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Measurement of auricle parameters for planning and post-operative evaluation presents substantial challenges due to the complex 3D structure of the human auricle. Traditional measurement methods rely on manual techniques, resulting in limited precision. This study introduces a novel automated surface-based three-dimensional measurement method for quantifying human auricle parameters. The method was applied to virtual auricles reconstructed from Computed Tomography (CT) scans of a cadaver head and subsequent measurement of important clinically relevant aesthetical auricular parameters (length, width, protrusion, position, auriculocephalic angle, and inclination angle). Reference measurements were done manually (using a caliper and using a 3D landmarking method) and measurement precision was compared to the automated method. The CT scans were performed using both a contemporary high-end and a low-end CT scanner. Scans were conducted at a standard scanning dose, and at half the dose. The automatic method demonstrated significantly higher precision in measuring auricle parameters compared to manual methods. Compared to traditional manual measurements, precision improved for auricle length (9×), width (5×), protrusion (5×), Auriculocephalic Angle (5–54×) and posteroanterior position (23×). Concerning parameters without comparison with a manual method, the precision level of supero-inferior position was 0.489 mm; and the precisions of the inclination angle measurements were 1.365 mm and 0.237 mm for the two automated methods investigated. Improved precision of measuring auricle parameters was associated with using the high-end scanner. A higher dose was only associated with a higher precision for the left auricle length. The findings of this study emphasize the advantage of automated surface-based auricle measurements, showcasing improved precision compared to traditional methods. This novel algorithm has the potential to enhance auricle reconstruction and other applications in plastic surgery, offering a promising avenue for future research and clinical application. [ABSTRACT FROM AUTHOR]

Household consumption has become an important field of carbon dioxide emissions. Urban–rural disparity in the household carbon emissions (HCEs) of residents and their influencing factors are relevant to HCE reduction. Taking Fujian as the study area, the LMDI and SDA models were used to analyze the effects of influencing factors for the direct household carbon emissions (DHCEs) and indirect carbon emissions (IHCEs) of urban and rural residents from 2006 to 2018. The HCEs continue to rise, approximately 65% from the IHCEs in 2017, and urban areas occupied 67% in 2018. The gap between urban and rural per capita HCEs is narrowing. In 2017, approximately 75% of urban per capita HCEs came from the IHCEs, while the per capita DHCEs' occupation exceeded the IHCEs in rural areas. Per capita consumption expenditure has the largest positive effect on the DHCEs and IHCEs in urban and rural areas. With the urbanization process, the inhibition effect of rural DHCEs is larger than the positive effect of the urban DHCEs, while the positive impact on urban areas is more substantial than on rural areas in the IHCEs. Combined with regional differences, urban and rural areas should take "common but differentiated" emission reduction responsibilities. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease with high prevalence rate among the elderly population. A large number of clinical studies have suggested repetitive transcranial magnetic stimulation (rTMS) as a promising non-invasive treatment for patients with mild to moderate AD. However, the underlying cellular and molecular mechanisms remain largely uninvestigated. In the current study, we examined the effect of high frequency rTMS treatment on the cognitive functions and pathological changes in the brains of 4- to 5-month old 5xFAD mice, an early pathological stage with pronounced amyloidopathy and cognitive deficit. Our results showed that rTMS treatment effectively prevented the decline of long-term memories of the 5xFAD mice for novel objects and locations. Importantly, rTMS treatment significantly increased the drainage efficiency of brain clearance pathways, including the glymphatic system in brain parenchyma and the meningeal lymphatics, in the 5xFAD mouse model. Significant reduction of Aβ deposits, suppression of microglia and astrocyte activation, and prevention of decline of neuronal activity as indicated by the elevated c-FOS expression, were observed in the prefrontal cortex and hippocampus of the rTMS-treated 5xFAD mice. Collectively, these findings provide a novel mechanistic insight of rTMS in regulating brain drainage system and β-amyloid clearance in the 5xFAD mouse model, and suggest the potential use of the clearance rate of contrast tracer in cerebrospinal fluid as a prognostic biomarker for the effectiveness of rTMS treatment in AD patients. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma represents a serious clinical challenge due to its widespread genomic alterations, tendency for drug resistance and distant metastasis. New treatment methods are urgently needed to address those treatment difficulties in osteosarcoma to improve patient prognoses. In recent years, small-molecule based anion transporter have emerged as innovative and promising therapeutic compound with various biomedical applications. However, due to a lack of efficient delivery methods, using ion transporters as therapeutic drugs in vivo remains a major challenge. Result: Herein, we developed self-assembled supramolecular drugs based on small-molecule anion transporters, which exhibited potent therapeutic effect towards osteosarcoma both in vitro and in vivo. The anion transporters can disrupt intracellular ion homeostasis, inhibit proliferation, migration, epithelial-mesenchymal transition process, and lead to osteosarcoma cell death. RNA sequencing, western blot and flow cytometry indicated reprogramming of HOS cells and induced cell death through multiple pathways. These pathways included activation of endoplasmic reticulum stress, autophagy, apoptosis and cell cycle arrest, which avoided the development of drug resistance in osteosarcoma cells. Functionalized with osteosarcoma targeting peptide, the assembled supramolecular drug showed excellent targeted anticancer therapy against subcutaneous xenograft tumor and lung metastasis models. Besides good tumor targeting capability and anti-drug resistance, the efficacy of the assembly was also attributed to its ability to regulate the tumor immune microenvironment in vivo. Conclusions: In summary, we have demonstrated for the first time that small-molecule anion transporters are capable of killing osteosarcoma cells through multiple pathways. The assemblies, OTP-BP-L, show excellent targeting and therapeutic effect towards osteosarcoma tumors. Furthermore, the supramolecular drug shows a strong ability to regulate the tumor immune microenvironment in vivo. This work not only demonstrated the biomedical value of small-molecule anion transporters in vivo, but also provided an innovative approach for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Flesh content of pomelos sometimes does not match the price due to thick peel, which reduces their commercial value and consumer satisfaction. This study demonstrated the potential use of X-ray imaging method for non-destructive evaluation of the edible rate and the flesh content of 'Hongrou' pomelos and 'Guanxi' pomelos. An adaptive threshold segmentation method was used to segment the X-ray image into background, flesh region and peel region. Then, 2D edible rate and 2D flesh content were defined based on region area ratio and gray level logarithmic sum, respectively, and the multiple linear regression (MLR) models of edible rate and flesh content were established for quantitative analysis. The results showed that the residual predictive deviation (RPD) value of edible rate of 'Hongrou' and 'Guanxi' pomelos in prediction set were up to 2.78 and 2.82, respectively. The hybrid model based on both two cultivars pomelos also achieved good prediction accuracy (RPD = 2.83). In terms of flesh content prediction, the model prediction performance of 'Hongrou' pomelo (RPD = 2.92) was obviously better than that of 'Guanxi' pomelo (RPD = 2.05), and the RPD value of hybrid model in prediction set was 2.62. Further, both two-grade and three-grade linear discriminant analysis (LDA) classifiers were trained to explore the feasibility of using X-ray images to classify the edible rate of pomelos, and the classification accuracy of hybrid samples were 96.7% and 90.0%, respectively. Overall, the features extracted from X-ray image of pomelo could allow the non-destructive evaluation of the edible rate for pomelo. • Two features of X-ray images for predicting the edible rate of pomelo were proposed. • The classification accuracy of pomelo sorting by edible rate was no less than 90%. • X-ray images in different directions could predict the edible rate of pomelo better. • Combining X-ray images with the shape of pomelo could obtain a better model. [ABSTRACT FROM AUTHOR]

A rat model of vascular dementia was used to compare the effects of involuntary exercise induced by functional electrical stimulation (FES), forced exercise and voluntary exercise on the recovery of cognitive function recovery and its underlying mechanisms. In an involuntary exercise (I-EX) group, FES was used to induce involuntary gait-like running on ladder at 12 m/min. A forced exercise group (F-EX) and a voluntary exercise group (V-EX) exercised by wheel running. The Barnes maze was used for behavioral assessment. Brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element binding protein (CREB) positive cells in hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were evaluated using immunohistochemical methods. Western blotting was used to assess the levels of BDNF, phosphorylated protein kinase B (Akt), tropomyosin receptor kinase B (TrkB), mitogen-activated protein kinase 1 and 2 (MEK1/2), ERK1/2 and CREB in BDNF-pCREB signaling in the hippocampus and prefrontal cortex. Involuntary, forced and voluntary exercises were all found to reverse the cognitive deficits of vascular dementia with about equal effectiveness. The number of BDNF, pCREB and pERK1/2 immunopositive cells was significantly increased in the hippocampal CA1, CA2/3 and DG regions in all three exercise groups. In addition, involuntary exercise activated BDNF and the phosphorylation of Akt, TrkB, MEK1/2, ERK1/2 and CREB in the hippocampus and prefrontal cortex equally as well as voluntary or forced exercise. These results suggest that involuntary exercise induced by FES may be as beneficial for alleviating cognitive deficits after cerebral ischemia. [ABSTRACT FROM AUTHOR]

Mycophenolate embryopathy (ME) is a congenital malformation induced by mycophenolic acid (MA). Microtia is the most common ME phenotype. This study aimed to identify the key genes in the pathological process of microtia caused by mycophenolate mofetil (MM) through bioinformatics methods, to explore the potential pathogenesis, and to provide a direction for future genetic research on aetiology. Genes related to MM and microtia were obtained from the GeneCards database for bioinformatics. Metacore was used to identify and visualize the upstream and downstream gene relationships in the protein-protein interaction (PPI) results of these genes. The clusterProfiler R software package was used to simulate and visualize the enrichment results based on data from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Fifty-nine genes were associated with microtia and MM/MA. The hub genes with the most significant effects on MM/MA-induced microtia pathogenesis included tumour protein P53 (p53), MDM2 proto-oncogene (MDM2), ribosomal protein L5 (RPL5) and ribosomal protein S14 (RBS14). The GO term with the most enriched genes was peptidyl-tyrosine phosphorylation. For the KEGG terms, there was significant enrichment regarding the haematopoietic cell lineage, apoptosis, p53 signalling, proteasome and necroptosis. We propose that an axis composed of MA, microtia, TP53 and related genes is involved in ME pathogenesis. The important role of TP53-associated ribosome stress in ME pathogenesis is consistent with our previous findings from MA-induced cleft lip and palate. Deregulation of genes protective against TP53 overexpression, such as MDM2, could be a strategy for constructing a microtia animal model. • An axis composed of MA, microtia, TP53 and related genes is involved in ME pathogenesis. • Associated genes like MDM2, RPL5 and RPS14 have been found to be involved in the regulation of this process. • Integrated bioinformatics approaches are used for the first time to screen pathogenetic genes and pathways of mycophenolic acid-induced microtia. [ABSTRACT FROM AUTHOR]

Ethanol used by women during pregnancy increases the risk for microtia in the foetus. Traditionally, laboratory experiments and Mouse Genome Informatics (MGI) have been used to explore microtia pathogenesis. The aim of this study was to screen and verify hub genes involved in ethanol-induced microtia and to explore the potential molecular mechanisms. Overlapping genes related to ethanol and microtia were acquired from the GeneCards database and filtered by confidence score. These genes were further analysed via bioinformatics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results were visualized with the clusterProfiler R package. A protein-protein interaction (PPI) network was constructed based on data from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Overall, 41 genes related to both ethanol and microtia were identified. The genes most relevant to ethanol-induced microtia pathogenesis included FGFR-2, FGFR-3, FGF-8, TP53, IGF1, SHH, CTNNB1, and PAX6, among others. Most genes were strongly enriched for tissue and organ development in GO analysis. Additionally, many genes were enriched in the Ras, FoxO, MAPK, and PI3K-Akt signalling pathways in KEGG analysis. Bioinformatics analysis was conducted on genes currently known to be related to ethanol-induced microtia pathogenesis. We propose that mechanisms involving FGF-family genes, TP53, IGF1 and SHH contribute significantly to ethanol-induced microtia and the accompanying malformation of other structures. [ABSTRACT FROM AUTHOR]

• RA patients' depression level correlates with disease activity and quality of life. • Hyperactive LHb drives depression-like behaviors and RA pathology in mice. • Cerebrovascular disruption in LHb associates with depression-like behaviors in RA mice. • Blocking LHb reduces plasma GM-CSF and KC levels, and synovial macrophages. Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression. [ABSTRACT FROM AUTHOR]

Objective: Microtia is a congenital auricular malformation with a hypoplastic external ear that ranges in severity from a slightly smaller auricle to complete the absence of the auricle. The present study was conducted to identify and analyze the characteristics of microtia-related articles published from 2006 to 2020 by using bibliometric analyses. Method: Microtia-related studies published from 2006 to 2020 were retrieved from the Web of Science Core Collection database. Keywords, first author, citations, date of publication, and publication journal were extracted and quantitatively analyzed using Bibliographic Item Co-Occurrence Matrix Builder software and the Bibliometric (https://bibliometric.com/app). VOSviewer was used to visualize research and form a network map on keywords and citations. Results: A total of 1031 articles from 2006 to 2020 were included. The number of articles showed an overall trend of growth over time. The United States and China are the top 2 countries in terms of the number of microtia-related articles. From the analysis of keyword clustering, keywords could be mainly divided into 4 clusters in the field of microtia research: surgery, tissue engineering, epidemiology, and rehabilitation including hearing-related treatments, evaluation of effects, and quality of life after surgery. The top 10 most frequently cited papers from 2006 to 2020 were also extracted and analyzed. Conclusion: A bibliometric research of microtia-related articles from 2006 to 2020 was conducted. This study may be helpful to understand the current research status of microtia and find the research trends in this field, thus proposing future directions for microtia research. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. Methods: GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher's exact test). Discussion: GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk–benefit profile of this treatment in the future. Trial registration: ClinicalTrials.gov NCT05291650. Registered on 23 March 2022. [ABSTRACT FROM AUTHOR]

Background: Work-related neck pain (WRNP) is a leading cause of disability and absenteeism. Patients with neck pain often have neck muscle tenderness and decreased cervical mobility, which are sometimes combined with psychosocial issues, such as pain catastrophising, thereby reducing their work ability. Whilst multidisciplinary treatments, including pharmacological interventions, manual therapy and specific neck exercises, have produced positive outcomes, effective personalised treatment modalities are still needed. Furthermore, manual therapies using the hands can bring fatigue to therapist. Occiflex is a computerised device that can provide personalised segmental joint mobilisation based on symptoms and injury of the patient and then provide a medium range of joint activities to improve range of cervical motion. This study aims to compare the effect of computerised mobilisation performed with Occiflex with that of traditional manual therapy on WRNP. Methods: We will conduct a prospective randomised controlled trial including 150 patients with WRNP. These patients will be randomly assigned to one of three groups: (i) home exercise (TE), (ii) home exercise plus Occiflex therapy and (iii) home exercise plus manual therapy delivered by a physical therapist. Ten treatment sessions will be performed in four weeks. During the trial, these patients will receive only the assigned treatment and the standard patient education and will be asked not to use any analgesics unless strictly necessary. Assessments by trained evaluators will occur at baseline, week 4 and week 12. The primary outcome measures will include visual analogue scale (VAS) for pain and neck disability index (NDI) at each time point. Secondary outcome measures will include cervical range of motion (CROM), pressure pain threshold (PPT), global perceived effect (GPE) and sick leave. Group by time differences will be analysed using linear mixed models with repeated measures. Discussion: This protocol describes the methods for a randomised controlled trial to compare the effectiveness of computerised versus manual mobilisation techniques in treating WRNP. The results will provide an alternative method (Occiflex) that is possibly effective for treating neck pain whilst minimising the manual work done by therapists. Trial registration: The study protocol was retrospectively registered at http://www.chictr.org.cn (registration number: ChiCTR2100053076) on November 10, 2021. [ABSTRACT FROM AUTHOR]

Background: Homozygous or compound heterozygous variants in the KLHL40 gene cause nemaline myopathy 8 (NEM8), a severe autosomal recessive muscle disorder characterized by prenatal polyhydramnios, fetal akinesia or hypokinesia, joint contractures, fractures, respiratory failure and dysphagia. Currently, 46 individuals with NEM8 have been described in the literature, and 30 variants in KLHL40 have been identified.Results: Here, we reported five individuals from four unrelated Chinese families who presented common features of nemaline myopathy and infrequent clinical characteristics. Whole-exome sequencing (WES) was used to identify the causative gene. WES identified a recurrent missense variant c.1516A>C (p.Thr506Pro) and a novel frameshift variant c.543del (p.Ser182Profs*17) in KLHL40 in patient 1, a nonsense variant c.602G>A (p.Trp201*) and a missense variant c.1516A>C (p.Thr506Pro) in KLHL40 in patient 2, and homozygous variant c.1516A>C (p.Thr506Pro) in KLHL40 in patient 3 and both siblings (patients 4 and 5), all of which were confirmed by Sanger sequencing. Next, we estimated the incidence of this disorder in the southern and northern Chinese population to be 4.59/106 and 2.95/106, respectively, based on the cumulative allele frequency of pathogenic variants in internal database.Conclusion: The results of our study expand the mutation spectrum of KLHL40 and enrich our understanding of the clinical characteristics of NEM8. Genetic counseling was provided for the four families involved in this study. Given the severity and the relatively high incidence of this condition, we strongly suggest that KLHL40 be incorporated into a carrier screening panel for the Chinese population. [ABSTRACT FROM AUTHOR]

• This comprehensive meta-analysis analyzes the intervention effect of rTMS on NP. • We systematically assessed the effects of rTMS on pain, depression, quality of life and safety in patients with NP. • Stimulation frequency, intervention site, and location of lesion are critical modulators of the rTMS effect. Neuropathic pain (NP) is a chronic pain condition caused by lesion or disease of the somatosensory nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a neuroregulatory tool that uses pulsed magnetic fields to modulate the cerebral cortex. This review aimed to ascertain the therapeutic effect of rTMS on NP and potential factors regulating the therapeutic effect of rTMS. Database search included Web of Science, Embase, Pubmed, and Cochrane Library from inception to July 2021. Eligible studies included randomized controlled studies of the analgesic effects of rTMS in patients with NP. Thirty-eight studies were included. Random effect analysis showed effect sizes of −0.66 (95 % CI, −0.87 to −0.46), indicating that real rTMS was better than sham condition in reducing pain (P < 0.001). This comprehensive review indicated that stimulation frequency, intervention site, and location of lesion were important factors affecting the therapeutic effect. The findings of this study may guide clinical decisions and future research. [ABSTRACT FROM AUTHOR]

Background: During the prenatal period, the number variation of chromosomes 13, 18, 21, X and Y accounts for more than 80% of the clinically significant chromosomal abnormalities diagnosed. Rapid tests for prenatal diagnosis of these abnormalities can improve pregnancy management and alleviate parental anxiety. Here, we present a molecular alternative method for detecting common aneuploidies. Methods: This method is based on co-amplification of segmental duplications located on two different chromosomes using a single pair of primers. Segmental duplications have a high degree of sequence identity, but have single-nucleotide differences in some regions. These sequence differences can be quantified using melting curve analysis of dual-labeled probes to estimate the relative dosages of different chromosomes. We designed two quadruplex real-time PCR assays to detect aneuploidies of chromosomes 13, 18, 21, X and Y. Results: We examined 75 aneuploid DNA samples and 56 unaffected DNA control samples using these two assays and correctly identified all samples. Four cases of unbalanced translocation were also accurately detected. The observed averaged ratio for each chromosomal disorder was similar to the theoretically expected value. Conclusions: Our real-time assay is a robust, rapid, and easy to conduct technique for prenatal diagnosis of common aneuploidies, representing a competitive alternative for use in diagnostic laboratories. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to set up an alternative automatic molecular diagnostic method for deletional α-thalassaemia mutations without gel electrophoresis. Methods Based on the sequence variation within the two Z boxes and melting curve analysis of dually labelled probes, a real-time PCR assay was developed and validated for the rapid detection of major α-genotypes (-- SEA /αα, -- SEA /-α 3.7 , -- SEA /-α 4.2 , -- SEA /-- SEA , -α 3.7 /-α 3.7 and -α 4.2 /-α 4.2 ). Results Samples with the -α 3.7 /-α 3.7 , -α 4.2 /-α 4.2 , -- SEA /αα, -- SEA /-α 3.7 , -- SEA /-α 4.2 , and -- SEA /-- SEA genotypes could be clearly distinguished. The accuracy of this technique for these samples was 100% sensitivity and specificity. Conclusion This technique is rapid and reliable, demonstrating feasibility for use in large-scale population screening and prenatal diagnosis of deletional Hb H disease and Hb Bart's hydrops fetalis. [ABSTRACT FROM AUTHOR]

• QST was used to evaluate the analgesic effects of tDCS in different brain regions. • M1-tDCS can effectively improve the efficiency of CPM in healthy individuals. • The role of DLPFC as a target for pain regulation deserves further exploration. Transcranial direct current stimulation (tDCS) is increasingly used in pain treatment. tDCS targeting both primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) may modulate the descending pain inhibitory system, however, it remains controversial regarding the optimal stimulation region for pain modulation. Therefore, this study aimed to explore the effects of high-definition anodic stimulation of M1 and DLPFC on conditioned pain modulation (CPM) and pain thresholds and establish a preferred stimulation setting. Twenty-six healthy adults were randomly assigned to M1-tDCS, DLPFC-tDCS, or sham-tDCS groups. During the three sessions, each participant received an active or sham stimulation of 2 mA for 20 min, with at least 3 days' interval between sessions. Quantitative sensory tests were performed to obtain pressure pain threshold (PPT), cold pain threshold (CPT), and CPM before and after the tDCS intervention. Only M1-tDCS significantly increased CPM in healthy individuals compared with sham control (P = 0.004). No statistically significant difference was found in PPT and CPT between tDCS vs. sham control (P > 0.05). Our findings further support the important role of M1 as a target in pain regulation. Further large-scale, multicenter studies in chronic pain populations are needed to validate the alterations of distinct target brain regions related to pain and thus for an optimal target stimulation strategy in pain management. [ABSTRACT FROM AUTHOR]

Bone pain is the primary problem for patients with osteoporosis. Ketoprofen is clinically used to treat osteoporotic pain, while long-term oral administration of ketoprofen can cause some side effects. In addition, osteoporosis is also accompanied by bone mass loss and inflammation. In this study, we designed a multifunctional drug (Ket@Mg-MOF-74) adopted Mg-MOF-74 to load ketoprofen to treat osteoporotic pain, bone loss and inflammation comprehensively. Mg-MOF-74 was prepared, and the physicochemical characterization proved that it had excellent physical and chemical stability. Ket@Mg-MOF-74 was synthesized by post-synthetic modification method and a high loading rate of ketoprofen was confirmed. Drug release and ion release experiments indicated Ket@Mg-MOF-74 had a good controlled release of ketoprofen and Mg in solution. Cell experiments in vitro proved the compound drug could significantly reduce the expression of pain-related genes of cyclooxygenase 2 (COX2), obviously up-regulated the expression of osteogenic cytokines and remarkably down-regulated the secretion of pro-inflammatory factors. Therefore, Ket@Mg-MOF-74 is believed a promising painkiller for osteoporotic bone pain, with the function of anti-inflammatory and promoting bone formation. • A new medicine Ket@Mg-MOF-74 based on Mg-MOF-74 and ketoprofen was developed. • Mg-MOF-74 not only acts as a drug carrier but exhibits certain biological effects in the new medicine. • The Ket@Mg-MOF-74 can relief pain, inhibit inflammation and promote bone growth. • The Ket@Mg-MOF-74 should effectively treat osteoporotic pain and osteoporosis. [ABSTRACT FROM AUTHOR]