma (SKCM) and the molecular mechanisms underlying its effects are still unclear. Method：We adopted a variety of bioinformatics methods to comprehensively analyze the potential carcinogenesis of AURKA in SKCM, and constructed a prognostic nomogram model. We also dentified an inhibitor targeting AURKA and verified its therapeutic effects against SKCM using the molecular docking technology. Results: We found that abnormally high expression of AURKA was responsible for driving the occurrence and development of SKCM, and affected various pathological factors in SKCM. In addition, AURKA was established as an independent marker of poor SKCM prognosis. We also characterized the potential mechanisms by which AURKA manifests its effects in SKCM and found that AURKA inhibits the infiltration of CD8+ T cells and promotes hypoxia by activating the TGF-β signaling pathway. At the same time, the high AURKA expression group had higher tumor stemness index and promoted cell proliferation and metastasis. Finally, the small molecule compound ZNC97018978 targeting AURKA screened by molecular docking technology can inhibit the proliferation, invasion and metastasis of SKCM. The possible mechanism is that ZNC97018978 induces apoptosis by arresting the cell cycle, thereby inhibiting cell proliferation. Conclusion: AURKA is the core hub gene driving the occurrence and development of SKCM, and its expression is regulated by epigenetic modifications. AURKA can regulate the infiltration level of various immune cells in the tumor microenvironment, reshape the immunosuppressive tumor microenvironment, and apoptosis, and hypoxia. Thus, it is a prognostic biomarker and potential therapeutic target in SKCM. ZNC97018978 is an effective and safe inhibitor of AURKA in vitro; its safety and effectiveness in vivo as a potential treatment for cutaneous melanoma should be further determined.

Cardiovascular disease is the main cause of mortality and morbidity in the world, especially in developing countries. Drug therapy is one of the main ways to treat cardiovascular diseases. Among them, great progress has been made in the treatment of cardiovascular diseases with traditional Chinese medicine. In terms of experimental research, the mechanism of traditional Chinese medicine in the treatment of cardiovascular diseases has been thoroughly discussed in vitro and in vivo. In terms of clinical treatment, traditional Chinese medicine with flavonoids, saponins and alkaloids as the main effective components has a definite effect on the treatment of cardiovascular diseases such as arrhythmia, myocardial ischemia, angina pectoris and myocardial infarction, with high safety and good application prospects. With the further research on the effective ingredients, mechanism and adverse reactions of traditional Chinese medicine, it will be beneficial to the effectiveness of traditional Chinese medicine, reduce side effects and promote the modernization of traditional Chinese medicine. Calycosin and its derivatives, the main bioactive flavonoids in Astragalus membranaceus have multiple biological effects, such as antioxidant, pro-angiogenesis, anti-tumour, and anti-inflammatory effects. Based on the above biological effects, calycosin has been shown to have good potential for cardiovascular protection. The potent antioxidant effect of calycosin may play an important role in the cardiovascular protective potential. For injured cardiac myocytes, calycosin and its derivatives can alleviate the cell damage mainly marked by the release of myocardial enzymes and reduce the death level of cardiac myocytes mainly characterized by apoptosis through various mechanisms. For vascular endothelial cells, calycosin also has multiple effects and multiple mechanisms, such as promoting vascular endothelial cell proliferation, exerting vasodilating effect and directly affecting the synthesis function of endothelial cells. The present review will address the bioactivity of calycosin in cardiovascular diseases such as protective effects on cardiac myocytes and vascular endothelial cells and elucidate main mechanism of calycosin and its derivatives to exert the above biological effects.

Backgrounds: Absent in melanoma 2 (AIM2) is a crucial developmental regulator for innate immune responses and recent reports suggest its vital function in the process of cancer development and progression, however, the mutations, copy number variations (CNV), methylation, and relationship with the tumor microenvironment (TME), along with the underlying molecular biological processes, remain unclear. Methods: the mutations, CNVs, and methylation patterns of AIM2 in patients with skin cutaneous melanoma (SKCM) were systematically analyzed in this study. Its effects on TME, immunotherapy, and prognoses of SKCM patients were also investigated. According to the findings of the multifactorial Cox regression analysis, a prognostic alignment diagram-based model was constructed. Results: The findings showed that AIM2 expression differed significantly in patients with SKCM. The CNVs and gene methylation patterns affected the level of AIM2 expression, and genetic alterations could influence the tumor immunophenotype. The prognostic alignment diagram model had better predictive efficacy and may improve survival rates in patients. The elevated expression of AIM2 led to enhanced immune responses in SKCM patients and could induce cellular pyroptosis, apoptosis, and necrosis. AIM2 could promote CD8+ T-cell infiltration by activating the PANoptosis pathway and M1 macrophage polarization., and this may be a possible mechanism of its action. In addition, significant associations of AIM2 expression with hot tumor, tumor mutational burden (TMB), immune checkpoint-related genes, and microsatellite instability (MSI), were observed. Conclusions:AIM2 is associated with increased abundance of effector CD8+ T-cells, positive responses to immune checkpoint blockade (ICB) treatment, and improved prognoses. Therefore, it could be a putative enhancer and prognostic biomarker for the treatment of SKCM.

Rationale Pilonidal sinus disease (PSD) involving the breast is extremely rare and has not been described in man. Patient concerns This current case report presents a case of a pilonidal cyst in a 46-year-old man which was surgically treated. He had intermittent pain in his left breast for 2 months and came for local rupture and discharge for 1 week. Diagnosis The initial diagnosis is male mastitis, on the basis of the histological features of H&E-stained specimens and immunohistochemistry of the resected lump, this case was diagnosed as PSD. Interventions The patient underwent "enlarged resection of the left breast lesion" under local anesthesia. Outcomes The patient's surgical area healed well, without any signs of recurrence. Conclusion PSD involving the breast is extremely rare in man, with no typically clinical manifestations, and could be easily ignored. This disease requires great attentions from clinicians.

Flap necrosis is generally regarded as the result of vasospasm, thrombosis, and infection.To improve skin flap survival and lower the risk of side effects due to systemic drug delivery, we formulated and evaluated compound gels for transdermal application. The transdermal delivery of 1% azithromycin (AZM), 0.5% amlodipine besylate (AB), and 300 IU/g low molecular weight heparin (LMWH) in compound gels, singly or in combinations, was measured across rat skin in vitro. The effects of AB and LMWH on flap blood circulation was investigated using fluorescein angiography, by transdermally applying the gel onto the surface of an in vivo ischaemic flap rat model; concentrations of the drugs were detected in both blood plasma and flap tissue at assigned timepoints. Finally, infected ischaemic flaps were treated to evaluate their anti-inflammatory effects and sizes of flap survival area.Each drug efficiently penetrated the in vitro skin in a time-dependent manner. In the in vivo ischaemic flaps, AB or LMWH increased the blood supply. All gel formulations that included AZM were associated with less flap inflammation. The surviving areas after treatment with AZM+LMWH or AZM+AB were significantly larger than that treated with the AZM-only gel, and the largest surviving area was that treated with AZM+AB+LMWH. Gels containing no AZM could not decrease flap inflammation or increase flap survival.Transdermal application of a compound gel with AZM, AB, and LMWH combined is a promising method to prevent and treat flap infection, improve blood circulation, and increase the survival of infected ischaemic flaps.

Oleuropein, the main glycoside present in olives, has been reported to have cardioprotective effect, but the exact mechanism has not been clearly elucidated. This study attempted to clarify the cardioprotective effect of oleuropein against simulated ischemia/reperfusion- (SI/R-) induced cardiomyocyte injury in vitro and further explore the underlying mechanism. Here we confirmed that oleuropein reduced the cell injury in neonatal rat cardiomyocyte induced by SI/R evidenced by decreasing MTT dye reduction and LDH activity in the culture medium. Meanwhile, the compound also inhibited reactive oxygen species excessive generation and stabilized mitochondrial membrane potential after SI/R. The flow cytometry assessment results indicated the inhibition of cellular apoptosis with oleuropein treatment. Furthermore, western blot analysis showed that oleuropein attenuated the expression of Cyt-C, c-caspase-3, and c-caspase-9, increased the Bcl-2/Bax ratio, and enhanced the phosphorylation of ERK1/2 and Akt after SI/R. However, the phosphorylation enhancement was partially abolished in the presence of LY294002 (PI3K inhibitor) and U0126 (ERK inhibitor). All these findings indicate that oleuropein has the protective potential against SI/R-induced injury and its protective effect may be partly due to the attenuation of apoptosis via the activation of the PI3K/Akt and ERK1/2 signaling pathways.

The study aims to test the effect of transdermal application of azithromycin in the prevention of skin flap infection in experimental rats. The accumulative penetration quantities of azithromycin through excised rat skin and the azithromycin quantities in flap tissues from rats given 1%, 2%, and 3% azithromycin gels were assayed by UV spectrophotometer. Staphylococcus aureus and pathogenic Escherichia coli were inoculated to the underneath of the random ischemic rat flaps to induce bacterial infection. The azithromycin gels were applied on the flaps daily for 7 days. The survival areas of flaps were measured by planimetry. The accumulative penetration quantities of azithromycin and the azithromycin quantities in flap tissues increased in a time-dependent manner (P < 0.05). Azithromycin gels decreased the inflammatory reaction and enhanced the survival area of flaps (P < 0.05). We concluded that 1% azithromycin gel could penetrate into the flap tissues and significantly increase survival area of infected flaps.

To investigate the effects of angelicanaphtha on proliferation, cell cycle, apoptosis, and collagen synthesis of human umbilical vein endothelial cells (HUVEC).HUVEC was cultured and passaged in Dulbecco's modified Eagle's medium (DMEM) and treated with angelicanaphtha 1 mg/ L, 4 mg/L, and 16 mg/L at 1, 3, 5, and 7 day respectively. The proliferation was measured with MTT method. The cell cycle and apoptosis were analyzed with flow cytometry and collagen synthesis was determined with radioimmunoassay.The proliferation of the HUVEC was accelerated by angelicanaphthaor =4 mg/L and inhibited by angelicanaphtha at 16 mg/L (P0.05). Lower concentration (or = 4 mg/L) of Angelicanaphtha decreased cells in G0/G1 phase and increased significantly cells in S phase and inhibited the apoptosis (P0.05). However, angelicanaphtha at 16 mg/L increased cells in G0/G1 phase and decreased cells in S phase and induced the apoptosis (P0.05). The collagen synthesis of HUVEC was inhibited by angelicanaphtha in concentration-dependent manner (P0.05 or 0.01).The proliferation effects of angelicanaphtha on HUVEC had dualistic regulation of increase by lower-concentration and inhibition by higher-concentration. Collagen synthesis of HUVEC was inhibited by angelicanaphtha in concentration-dependent manner.

To study the roles of protein kinase C (PKC) in effect of interferon-gamma (IFN-gamma) on wound healing and cicatrization.IFN-gamma was applied on the wound and into the scar tissues of rabbit ear before or after wound healing. PKC activities in the tissues from 0, 3, 6 d, 11-16 d post-wounding and from 14, 30 and 45d post-epithelization were measured by phosphorus (32p) incorporation. The time of wound epithelization and scar changes were also observed.The PKC activity in granulation tissue, wound margin tissue and scar tissue elevated obviously in comparing with that of normal skin (P0.01). IFN-gamma did not change PKC activity (P0.05). But it delayed the wound healing (P0.01) and inhibited scar hyperplasia (P0.05).PKC might not mediate the signal of IFN-gamma inhibiting the wound healing and scar hyperplasia. But PKC might be related to the wound healing and scar hyperplasia.

To study the signal roles of protein tyrosine kinase (PTK) on proliferation and collagen synthesis of fibroblasts derived from hypertrophic scar(HS-FB) and normal skin (NS-FB) by interferon-gamma (IFN-gamma) or transforming growth factor beta1 (TGF-beta1).HS-FB and NS-FB were cultured and passaged in Dulbecco's modified Eagle's medium(DMEM). The PTK activity in unstimulated or IFN-gamma or TGF-beta1-stimulated HS-FB and NS-FB (10,30,60 and 120 min) were assayed by phosphorus (32P) incorporation. Cell proliferation was determined with MTT stain. The type III procollagen was measured by radioimmunoassay.TGF-beta1 did not change PTK activity but it increased predominately proliferation and collagen synthesis of HS-FB and NS-FB in time-dependent fashion. Genistein, an inhibitor of PTK, inhibited HS-FB and NS-FB to proliferate and synthesize collagen but it could not change the roles on proliferation and collagen synthesis by TGF-beta1. IFN-gamma activated transiently PTK (P0.05) and increased proliferation and collagen synthesis of both fibroblast (P0.05, at 30 min, 60 min). As the recovery of PTK activity, the proliferation and collagen synthesis were inhibited by IFN-gamma at 120 min. Furthermore, Genistein abrogated the transient increased roles and partly reversed the longterm inhibitory functions by IFN-gamma (P0.05) . There were no difference on PTK activity, proliferation and collagen synthesis between HS-FB and NS-FB.PTK did not mediate the signal of TGF-beta1 but transduced the signal of transient increased roles of IFN-gamma. Inhibited or activated PTK might mediate the signal of decreasing or increasing proliferation and collagen synthesis of fibroblast.