Intelligent and Bioactive Osseointegration of the Implanted Piezoelectric Bone Cement with the Host Bone Is Realized by Biomechanical Energy.

Poly methyl methacrylate (PMMA) bone cement is widely used in orthopedic surgeries, including total hip/knee arthroplasty and vertebral compression fracture treatment. However, loosening due to bone resorption is a common mid-to-late complication. Therefore, developing bioactive bone cement that promotes bone growth and integration is key to reducing aseptic loosening. In this study, we developed a piezoelectric bone cement comprising PMMA and BaTiO3 with excellent electrobioactivity and further analyzed its ability to promote bone integration. Experiments demonstrate that the PMMA and 15 wt % BaTiO3 cement generated an open-circuit voltage of 37.109 V under biomimetic mechanical stress, which effectively promoted bone regeneration and interfacial bone integration. In vitro experiments showed that the protein expression levels of ALP and RUNX-2 in the 0.65 Hz and 20 min group increased by 1.74 times and 2.31 times. In vivo experiments confirmed the osteogenic ability of PMMA and 15 wt % BaTiO3, with the increment of bone growth in the non-movement and movement groups being 4.67 and 4.64 times, respectively, at the second month after surgery. Additionally, Fluo-4 AM fluorescence staining and protein blotting experiments verified that PMMA and 15 wt % BaTiO3 electrical stimulation promoted osteogenic differentiation of BMSCs by activating calcium-sensitive receptors and increasing calcium ion inflow by 1.41 times when the stimulation reached 30 min. Therefore, piezoelectric bioactive PMMA and 15 wt % BaTiO3 cement has excellent application value in orthopedic surgery systems where stress transmission is prevalent.

Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer.

To investigate the role and potential mechanism of serine/threonine kinase 36 (STK36) in docetaxel resistance-prostate cancer (PCa). The expression of STK36 in PCa and the correlation with clinicopathological characteristics of PCa patients were analyzed using the data from different databases and tissue microarrays. To investigate the role of STK36 on cell proliferation, invasion, and migration, STK36 was overexpressed and silenced in DU-145 and PC-3 cell lines. Cell counting kit-8 (CCK8) was used to test cell proliferation. Cell invasion and migration were detected by cell wound scratch assay and trans well, respectively. The expression profile of STK36, E-Cadherin, and Vimentin was analyzed by Western blot. Cell apoptosis was detected by the TUNEL assay. STK36 expression was upregulated in PCa tissue compared with adjacent benign PCa tissue; it was higher in patients with advanced stages compared with lower stages and was significantly correlated with decreased overall survival. Up-regulation of STK36 significantly promoted the proliferation, invasion, and migration of DU-145 and PC-3 cells and compensated for the suppression caused by docetaxel treatment in vitro. A striking apoptosis inhibition could be observed when dealing with docetaxel, although the apoptosis of DU-145 and PC-3 cells was not affected by the STK36 exclusive overexpression. Besides, E-Cadherin expression was restrained while the expression levels of vimentin were all enhanced. The knockdown of STK36 reversed the above process. STK36 up-regulation could accelerate the biological behavior and docetaxel resistance of PCa by epithelial-mesenchymal transition (EMT) activation. STK36 may be potentially used as a target in PCa resolvent with docetaxel.

A systematic review and meta-analysis of efficacy and safety of compound glycyrrhizin combined with second-generation non-sedated antihistamine for the treatment of chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is a prevalent dermatologic disease that negatively affects life, current therapies remain suboptimal. Hence, there is an urgent need to identify effective and safe treatment. OBJECTIVE: Assess the efficacy and safety of compound glycyrrhizin (CG) combined with second-generation nonsedated antihistamine for the treatment of CU. METHODS: Nine databases were queried to screen RCTs related. Two reviewers independently assessed the risk of bias using Cochrane Collaboration. Primary objective was the total efficiency rate, while secondary was rate of recurrence, adverse events, and cure. Statistical analyses using Review Manager 5.4 and Stata17. RESULTS: Twenty-four RCTs were identified. Significant differences were noted in rate of total efficiency (n = 2649, RR = 1.36, 95%CI:1.30-1.43, p < 0.00001), cure (n = 2649, RR = 1.54, 95%CI:1.42-1.66, p < 0.00001) and recurrence (n = 446, RR = 0.34, 95%CI:0.20-0.58, p < 0.00001) between the combination of CG with second-generation non-sedated antihistamine and antihistamine monotherapy. Contrastingly, adverse events rate (n = 2317, RR = 0.76, 95% CI:0.59-0.97, p = 0.03) was comparable between the two groups. Our results indicated that CG combined with second-generation non-sedated antihistamine could significantly mitigate the symptoms in CU compared with antihistamine monotherapy. No serious adverse events were reported. CONCLUSIONS: CG combined with second-generation nonsedated antihistamine is effective for CU. Nevertheless, higher-quality studies are warranted to validate our results.

Intraoperative radiographic analysis and adjustment of the optimal position of plate in high tibial osteotomy.

BACKGROUND: When high tibial osteotomy is performed for genu varus deformity, it is not easy to determine the accurate placement of the plate. PURPOSE: To determine a simple way to assess the position of the plate, to provide more effective mechanical support and to reduce the risk of implant rupture and vascular injury. MATERIAL AND METHODS: Two human anatomical marks, the patellar ligament and semimembranosus, were connected and divided into four parts to identify points Ⅰ, Ⅱ, and Ⅲ. These points determined the areas for Tomofix placement: anterior, anterolateral, and lateral. Simulated internal fixation placed hole B of Tomofix at points Ⅰ (anterior), Ⅱ (anterolateral), and Ⅲ (lateral). We analyzed the pointing direction of the locking screws in Tomofix holes on MRI to assess potential injury risk to the popliteal neurovascular bundle. RESULTS: In the X-ray: holes B and C appeared as the plate in the anterior, only hole C appeared as the plate in the anterolateral, and none of the holes appeared as the plate in the lateral. In the general view of the sawbones, the screw pointed towards the popliteal neurovascular bundle when the plate was in the anterior. CONCLUSION: If a small number of holes on the plate is visible under fluoroscopy, then several lateral positions of the plate can be obtained; the direction of the screw tunnel tends to deviate from the popliteal neurovascular bundle with the posterior position of the plate.

Disease-Related Factors Associated with Acupuncture Response in Patients with Chronic Tension-Type Headache: A Secondary Analysis of A Randomized Controlled Trial.

OBJECTIVE: To explore the demographic and disease-related factors associated with acupuncture response in patients with chronic tension-type headache (CTTH). METHODS: Using data from a randomized clinical trial (218 cases) consisting of 4 weeks of baseline assessment, 8 weeks of treatment, and 24 weeks of follow-up, participants were regrouped into responders (at least a 50% reduction in monthly headache days at week 16 compared with baseline) and non-responders. Twenty-three demographic and disease-related factors associated with acupuncture response in 183 participants were analyzed by multivariable logistic regression. RESULTS: One hundred and nineteen (65.0%) participants were classified as responders. Four factors were significantly independently associated with acupuncture response, including treatment assignment, headache intensity at baseline, and 2 domains [general health (GH) and social functioning (SF)] from the 36-Item Short Form Health Survey quality of life questionnaire. Treatment assignment was associated with non-response: participants receiving true acupuncture were 3-time more likely to achieve a CTTH response than those receiving superficial acupuncture [odds ratio (OR) 0.322, 95% confidence interval (CI) 0.162 to 0.625, P=0.001]. Compared with patients with mild-intensity headache, patients with moderate-intensity headache were twice as likely to respond to acupuncture (OR 2.001, 95% CI 1.020 to 4.011, P=0.046). The likelihood of non-response increased by 4.5% with each unit increase in the GH grade (OR 0.955, 95% CI 0.917 to 0.993, P=0.024) while decreased by 3.8% with each unit increase in the SF grade (OR 1.038, 95% CI 1.009 to 1.069, P=0.011). CONCLUSIONS: Greater headache intensity, lower GH score, and higher SF score were associated with better acupuncture responses in CTTH patients. These 3 factors require independent validation as predictors of acupuncture effectiveness in CTTH.

Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.

The efficacy and safety of high-dose nonsedating antihistamines in chronic spontaneous urticaria: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Standard doses of second-generation H1-antihistamines (sgAHs) as first-line treatment are not always effective in treating chronic spontaneous urticaria (CSU), and hence an increase in the dose of sgAHs is recommended. However, literature evaluating the efficacy and safety of this treatment remains inconclusive, highlighting the need for a systematic review and meta-analysis. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of high-dose sgAHs compared with standard-dose sgAHs in treating CSU. METHODS: A systematic literature search of double-blind, randomized controlled trials (RCT) utilizing multiple doses of sgAHs was performed by searching the electronic databases Medline, Embase, PsycInfo, Cochrane databases, and Web of Science. Bibliographies were also manually searched. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The response rate, the number of adverse events, somnolence, and withdrawal due to adverse events were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. RevMan (V5.3) software was used for data synthesis. RESULTS: A total of 13 studies were identified, seven of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that high-dose sgAHs was associated with a significantly higher response rate than standard-dose (RR 1.13, 95% CI 1.02 to 1.26; P = 0.02). Conversely, high doses of sgAHs were associated with significantly higher somnolence rates than standard dose (RD 0.05, 95% CI 0.01 to 0.09; P = 0.02). There was no significant difference in adverse events or withdrawal due to adverse events between standard- and high-dose treatments. CONCLUSIONS: Our analyses showed that a high dose of sgAHs (up to two times the standard dose) might be more effective than a standard dose in CSU treatment. High-dose and standard-dose sgAHs showed similar adverse events, except for somnolence, where incidence was found to be dose-dependent in some studies. However, given the limited number of studies, our meta-analysis results should be interpreted with caution.

Hsa_circ_0063329 inhibits prostate cancer growth and metastasis by modulating the miR-605-5p/tgif2 axis.

Circular RNAs play crucial regulatory roles in the progression of various cancers. Nevertheless, the underlying mechanisms of circRNAs in prostate cancer (PCa) proliferation and metastasis remain largely uncertain. Here, we performed circRNA microarray analyses to identify differentially expressed circRNAs in a normal prostate epithelial cell line and PCa cell lines. We found that hsa_circ_0063329 was significantly downregulated in PCa. A series of in vitro and in vivo functional assays showed that overexpression of hsa_circ_0063329 inhibits PCa cell progression, while silencing of hsa_circ_0063329 achieved the opposite effects. Mechanistically, bioinformatics analysis, RNA pulldown, RNA-seq and dual-luciferase reporter assays demonstrated that hsa_circ_0063329 exerts its effect by sponging miR-605-5p to derepress TG-interacting factor 2 (TGIF2) and inactivate the TGF-ß pathway. In conclusion, hsa_circ_0063329 inhibits the proliferation and metastasis of PCa via modulation of the miR-605-5p/TGIF2 axis, and targeting hsa_circ_0063329 may provide a promising treatment strategy for aggressive PCa.

Applying OHSA to Detect Road Accident Blackspots.

With increasing numbers of crashes and injuries, understanding traffic accident spatial patterns and identifying blackspots is critical to improve overall road safety. This study aims at detecting blackspots using optimized hot spot analysis (OHSA). Traffic accidents were classified by their participants and severity to explore the relationship between blackspots and different types of accidents. Based on the outputs of incremental spatial autocorrelation, OHSA was then implemented on different types of accidents. Finally, the performance of OHSA in evaluating the road safety level of the proposed RBT index are examined using a binary correlation analysis (i.e., R2 = 0.89). The results show that: (1) The optimal scale distance varies from 0.6 km to 2.8 km and is influenced by the distance of the travel mode. (2) Central cities, with 54.6% of the total accidents, experiences more rigorous challenges regarding traffic safety than satellite cities. (3) There are many types of black spots in vulnerable communities, but in some specific areas, there are only black spots of non-motor vehicle accidents. Considering the practical significance of the above results, policy makers and traffic engineers are expected to give higher attention to central cities and vulnerable communities or prioritize the implementation of relevant optimization measures.

Grim-19 plays a key role in mitochondrial steroidogenic acute regulatory protein stability and ligand-binding properties in Leydig cells.

Grim-19 (gene associated with retinoid-IFN-induced mortality 19), the essential component of complex I of mitochondrial respiratory chain, functions as a noncanonical tumor suppressor by controlling apoptosis and energy metabolism. However, additional biological actions of Grim-19 have been recently suggested in male reproduction. We investigated here the expression and functional role of Grim-19 in murine testis. Testicular Grim-19 expression was detected from mouse puberty and increased progressively thereafter, and GRIM-19 protein was observed to be expressed exclusively in interstitial Leydig cells (LCs), with a prominent mitochondrial localization. In vivo lentiviral vector-mediated knockdown of Grim-19 resulted in a significant decrease in testosterone production and triggered aberrant oxidative stress in testis, thus impairing male fertility by inducing germ cell apoptosis and oligozoospermia. The control of testicular steroidogenesis by GRIM-19 was validated using the in vivo knockdown model with isolated primary LCs and in vitro experiments with MA-10 mouse Leydig tumor cells. Mechanistically, we suggest that the negative regulation exerted by GRIM-19 deficiency-induced oxidative stress on steroidogenesis may be the result of two phenomena: a direct effect through inhibition of phosphorylation of steroidogenic acute regulatory protein (StAR) and subsequent impediment to StAR localization in mitochondria and an indirect pathway that is to facilitate the inhibiting role exerted by the extracellular matrix on the steroidogenic capacity of LCs via promotion of integrin activation. Altogether, our observations suggest that Grim-19 plays a potent role in testicular steroidogenesis and that its alterations may contribute to testosterone deficiency-related disorders linked to metabolic stress and male infertility.

Acupuncture and Related Therapies for Chronic Urticaria: A Critical Overview of Systematic Reviews.

Background: Chronic urticaria (CU) can severely impair the quality of life. Acupuncture and related therapies have been widely used in the treatment of CU in China. This study aimed to summarize and critically evaluate the methodological and reporting quality of relevant systematic reviews (SRs) and present objective and comprehensive evidence on the effectiveness and safety of acupuncture and related therapies for CU. Methods: Eight electronic databases were searched from inception to October 2021 for SRs examining acupuncture and related therapies for CU, and gray literature was manually searched. Two authors independently identified SRs and extracted data. The methodological and reporting quality of these SRs were assessed by the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and preferred reporting items for SRs and meta-analyses (PRISMA, 2020), respectively. In addition, the risk of bias in systematic reviews (ROBIS) was used to evaluate the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was applied to evaluate the quality of evidence for outcome measures. Results: In total, 23 SRs, including a total of 11 outcome indicators, were published before October 2021. The AMSTAR-2 results showed that the methodological quality of all SRs was critically low; items 2, 3, 7, 9, 10, and 16 were found to have particularly low quality. For PRISMA, the reporting quality of the included SRs was unsatisfactory, and major reporting flaws were observed in the search strategy, synthesis method, certainly assessment, reporting biases, registrations, and financial support of the included SRs. For ROBIS, 22 SRs (95.65%) had a high risk of bias. Among the 55 outcomes assessed using the GRADE framework, there were 3 (5.45%) outcomes with moderate-quality evidence, 6 (10.91%) outcomes with low-quality evidence, and 46 (83.64%) outcomes with very low-quality evidence. We found the moderate quality of evidence indicating that the total effective rate and curing rate of the acupuncture group were higher than those of the western medicine group, and the recurrence rate was lower than that of the western medicine group. Conclusions: Acupuncture and related therapies for the treatment of CU are supported by low-quality evidence-based medicine. However, considering the poor quality of these SRs, we suggest that studies with more rigorous designs, larger sample sizes, and higher methodological and reporting quality are necessary to provide stronger evidence. Registration. The protocol for this study has been registered (PROSPERO registration number: CRD42021259131).

Functional connectivity impairment of thalamus-cerebellum-scratching neural circuits in pruritus of chronic spontaneous urticaria.

Pruritus of chronic spontaneous urticaria (CSU) is one of the most common and irritating sensations that severely affects the quality of life. However, the changes in the functional connectivity (FC) between thalamic subregions and other brain regions have not been fully elucidated. This study aimed to explore the potential changes in brain neural circuits by focusing on various subregions of the thalamus in patients with CSU pruritus to contribute to the understanding of chronic pruritus from the perspective of central mechanisms. A total of 56 patients with CSU and 30 healthy controls (HCs) completed the data analysis. Urticaria Activity Score 7 (UAS7), pruritus visual analog score (VAS-P), Dermatological Life Quality Index (DLQI), and immunoglobulin E (IgE) values were collected to assess clinical symptoms. Seed-based resting-state functional connectivity (rs-FC) analysis was used to assess relevant changes in the neural circuits of the brain. Compared to HCs, seeds within the caudal temporal thalamus (cTtha) on the right side of patients with CSU showed increased rs-FC with the cerebellum anterior lobe (CAL). Seeds within the lateral prefrontal thalamus (lPFtha) on the right side showed increased rs-FC with both CAL and pons, while those within the medial prefrontal thalamus (mPFtha) on the right side showed increased rs-FC with both CAL and the dorsal lateral prefrontal cortex (dlPFC) on the right side. Seeds within the posterior parietal thalamus (PPtha) on the right side showed increased rs-FC with the cerebellum posterior lobe (CPL) on the left side. The UAS7 values and IgE levels were positively correlated with the rs-FC of the right dlPFC. Our results suggest that patients with CSU may exhibit stronger rs-FC alterations between certain thalamic subregions and other brain regions. These changes affect areas of the brain involved in sensorimotor and scratching. Trial registration number: [http://www.chictr.org.cn], identifier [ChiCTR1900022994].

Impact of Femoral Neck Cortical Bone Defect Induced by Core Decompression on Postoperative Stability: A Finite Element Analysis.

Objective: To analyze the impact of femoral neck cortical bone defect induced by core decompression on postoperative biomechanical stability using the finite element method. Methods: Five finite element models (FEMs) were established, including the standard operating model and four models of cortical bone defects at different portions of the femoral neck (anterior, posterior, superior, and inferior). The maximum stress of the proximal femur was evaluated during normal walking and walking downstairs. Results: Under both weight-bearing conditions, the maximum stress values of the five models were as follows: femoral neck (inferior) > femoral neck (superior) > femoral neck (posterior) > femoral neck (anterior) > standard operation. Stress concentration occurred in the areas of femoral neck cortical bone defect. Under normal walking, the maximum stress of four bone defect models and its increased percentage comparing the standard operation were as follows: anterior (17.17%), posterior (39.02%), superior (57.48%), and inferior (76.42%). The maximum stress was less than the cortical bone yield strength under normal walking conditions. Under walking downstairs, the maximum stress of four bone defect models and its increased percentage comparing the standard operation under normal walking were as follows: anterior (36.75%), posterior (67.82%), superior (83.31%), and inferior (103.65%). Under walking downstairs conditions, the maximum stress of bone defect models (anterior, posterior, and superior) was less than the yield strength of cortical bone, while the maximum stress of bone defect model (inferior) excessed yield strength value. Conclusions: The femoral neck cortical bone defect induced by core decompression can carry out normal walking after surgery. To avoid an increased risk of fracture after surgery, walking downstairs should be avoided when the cortical bone defect is inferior to the femoral neck except for the other three positions (anterior, posterior, and superior).

Biomechanical analysis of the drilling parameters for early osteonecrosis of the femoral head.

BACKGROUND AND OBJECTIVE: Core decompression is a surgical procedure commonly used to treat the early osteonecrosis of the femoral head. However, It is not known whether different drilling parameters affect postoperative biomechanical strength. This study aimed to analyze the mechanical stability of different drilling locations and diameters of core decompression using finite element analysis. METHODS: Finite element models were established based on computed tomography images obtained from five healthy participants, including the different drilling locations (Lesser trochanter: Above, Parallel, and Below) and diameters. Biomechanical parameters including stiffness and stress were evaluated under slow running loads. RESULTS: At the same drilling diameter, the femoral stiffness was highest (p < 0.05) in the Above group and lowest in the Below group, while the maximum equivalent stress of the entry area and the necrotic area was highest (p < 0.05) in the Below group and lowest in the Above group. With the increase of drilling diameters, the stiffness decreased and its decreased percentage comparing the preoperative: Above (1.06-8.82%), Parallel (2.51-13.61%), and Below (3.99-15.06%). The maximum equivalent stress of the entry area and necrotic area increased as the drilling diameter increased, and its increased percentage comparing the preoperative, for the entry area: Above (14.11-219.58%), Parallel (35.91-306.37%), and Below (46.12-240.98%); for the necrotic area: Above (13.64-114.69%), Parallel (29.37-187.76%), and Below (44.76-202.10%). The range of safety drilling parameters (SDP) was obtained (Below<9 mm, Parallel<11 mm, and Above<13 mm) by comparing the maximum equivalent stress of two areas and its yield strength. For patients of different sizes and normal bone mineral density (BMD), the maximum equivalent stress of the two areas did not exceed its yield strength using the range of SDP, except for the patients with abnormal BMD (Osteoporosis) or high body mass index (BMI≥28 kg/m2). CONCLUSIONS: The biomechanical properties of early osteonecrosis of the femoral head deceased with increasing drilling diameters parameters, especially at the location below the lesser trochanter. The SDP (Below<9 mm, Parallel<11 mm, and Above<13 mm) is a suitable reference for most patients to perform slow running postoperatively, while it may be not suitable for patients with osteoporosis or obesity.

The role of short-chain fatty acids in inflammatory skin diseases.

Short-chain fatty acids (SCFAs) are metabolites of gut microbes that can modulate the host inflammatory response, and contribute to health and homeostasis. Since the introduction of the gut-skin axis concept, the link between SCFAs and inflammatory skin diseases has attracted considerable attention. In this review, we have summarized the literature on the role of SCFAs in skin inflammation, and the correlation between SCFAs and inflammatory skin diseases, especially atopic dermatitis, urticaria, and psoriasis. Studies show that SCFAs are signaling factors in the gut-skin axis and can alleviate skin inflammation. The information presented in this review provides new insights into the molecular mechanisms driving gut-skin axis regulation, along with possible pathways that can be targeted for the treatment and prevention of inflammatory skin diseases.

Exosomal miR-1275 Secreted by Prostate Cancer Cells Modulates Osteoblast Proliferation and Activity by Targeting the SIRT2/RUNX2 Cascade.

Prostate cancer (PCa) is one of the most frequently diagnosed malignancies and the second leading cause of cancer mortality among men worldwide. Modulation of osteoblast activity is involved in PCa metastasis, and miR-1275 is also reported to regulate PCa metastasis; however, the association between cancer-derived exosomal miR-1275 and osteoblast activity is unclear. Here, we isolated exosomes from PC3-derived conditioned medium by ultracentrifugation. We found that miR-1275 could be transferred from PCa cells to osteoblasts via exosomes. Exosomal miR-1275 significantly accelerated the proliferation of osteoblasts and the expression levels of osteoblast-specific genes, such as osteocalcin (OCN), type I collagen (COL-1), and osteopontin (OPN). Moreover, exosomal miR-1275 increased the expression of RUNX2, a master modulator of osteoblast activity, by down-regulation of SIRT2, which in turn influenced the growth and activity of osteoblasts. Our findings indicate that PCa-derived exosomal miR-1275 promotes the proliferation and activity of osteoblasts via modulation of SIRT2/Runx2 signaling.

MicroRNA-126 engineered muscle-derived stem cells attenuates cavernosa injury-induced erectile dysfunction in rats.

BACKGROUND: Cavernosa injury is a common cause of organic erectile dysfunction (ED), which requires safe and effective treatments. In the present study, the therapeutic efficiency of muscle-derived stem cells (MDSCs) modified with microRNA-126 (miR-126) was determined in rats with cavernosa injury. METHODS: MDSCs were transfected with miR-126 and then were transplanted into rats with cavernosa injury. Erectile function, vascular function (western blot and immunofluorescence), extraction, and detection of exosomes were then undertaken. RESULTS: On the 28th day after transplantation, the highest value of intra-cavernous pressure (ICP)/mean arterial pressure (MAP) in rats of miRNA-126 group (0.84 ± 0.14) was observed (Control: 0.38 ± 0.07; MDSC: 0.54 ± 0.11, Vector: 0.60 ± 0.02; respectively). Treatment of miRNA-126-modified-MDSCs remarkably strengthened vascular structure, supported by hematoxylin-eosin staining. The expression of CD31, von Willebrand Factor and vascular endothelial factors were higher than those in other groups, indicating improved vascular function. In vitro mechanism studies showed that exosomes containing miR-126 isolated from MDSCs promoted angiogenesis and attenuated apoptosis of human umbilical venous endothelial cells. Finally, insulin receptor substrate 1 and Krüppel-like factor 10 were determined as the direct target genes of miR-126. CONCLUSIONS: MiR-126 engineered MDSCs notably repaired cavernosa injury in rats via vascular reconstruction by directly targeting IRS1 and KLF10, in which the exosomes secreted by MDSCs played a critical role.

Comparative Analysis of Paper-Based and Web-Based Versions of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) Questionnaire in Breast Cancer Patients: Randomized Crossover Study.

BACKGROUND: Breast cancer remains the most common neoplasm diagnosed among women in China and globally. Health-related questionnaire assessments in research and clinical oncology settings have gained prominence. The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) is a rapid and powerful tool to help evaluate disease- or treatment-related symptoms, both physical and emotional, in patients with breast cancer for clinical and research purposes. Prevalence of individual smartphones provides a potential web-based approach to administrating the questionnaire; however, the reliability of the NFBSI-16 in electronic format has not been assessed. OBJECTIVE: This study aimed to assess the reliability of a web-based NFBSI-16 questionnaire in breast cancer patients undergoing systematic treatment with a prospective open-label randomized crossover study design. METHODS: We recruited random patients with breast cancer under systematic treatment from the central hospital registry to complete both paper- and web-based versions of the questionnaires. Both versions of the questionnaires were self-assessed. Patients were randomly assigned to group A (paper-based first and web-based second) or group B (web-based first and paper-based second). A total of 354 patients were included in the analysis (group A: n=177, group B: n=177). Descriptive sociodemographic characteristics, reliability and agreement rates for single items, subscales, and total score were analyzed using the Wilcoxon test. The Lin concordance correlation coefficient (CCC) and Spearman and Kendall τ rank correlations were used to assess test-retest reliability. RESULTS: Test-retest reliability measured with CCCs was 0.94 for the total NFBSI-16 score. Significant correlations (Spearman ρ) were documented for all 4 subscales-Disease-Related Symptoms Subscale-Physical (ρ=0.93), Disease-Related Symptoms Subscale-Emotional (ρ=0.85), Treatment Side Effects Subscale (ρ=0.95), and Function and Well-Being Subscale (ρ=0.91)-and total NFBSI-16 score (ρ=0.94). Mean differences of the test and retest were all close to zero (≤0.06). The parallel test-retest reliability of subscales with the Wilcoxon test comparing individual items found GP3 (item 5) to be significantly different (P=.02). A majority of the participants in this study (255/354, 72.0%) preferred the web-based over the paper-based version. CONCLUSIONS: The web-based version of the NFBSI-16 questionnaire is an excellent tool for monitoring individual breast cancer patients under treatment, with the majority of participants preferring it over the paper-based version.

Does patient's expectation benefit acupuncture treatment?: A protocol for systematic review and meta-analysis.

BACKGROUND: Patients' expectation to treatment response is one source of placebo effects. A number of randomized controlled trials (RCTs) reported that expectation benefits to acupuncture treatment, while some did not. Previous systematic reviews failed to draw a confirmative conclusion due to the methodological heterogeneity. It is necessary to conduct a new systematic review to find out whether expectation can influence acupuncture outcomes. METHODS: We systematically search English and Chinese databases from their inception to 3rd October, 2020, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese BioMedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Periodical Database (VIP). RCTs that evaluated the relationship between expectation and treatment response following acupuncture for adults will be included. Study selection, data extraction, and risk of bias assessment will be conducted independently. Risk of bias will be assessed by the Cochrane risk of bias assessment tool. Data synthesis will be performed by Review Manager (RevMan) software if the data is suitable for synthesis. RESULTS: This systematic review will provide evidence that whether patients' expectation impacts on the therapeutic effects of acupuncture. This protocol will be performed and reported according to the Preferred Reporting Items from Systematic Reviews and Meta-analysis Protocols (PRISMA-P) statement. The findings of this review will be disseminated through peer-reviewed publications and conference presentations. CONCLUSION: This systematic review aims to assess whether a higher level of patient's expectation contributes to a better outcome after acupuncture treatment, and in which medical condition this contribution will be more significant. INPLASY REGISTRATION NUMBER: INPLASY2020100020 on International Platform of Registered Systematic Review and Meta-analysis Protocols.