Molecular Pain最新文献

{"title":"Advanced cancer perineural invasion induces profound peripheral neuronal plasticity, pain, and somatosensory mechanical deactivation, unmitigated by the lack of TNFR1. Part. 1: Behavior and single-cell in vivo electrophysiology.","authors":"Silvia Gutierrez, Renee A Parker, Morgan Zhang, Maria Daniela Santi, Yi Ye, M Danilo Boada","doi":"10.1177/17448069251314738","DOIUrl":"10.1177/17448069251314738","url":null,"abstract":"<p><p>Patients with cancer perineural invasion (PNI) report greater spontaneous pain and mechanical allodynia. Here, we examine the impact of the disease on the peripheral sensory system, the excitability changes induced by PNI at the dorsal root ganglia, and the potential protective role of the absence of Tumor Necrosis Factor-α Receptor 1 (TNFR1). To study these effects, we use a murine model generated by injecting mouse oral cancer squamous cell carcinoma (MOC2) into the sciatic nerve (MOC2-PNI) in both male and female mice. We found that MOC2-PNI induces a profound change in the somatosensory landscape by deactivating/blocking the peripheral inputs while modulating the afferent's sensibility (tactile desensitization with concurrent nociceptive sensitization) and demyelination without inducing spontaneous activity. All these changes caused by MOC2-PNI are unmitigated by the absence of TNFR1. We conclude that MOC2-PNI induces an aberrant neuronal excitability state and triggers extreme gender-specific neuronal plasticity. These data allow us to speculate on the role of such plasticity as a powerful defense mechanism to prevent terminal sensory dysfunction, the rise of chronic pain, and extend animals' survivability.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251314738"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss and damage in large-diameter sensory neurons in the db/db diabetic mouse.","authors":"Reham M Filfilan, Mohammed A Nassar","doi":"10.1177/17448069251328521","DOIUrl":"10.1177/17448069251328521","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. Half of DPN patients experience sensory deficits including loss of sensation and pain. Loss of sensation increases the risk of unnoticed foot injuries which combined with poor circulation and healing lead to amputation. Type 2 diabetes accounts for 50% of foot amputation highlighting the significant impact sensory loss can have on patients' quality of life. However, the cellular basis underlying sensory loss in DPN remains unclear. We characterized diabetes-induced neuronal loss and damage in dorsal root ganglia (DRG) in the db/db mouse model of type 2 diabetes. Morphometric characterization was carried out on two neuronal populations in lumbar DRGs of 32-week diabetic (db/db) mice. These are the N200-positive neurons, a marker for low and high-threshold mechanosensitive sensory and proprioceptive neurons, and peripherin (PRPH)-positive neurons, a marker for pain sensing neurons. In diabetic mice, N200-positive neurons were reduced by 30%. Furthermore, diabetes increased the percentage of N200-positive neurons with cytoplasmic vacuoles, a sign of damage and stress, by 2.44 fold. In addition, the average number of vacuoles was 1.6 fold higher in diabetic mice. Therapies aimed at reducing this loss could help patients better protect their limbs from injuries and thus reduce amputations.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251328521"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM14-NF-κB pathway in the anterior cingulate cortex modulates comorbid depressive symptoms in chronic pain.","authors":"Jia-Hao Dai, Zhen-Hua Xu, Qiu-Lan Li, Jie Huang, Zheng Niu, Chen-Hao Zhang, Shufen Hu, Ren Sun, Yong-Chang Li","doi":"10.1177/17448069251335503","DOIUrl":"10.1177/17448069251335503","url":null,"abstract":"<p><p>Depression is commonly observed in individuals suffering from chronic pain, but the exact molecular mechanisms behind these symptoms are still not fully understood. This study highlights the important role of the TRIM14-NF-κB pathway in the anterior cingulate cortex (ACC) in regulating comorbid depressive symptoms associated with chronic pain. Our results show that the CFA model induces both chronic pain and depression-like behaviors in mice, with significant activation of the ACC brain regions. Specifically, the protein expression of TRIM14 was notably elevated in the ACC of CFA mice. Furthermore, reducing TRIM14 expression alleviated both chronic pain and depression-like behaviors in these mice. In addition, we also discovered that NF-κB may act as a downstream target of TRIM14, as silencing TRIM14 expression led to a reduction in the levels of phosphorylated NF-κB. Notably, inhibiting NF-κB produced similar improvements in chronic pain and depression-like behaviors, mirroring the effects observed with TRIM14 knockdown. In summary, our findings emphasize the critical role of the TRIM14-NF-κB pathway in regulating chronic pain and depression-like behaviors in the CFA mouse model. These insights provide a foundation for further exploration of the molecular mechanisms underlying chronic pain and depression, and may guide the development of targeted therapeutic strategies.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251335503"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring novel non-opioid pathways and therapeutics for pain modulation.","authors":"Isabella Alessi, Kaysie L Banton, Sliter J, Zaw-Mon C, Palacio Ch, Ryznar Rj, Bar-Or D","doi":"10.1177/17448069251327840","DOIUrl":"10.1177/17448069251327840","url":null,"abstract":"<p><p>The opioid crisis has highlighted the urgent need for alternative pain management strategies. This review explores novel non-opioid targets and pathways involved in pain modulation, highlighting advancements in understanding and therapeutic potential. Pain, a multifaceted phenomenon with nociceptive, neuropathic, and inflammatory components, involves intricate molecular signaling cascades. Key pathways reviewed include voltage-gated sodium channels (Nav1.7, Nav1.8, Nav1.9), inflammasome complexes (NLRP3), the kynurenine pathway, prostaglandins, and bradykinin-mediated signaling. Emerging therapeutics such as selective Nav channel blockers, NLRP3 inhibitors, kynurenine pathway modulators, EP receptor antagonists, and bradykinin receptor antagonists offer promising alternatives to opioids. Despite challenges in clinical translation, these developments signal a paradigm shift in pain management, with precision-focused therapies poised to address unmet needs. This review emphasizes the importance of integrating molecular insights into the development of safer, more effective analgesics, setting the stage for transformative advancements in non-opioid pain relief.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251327840"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the PVN^Glu-PrL^Glu circuit: A new frontier in chronic pain management for lumbar disc herniation.","authors":"Qianliang Wang, Jianpeng Chen, Kang Jia, Yujian Peng, Yuanbin Wang, Qianqian Chen, Jun Yan","doi":"10.1177/17448069251342984","DOIUrl":"10.1177/17448069251342984","url":null,"abstract":"<p><p>Lumbar disc herniation (LDH) refers to a pathological state in which the nucleus pulposus (NP) protrudes, leading to compression or irritation of nerve roots. This condition manifests with clinical symptoms including lower back and leg pain, hyperalgesia, and altered sensory perceptions. Depending upon clinical observations, the administration of centrally acting analgesic has been associated with the alleviation of pain symptoms LDH patients. The central nervous system sensitization performs a crucial role in pain-regulating perception in LDH. Nevertheless, the precise neural circuitry and mechanism of action remain enigmatic. In the present study, we observed the activation of glutamatergic neurons in the Paraventricular nucleus of the hypothalamus (PVN) and Prelimbic cortex (PrL) in LDH rats. Experimental validation using viral tracers confirmed the existence of a projection pathway between the PVN and PrL. Inhibition of the input from PVN glutamatergic neurons to PrL glutamatergic neurons alleviates chronic pain in LDH, whereas activation of the PVN^Glu-PrL^Glu projection induces chronic pain in rats. These findings imply a pivotal role for the PVN^Glu-PrL^Glu circuit in the regulation of chronic pain in LDH.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251342984"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative reactive oxygen species exacerbate postoperative hyperalgesia by aggravating neuroinflammation through galectin-3.","authors":"Xuemei Zheng, Bin Shu, Ai Yan, Yonggang Liang, Niannian Huang, Houping Wang, Weilong Hong, Yongqin Chen, He Huang, Guangyou Duan","doi":"10.1177/17448069251353026","DOIUrl":"10.1177/17448069251353026","url":null,"abstract":"<p><p>Patients with preoperative pathological conditions such as anxiety, depression, and sleep disorders experience more severe postoperative pain, suggesting that preoperative pathological changes in patients may affect postoperative pain. However, the potential pathophysiological changes associated with postoperative pain remain unknown. Here, this study initially employed clinical research to investigate potential pathophysiological changes related to postoperative pain. Subsequently, animal behavioral experiments and mechanistic explorations were conducted accordingly. Pregnant women undergoing cesarean sections who could provide preoperative cerebrospinal fluid were selected as subjects. Preoperative cerebrospinal fluid proteomics, postoperative pain intensity, and neutrophil-to-lymphocyte ratio (NLR) were analyzed. Rats were used to model the corresponding preoperative pathological state. Mechanical pain thresholds were measured after plantar incision and spinal cords were harvested for analysis. Clinical studies showed that one-quarter of the proteins positively correlated with postoperative pain were related to reactive oxygen species (ROS). Furthermore, the NLR-Ratio, reflecting postoperative inflammation level, increased with the severity of postoperative pain. Establishing a preoperative ROS-increased model with oxidant t-BOOH enhanced postoperative acute mechanical hyperalgesia and spinal neuroinflammation in rats. Conversely, preoperative administration of antioxidant VE, reducing ROS, alleviated postoperative hyperalgesia and spinal neuroinflammation. galectin-3 inhibitors mitigated postoperative hyperalgesia and neuroinflammation in the preoperative ROS-increased model. Additionally, The effects of galectin-3 on pain sensitization and pro-inflammation in vitro were mediated by the TLR4 receptor. Thus, this study demonstrated that preoperative ROS exacerbated postoperative hyperalgesia via galectin-3-mediated neuroinflammation, suggesting that galectin-3 may be a potential therapeutic target for alleviating postoperative pain in clinical patients.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251353026"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGK1-HDAC4-HMGB1 signaling pathway in the spinal cord dorsal horn participates in diabetic neuropathic pain.","authors":"Mao-Biao Zhang, Jia-Li Chen, Jia-Hui Lu, Gai-Li Jia, Hong Cao, Jun Li","doi":"10.1177/17448069251321143","DOIUrl":"10.1177/17448069251321143","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to determine whether serum-and glucocorticoid-inducible kinase1 (SGK1) activation-dependent histone deacetylase 4 (HDAC4) phosphorylation, nucleocytoplasmic trafficking, and subsequent regulation of high-mobility group protein box 1 (HMGB1) expression are involved in type 2 diabetic neuropathic pain (DNP).</p><p><strong>Methods: </strong>The type 2 diabetic neuropathic pain model was established in rats by feeding them with a high-fat and high-sugar diet for 8 weeks and then fasting them for 12 h, followed by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). SGK1 was inhibited in the spinal cord by intrathecal administration of the SGK1 inhibitor GSK-650394.</p><p><strong>Results: </strong>The present study revealed that pSGK1/tSGK1 was persistently upregulated in the spinal cord of rats with type-2 DNP. The downregulation of pSGK1/tSGK1 through the intrathecal injection of the SGK1 inhibitor GSK-650394 significantly ameliorated the pain hypersensitivity, relieved the abnormal expression of pHDAC4/tHDAC4 and HMGB1, and affected HDAC4 nucleocytoplasmic trafficking in DNP rats.</p><p><strong>Conclusion: </strong>Our data suggest that SGK1 in the spinal cord modulates type-2 DNP by regulating the HDAC4/HMGB1 pathway.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251321143"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture intervention relieves pain by stimulating the STING/IFN-I pathway in rat models of cancer-induced bone pain.","authors":"Yi-Ming Gu, Xiang Meng, Jia-Yi Liang, Yong Xia, Jun-Wei Huang, Ke Wang, Zi-Yong Ju","doi":"10.1177/17448069251342240","DOIUrl":"10.1177/17448069251342240","url":null,"abstract":"<p><p>This study aimed to evaluate the effects of electroacupuncture (EA) on cancer-induced bone pain (CIBP) and investigate its interaction with the STING/IFN-I pathway. A CIBP model was established in female rats. EA was administered for six consecutive days at bilateral L3-L5 Jia Ji points (EX-B2). EA-induced antinociception was evaluated through mechanical, thermal, and cold sensitivity assessments. EA significantly increased the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in rats with CIBP (<i>p</i> < 0.01). In the spinal cord of CIBP model rats, western blot analysis demonstrated that the application of EA upregulated the expression of STING, IRF3, and IFNAR (<i>p</i> < 0.05). The ELISA results indicated that EA significantly increased the expression of IFN-α (<i>p</i> < 0.005) and IFN-β (<i>p</i> < 0.01) and reduced the expression of TNF-α and IL-1β (<i>p</i> < 0.05). Immunofluorescence analysis revealed that STING was predominantly localized in microglia, with a minimal presence in neuronal cells. Furthermore, intrathecal administration of the STING antagonist C-176 attenuated the analgesic effects of EA in CIBP (<i>p</i> < 0.05). Both EA and STING agonist were effective in alleviating pain in rats with CIBP, possibly through the activation of the STING/IFN-I pathway. Notably, EA treatment reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. In contrast, while the STING agonist exhibited analgesic effects, it was associated with elevated levels of pro-inflammatory cytokines. These finding underscore the therapeutic potential of EA in the management of CIBP.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251342240"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study identifies novel genetic variants associated with widespread pain in the UK Biobank (<i>N</i> = 172,230).","authors":"Qi Pan, Tengda Cai, Yiwen Tao, Luning Yang, Roger Compte, Maryam Kazemi Naeini, Mainul Haque, Tania Dottorini, Frances Mk Williams, Weihua Meng","doi":"10.1177/17448069251346603","DOIUrl":"10.1177/17448069251346603","url":null,"abstract":"<p><strong>Objectives: </strong>Widespread pain is a hallmark characteristic of fibromyalgia, commonly affecting older individuals. This study aimed to identify novel genetic variants associated with widespread pain by utilizing the extensive UK Biobank dataset.</p><p><strong>Methods: </strong>We conducted a primary genome-wide association study (GWAS) using a novel definition of widespread pain, defined as pain experienced all over the body during the past month. Sex-stratified GWAS analysis approach was also performed to analyze the impact of sex on widespread pain.</p><p><strong>Results: </strong>The primary GWAS identified one novel significant genetic locus (rs34691025, <i>p</i> = 1.76 × 10^-8) on chromosome 5q13.2 within the <i>ARHGEF28</i> gene and several loci that approached genome-wide significance. The sex-stratified GWAS outputs revealed biological difference widespread pain between males and females, with a novel locus identified in the female-specific analysis within the <i>LRMDA</i> gene on chromosome 10. Genetic Correlation analysis demonstrated significant genetic correlations between widespread pain and other phenotypes, including joint disorders and spondylosis. The PheWAS revealed associations between the significant genetic variants with hearing disorders and cardiovascular diseases. A two-sample Mendelian randomization analysis found no significant causal association between hearing loss and widespread pain.</p><p><strong>Conclusions: </strong>Our study advances the understanding of the genetic factors contributing to widespread pain, highlighting notable differences between males and females and identifying a novel genetic locus associated with this condition.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"21 ","pages":"17448069251346603"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of excitatory synaptic transmission in the retrosplenial cortex of adult mice.","authors":"Jinjin Wan, Yujie Ma, Xuanying Chen, Wucheng Tao, Shun Hao, Wujun Geng, Yili Wu, Min Zhuo","doi":"10.1177/17448069251335500","DOIUrl":"10.1177/17448069251335500","url":null,"abstract":"<p><p>The retrosplenial cortex (RSC) plays an important role in navigation, memory and pain. However, there are few studies on excitatory synaptic transmission in the RSC. Here, we used a multi-electrode array recording system (MED64) to study the characteristics of excitatory synaptic transmission in the RSC and the contribution of different types of voltage-gated Ca²⁺ channels (VGCCs) in excitatory synaptic transmission. We found that glutamate is the major excitatory transmitter for RSC, and postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors contribute to excitatory synaptic transmission. We also found that the N-type calcium channel blocker ω-conotoxin GVIA (ω-Ctx GVIA) had an inhibitory effect on basal synaptic transmission. The inhibitory effect was not consistent across channels, suggesting the actions effect of N-type VGCCs in RSC was inhomogeneous in spatial distribution. Our findings provide strong evidence that excitatory synaptic transmission in the RSC is mainly mediated by AMPA receptors and that N-type VGCCs mediate fast synaptic transmission in the RSC of adult mice.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251335500"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}