Haisheng Huang , Fang Ji , Guobin Qi , Yuting Cao , Xuecheng He , Hao Wang , Zengxin Jiang
{"title":"Rehmannioside A promotes the osteoblastic differentiation of MC3T3-E1 cells via the PI3K/AKT signaling pathway and inhibits glucocorticoid-induced bone loss in vivo","authors":"Haisheng Huang , Fang Ji , Guobin Qi , Yuting Cao , Xuecheng He , Hao Wang , Zengxin Jiang","doi":"10.1016/j.jphs.2024.11.001","DOIUrl":"10.1016/j.jphs.2024.11.001","url":null,"abstract":"<div><div>Glucocorticoid-induced osteoporosis (GIOP) is a widespread disease characterized by low bone density. There remains a lack of effective means for osteoporosis. Rehmannioside A (ReA), an iridoid glycoside, exhibits various pharmacological activities. This study aimed to explore the role and mechanism of ReA in osteogenic differentiation of osteoblasts. Cell viability, reactive oxygen species (ROS) generation, and cell apoptosis were assessed using corresponding assay kits. Real-time quantitative polymerase chain reaction, Western blotting, and alkaline phosphatase (ALP) staining were performed to evaluate the osteogenic differentiation of MC3T3-E1 cells. Alizarin red S staining was used to assess the mineralization of MC3T3-E1 cells. Protein expression associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was analyzed using Western blotting. Micro-computed tomography, histopathological, and immunohistochemical analyses were performed to determine the therapeutic effect of ReA on GIOP <em>in vivo</em>.The results showed that ReA promoted the osteogenic differentiation of MC3T3-E1 cells by regulating the PI3K/AKT signaling pathway and protected mice against glucocorticoid-induced bone loss by promoting osteoblast-mediated bone formation <em>in vivo</em>. The findings of the current study revealed that ReA is a potential therapeutic agent for osteoporosis.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 247-257"},"PeriodicalIF":3.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663088","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}
Jozef Mažerik , Eduard Gondáš , Matúš Dohál , Lukáš Smieško , Marta Jošková , Soňa Fraňová , Martina Šutovská
{"title":"Targeting TMEM16A ion channels suppresses airway hyperreactivity, inflammation, and remodeling in an experimental Guinea pig asthma model","authors":"Jozef Mažerik , Eduard Gondáš , Matúš Dohál , Lukáš Smieško , Marta Jošková , Soňa Fraňová , Martina Šutovská","doi":"10.1016/j.jphs.2024.10.004","DOIUrl":"10.1016/j.jphs.2024.10.004","url":null,"abstract":"<div><div>Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, inflammation, and remodeling. Calcium (Ca<sup>2+</sup>)-activated chloride (Cl<sup>−</sup>) channels, such as TMEM16A, are inferred to be involved in asthma. Therefore, the present study investigated the therapeutic potential of TMEM16A inhibition in a guinea pig model of ovalbumin (OVA)-induced allergic asthma. Guinea pigs were treated with a specific blocker, CaCCinh-A01 (10 μM), administered via inhalation. A significant reduction in cough reflex sensitivity and specific airway resistance was observed in animals treated with CaCCinh-A01, highlighting its potential to improve airway function. Despite a reduction in ciliary beating frequency (CBF), CaCCinh-A01 reduced airway mucus viscosity by decreasing the production of mucin-5AC (MUC5AC). The nonspecific reduction in the Th1/Th2 cytokine spectrum following CaCCinh-A01 treatment indicated the suppression of airway inflammation. Additionally, markers associated with airway remodeling were diminished, suggesting that CaCCinh-A01 may counteract structural changes in airway tissues. Therefore, inhibition appears to mitigate the pathological aspects of asthma, including airway hyperresponsiveness, inflammation, and remodeling. However, further studies are required to comprehensively evaluate the potential of TMEM16A as a therapeutic target for asthma.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 239-246"},"PeriodicalIF":3.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552112","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":"Glucosylceramide synthase inhibitor ameliorates chronic inflammatory pain","authors":"Shun Watanabe , Misa Oyama , Takashi Iwai , Mitsuo Tanabe","doi":"10.1016/j.jphs.2024.10.003","DOIUrl":"10.1016/j.jphs.2024.10.003","url":null,"abstract":"<div><div>Gangliosides play pivotal roles in neuronal tissue processes, such as axonal elongation, synaptic transmission, and neuronal degeneration. Several studies have shown that mice injected with gangliosides synthesized from glucosylceramide exhibit mechanical allodynia. Thus, we hypothesized that glucosylceramide synthase inhibitors affect nociceptive behavior. We investigated the analgesic effect of intrathecal glucosylceramide inhibition on bilateral allodynia caused by prolonged unilateral hind paw inflammation in mice. Repeated administration of a glucosylceramide inhibitor reduced mechanical allodynia in both inflamed and non-inflamed hind paws. These results suggested that ganglioside reduction is critical for analgesia during inflammatory pain.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 235-238"},"PeriodicalIF":3.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528449","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":"Analgesic effect of Keishinieppiittokajutsubu on low barometric pressure-induced pain response in arthritic model rats","authors":"Yuki Kurauchi , Kana Inoue , Tomoka Kawakami , Manami Ueda , Tomoko Yamaguchi , Junji Akaki , Masahiko Komorisono , Hiroshi Katsuki","doi":"10.1016/j.jphs.2024.10.002","DOIUrl":"10.1016/j.jphs.2024.10.002","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a disease that causes inflammation of joints, resulting in pain and swelling. Reduced barometric pressure induces painful symptom of RA, but there is no appropriate animal model and pharmacological evaluation. Keishinieppiittokajutsubu (KNEIJB), a Kampo medicine used to treat RA; however, its mechanism of action is not clear. Here, we found that KNEIJB suppressed the low barometric pressure (LP)-induced pain response in CFA-induced arthritic model rats. Furthermore, we found that KNEIJB reduced plasma IL-6 levels. These results suggest that KNEIJB might be beneficial in the treatment of RA or some other arthralgia induced by LP.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 230-234"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438213","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":"TND1128, a 5-deazaflavin derivative with auto-redox ability, facilitates polarization of mitochondrial membrane potential (ΔΨm) and on-demand ATP synthesis in mice brain slices","authors":"Nanae Takahashi , Tomohisa Nagamatsu , Norio Akaike , Yoshihisa Kudo","doi":"10.1016/j.jphs.2024.10.001","DOIUrl":"10.1016/j.jphs.2024.10.001","url":null,"abstract":"<div><div>TND1128, a 5-deazaflavin derivative, is a drug with self-redox ability. We examined the effect of TND1128 on the level of mitochondrial membrane potential (ΔΨ<sub>m</sub>), which is the most critical motive power for the biosynthesis of ATP. We prepared brain slices from mice pretreated with TND1128 (0.1–10 mg/kg, intraperitoneally) and detected ΔΨ<sub>m</sub> level with JC-1, a fluorescence ΔΨ<sub>m</sub> indicator. We further examined the depolarization of ΔΨ<sub>m</sub> under 5-min exposure to 25 mM KCl-ACSF (25K-ACSF), which activated neuronal voltage-dependent Ca<sup>2+</sup> channels. We evaluated the effect of TND1128 by using the inverse number of the ΔΨ<sub>m</sub> value as the ATP synthesis index (ASI). The level of ΔΨ<sub>m</sub> increased significantly by 24-h pretreatment with TND1128 (10 mg/kg), and significantly higher depolarization of the ΔΨ<sub>m</sub> was observed with 25K-ACSF exposure than in non-treated control. We found a significant decrease in 25K-ACSF induced [Ca<sup>2+</sup>]<sub>c</sub> and [Ca<sup>2+</sup>]<sub>m</sub> levels in the TND1128-pretreated preparations. We confirmed the dose and time-dependent facilitatory effects of TND1128 on the ASI. This study suggested that TND1128 could be incorporated into the TCA cycle and electron transfer chains to facilitate the polarization of ΔΨ<sub>m</sub> and activate on-demand ATP synthesis. TND1128 might rescue neurons in various brain diseases caused by energy defects. (198)</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 218-229"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432368","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":"Involvement of Cav3.2 T-type Ca2+ channels and cystathionine-β-synthase in colitis-related visceral hypersensitivity in mice","authors":"Maho Tsubota , Yuriko Iba , Tsukasa Hatakeyama , Myu Honda , Yoshihito Kasanami , Fumiko Sekiguchi , Atsushi Kawase , Takuya Okada , Naoki Toyooka , Atsufumi Kawabata","doi":"10.1016/j.jphs.2024.09.003","DOIUrl":"10.1016/j.jphs.2024.09.003","url":null,"abstract":"<div><div>We tested the hypothesis that Ca<sub>v</sub>3.2 T-type Ca<sup>2+</sup> channels, which can be rebooted by sulfides from Zn<sup>2+</sup> inhibition under physiological conditions, and sulfide-generating enzymes including cystathionine-β-synthase (CBS) would participate in the colitis-related visceral pain in mice treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS). The visceral hypersensitivity following TNBS-induced colitis was abolished by an inhibitor or genetic deletion of Ca<sub>v</sub>3.2 and by a CBS inhibitor, and accompanied by CBS upregulation in the colon. Our data thus suggest that the enhanced activity of Ca<sub>v</sub>3.2 brought about by sulfides generated by upregulated CBS is involved in the colitis-related visceral hypersensitivity.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 209-213"},"PeriodicalIF":3.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000665/pdfft?md5=6b4df60c74f8375ac528d0445f540a97&pid=1-s2.0-S1347861324000665-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314430","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}
Shihu Men , Zaiqiang Yu , Xu Liu , Kazuyuki Daitoku , Mayuki Tachizaki , Shogo Kawaguchi , Tadaatsu Imaizumi , Masahito Minakawa , Kazuhiko Seya
{"title":"Role of CD34 in calcification of human aortic valve interstitial cells from patients with aortic valve stenosis","authors":"Shihu Men , Zaiqiang Yu , Xu Liu , Kazuyuki Daitoku , Mayuki Tachizaki , Shogo Kawaguchi , Tadaatsu Imaizumi , Masahito Minakawa , Kazuhiko Seya","doi":"10.1016/j.jphs.2024.09.002","DOIUrl":"10.1016/j.jphs.2024.09.002","url":null,"abstract":"<div><p>Various osteogenic factors are involved in ectopic human aortic valve calcification; however, the key cell species involved in calcification remains unclear. In a previous study, we reported that mesenchymal stem (CD73, 90, 105) and endothelial (VEGFR2) cell markers are positive in almost all human aortic valve interstitial cells (HAVICs) obtained from a patient with calcified aortic valve stenosis (CAVS). Further, CD34-negative HAVICs are highly sensitive to calcification stimulations. Here, we aimed to pathophysiologically clarify the role of CD34 in HAVICs obtained from individual patients with severe CAVS. A DNA microarray between CD34-positive and CD34-negative HAVICs, separated by fluorescence-activated cell sorting, indicated that tenascin X (TNX) mRNA expression significantly decreased in CD34-negative cells. Furthermore, the inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β significantly downregulated CD34 expression in HAVICs. TGF-β, a key cytokine of endothelial-mesenchymal transition, did not affect HAVIC calcification. CD34 overexpression strongly inhibited TNF-α- and IL-1β-induced calcification and maintained TNX mRNA expression. These results suggest one possibility that CD34 is an inhibitory regulator of valve calcification. Furthermore, TNF-α- and IL-1β-induced CD34 downregulation in HAVICs contributes to HAVIC calcification by downregulating TNX protein expression.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 198-207"},"PeriodicalIF":3.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000653/pdfft?md5=b79f6f3c23bb64cde0cdbebb1b3c1e17&pid=1-s2.0-S1347861324000653-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233063","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":"Evaluation of inhibitory actions of antidepressants on muscarinic receptors assessed by a binding assay in the mouse cerebral neocortex","authors":"Keisuke Obara, Yuki Usami, Risa Okamoto, Kento Yoshioka, Yoshio Tanaka","doi":"10.1016/j.jphs.2024.09.001","DOIUrl":"10.1016/j.jphs.2024.09.001","url":null,"abstract":"<div><div>We investigated the inhibitory effects of 32 antidepressants on [<sup>3</sup>H]<em>N</em>-methylscopolamine ([<sup>3</sup>H]NMS)-specific binding in the mouse cerebral neocortex to determine which antidepressants should be recommended for patients with Alzheimer's disease (AD). Of those tested, nine antidepressants (10<sup>−4</sup> M) exhibited less inhibitory effect on [<sup>3</sup>H]NMS-specific binding (<35%): tianeptine (a tricyclic); trazodone (a serotonin 5-HT<sub>2A</sub> blocker); sulpiride (a dopamine D<sub>2</sub> blocker); fluvoxamine (a selective serotonin reuptake inhibitor (RI)); milnacipran, levomilnacipran, venlafaxine, and desvenlafaxine (serotonin and noradrenaline RIs); and bupropion (a noradrenaline and dopamine RI). Therefore, these antidepressants show little anticholinergic effect in the brain and are recommended for use in patients with AD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 214-217"},"PeriodicalIF":3.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425178","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}
Zhihang Zhang , Yalan Luo , Xijing Zhuang , Haifeng Gao , Qi Yang , Hailong Chen
{"title":"Emodin alleviates lung injury via the miR-217-5p/Sirt1 axis in rats with severe acute pancreatitis","authors":"Zhihang Zhang , Yalan Luo , Xijing Zhuang , Haifeng Gao , Qi Yang , Hailong Chen","doi":"10.1016/j.jphs.2024.08.007","DOIUrl":"10.1016/j.jphs.2024.08.007","url":null,"abstract":"<div><p>Acute lung injury (ALI) is closely related to high mortality in severe acute pancreatitis (SAP). This study unveils the therapeutic effect and mechanism of miR-217-5p on SAP-associated ALI. The miR-217-5p RNA expression was significantly up-regulated in lipopolysaccharide (LPS)-stimulated primary rat alveolar epithelial type II cells (AEC II) and sodium taurocholate-treated pancreas and lung in SAP rats. miR-217 inhibition protected AEC II from LPS-induced damage by inhibiting apoptosis and reducing the TNF-α, IL-6, and ROS levels. miR-217 inhibition suppressed apoptosis and alleviated mitochondrial damage through mitochondria-mediated apoptotic pathway <em>in vitro</em>. Sirt1 is a direct target of miR-217-5p. Dual-luciferase reporter assay confirmed the binding of miR-217-5p to Sirt1 mRNA 3′-UTR. The rescue experiment identified that the anti-apoptotic, anti-inflammatory, and anti-oxidative effects of miR-217 inhibition were mediated by Sirt1 <em>in vitro</em>. Emodin (EMO) protected AEC II from LPS-induced damage and alleviated pancreatic and lung tissue injuries. EMO exerted similar effects as miR-217 inhibition <em>in vitro</em> and <em>in vivo</em>. The effects of EMO were abolished by miR-217 overexpression. In conclusion, miR-217-5p inhibition exerts protective effects on SAP-ALI <em>in vitro</em> and <em>in vivo</em> by repressing apoptosis, inflammation, and oxidative stress through Sirt1 activation. EMO protects against lung injuries in SAP-associated ALI rats through miR-217-5p/Sirt1 axis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 188-197"},"PeriodicalIF":3.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400063X/pdfft?md5=3d53035ef4c6f969c6fe0d4f04792bd1&pid=1-s2.0-S134786132400063X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167512","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":"Effect of antiemetics on zolbetuximab-induced gastric injury and emesis in ferrets","authors":"Fumitaka Kinugasa , Satoru Kajikawa , Jane Weng , Tohru Ugawa , Hiroshi Fushiki , Yosuke Yamanaka , Masanori Nagata , Gillian Haggerty , Shinobu Akuzawa , Taisuke Nakazawa , Hiroshi Suzuki , Taiji Sawamoto","doi":"10.1016/j.jphs.2024.08.005","DOIUrl":"10.1016/j.jphs.2024.08.005","url":null,"abstract":"<div><p>Claudin-18 splice variant 2 (CLDN18.2), a tight junction protein, is a highly cell type–specific antigen that is expressed by differentiated gastric mucosa cells. The expression of CLDN18.2 in gastric mucosa cells may be retained upon malignant transformation and is displayed on the surface of several tumors, including gastric/gastroesophageal junction adenocarcinoma. Zolbetuximab is a genetically engineered, highly purified chimeric (mouse/human IgG1) antibody directed against CLDN18.2. Nausea and vomiting were observed as adverse events of zolbetuximab. To investigate the mechanism of nausea and vomiting in humans, we evaluated emesis (retching and vomiting) and conducted histopathologic assessment in ferrets after the administration of zolbetuximab. Emesis was frequently observed in all ferrets treated with zolbetuximab in the first hour after administration. Histopathologic assessment revealed the surface of the gastric mucosa was the primary site of emesis-associated tissue damage. The effect of antiemetics (dexamethasone, ondansetron, fosaprepitant, and olanzapine) on emesis induced by zolbetuximab was investigated. Fosaprepitant showed suppressive effects on emesis, and use of dexamethasone or concomitant use of fosaprepitant with other antiemetics tended to alleviate gastric tissue damage. The onset of emesis in humans receiving zolbetuximab may be associated with damage in the gastric mucosa, and antiemetics may mitigate gastrointestinal adverse events.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 3","pages":"Pages 161-170"},"PeriodicalIF":3.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000616/pdfft?md5=9b59c0d1648aac137bdf955240f12ad2&pid=1-s2.0-S1347861324000616-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076865","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}