Self-assembling peptide hydrogel scaffold integrating stem cell-derived exosomes for infected bone defects.

Infected bone defect (IBD) is a great challenge in orthopedics, which involves in bone loss and infection. Here, a self-assembling hydrogel scaffold (named AMP-RAD/EXO), integrating antimicrobial peptides(AMPs), RADA16 and BMSCs exosomes with an innovative strategy, is developed and applied in IBD treatment for sustained antimicrobial ability, accelerating osteoblasts proliferation and promoting bone regeneration. AMPs present an excellent ability to inhibit infection, RADA16 is a self-assembling peptide hydrogel for AMPs delivery, and BMSCs exosomes can promote the bone regeneration. The prepared AMP-RAD/EXO exhibited a polyporous 3D structure for imbibition of BMSCs exosomes and migration of osteoblasts. In vitro studies indicate AMP-RAD/EXO can inhibit the growth of Staphylococcus aureus, accelerate the proliferation and migration of BMSCs. More importantly, in vivo results also prove that AMP-RAD/EXO exhibit an excellent effect on IBD treatment. Thus, the prepared AMP-RAD/EXO provides a multifunctional scaffold concept for bone tissue engineering technology.

Unsaturated bond recognition leads to biased signal in a fatty acid receptor.

Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and Gi or Giq trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single-nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds. The knowledge gleaned here may facilitate rational drug design targeting to GPR120.

Comparison of environmental controls on daily actual evapotranspiration dynamics among different terrestrial ecosystems in China.

Terrestrial actual evapotranspiration (ETa) is a key state variable modulating land surface processes; however, it remains challenging to recognize how daily ETa responses to environmental variables vary with ecosystems, which is relevant for understanding various ecosystem processes. To this end, comprehensive datasets were synthesized for 22 field sites equipped with eddy covariance towers from the ChinaFLUX network and the National Tibetan Plateau Data Center, which included four different ecosystems across China (e.g., barren or sparsely vegetated-BAR, grassland, forest, and cropland ecosystems). The impacts of environmental variables on daily ETa variations at each field site were assessed by the boosted regression tree (BRT) method. Overall, the BRT results showed that invariant of ecosystem types, net radiation (Rn) was the primary control on daily ETa dynamics with an average contribution of 62.9 % for all the sites, followed by leaf area index-LAI (18.4 %), vapor pressure deficit (8.2 %), soil water content-SWC (7.4 %), and wind speed (3.1 %). More importantly, it was revealed that the interactions of daily ETa with energy (Rn) and water (SWC) supplies could be significantly modified by vegetation through various regulation mechanisms. Specifically, for the BAR and grassland ecosystems, the influences of vegetation on daily ETa highly depended on local land cover and hydrological conditions (e.g., groundwater). For the forest ecosystem, the contrasting impacts of LAI between evergreen and temperate forests were largely attributed to the differences in LAI dynamics over growing seasons, while physiological differences in crops affected the daily ETa responses to LAI variations at cropland sites. This study underscored the varying interactions of daily ETa with Rn and SWC, which could be further shaped by vegetation through a variety of regulation mechanisms across different ecosystems.

Research hotspots and frontiers of neuromodulation techniques in disorders of consciousness: a bibliometric analysis.

Background: The characteristics of disorders of consciousness (DOC) are changes in arousal and/or awareness caused by severe brain injuries. To date, the management of DOC patients remains a complex and challenging task, and neuromodulation techniques offer a promising solution. However, a bibliometric analysis focusing on neuromodulation techniques in DOC is currently absent. The aim of this study is to provide a bibliometric visualization analysis to investigate the research hotspots and frontiers in the field of neuromodulation techniques in DOC from 2012 to 2022. Methods: The publications were collected and retrieved from the Web of Science (WoS) from 2012 to 2022. CiteSpace and Microsoft Excel were utilized perform the first global bibliographic analysis of the literature related to neuromodulation techniques for DOC. Results: The analysis included a total of 338 publications. From 2012 to 2022, a consistent yet irregular increase in the number of articles published on neuromodulation techniques in DOC was observed. Frontiers in Neurology published the highest number of papers (n = 16). Neurosciences represented the main research hotspot category (n = 170). The most prolific country, institution, and author were the USA (n = 105), the University of Liege (n = 41), and Laureys Steven (n = 38), respectively. An analysis of keywords revealed that UWS/VS, MCS, and TMS constituted the primary research trends and focal points within this domain. Conclusion: This bibliometric study sheds light on the current progress and emerging trends of neuromodulation techniques in DOC from 2012 to 2022. The focal topics in this domain encompass the precise diagnosis of consciousness levels in patients suffering from DOC and the pursuit of efficacious neuromodulation-based evaluation and treatment protocols for such patients.

Prolonged Continuous Theta Burst Stimulation Can Regulate Sensitivity on Aß Fibers: An Functional Near-Infrared Spectroscopy Study.

Objective: High-frequency repetitive transcranial magnetic stimulation (rTMS) induces analgesic effects in both experimental pain and clinical pain conditions. However, whether rTMS can modulate sensory and pain thresholds on sensory fibers is still unclear. Here, we compared the effects of three rTMS paradigms on sensory and pain thresholds conducted by different sensory fibers (Aß, Aδ, and C fibers) with sham stimulation and investigate the potential brain activation using functional near-infrared spectroscopy (fNIRS). Methods: Forty right-handed healthy subjects were randomly allocated into one of four groups. Each subject received one session rTMS [prolonged continuous theta-burst stimulation (pcTBS), intermittent theta-burst stimulation (iTBS), 10 Hz rTMS or sham]. Current perception threshold (CPT), pain tolerance threshold (PTT), and fNIRS were measured at baseline, immediately after stimulation, and 1 h after stimulation, respectively. Results: Significant differences between treatments were observed for changes for CPT 2,000 Hz between baseline and 1 h after rTMS (F = 6.551, P < 0.001): pcTBS versus sham (P = 0.004) and pcTBS versus 10 Hz rTMS (P = 0.007). There were significant difference in average HbO µm in the right frontopolar cortex (FPC) [channel 23: P = 0.030 (pcTBS versus sham: P = 0.036)], left dorsolateral prefrontal cortex (DLPFC) [channel 7: P = 0.006 (pcTBS versus sham: P = 0.004)], left FPC [channel 17: P = 0.014 (pcTBS versus sham: P = 0.046), channel 22: P = 0.004 (pcTBS versus sham: P = 0.004)] comparing four group in 1 h after stimulation in PTT 2000 Hz (Aß-fiber). Conclusion: Prolonged continuous theta-burst stimulation can regulate sensitivity on Aß fibers. In addition, single-session pcTBS placed on left M1 can increase the excitability of DLPFC and FPC, indicating the interaction between M1 and prefrontal cortex may be a potential mechanism of analgesic effect of rTMS. Studies in patients with central post-stroke pain are required to confirm the potential clinical applications of pcTBS.

Integrated Bioinformatics-Based Identification of Potential Diagnostic Biomarkers Associated with Diabetic Foot Ulcer Development.

The present study was designed to detect possible biomarkers associated with diabetic foot ulcer (DFU) incidence in an effort to develop novel treatments for this condition. The GSE7014 and GSE29221 gene expression datasets were downloaded from the Gene Expression Omnibus (GEO) database, after which differentially expressed genes (DEGs) were identified between DFU and healthy samples. These DEGs were then arranged into a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were performed to explore the functional roles of these genes. In total, 1192 DEGs were identified in the GSE7014 dataset (900 upregulated, 292 downregulated), while 1177 were identified in the GSE29221 dataset (257 upregulated, 919 downregulated). GO analyses revealed these DEGs to be significantly enriched in biological processes including sarcomere organization, muscle filament sliding, and the regulation of cardiac conduction, molecular functions including structural constituent of muscle, protein binding, and calcium ion binding, and cellular components including Z disc, myosin filament, and M band. These DEGs were also enriched in the adrenergic signaling in cardiomyoctes, dilated cardiomyopathy, and tight junction KEGG pathways. Together, the findings of these bioinformatics analyses thus identified key hub genes associated with DFU development.

Factors associated with public attitudes towards persons with disabilities: a systematic review.

OBJECTIVE: The aim of this review is to identify and summarize factors that are associated with public attitudes towards people with various disabilities systematically. METHODS: An electronic search of three databases was performed (Medline, EMBASE and Cochrane) covering the period from 1950 to present. A comprehensive search strategy was developed and the lists of citations were screened for potential eligible studies. Only quantitative studies using valid measurements were included, and the methodological quality of included studies was appraised based on three criteria (sample, measurement, analysis) by two independent reviewers. RESULTS: The initial electronic search yielded 995 articles after duplicates removed, and 27 studies met the eligibility criteria were included in the study. Three categories of the factors were found to be associated with the public attitudes, which are related to the attitude provider, disabled people, and society respectively. Specifically, the more people know about disabilities, the more likely they were to have positive attitude; and the frequency and quality of the contact with the disabled are also proved to be influential to the attitudes. Meanwhile, the type of disability is also closely correlated to the public's attitude towards the disabilities. CONCLUSION: People's knowledge of the disability and their contact with individuals with disabilities are the main influential factors in public attitudes towards persons with disabilities.

Functional Analysis of Estrogen Receptor 1 in Diabetic Wound Healing: A Knockdown Cell-Based and Bioinformatic Study.

BACKGROUND Diabetic wound (DW) treatment is a serious challenge for clinicians, and the underlying mechanisms of DWs remain elusive. We sought to identify the critical genes in the development of DWs and provide potential targets for DW therapies. MATERIAL AND METHODS Datasets of GSE38396 from the Gene Expression Omnibus (GEO) database were reviewed. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology term analyses were carried out, and Cytoscape software (Cytoscape 3.7.2) was used to construct the protein interaction network. Serum samples from patients with diabetes and control participants were collected, and the expression of estrogen receptor 1 (ESR1) was measured by quantitative reverse-transcription polymerase chain reaction. In addition, the function of ESR1 in human skin fibroblasts was investigated in vitro. RESULTS Eight samples were analyzed using the Morpheus online tool, which identified 637 upregulated and 448 downregulated differentially expressed genes. The top 5 KEGG pathways of upregulated differentially expressed genes were associated with sphingolipid metabolism, estrogen signaling, ECM-receptor interaction, MAPK signaling, and PI3K-Akt signaling. The hub genes for DWs were JUN, ESR1, CD44, SMARCA4, MMP2, BMP4, GSK3B, WDR5, PTK2, and PTGS2. JUN, MMP2, and ESR1 were the upregulated hub genes, and ESR1 was found to be consistently enriched in DW patients. Inhibition of ESR1 had a stimulative role in human skin fibroblasts. CONCLUSIONS ESR1 was identified as a crucial gene in the development of DWs, which suggests potential therapeutic targets for DW healing.

Association between genetic polymorphism and antidepressants in major depression: a network meta-analysis.

This network meta-analysis was conducted to compare the predictive value of eight SNPs on the efficacy of antidepressants in major depressive disorder (MDD), including 5-HTTLPR, 5HTR2A (rs6311, rs6314, rs7997012 and rs6313), 5HTR2A (rs6295), BDNF (rs6265) and 5HTTSTin2. Databases were searched for related studies published up to December 2019. A total of 16 studies were included in this study. The predictive value were evaluated by the use of the odd ratios (OR) and drawing surface under the cumulative ranking curves (SUCRA). The pairwise meta-analysis indicated that in terms of overall response ratio, the SNPs were not associated with the efficacy of antidepressants in MDD. The result of this network meta-analysis suggested that there was no significant difference in predictive value of eight SNPs on the efficacy of antidepressants in MDD. More research is needed to explore the relationship between SNPs and antidepressant response.

A Hybrid Repair Technique Combining Single-Bundle Reconstruction and Primary Repair With Internal Brace Augmentation for Anterior Cruciate Ligament Injury.

Recently, favorable outcomes of primary anterior cruciate ligament (ACL) repair have been reported in patients with proximal tears and good tissue quality. If the tear involves the midsubstance of the ACL fibers or Sherman type II or III injury, independent primary repair will cause a higher failure rate at long-term follow-up. For these cases, we conduct primary repair and apply an internal brace and single-bundle reconstruction as hybrid augmentation. This hybrid repair technique encourages natural healing of the primary ligament by the internal brace and single-bundle graft as a provisional scaffold during the healing phase, as well as early mobilization. We describe our ACL hybrid repair technique, using a video and illustrations.

Effectiveness of auricular point therapy for cancer-related fatigue: A systematic review and meta-analysis.

AIMS: To systemically review the efficacy and safety of auricular point therapy in patients with cancer-related fatigue. DESIGN: A systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Eight electronic databases (PubMed, CENTRAL, Embase, CINAHL, Web of Science, China Biology Medicine, China National Knowledge Infrastructure and WanFang Data Knowledge Service Platform) were explored for randomized controlled trials from their inception to 1 December 2018. REVIEW METHODS: The risk of bias assessment tool was adopted in accordance with Cochrane Handbook 5.3.0. All included studies reported the effects on cancer-related fatigue as the primary outcome. Effect size was estimated using relative risk, standardized mean difference or mean difference with a corresponding 95% confidence interval. Review Manager 5.3 was used for meta-analysis. RESULTS: Six studies comprising 394 patients were included. The results of meta-analysis showed that auricular point therapy plus standard care produced more positive effects on cancer-related fatigue and quality of life than standard care alone. It could significantly improve the role, emotional, cognitive, and social functions of patients with cancer-related fatigue. CONCLUSIONS: Auricular point therapy may be a safe therapy to relieve cancer-related fatigue and enhance the quality of life of patients with cancer. However, the evidence was inconclusive due to limitations on the quantity and quality of included studies. Rigorously designed randomized controlled trials should be conducted to verify the results. IMPACT: Auricular point therapy is a simple and safe therapeutic approach that may alleviate cancer-related fatigue of common complications in patients with cancer and it is worth promoting in the community, family, and hospital. Moreover, the research findings can provide suggestions and inspiration for nurses and researchers to implement the proposal, which is conducive to design more rigorous and high-quality randomized controlled trials.

[Effect of acupuncture at "reflection points" of the affected side on the peripheral facial paralysis in acute phase].

OBJECTIVE: To explore the effect of acupuncture at the "reflection points" of affected side on the peripheral facial paralysis in acute phase. METHODS: Ninety patients with peripheral facial paralysis in acute phase were randomly divided into a reflection group (group A), a conventional acupuncture group (group B) and a physiotherapy group (group C), 30 cases in each group. The same basic medication were given in all three groups. In the group A, acupuncture at "reflection points" of the affected side and local acupoints in acute phase, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group B, acupuncture at Yifeng (TE 17) of the affected side in acute phase and local acupoints, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group C, ultrashort wave on Yifeng (TE 17) of the affected side in acute phase was applied, and the treatment in the stationary phase and the recovery phase was the same as the group B. The treatment was given once every day, 5 times as one course for 4 courses. The House-Brackmann (H-B) grading scale, facial disability index scale, the symptom and physical score integral scale were used to score before and after treatment, and the clinical effects of the three groups were compared. RESULTS: After treatment, the functional grade of H-B facial nerve was better than that before treatment in the three groups (P<0.01). There was no significant difference among the three groups after treatment (P>0.05). After treatment, the course of treatment required to reflect the healing in the group A was shorter than that in the group B and the group C (P<0.01); the body function scores and social function scores in the three groups were better than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). The scores of symptoms and signs in the three groups were lower than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). H-B facial nerve function grading scale and facial disability index (FDI) scale were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B and 46.7% (14/30) in the group C, the curative rate in the group A was better than the other two groups (P<0.05). The curative and markedly effective rate in the group A was 83.3% (25/30), 70.0% (21/30) in the group B and 63.3% (19/30) in the group C, the curative and markedly effective rate in the group A was better than the other two groups (P<0.05). The scores of symptoms and signs were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B, and 46.7% (14/30) in the group C. The curative rate in the group A was better than the other two groups (P<0.05). CONCLUSION: Compared with general acupuncture and physiotherapy, acupuncture at the "reflection points" of the affected side on the peripheral facial paralysis in acute phase could shorten the course of treatment and improve the curative effect.

Postprocedure Intravenous Patient-Controlled Analgesia Compared to Epidural Patient-Controlled Analgesia Use after Uterine Fibroid Embolization: A Clinical Audit.

PURPOSE: Postprocedure epidural analgesia has a proven benefit over intravenous (i.v.) analgesia for pain management, but has not yet been demonstrated for uterine fibroid embolization (UFE). The objectives of this clinical audit were to determine if epidural patient-controlled analgesia (PCA) was beneficial to patient outcome as compared to i.v. PCA in decreasing parenteral opioid requirements and its associated side effects and determine if there is a difference in required oral opioids after the PCA is stopped. MATERIALS AND METHODS: This manuscript audited postprocedural pain management of 51 patients after UFE was performed. 20 patients received an i.v. PCA for post-UFE pain control and 31 received an epidural PCA for post-UFE pain control. Total hydromorphone dose, the frequency of anti-nausea medication use, the frequency of anti-pruritus medication use, and patient pain satisfaction data was collected. RESULTS: Total hydromorphone dose administered to patients post-UFE using epidural PCA was significantly less than patients using an i.v. PCA (P = 0.001). However, the frequency of nausea and pruritus between the two groups did not achieve statistical significance with (P = 0.663) and (P = 0.639) respectively. CONCLUSION: Our clinical audit found that parenteral opioid requirements administered after UFE can be significantly reduced by using epidural PCA instead of i.v. PCA. However, we found no statistically significant difference in medication related side effects or oral opioid use thereafter.

Correlation Analysis of Magnetic Resonance Imaging-Based Graft Maturity and Outcomes After Anterior Cruciate Ligament Reconstruction Using International Knee Documentation Committee Score.

OBJECTIVE: The correlation between the signal/noise quotient values of an anterior cruciate ligament graft and the International Knee Documentation Committee Subjective Knee Form 2000 scores after anterior cruciate ligament reconstruction was evaluated. DESIGN: Magnetic resonance imaging and clinical evaluation using International Knee Documentation Committee scores were used to calculate the signal intensity of the graft maturity at the 6-mo and 12-mo follow-up points postoperatively. The associations between the signal/noise quotient values at the 6-mo follow-up point and International Knee Documentation Committee scores at the 12-mo follow-up point were evaluated. RESULTS: A total of 42 male patients completed our trial and returned to normal activity level before the surgery. The mean ± SD age of these patients was 29.07 ± 8.11 yrs (range, 17-47 yrs). The mean ± SD body mass index was 26.00 ± 2.59 kg/m. Notably, the Pearson correlation analysis showed that the International Knee Documentation Committee scores obtained at 12 mos were significantly associated with the signal/noise quotient values measured in the sixth month and twelfth month, respectively (r = -0.454, P = 0.003; r = -0.478, P = 0.001). CONCLUSIONS: According to this study, early measurement of graft maturity might predict the clinical outcome afterward. The sensitive predictive value of signal/noise quotient could be used to maximize the patient outcomes.

Uterine anteversion after uterine fibroid embolization.

Uterine fibroid embolization has been proven effective in treating symptomatic uterine fibroids for appropriately selected patients as an alternative option to surgical approaches. The most common adult uterine position is anteverted followed by a retroverted uterus which can be found in roughly 15%-20% of normal adult females. The positioning of the uterus can change from anteversion to retroversion due to the filling of bladder or during pregnancy; however, changing from retroverted to anteverted position without prior pregnancy or endometriosis is rather uncommon. Here, we describe a case of uterine orientation change from retroversion to anteversion presenting 6 months after uterine fibroid embolization.

Analysis of Staged Treatment for Gustilo Anderson IIIB/C Open Tibial Fractures.

BACKGROUND: Gustilo Anderson III B/C open tibial fractures are more difficult to manage than I, II, and III A fractures. These open tibial fractures are often associated with wound infection, soft tissue necrosis, bone nonunion, osteomyelitis or amputation. Staged treatment for this severe trauma is very necessary. MATERIALS AND METHODS: 25 cases of Gustilo Anderson IIIB/C open tibial fractures with serious soft-tissue defects treated between January 2010 and January 2015 were included in this study. The treatment was administered in three stages. The first stage included emergency debridement, external fixation, repair of damaged main blood vessels and nerves, covering of the wound, and infection control. The second stage involved skin flap or skin graft placement to repair wounds. The third stage involved replacement of the external fixator with an internal fixator and the placement of bone grafts. RESULTS: All the skin flaps or skin grafts survived, and a small necrotic area in the distal flap was observed in only two cases (which resolved spontaneously after the dressing was changed). Bone union occurred at the predicted time in 23 cases, while it was delayed in 2 cases. The rate of excellent and good was 88%. CONCLUSION: Staged treatment was safe and effective for Gustilo Anderson IIIB/C tibial fractures. The timing for the placement of internal and external fixators and choosing the appropriate skin flap repair technique are important.

Classification of Whole Mammogram and Tomosynthesis Images Using Deep Convolutional Neural Networks.

Mammography is the most popular technology used for the early detection of breast cancer. Manual classification of mammogram images is a hard task because of the variability of the tumor. It yields a noteworthy number of patients being called back to perform biopsies, ensuring no missing diagnosis. The convolutional neural network (CNN) has succeeded in a lot of image classification challenges during the recent years. In this paper, we proposed an approach of mammogram and tomosynthesis classification based on CNNs. We had acquired more than 3000 mammograms and tomosynthesis data with approval from an institutional review board at the University of Kentucky. Different models of CNNs were built to classify both the 2-D mammograms and 3-D tomosynthesis, and every classifier was assessed with respect to truth-values generated by histology results from the biopsy and two-year negative mammogram follow-up confirmed by expert radiologists. Our outcomes demonstrated that CNN-based models we had built and optimized utilizing transfer learning and data augmentation have good potential for automatic breast cancer detection based on the mammograms and tomosynthesis data.