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Current wavelet thresholding methods for cardiogram signals captured by flexible wearable sensors face a challenge in achieving both accurate thresholding and real-time signal denoising. This paper proposes a real-time accurate thresholding method based on signal estimation, specifically the normalized ACF, as an alternative to traditional noise estimation without the need for parameter fine-tuning and extensive data training. This method is experimentally validated using a variety of electrocardiogram (ECG) signals from different databases, each containing specific types of noise such as additive white Gaussian (AWG) noise, baseline wander noise, electrode motion noise, and muscle artifact noise. Although this method only slightly outperforms other methods in removing AWG noise in ECG signals, it far outperforms conventional methods in removing other real noise. This is attributed to the method's ability to accurately distinguish not only AWG noise that is significantly different spectrum of the ECG signal, but also real noise with similar spectra. In contrast, the conventional methods are effective only for AWG noise. In additional, this method improves the denoising visualization of the measured ECG signals and can be used to optimize other parameters of other wavelet methods to enhancing the denoised periodic signals, thereby improving diagnostic accuracy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Medical image segmentation faces current challenges in effectively extracting and fusing long-distance and local semantic information, as well as mitigating or eliminating semantic gaps during the encoding and decoding process. To alleviate the above two problems, we propose a new U-shaped network structure, called CFATransUnet, with Transformer and CNN blocks as the backbone network, equipped with Channel-wise Cross Fusion Attention and Transformer (CCFAT) module, containing Channel-wise Cross Fusion Transformer (CCFT) and Channel-wise Cross Fusion Attention (CCFA). Specifically, we use a Transformer and CNN blocks to construct the encoder and decoder for adequate extraction and fusion of long-range and local semantic features. The CCFT module utilizes the self-attention mechanism to reintegrate semantic information from different stages into cross-level global features to reduce the semantic asymmetry between features at different levels. The CCFA module adaptively acquires the importance of each feature channel based on a global perspective in a network learning manner, enhancing effective information grasping and suppressing non-important features to mitigate semantic gaps. The combination of CCFT and CCFA can guide the effective fusion of different levels of features more powerfully with a global perspective. The consistent architecture of the encoder and decoder also alleviates the semantic gap. Experimental results suggest that the proposed CFATransUnet achieves state-of-the-art performance on four datasets. The code is available at https://github.com/CPU0808066/CFATransUnet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The morbidity of skin tumors (ST) in China is a great concern as the population ages. No epidemiological survey on ST in elderly communities in China has been reported. A questionnaire survey was conducted among the residents over 60 years old in a community in Shanghai, China from May 1, 2011 to November 30, 2011. The prevalence of cutaneous tumors and associated factors were analyzed. Among 2038 valid cases, a total of 78 (3.8%, 95% CI 3.0-4.7) skin cancers (SC) were confirmed. According to the final multivariate regression analysis, age, gender and previous occupation were the significantly influential factors for SC. Actinic keratosis (AK) accounted for the largest proportion (63, 3.1%) in SC. The head and neck was the physiological site with the highest incidence of SC (64, 82.1%), and AK was the most common (55, 87.3%) in head and neck SC. The common concomitant diseases of SC were hypertension (26, 33.3%) and diabetes mellitus (9, 11.5%). Seborrheic keratosis (SK) was the most common benign skin tumor with a prevalence of 100%. Men and women developed SK in significantly different parts of the body (P < 0.0001). The incidence of ST in the elderly population in Shanghai community increased with age. ST preferred to occur in the head and neck, which might be attributed to excessive ultraviolet (UV) exposure in these areas. Therefore, early diagnosis and sun-protection education are essential interventions for ST in the elderly., (© 2023. The Author(s).)

Objective: Photoaging is characterized by wrinkles in the skin and the deterioration of the skin barrier function, mainly caused by long-term exposure to ultraviolet (UV) radiation. Photodynamic therapy (PDT) has been shown to treat photoaging. The novel photosensitizer ShengTaiBuFen(STBF) is a derived substance of Chlorin e6(Ce6) that can exert photodynamic effects directly. In this study, we investigated the availability and the mechanism of STBF-PDT in the treatment of photoaging., Methods: Fluorophotometer was used to determine therapeutic parameters for in vivo experiments. Camera photographs, dermoscopy, HE and Masson staining, skin pH, trans epidermal water loss (TEWL), epidermal water content, and sebum testing were used together to evaluate the results of the treatment. Dark toxicity and therapeutic parameters for in vitro experiments were determined by CCK8 analysis. Scratch assay was used to identify the cell migration of STBF-PDT on HaCaT cells. qPCR and Western blot were used to evaluate the TGF-β/Smad signaling pathway in human dermal fibroblast (HDF) cells., Results: We investigated the optimal STBF concentration and time of incubation in vivo and in vitro experiments. STBF-PDT improved the skin phenotype of photoaged mice. The skin of photoaged mice treated with 80 J/cm 2 STBF-PDT became smooth, while skin flakes were reduced. The epidermis of STBF-PDT-treated mice was thinner, and the cells were neatly arranged, with increased dermal collagen. In vitro, STBF-PDT promoted the migration of HaCaT cells below a light dose of 0.1 J/cm 2 . HDF cells co-cultured with HaCaT cells treated with low-dose STBF-PDT showed activation of the TGF-β pathway., Conclusion: As a novel photosensitizer, STBF-mediated low-dose PDT could reverse photoaging via the TGF-β pathway., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Diabetic ulcer is a common complication of diabetes. Therapies of diabetic ulcer are still challenging due to the complicated aetiology. Ruyi Jinhuang Powder (RJP) is gradually adopted to treat diabetic ulcer and has a significant therapeutic effect., Aim of the Study: To investigate the therapeutic potential for diabetic ulcer in vivo and in vitro, we explored whether and how RJP influences wound healing in mice and fibroblasts at the tissular, cellular and molecular levels., Materials and Methods: The chemical composition of RJP was identified by HPLC. Streptozotocin (STZ) induced diabetic mice were used to confirm the curative effect of RJP in vivo. Besides, the impact of RJP in stimulating fibroblasts proliferation, migration and reducing inflammation was studied through CCK-8 assay, cell scratch assay, PCR, WB, etc. RESULTS: A total of 17 compounds were identified in RJP by HPLC. Our data indicated that RJP promoted fibroblasts proliferation and migration via activating Wnt/β-catenin signaling pathway. Consistently, RNA-seq analysis of mice skin samples also showed that the shared differentially expressed genes (DEGs) between RJP group and control group were most enriched in wnt signaling pathway. These DEGs were closely related with wound repair. In addition, the anti-inflammation effect of RJP was also confirmed through downregulation of IL-1α, IL-1β, IL-6 and IL-10 expression levels. These biological effects were reduced when the Wnt/β-catenin signaling was blocked. The in vivo study also demonstrated the effect of RJP in improving epidermal wound closure, which was consistent with the in vitro results., Conclusions: Topical application of RJP was effective in treating diabetic ulcer. This research is helpful to provide new insights and evidence into the role of RJP in accelerating unhealing wound and reducing wound inflammation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: 5-aminolevulinic acid-mediated PDT (ALA-PDT) has been used in a variety of skin diseases including cSCC (cutaneous squamous cell carcinoma). Halofuginone (HL) is a less-toxic febrifugine derivative and has inhibitory effects on a variety of cancer cells. For now, there are no published study focusing on the combination use of ALA-PDT with HL to improve clinical efficacy of cSCC., Objective: In this study, we will examine the effectiveness of combined treatment of ALA-PDT and HL in cSCC as well as its underlying mechanism., Methods: The human epidermoid carcinoma cell line SCL-1 was treated with ALA-PDT or/ and HL, and cell viability, cell migration, ROS production, apoptosis were evaluated by CCK-8, colony formation, scratch assay, DCFH-DA probe, flow cytometry, respectively. The protein expression of NRF2 signaling was examined by western blot., Results: HL strengthened ALA-PDT's inhibition of SCL-1 cell viability, migration, as well as NRF2 related β-catenin, p-Erk1/2, p-Akt and p-S6K1 expression. Overexpression of NRF2 conferred resistance to co-treatment's effects on c-Myc, Cyclin D1, Bcl-2, as well as cell proliferation. HL also strengthened ALA-PDT's inhibition of tumor volume in cSCC mouse model and elevated ROS generation of ALA-PDT., Conclusion: HL enhances the anti-tumor effect of ALA-PDT in vitro and in vivo. HL has the potential to enhance the anti-tumor effect of ALA-PDT in cSCC via inhibiting NRF2 signaling., (Copyright © 2021. Published by Elsevier B.V.)

Background: A distressing issue of diabetic ulcer (DU) is its poor healing feature with limited clinical solutions. We have previously shown that 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a promising alternative to the currently limited measures for DU. Mesenchymal stem cells (MSCs) transplantation has been believed to impose certain therapeutic effect on restoration of injury. Thus, this study aims to explore whether the combination of MSCs and ALA-PDT will exert a more advanced curative effect on DU., Methods: Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg/d) for consecutive 5 days. A full-thickness skin injury (diameter 6 mm) was created in the center of the back of each mouse, and then 10 μl of methicillin-resistant Staphylococcus aureus (MRSA) suspension was added to establish an infected DU model. All DU models were randomly divided into four groups: Untreated group, MSCs group, ALA-PDT group, and ALA-PDT combined with human umbilical cord mesenchymal stem cells (hUC-MSCs) (ALA-PDT + MSCs) group. The wound sizes were recorded by a digital camera, and the healing rates were calculated using Image J software. Bacterial loads on wounds were measured using CFU (Colony forming units) analysis. The epithelialization, inflammatory cells infiltration and granulation tissue formation were monitored by Haematoxylin and eosin (H&E) staining, and the corresponding semi-quantitative score was matched. Growth and pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA)., Results: Either ALA-PDT or injection of hUC-MSCs resulted in a rapid wound closure compared with the untreated, while their combination brought about the most prominent healing. On day 12, healing rates of the untreated, MSCs, ALA-PDT and ALA-PDT + MSCs were 40.56% ± 7.06%, 74.23 ± 4.83%, 84.03 ± 3.53%, 99.67 ± 0.49%, respectively. The bacterial burden reductions were approximately 1.58 logs (97.36%, P < 0.05), 2.34 logs (99.54%, P < 0.01), 4.50 logs (nearly 100%, P < 0.001) for MSCs, ALA-PDT and ALA-PDT + MSCs, respectively. Histology revealed reduced inflammatory cells and improved collagen precipitation and angiogenesis after hUC-MSCs and ALA-PDT treatment compared to the untreated. The combined therapy leaded to a more intact epithelium, similar to the healthy. Finally, ELISA revealed that the property of ALA-PDT to stimulate transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) and inhibit IL (interleukin) -1β and IL-6 outweighed that of hUC-MSCs, and this function of the combination overwhelmed that of any single therapy., Conclusions: Our findings indicated that the strategy of combining ALA-PDT with hUC-MSCs possessed a significantly enhanced therapeutic effect over either single therapy, providing a promising innovative therapeutic candidate for refractory wounds., (Copyright © 2021. Published by Elsevier B.V.)

Keratoacanthoma (KA)-like squamous cell carcinoma (SCC) is inclined to be diagnosed as KA due to its resemblance to KA in appearance. A giant facial KA-like SCC has aggressive growth and malignant metastasis, and seriously affects health and aesthetics. Prompt and appropriate treatment is extremely crucial and is a great challenge. Herein, we report a case of surgery combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the successful management of a giant KA-like SCC in the left eyebrow of an elderly woman, providing reference for more efficient disposal of such cases in clinic., (Copyright © 2021. Published by Elsevier B.V.)

Objective: This study sought to estimate the effect of a liquid octenidine dihydrochloride (OCT)-impregnated gauze dressing in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) biofilm-infected wounds., Method: In this animal study, a six-millimetre punch full-thickness wound on each mouse back was inoculated with MRSA suspension, and then covered with a Tegaderm (3M Health Care, US) dressing for an established biofilm model. Animals were divided into three groups for topical application: control group (treated with phosphate-buffered saline, PBS); mupirocin group (treated with 2% mupirocin); and OCT group (treated with OCT). All applications were administrated once 24 hours post-wounding. The bioburden was determined by counting colony-forming units (cfus) and the biofilm architecture was viewed using fluorescent staining and scanning electron microscopy (SEM) on day two. The tissue repair was evaluated histologically and the related genes were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on day 15., Results: The results suggested OCT accelerated healing and reduced by >3.6 log cfu/g bacterial counts on the wounds relative to the PBS-treated control (p<0.05). Histological analysis showed OCT-treated tissue exhibited lower burden of the inflammatory cells, more mature collagen fibres and well-defined epithelialisation. LIVE/DEAD fluorescent staining and SEM confirmed OCT induced a substantial destruction to biofilm structure. RT-qPCR further demonstrated that OCT therapy could inhibit the expression of MRSA and its biofilm genes by nearly 100% (p<0.05)., Conclusion: This investigation provides a rare in vivo experimental basis for OCT improvement on MRSA-infected wound healing and the superior efficacy implies OCT topical application may represent an ideal choice to address established bacterial biofilm in hard-to-heal wounds.

Methicillin-resistant Staphylococcus aureus (MRSA) is the most important representative pathogen which causes clinically relevant infections in diabetic ulceration. We report our investigations on the efficacy of antimicrobial photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) on diabetic murine infected wound models induced with a MRSA SA325 strain. A solution of 10 % 5-aminolevulinic acid (ALA) was placed into the wounds followed by delivery of 25 J/cm 2 (635 nm). The ALA-PDT treated wounds healed earlier as compared to others (P < 0.5). A significant reduction of bacterial counts (2.05 logs) was detected in wounds after ALA-PDT on Day 2 (P < 0.5). Additionally, histological analysis revealed that wounds treated with ALA-PDT exhibited a more complete re-epithelialization, blood micro-vessels, collagen-volume fraction and considerable decrease in inflammatory cells infiltration. Immunohistochemistry assay demonstrated considerable reduction of proinflammatory cytokines interleukin-1β (IL-1β), earlier expression of vascular endothelial growth factor A (VEGF-A), increase of basic fibroblast growth factor (bFGF) and Ki-67 in the ALA-PDT group (P < 0.5). These data imply that the therapeutic effect of ALA-PDT revealed an accelerated diabetic wound closure rate, together with reduced hyperinflammatory response and elevated growth factors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The emergence of drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has brought great difficulties to clinical treatment. Antibacterial photodynamic therapy (aPDT) is a new non-antibiotic treatment strategy for a variety of drug-resistant bacteria. However, there are few studies on the antimicrobial mechanism of a PDT mediated by 5-aminolevulinic acid (ALA-PDT) for MRSA. In this study, we observed the bactericidal effect of ALA-PDT on MRSA. We found that ALA-PDT had the strongest bactericidal effect when ALA was at 0.05 mM, and the bactericidal activity of aPDT increased with the increase of light dose. MRSA was almost completely eliminated at 0.05 mM and 384 Jcm -2 . In addition, the bactericidal morphology was also observed under a fluorescence microscope using a LIVE/DEAD® BacLight™ Bacterial Viability Kit and an electron microscope. It was also found that proteins and DNA were damaged by ALA-PDT. Finally, the transcription level of the specific gene of MRSA, nuc, was decreased by 0.74-fold (P < 0.05) after ALA-PDT treatment by qRT-PCR analysis. The findings suggest that ALA-PDT can effectively inhibit MRSA by damaging cell membrane, cytoplasm, proteins and nucleic acid., (Copyright © 2019. Published by Elsevier B.V.)

Background: Treatment of psoriasis is always difficult, which requires intensive scientific research., Objective: Tripterygium wilfordii Hook F (TwHF) with acitretin(TwHF + acitretin) is normally used in treating psoriasis. This study aimed to investigate the correlation of plasma miR-126 expression with risk and severity of psoriasis, and its predictive value of response to TwHF + acitretin treatment in psoriasis., Methods: MiRNA-126(MiR-126) expression in plasma was analyzed in psoriasis patients at month 0 (M0), M1, M3 and M6 and in health controls (HCs) at enrollment by qPCR. Psoriasis-affected body surface area (BSA) and Psoriasis Area and Severity Index (PASI) score were used to assess severity and treatment response., Results: Plasma miR-126 levels were decreased in psoriasis patients compared with HCs (P < 0.001), with area under the curve (AUC) of 0.771. MiR-126 expression was negatively correlated with PASI score (P = 0.001), and negatively associated with psoriasis-affected BSA (P = 0.825). At M6, 65.3% and 36.1% patients achieved PASI 50 and 75, respectively. MiR-126 increased at M1, M3 and M6 after TwHF + acitretin treatment when comparing with M0 (all P < 0.001). Meanwhile, miR-126 expression baseline in PASI 50 group declined when comparing with non-PASI 50 group (P < 0.001). Additionally, data revealed that the cause of high miR-126 baseline level was due to unsuccessfully achieving PASI 50 at M6 after TwHF + acitretin treatment (P < 0.001). However, miR-126 baseline expression was not a predictive factor for PASI 75 achievement (P > 0.05)., Conclusion: Plasma miR-126 expression is negatively correlated with psoriasis risk and severity, and its high baseline level can be used as a biomarker to predict worse clinical response to TwHF + acitretin treatment in psoriasis., (Copyright © 2019. Published by Elsevier Masson SAS.)

Chronic ulcer, including diabetic ulcer, varicose ulcer, and pressure ulcer, negatively affects patients' quality of life. As microbiology plays an important role in the mechanism of pathology for chronic wound healing, this study concentrates on microecology environment of the wound and how Traditional Chinese Medicine (TCM) regulates wound bacteria. Method . The study took wound samples from 35 patients and analyzed bacteria variation before and after TCM treatment by 16s rRNA sequencing. All samples were evaluated from aspects of α -diversity, β -diversity, and Simpson's Diversity index. Result . After total DNA extraction, PCR, and 16S rRNA sequencing of wound bacteria from 35 individuals, it was discovered that younger patients with shorter course of disease have a higher microbial diversity and were easier to recover from ulcers. Additionally, gender also played a vital role in wound healing, and a significant microbial diversity existed between male and female patients. Conclusion . Patients with chronic ulcers achieved a positive effect after TCM treatment (skin-producing ointment). Mechanistically, TCM helped promote wound healing by regulating the wound microbiota.

Psoriasis is a chronic inflammatory cutaneous disease characterized by clinical manifestations of erythema and white scales. The pathogenesis of psoriasis is not yet clear. Despite a combination of hormonal therapy and physiotherapy used in Western medicine, the condition often relapses after withdrawal of drugs. Traditional Chinese medicine (TCM) has therapeutic features and may be a clinically effective formula by regulating unbalanced immune systems, such as by targeting interleukins. In this paper, we review recent research about how Chinese medicine immunoregulates psoriasis via interleukins, and systematically summarizes the related mechanisms. There are three common pathways leading to psoriasis: (1) Th17 cells secrete IL-17, which is stimulated by IL-23; (2) Th1 cells secrete IL-21, TNF-[Formula: see text] and IFN-[Formula: see text], with the help of Th17 cells; (3) Th22 cells secrete IL-22 under the stimulation of Th17 cells. Clinical and experiment data indicate that TCM could modify psoriasis by antagonizing or regulating interleukin and IL-23/IL-17 axis to inhibit the main pathways.

Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (ΔΨm) and mitochondrial fragmentation. Cambogin also promotes the mutual complex formation of the membrane-bound subunit p22phox of NADPH oxidase 1 (NOX1), as well as the phosphorylation of the cytosolic subunit p47phox, subsequently enhancing membrane-bound NOX1 activity, which leads to increases in intracellular and mitochondrial levels of O2.- and H2O2. Pharmacological inhibition of NOX1 using apocynin (pan-NOX inhibitor), ML171 (NOX1 inhibitor) or siRNA against NOX1 prevents the increases in O2.- and H2O2 levels and the anti-proliferative effect of cambogin. Antioxidants, including SOD (superoxide dismutase), CAT (catalase) and EUK-8, are also able to restore cell viability in the presence of cambogin. Besides, cambogin increases the dissociation of thioredoxin-1 (Trx1) from ASK1, switching the inactive form of ASK1 to the active kinase, subsequently leads to the phosphorylation of JNK/SAPK, which is abolished upon ML171 treatment. The proapoptotic effect of cambogin in breast cancer cells is also aggravated upon knocking down Trx1 in MCF-7 cells. Taken in conjunction, these data indicate that the anti-proliferative and pro-apoptotic effect of cambogin is mediated via inducing NOX1-dependent ROS production and the dissociation of ASK1 and Trx1., Competing Interests: No potential conflicts of interest were disclosed.