Water-Responsive Self-Contractive Silk-Based Skin Anti-Aging Tensioners with Customizable Biofunctions.

Skin anti-aging treatments have become increasingly popular. Currently, the prevalent treatment method involves implanting skin tension regulation threads (skin lifting threads) under the skin, and radiofrequency treatments. In this study, inspired by the natural supercontraction of spider silk, the molecular structure of silk fibroin fibers is modulated into an oriented configuration. This modification endows silk proteins with water-responsive self-contraction capabilities, leading to the development of innovative self-contracting silk-based skin tensioners (SSSTs). To align with clinical requirements, skin tension regulation materials are functionalized by testing for their self-contraction, near-infrared laser heating function, and bacteriostatic properties. The SSSTs exhibited remarkable self-contraction properties, drug-loading and sustained-release capabilities, notable antibacterial effects, controllable degradation, and good biocompatibility. Moreover, the near-infrared light heating function effectively increased subcutaneous temperature, demonstrating its potential for enhancing and prolonging skin lifting effects. Therefore, SSSTs can be applied for skin tension regulation to improve and delay skin aging. The results may pave the way for novel strategies in skin rejuvenation, with broad implications for the field of skin anti-aging.

[Hunyuan moxibustion for diarrhea-predominant irritable bowel syndrome of spleen and kidney yang deficiency: a randomized controlled trial].

OBJECTIVE: To compare the therapeutic effect between Hunyuan moxibustion and oral western medication on diarrhea-predominant irritable bowel syndrome（IBS-D）of spleen and kidney yang deficiency. METHODS: Sixty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a Hunyuan moxibustion group and a western medication group, 30 cases each group. The Hunyuan moxibustion group was treated with Hunyuan moxibustion at Guanyuan（CV 4），40 min each time, once a day; in the western medication group，loperamide hydrochloride capsules (2 mg each time, 3 times a day) and bacillus licheniformis live capsules (0.5 g each time, 3 times a day) were given orally.Both groups were treated for 20 days. The scores of irritable bowel syndrome（IBS）symptom severity scale（IBS-SSS）, IBS quality of life scale (IBS-QOL) and TCM symptom grading quantitative were observed before and after treatment, and the clinical efficacy and safety were evaluated in the two groups. RESULTS: After treatment，each item scores and total scores of IBS-SSS in the two groups were lower than those before treatment（P<0.05）, and the total scores of IBS-QOL were higher than those before treatment (P<0.05)；each item score and total score of IBS-SSS in the Hunyuan moxibustion group were lower than those in the western medication group (P<0.05), and the total score of IBS-QOL in the Hunyuan moxibustion group was higher than that in the western medication group (P<0.05).After treatment, each item score and total score of TCM symptom grading quantitative in the Hunyuan moxibustion group were lower than those before treatment (P<0.05), the abdominal pain, diarrhea, lack of appetite scores and total score in the western medication group were lower than those before treatment (P<0.05)；and the abdominal pain, soreness and weakness of waist and knees, fear to cold and cold limbs scores and total score in the Hunyuan moxibustion group were lower than those in the western medication group (P<0.05).The total effective rate was 90.0%（27/30）in the Hunyuan moxibustion group, which was higher than 73.3%（22/30）in the western medication group (P<0.05). No adverse reactions occurred in both groups during treatment. CONCLUSION: Hunyuan moxibustion can effectively improve the symptom severity and quality of life in patients with IBS-D of spleen and kidney yang deficiency, especially in improving the symptoms of abdominal pain, soreness and weakness of waist and knees, fear to cold and cold limbs.Its therapeutic effect is superior to western medication.

[Therapeutic effect of long-snake moxibustion combined with western medication on diarrhea type irritable bowel syndrome of spleen and kidney yang deficiency].

OBJECTIVE: To compare the therapeutic effect between long-snake moxibustion combined with western medication and simple medication on diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: A total of 60 patients with IBS-D of spleen and kidney yang deficiency were randomized into an observation group and a control group, 30 cases in each one. In the control group, loperamide hydrochloride capsule (2.0 mg each time, 3 times a day) and bacillus licheniformis live capsule (0.5 mg each time, 3 times a day) were given orally. In the observation group, long-snake moxibustion was added on the basis of the treatment in the control group, ginger-partitioned moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) of governor vessel, once a week. The treatment was given for 8 weeks in both groups. The scores of main symptom and IBS quality of life questionnaire (IBS-QOL) were observed before and after treatment, and the therapeutic effect was evaluated in both groups. RESULTS: Compared before treatment, the symptom scores of abdominal pain, defecation frequency, mucous stool and appetite reduction were decreased (P<0.05), the scores of daily social intercourse, daily activity, diet, work, emotion, sleep quality, mental state and energy change were increased in both groups (P<0.05). After treatment, each sub-item score of main symptom in the observation group was lower than the control group (P<0.05), each sub-item score of IBS-QOL was higher than the control group (P<0.05). The total effective rate was 96.7% (29/30) in the observation group, which was superior to 73.3% (22/30) in the control group (P<0.05). CONCLUSION: Long-snake moxibustion combined with western medication can effectively treat the IBS-D of spleen and kidney yang deficiency, relieve the clinical symptoms and improve the quality of life, the effect is superior to the simple treatment of oral western medication.

The Efficacy and Safety of Simple-Needling Therapy for Treating Ankylosing Spondylitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clinical investigators have found that the use of needling in the treatment of ankylosing spondylitis (AS) has a good clinical application prospect in recent years. However, these studies were insufficient to provide evidence for the efficacy and safety of simple-needling for AS. So, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of simple-needling for treating AS. METHODS: We searched the PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wangfang database (Wanfang), Chinese Science and Technology Periodical Database (VIP), and any other gray literature sources for randomized controlled trials (RCTs) that used simple-needling to treat AS before June 2019 with the language restriction of Chinese and English. Researchers evaluated the retrieved literature studies and extracted valid data according to relevant requirements and used RevMan5.3 software for meta-analysis. RESULTS: A total of 10 studies were included, all of which were Chinese literature studies, involving 729 patients. Compared with the control groups, simple-needling groups had a better effect on the clinical effective rate (RR = 1.20, 95% CI (1.11, 1.29), P < 0.00001), TCM syndrome score (MD = -5.26, 95% CI (-5.99, -4.53), P < 0.00001), symptom score (MD = -8.08, 95% CI (-10.18, -5.97), P < 0.00001), and Schober test outcome (MD = 0.39, 95% CI (0.15, 0.64), P=0.002). Sensibility analysis was based on the leave-one-out cross-validation procedure, and the results showed no significant changes. Most studies did not describe adverse reactions. The funnel plot suggested publication bias on clinical effectiveness. CONCLUSIONS: This systematic review and meta-analysis demonstrated that simple-needling was effective as an intervention for AS. However, due to the low quality of the methodology of included studies, the designs of clinical trials were not rigorously standardized. Therefore, it is necessary to carry out multiquality RCTs for verification.

[Clinical effect of long-snake moxibustion on lumbago of cold-dampness type].

OBJECTIVE: To observe the effect of long-snake moxibustion on pain, functional disorder and body constitution in the patients with lumbago of cold-dampness type. METHODS: A total of 90 patients with lumbago of cold-dampness type were randomized into long-snake moxibustion, acupuncture and medication groups, 30 cases in each group. In the long-snake moxibustion group, long-snake moxibustion was exerted on the spinal (between Dazhui[GV14] and Yaoshu[GV2]) with the self-prepared moxa powder formula combined with fresh ginger and moxa wool, once a week, for 4 weeks. Regular acupuncture was given to the acupuncture group, 30 min each time, once a day, 8 times as a treatment course, at the interval of 2 days between the courses. The duration of treatment was 1 month. In the medication group, Diclofenac Sodium was prescribed for oral administration, 25 mg each time, three times a day, and Mecobalamine tablets, 0.5 mg each time, 3 times a day. The duration of medication was 1 month. Before and after treatment, the differences were evaluated in the scores of visual analog scale (VAS), the present pain intensity(PPI), Oswestry disability index (ODI) and the scale of yang-deficiency body constitution among the 3 groups. RESULTS: After the treatment, VAS and PPI score and ODI were significantly reduced in the patients of the 3 groups as compared with those before treatment (all P<0.05). Compared with the medication group, ODI score was significantly reduced in the long-snake moxibustion group and the acupuncture group (P<0.05). After the treatment, the scores of the scale of yang-deficiency body constitution were significantly reduced in the long-snake moxibustion group and the acupuncture group (P<0.05) as compared with those before the treatment, but not statistically significant in the medication group in comparison before and after the treatment (P>0.05). The score of the scale of yang-deficiency body constitution in the long-snake moxibustion group was significantly lower than that in the acupuncture group and the medication group (P<0.05). Regarding the clinical effect, the effective rate was 93.33% (28/30) in the long-snake moxibustion group and it was 86.67% (26/30) in the acupuncture group and 73.33% (22/30) in the medication group after the treatment. The effective rate in the long-snake moxibustion group was significantly higher than those in the acupuncture group and the medication group (P<0.05). CONCLUSION: The long-snake moxibustion therapy can achieve significant effect on lumbago of cold-dampness type. This therapy can alleviate pain, relieve the functional disorders and improve the conditions of body constitution in the patients. Hence, it is applicable for the clinical promotion.

Incorporation of ROS-Responsive Substance P-Loaded Zeolite Imidazolate Framework-8 Nanoparticles into a Ca2+-Cross-Linked Alginate/Pectin Hydrogel for Wound Dressing Applications.

PURPOSE: Wound healing, especially of extensive full-thickness wounds, is one of the most difficult problems in clinical studies. In this study, we prepared a novel substance P (SP)-delivery system using zeolite imidazolate framework-8 (ZIF-8) nanoparticles. METHODS: We synthesized ZIF-8 nanoparticles using a modified biomimetic mineralization method. We then coated SP-loaded ZIF-8 nanoparticles (SP@ZIF-8) with polyethylene glycol-thioketal (PEG-TK) to fabricate SP@ZIF-8-PEG-TK nanoparticles, and encapsulated them in injectable hydrogel composed of sodium alginate and pectin and cross-linked using calcium chloride. The final hydrogel wound dressing containing SP@ZIF-8-PEG-TK nanoparticles was called SP@ZIF-8-PEG-TK@CA. RESULTS: The fabricated ZIF-8 nanoparticles had high SP-loading efficiency. SP-release assay showed that the SP@ZIF-8-PEG-TK nanoparticles maintained drug activity and showed responsive release under stimulation by reactive oxygen species. The SP@ZIF-8-PEG-TK nanoparticles promoted proliferation of human dermal fibroblasts, up-regulated expression levels of inflammation-related genes in macrophages, and exhibited favorable cytocompatibility in vitro. Full-thickness excision wound models in vivo confirmed that SP@ZIF-8-PEG-TK@CA dressings had excellent wound-healing efficacy by promoting an early inflammatory response and subsequent M2 macrophage polarization in the wound-healing process. CONCLUSION: In conclusion, these findings indicated that SP@ZIF-8-PEG-TK@CA dressings might be useful for wound dressing applications in the clinic.

Immune Infiltration Landscape in Clear Cell Renal Cell Carcinoma Implications.

The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor infiltrating immune cells (TIICs) recruited to the cancer microenvironment. Clear cell renal cell carcinoma (ccRCC) immune microenvironment plays an important role in the tumorigenesis. This research investigated the characteristics of immune cell invasion of renal cell carcinoma and provided clues for future clinical implementation. Retrospectively, ccRCC gene expression was analyzed with appropriate clinicopathological data from the Cancer Genome Atlas (TCGA) and GEO database up to December 2019. The CIBERSORT algorithm, meta-analysis, principal component analysis (PCA), Single-Sample Gene Set Enrichment Analysis (ssGSEA) and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. We also focused on evaluating the association with TIICs subpopulations and clinical features and molecular subtypes. TIICs subpopulation, especially Macrophages subgroup, T follicular helper (Tfh) cells and CD8 T cells, all contribute to tumorigenesis. Unsupervised clustering analysis revealed that there existed two distinct TIICs subgroups with different survival patterns. TIICs are extensively involved in the pathogenesis and development of the ccRCC. Characterizing the composition of TIICs influences the metabolism of tumors, activity, level, stage, and survival of patients. Collectively, the TIIC analysis has the potential to assist in the assessment and selection of ccRCC prognosis and treatment.

Rip 1-dependent endothelial necroptosis participates in ischemia-reperfusion injury of mouse flap.

BACKGROUND: Ischemia reperfusion injury plays an important role in free flap necrosis. However, the detailed mechanism is not clear, and effective methods for improving the survival rate of skin flap are still lacking. OBJECTIVE: To investigate the regulation and functional link between necroptosis and ischemia-reperfusion injury of mouse flap. METHODS: We established a mouse ischemia-reperfusion injury flap model and a cell Oxygen Glucose Deprivation (OGD) model intervened with Necrostatin-1. The mouse flap tissues were harvested in vivo for histological immunofluorescence analysis and western blotting analyses. The HUVECs cells with various treatments in vitro were assessed by using Transwell assay, tube formation assay, cell counting kit-8 analysis and flow cytometry. A Rip3-knockout cell line and a TNFR1-knockout cell line were generated from HUVEC cells using the CRISPR-Cas9 technology and were subsequently used to explore the related mechanisms. RESULTS: The expression of p-Rip3 is positive in both mouse and cell culture models. When necroptosis is completely or partially inhibited in vivo, damaged tissues are repaired with better efficiency. The cells treated with Necrostatin-1 in vitro exhibit faster migration, proliferation and better tube formation. Deficiency of TNFR1 can block the necroptosis pathway by blocking the phosphorylation of Rip3 in HUVEC OGD/ROG model. Meanwhile, the levels of APJ, HIF-1α, and VEGF are reduced when necroptosis is inhibited by Necrostatin-1. CONCLUSION: TNFR1 mediates Rip1/Rip3 in ischemia-reperfusion injury. Inhibition of necroptosis attenuates the ischemia-reperfusion injury of flap and may enhance hypoxic tolerance of HUVECs and vascular homeostasis through regulation of the HIF-1α signaling pathways.

[Ginger-separated Snake Moxibustion Improves Yang Deficiency Constitution by Up-regulating Serum Adrenocorticotropic Hormone and Cortisol Levels in Yang Deficiency Constitution Volunteers].

OBJECTIVE: Yang deficiency constitution may bring with different types of illnesses in many people. The present study was designed to observe the effect of ginger-separated snake moxibustion on yang deficiency symptom, and serum adrenocorticotropic hormone (ACTH) and cortisol (CORT) contents in yang deficiency constitution subjects, so as to explore its mechanism underlying improvement of yang deficiency constitution. METHODS: Ninety subjects with yang deficiency type constitution were equally and randomly assigned to control A group (19 men and 26 women, 18－60 years in age) and moxibustion group (16 men and 29 women, 18－60 years in age) and 45 normal subjects with mild constitution (18 men and 27 women, 18－60 years in age) were assigned to control B group. An snake-like moxa-cone was placed at a moxa-holder covering the middle back of human body from Dazhui (GV 14) to Yaoshu (GV 2) after paving a layer (about 1 cm thick) of fresh ginger in the holder, and then ignited, followed by the next moxa-cone, 3 cones altogether every time for each participant. The treatment was conducted once a week, 12 times in total. The subjects' constitution was scored according to the "Classification and Evaluation of Constitution of Traditional Chinese Medicine" formulated by China Association of Chinese Medicine. The serum ACTH and CORT contents were measured by radioimmunoassay before and at the end of the treatment and 6 months after the treatment. RESULTS: The constitation scores of the moxibustion group and control A group were significantly higher than that of the control B group before treatment (P<0.01). At the end of the treatment, the constitution score was significantly decreased in the moxibustion group (P<0.01) rather than in the control A group relevant to its own pre-treatment (P>0.05). The serum CORT and ACTH contents were significantly decreased in both the moxibustion and control A groups in comparison to the control B group before treatment (P<0.01), and obviously increased at the end of treatment in the moxibustion group compared with its own pre-treatment (P<0.01). No significant differences were found among the three groups in the constitution score, and serum CORT and ACTH levels at the 6th month after the treatment compared with their own post-treatment (P>0.05)．. CONCLUSION: The ginger-separated snake moxibustion treatment may improve the constitution of yang deficiency participants by increasing the levels of serum ACTH and CORT, which may be helpful in resisting diseases.