Frontiers in Pharmacology
·
2024
·
IF 4.4
Dalin Sun,Dong Xing,Dandan Wang,Yuanyuan Liu,Bin Cai,Weimin Deng,Qinglin Hu,Wenjun Ma,Baofang Jin
Background: Chronic non-bacterial prostatitis (CNP), one of the most common chronic diseases in urology, leads to pain in the prostate and dysuria, critically affecting the physical or mental health of patients. However, there are no standard treatment approaches for the treatment of CNP in the clinic. Although the clinical application of Bushen Daozhuo granule (BSDZG) offers hope to CNP patients in China, the mechanisms of BSDZG in treating CNP are still not entirely clear. Hence, we aimed to investigate the novel therapeutic mechanisms of BSDZG on CNP. Methods: In this study, we first assayed the prostate index of rats and then determined the anti-inflammatory and anti-apoptotic effects of BSDZG on CNP in vivo and in vitro by employing ELISA kits and TUNEL staining. Next, we investigated whether the anti-inflammatory and anti-apoptotic mechanisms of BSDZG on prostate protein-induced rats and lipopolysaccharide (LPS) induced RWPE-1 cells were related to the AKT, p38 MAPK, and NF-κB pathways with the help of Western blot. Finally, the influence of BSDZG on the interaction between the p38 MAPK and NF-κB pathway in LPS-induced RWPE-1 cells was explored by adopting dehydrocorydaline (DHC, p38 MAPK activator) with the help of ELISA kits and Western blot. Results: In vivo , BSDZG effectively reduced the prostate index. In vivo and in vitro , BSDZG dramatically declined the level of two pro-inflammatory cytokines, TNF-α and IL-1β, as well as the apoptosis rate. Moreover, in vivo and in vitro , BSDZG memorably upregulated the expression level of p-AKT, and substantially downregulated the expression level of p-p38 MAPK and NF-κB2. The activation of p38 MAPK significantly reversed the moderation effects of BSDZG on the level of TNF-α and IL-1β, as well as the expression level of p-p38 MAPK and NF-κB2 in vitro . Conclusion: To sum up, the in vivo and in vitro therapeutic mechanisms of BSDZG on CNP were reflected as the anti-inflammation and anti-apoptosis that was formed by inhibiting the level of pro-inflammatory cytokines, TNF-α and IL-1β, to regulate the AKT, p38 MAPK, and NF-κB pathways, and the anti-inflammatory effect of BSDZG was realized by suppressing the p38 MAPK pathway to inhibit the downstream NF-κB pathway.
研究领域:
泌尿外科
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药理学
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分子生物学
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炎症研究
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2018
·
IF 3.04
Yulong Kong,Xiaoguang Gao,Changyuan Wang,Chenqing Ning,Kexin Liu,Zhihao Liu,Huijun Sun,Xiaodong Ma,Pengyuan Sun,Qiang Meng
Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin , a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice. Serum biomarkers and H&E staining were used to identify the amelioration of cholestasis after yangonin treatment. Mice hepatocytes culture, gene silencing experiment, real-time PCR and Western blot assay were used to elucidate the mechanisms underlying yangonin hepatoprotection . The results indicated that yangonin promoted bile acid efflux and reduced hepatic uptake via an induction in FXR-target genes Bsep , Mrp2 expression and an inhibition in Ntcp , all of which are responsible for bile acid transport. Furthermore, yangonin reduced bile acid synthesis through repressing FXR-target genes Cyp7a1 and Cyp8b1, and increased bile acid metabolism through an induction in gene expression of Sult2a1, which are involved in bile acid synthesis and metabolism. In addition, yangonin suppressed liver inflammation through repressing inflammation-related gene NF-κB, TNF-α and IL-1β. In vitro evidences showed that the changes in transporters and enzymes induced by yangonin were abrogated when FXR was silenced. In conclusions, yangonin produces protective effect against LCA-induced hepatotoxity and cholestasis due to FXR-mediated regulation. Yangonin may be an effective approach for the prevention against cholestatic liver diseases.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Yanfang Li,Ming Li,Jiaping Liu,Wenhao Zheng,Yaqiong Zhang,Tongcheng Xu,Boyan Gao,Liangli Yu
The profiles of soluble and insoluble phenolic compounds in 11 commercial red sorghums (B11, B12, B13, B14, J124, J127, J138, J140, J142, J152, and J158) were investigated using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) analysis. A total of 48 phenolic compounds including 35 phenolic acids and their derivatives, 12 flavonoids, and 1 proanthocyanidin were identified, and 8 phenolic compounds were reported for the first time in sorghums. Four major 3-deoxyanthocyanidins were also quantified, with their soluble forms accounting for 99.75–99.87% of the total contents. Pearson’s correlation analyses indicated that 3-deoxyanthocyanidins significantly contributed to the antioxidant capacities of the red sorghums and that 5-methoxy-luteolinidin showed the strongest correlation. Besides, the soluble phenolic fraction of B13 dose-dependently inhibited the proliferation of Caco-2 cells and the secretion of IL-1β and NO in RAW264.7 macrophages, which might be attributed to its relatively high total phenolic (TPC), flavonoid (TFC), and proanthocyanidin content (TPAC) values and radical scavenging capacities.
研究领域:
食品科学
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营养学
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药理学
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分析化学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
·
IF 6.1
Qiaoqiao Luo,Pengfei Gong,Ruoyu Shi,Wei Chen,Chengtao Wang,Chan Zhang,Zhe Wu
Inflammatory bowel disease is known to be associated with alterations in gut microbiota. The bioactive compound syringic acid has been shown to alleviate inflammatory bowel disease, but its interaction with gut microbiota and mechanism of action remain unclear. To address this, we conducted a study in which we investigated the potential benefits of syringic acid in a mouse model of dextran sulfate sodium-induced colitis through gut microbiota modulation. Our results show that oral administration of syringic acid effectively reduced symptoms of colitis, as indicated by reduced disease activity index, and histopathology scores. Moreover, syringic acid administration enriched the abundance of Alistipes and norank_f__norank_o__Gastranaerophilales in mice, suggesting a restoration of impaired gut microbiota. Notably, we found that the effects of syringic acid were similar to those of fecal microbiota transplantation in dextran sulfate sodium-induced mice. Further analysis revealed that syringic acid inhibited the NLRP3-Cas-1-GSDMD-IL-1β inflammatory vesicle signaling pathway, leading to amelioration of colonic inflammation in a gut microbiota-dependent manner. Our findings demonstrate the potential of syringic acid as a preventive and therapeutic agent for inflammatory bowel disease.
研究领域:
胃肠病学
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免疫学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-11
·
IF 4.6
Lan Xiang,Qi Dongdong,Ren Hao,Liu Tao,Shao Hong,Zhang Jiantao
Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. We isolated and cultured cow lamellar keratinocytes using the Dispase II and collagenase methods. We purified them by differential digestion and differential velocity adherent methods at each passaging and identified them by keratin 14 immunofluorescence. We established an in vitro model of inflammation in laminar keratinocytes using LPS and investigated whether chicoric acid protects against inflammatory responses by inhibiting the activation of the TLR4/MAPK/NF-κB signaling pathway. The results showed that cow lamellar keratinocytes were successfully isolated and cultured by Dispase II combined with the collagenase method. In the in vitro inflammation model established by LPS, the Chicoric acid decreased the concentration of inflammatory mediators (TNF-α, IL-1β, and IL-6), down-regulated the mRNA expression of TLR4 and MyD88 (P < 0.01), down-regulated the expression of TLR4, MyD88, p-ERK, p-p38, IKKβ, p-p65, p-p50 (P < 0.05), and increased the IκBα protein expression (P < 0.05). In conclusion, Chicoric acid successfully protected cow lamellar keratinocytes from LPS-induced inflammatory responses by modulating the TLR4/MAPK/NF-κB signaling pathway and downregulating inflammatory mediators.
研究领域:
兽医学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
RSC Medicinal Chemistry
·
2024
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IF 4.1
Die Zhang,Wenping Wang,Huiping Ou,Jinhua Ning,Yingxun Zhou,Jin Ke,Anguo Hou,Lingyun Chen,Peng Li,Yunshu Ma,Wenbin Jin
To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of novel chalcone analogues were designed and synthesized. In vitro anti-inflammatory activity of these compounds has been evaluated by screening inhibitory effects of the NO production in RAW264.7 cell lines. The most promising compounds 3h and 3l were selected to further investigated by assessment of their dose-dependent inhibitory activity against cytokines such as TNF-α, IL-1β, IL-6, and PGE2 release. The further study also indicated that 3h and 3l could significantly suppress expressions of iNOS and COX-2 through NF-κB/JNK signaling pathway. Furthermore, compounds 3h and 3l could also remarkably inhibit the mRNAs expressions of inflammation-related genes. Docking simulation was conducted to position compounds 3h and 3l into the iNOS binding site to predict the probable binding mode. In conclusion, a series of chalcone analogues with reasonable drug-likeness obtained by in silico rapid prediction could be used as promising lead candidates.
研究领域:
药理学
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炎症研究
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药物发现
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2020
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IF 4.96
Junke Song,Li Zhang,Yanfeng Xu,Dezhi Yang,Li Zhang,Shiying Yang,Wen Zhang,Jinhua Wang,Shuo Tian,Shengqian Yang,Tianyi Yuan,Ailin Liu,Qi Lv,Fengdi Li,Hongqi Liu,Biyu Hou,Xiaozhong Peng,Yang Lu,Guanhua Du
Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 μM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form β of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1β and TNF-α in serum. In conclusion, oral administration of crystal form β of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.
研究领域:
药理学
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病毒学
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免疫学
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治疗学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
·
2019
·Vol. 127
·期 6
·1716-1726
·
IF 2.683
Cheng R.,Wang L.,Li J.,Fu R.,Wang S.,Zhang J.
AimsTo purify and characterize an exopolysaccharide (EPS) from an Agrobacterium strain ZCC3656 with high EPS‐secreting performance and investigate its anti‐inflammatory activity using lipopolysaccharide (LPS)‐induced macrophage cells in an acute liver injury mouse model.Methods and ResultsTwelve rhizobial strains were compared for EPS fermentation production in modified M9 salts supplemented with mannitol or sucrose as the sole carbon source. Agrobacterium sp. ZCC3656 exhibited the highest EPS yield (21·1 g l−1) and was characterized for EPS production by carbon source utilization, time course fermentation and serial subcultivation assays. The EPS, designated Riclin, was purified by deproteinization using the Sevag method. The combined results of gel permeation chromatography, monosaccharide composition, methylation analysis and nuclear magnetic resonance analyses indicated that Riclin is a succinoglycan‐like polysaccharide comprised of glucose, galactose, succinate and pyruvate at a ratio of 7·8. : 1·0 : 0·9 : 1·1 and has an molecular weight of approximately 2·5 × 106 Da. Riclin inhibited TNF‐α, IL‐1β and IL‐6 expression in LPS‐stimulated RAW 264.7 macrophage cells in a dose‐dependent manner. In addition, Riclin pretreatment increased the survival rate of D‐Gal/LPS treated mice, inhibited serum ALT and AST activities and reduced the production of the inflammatory mediators TNF‐α, IL‐1β and IL‐6.ConclusionsAgrobacterium sp. ZCC3656 is a highly stable EPS‐producing strain. The EPS Riclin from ZCC3656 is a succinoglycan‐type polysaccharide that is noncytotoxic and exhibits remarkable anti‐inflammatory effects in vivo and in vitro.Significance and Impact of the StudySuccinoglycans are well known for good rheological properties and their physiological interactions with plants. However, their potential activity towards mammals has received little attention. Our study revealed that the succinoglycan Riclin exhibited excellent anti‐inflammatory activities and could be considered as a promising reagent in anti‐inflammatory treatment.
研究领域:
微生物学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
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IF 5.3
Yongze Liu,Lei He,Dingding Liu,Xuefeng Jiang,Feng Chen,Xiaofeng Ma,Saijie Song,Jun Zhang,Jian Shen,Xia Gao
Acute rhinosinusitis is among the most prevalent disease across the world. Recently, researchers have found that traditional Chinese medicine (TCM) can effectively treat acute rhinosinusitis. Nanomaterial-based drug delivery systems (DDSs) have attracted widespread attention in disease treatment. In this work, we herein reported curcumin-loading black phosphorus nanosheet (BP-C@PEG) nanodrugs for acute rhinosinusitis therapy. The as-prepared BP-C@PEG showed excellent solubility and stability in aqueous solution and performed sustained release behavior. In addition, it also exhibited good anti-inflammatory action for the treatment of acute rhinosinusitis. The anti-inflammation mechanism of BP-C@PEG was also studied. We found that LPS-induced inflammation in nasal epithelial cells was eased through downregulating HDAC3 and NLRP3 inflammasomes and lowering IL-1β levels. Moreover, the in vivo experiments verified that BP-C@PEG could effectively alleviate the cilium injury and the recruitment of inflammatory cells in the nasal mucosa of mice, further demonstrating its promising therapeutic efficiency in acute rhinosinusitis. Overall, this study provides a potential approach for acute rhinosinusitis therapy by using BP-C@PEG nanodrugs, which may broaden the application of TCM in the biomedical field.
研究领域:
药学
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纳米技术
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中医药
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炎症研究
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产品关联
DOI
高影响因子
Tissue Engineering and Regenerative Medicine
·
2021
·Vol. 18
·期 1
·113-125
·
IF 4.169
Mou Donggang,Yu Qunying,Zhang Jimei,Zhou Jianping,Li Xinmin,Zhuang Weiyi,Yang Xuming
Background: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment. Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of long-term maintenance of efficacy. Methods: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N -carboxyethyl chitosan ( N -chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD). Results: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-α, IL-1β, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. Conclusion: This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.
研究领域:
骨科
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生物材料
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药理学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Ying Lu,Dan Xu,Jingyao Liu,Lina Gu
Sophocarpine (SOP) is a tetracyclic quinolizidine alkaloid isolated from Sophora alopecuroides L. A number of studies have shown that SOP has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The purpose of this study was to investigate the protective effects of SOP on LPS-induced acute lung injury (ALI) in mice. Lung histological alterations, edema, and MPO activity were measured in this study. Furthermore, the production of inflammatory cytokines and the expression of NF-κB and MAPKs signaling pathways were measured. The results showed that the LPS-induced lung histological alterations, edema, protein concentration, inflammatory cell level in BALF, MDA content, and MPO activity were significantly attenuated by SOP. The LPS-induced inflammatory cytokine TNF-α, IL-1β, and IL-6 were also inhibited by SOP. SOP also inhibited the LPS-induced IL-6 and IL-8 production in A549 cells. Western blot analysis demonstrated that SOP remarkably inhibited the phosphorylation of IκBα and NF-κB. LPS-induced MAPKs activation and TLR4 expression were also suppressed by treatment with SOP. In conclusion, the results indicate that SOP protects against LPS-induced ALI by inhibiting TLR4 signaling pathway.
研究领域:
药理学
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免疫学
·
肺病学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Haibo Xie,Hanfei Chai,Xiaohong Du,Rongna Cui,Yinan Dong
Sepsis, resulting from infections, is a systemic inflammatory response syndrome with a high fatality rate. The present study revolves around probing into the function and molecular mechanism of long non-coding RNA OIP5 antisense RNA 1 (lncRNA OIP5-AS1) in modulating acute lung injury (ALI) mediated by sepsis. Here, a sepsis model was constructed using cecal ligation and puncture (CLP) surgery in vivo. The alveolar macrophage cell line NR8383 and the alveolar type II cell line RLE-6TN were dealt with lipopolysaccharide (LPS) for in-vitro experiments. We discovered that OIP5-AS1 and Sirtuin1 (SIRT1) were markedly down-regulated in sepsis models elicited by CLP or LPS, while miR-128-3p experienced a dramatic up-regulation. OIP5-AS1 overexpression attenuated NR8383 and RLE-6TN cell apoptosis triggered by LPS and suppressed the expressions of nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in NR8383 and RLE-6TN cells, whereas miR-128-3p overexpression resulted in the opposite phenomenon. Moreover, OIP5-AS1 overexpression relieved lung edema, lung epithelial cell apoptosis, infiltration of myeloperoxidase (MPO)-labeled polymorphonuclear neutrophils (PMN), inflammatory responses triggered by CLP in vivo. Mechanistically, miR-128-3p, which targeted SIRT1, was hobbled by OIP5-AS1. All in all, OIP5-AS1 overexpression enhanced sepsis-induced ALI by modulating the miR-128-3p/SIRT1 pathway, which helps create new insights into sepsis treatment.
研究领域:
分子生物学
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传染病学
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呼吸病学
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重症医学
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DOI
PubMed
高影响因子