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Article ; Online: Huang-Lian-Jie-Du decoction alleviates depressive-like behaviors in dextran sulfate sodium-induced colitis mice via Trem2/Dap12 pathway.

Zheng, Jia-Yi / Li, Xiao-Xiao / Lin, Wei-Yao / Su, Shan / Wu, Hai-Cui / Hu, Rui-Dan / Pan, Hua-Feng / Ye, Jiang-Hong / Cai, Ye-Feng / Zhang, Shi-Jie

Journal of ethnopharmacology

2023 Volume 315, Page(s) 116658

Abstract: Ethnopharmacological relevance: Huang-Lian-Jie-Du decoction (HLJD), a traditional Chinese medicine ...

Abstract	Ethnopharmacological relevance: Huang-Lian-Jie-Du decoction (HLJD), a traditional Chinese medicine prescription, has been implicated as effective in treating colitis, depression and inflammation-related diseases. Whether HLJD decoction could ameliorate colitis-induced depression was still unknown and the underlying mechanism was needed to be clarified. Aim of the study: Our study aimed to explore the effect and the underlying mechanism of HLJD treatment on colitis-induced depression and the involvement of the inflammatory factors and microglial-activated related genes. Materials and methods: The chronic colitis model was established by treating male mice with 1% dextran sulfate sodium (DSS) for 8 weeks. One week after DSS-treated, HLJD decoction was administered orally with 2 and 4 g/kg daily for 7 weeks. Behavior tests (Open field/Elevated plus maze/Novel object recognition) and TUNEL staining were then assessed. The expression of inflammatory-related genes and microglial dysregulation were measured by RT-PCR and the expression of Trem2, Danp12 and Iba1 were assessed by immunofluorescence methods. Results: Depressive-like behaviors were observed in mice treated with DSS, which suffered colitis. Compared to normal control (NC-V) mice, the density of TUNEL + cells in the habenula (Hb), hippocampus (HIP), and cortex were significantly higher in colitis (DSS-V) mice, especially in Hb. Compared to NC-V and several brain regions, the expression levels of the Il-1β, Il-10 and Dap12 mRNA were significantly increased in the lateral habenula (LHb) of colitis mice. Moreover, the expression of Trem2, Dap12 and Iba1 were increased in LHb of DSS-V mice. HLJD treatment could alleviate depressive-like behaviors, reduce the density of TUNEL + cells in Hb and the expression of Il-6, Il-10 and Dap12 mRNA in LHb of DSS-V mice. The overexpression of Trem2, Dap12 and Iba1 in LHb of DSS-V mice were reversed after HLJD treatment. Conclusion: These results reveal LHb is an important brain region during the process of colitis-induced depression. HLJD treatment could alleviates depressive-like behaviors in colitis mice via inhibiting the Trem2/Dap12 pathway in microglia of LHb, which would contribute to the precise treatment. It provides a potential mechanistic explanation for the effectiveness of HLJD treatment in colitis patients with depression.
MeSH term(s)	Male ; Animals ; Mice ; Interleukin-10/metabolism ; Dextran Sulfate ; Colitis/chemically induced ; Colitis/drug therapy ; Colitis/metabolism ; Drugs, Chinese Herbal/adverse effects ; Mice, Inbred C57BL ; Disease Models, Animal ; Colitis, Ulcerative/drug therapy ; Colon ; Membrane Glycoproteins/metabolism ; Receptors, Immunologic/metabolism
Chemical Substances	oren gedoku to ; Interleukin-10 (130068-27-8) ; Dextran Sulfate (9042-14-2) ; Drugs, Chinese Herbal ; Trem2 protein, mouse ; Membrane Glycoproteins ; Receptors, Immunologic
Language	English
Publishing date	2023-05-30
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2023.116658
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Article ; Online: Huang Lian Jie Du Decoction enhances the anti-tumor efficacy of immune checkpoint inhibitors by activating TLR7/8 signalling in melanoma.

Liu, Suqing / Zhang, Yaohua / Zhu, Xiaohua / He, Shan / Liu, Xiao / Lv, Xiang / Zuo, Fuguo / Wu, Jinfeng

BMC complementary medicine and therapies

2024 Volume 24, Issue 1, Page(s) 156

Abstract: ... Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous ...

Abstract	Background: The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms. Methods: The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue. Results: HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4 Conclusions: HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells.
MeSH term(s)	Mice ; Animals ; Immune Checkpoint Inhibitors/pharmacology ; Coptis chinensis ; Toll-Like Receptor 7 ; Melanoma/drug therapy ; Signal Transduction ; Drugs, Chinese Herbal
Chemical Substances	oren gedoku to ; Immune Checkpoint Inhibitors ; Toll-Like Receptor 7 ; Drugs, Chinese Herbal
Language	English
Publishing date	2024-04-11
Publishing country	England
Document type	Journal Article
ISSN	2662-7671
ISSN (online)	2662-7671
DOI	10.1186/s12906-024-04444-y
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Article: Elucidation of the anti-lung cancer mechanism of Juan-Liu-San-Jie prescription based on network pharmacology and experimental validation.

Wang, Yuli / Pan, Yanbin / Luo, Yingbin / Wu, Jianchun / Fang, Zhihong / Teng, Wenjing / Guan, Yu / Li, Yan

Heliyon

2023 Volume 9, Issue 8, Page(s) e18298

Abstract: ... being the most prevalent subtype. Our preliminary studies have demonstrated that the Juan-Liu-San-Jie ...

Abstract	Lung cancer is a malignancy characterized by high morbidity and mortality, with lung adenocarcinoma being the most prevalent subtype. Our preliminary studies have demonstrated that the Juan-Liu-San-Jie (JLSJ) prescription, a Traditional Chinese Medicine prescription, possesses anti-lung adenocarcinoma cancer properties. However, the molecular mechanism underlying the therapeutic effects of the JLSJ prescription for lung adenocarcinoma remains incompletely elucidated. To address the knowledge gap, the present study employed network pharmacology to identify potential therapeutic targets. Specifically, the study utilized TCMSP, TCMID, and related references, as well as ChemMapper, to identify and predict the main active components and potential targets. Additionally, differentially expressed genes associated with the disease were obtained from the microarray dataset GSE19804 and GSE118370. The protein-protein Interaction network and Target-pathway network were then constructed. We also conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and subsequently presented the top 20 enriched pathways. The results indicated that the anti-lung cancer effects of JLSJ prescription may be attributed to its ability to mediate apoptosis of tumor cells, potentially through the PI3K/Akt signaling pathway. Then, a series of in vitro and in vivo experiments were conducted to validate the molecular mechanism predicted by network pharmacology. The findings of the in vivo study suggested that the JLSJ prescription could inhibit the growth of xenograft tumors of lung adenocarcinoma with fewer adverse effects. Also, the in vitro experiments corroborated that the JLSJ prescription could induce apoptosis of A549 cells. Furthermore, the upregulation of pro-apoptosis-related proteins and mRNAs, coupled with the downregulation of anti-apoptotic-related proteins and mRNAs, was observed. In conclusion, inducing apoptosis by inhibiting the PI3K/Akt signaling pathway was one of the underlying mechanisms by which the JLSJ prescription exerted its anti-lung adenocarcinoma effect.
Language	English
Publishing date	2023-07-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e18298
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Article ; Online: Evaluating traditional Chinese medicine (TCM) Jie Geng and Huang Qi combination on reducing surgical site infections in colorectal cancer surgeries: A systematic review and meta-analysis.

Chen, Shiwang / Tian, Xudong / Li, Shengcai / Wu, Zhengquan / Li, Yanlong / Liao, Ting / Liao, Zhifeng

International wound journal

2024 Volume 21, Issue 2, Page(s) e14769

Abstract: ... evaluated the efficacy of the traditional Chinese medicine (TCM) combination of Jie Geng and Huang Qi ... 95% CI: 0.16 to 0.36, p < 0.01). These findings suggest that Jie Geng and Huang Qi in TCM could be ...

Abstract	Postoperative wound infections (PWIs) pose a significant challenge in colorectal cancer surgeries, leading to prolonged hospital stays and increased morbidity. This systematic review and meta-analysis evaluated the efficacy of the traditional Chinese medicine (TCM) combination of Jie Geng and Huang Qi in reducing PWIs following colorectal cancer surgeries. Adhering to PRISMA guidelines, we focused on seven randomized controlled trials (RCTs) involving 1256 patients, examining the incidence of PWIs within 30 days post-surgery, alongside secondary outcomes such as length of hospital stay and antibiotic use. The analysis revealed a significant reduction in PWI incidence in the TCM-treated group compared to controls, with a Risk Ratio of 0.21 (95% CI: 0.14 to 0.30, p < 0.01), a notable decrease in hospital stay (Mean Difference: 1.2 days, 95% CI: 0.15 to 1.28 days, p < 0.01) and a significant reduction in antibiotic use (Risk Ratio: 0.24, 95% CI: 0.16 to 0.36, p < 0.01). These findings suggest that Jie Geng and Huang Qi in TCM could be an effective adjunct in postoperative care for colorectal cancer surgeries, underscoring the need for further high-quality RCTs to substantiate these results and explore the underlying mechanisms.
MeSH term(s)	Humans ; Medicine, Chinese Traditional ; Surgical Wound Infection/prevention & control ; Drugs, Chinese Herbal/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Colorectal Neoplasms/surgery ; Astragalus propinquus
Chemical Substances	Huang Qi (922OP8YUPF) ; Drugs, Chinese Herbal ; Anti-Bacterial Agents
Language	English
Publishing date	2024-02-13
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2170920-8
ISSN	1742-481X ; 1742-4801
ISSN (online)	1742-481X
ISSN	1742-4801
DOI	10.1111/iwj.14769
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Zs.A 6006: Show issues

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Article ; Online: The Herbal Combination Shu Gan Jie Yu Regulates the SNCG/ER-a/AKT-ERK Pathway in DMBA-Induced Breast Cancer and Breast Cancer Cell Lines Based on RNA-Seq and IPA Analysis.

Zhao, Yi / Zhao, Linan / Wang, Tao / Liu, Zhenghao / Tang, Suyuan / Huang, Hongxia / Wu, Li / Sun, Youzhi

Integrative cancer therapies

2024 Volume 23, Page(s) 15347354241233258

Abstract: Background: Soothing the liver (called : The aim of the study: To investigate the inhibiting effect of SGJY on breast cancer in vivo and vitro, and to explore the potential mechanisms.: Materials and methods: SGJY herbal combination was extracted ... ...

Abstract	Background: Soothing the liver (called The aim of the study: To investigate the inhibiting effect of SGJY on breast cancer in vivo and vitro, and to explore the potential mechanisms. Materials and methods: SGJY herbal combination was extracted using water. A breast cancer rat model was developed by chemical DMBA by gavage, then treated with SGJY for 11 weeks. The tumor tissue was preserved for RNA sequencing and analyzed by IPA software. The inhibition effects of SGJY on MCF-7 and T47D breast cancer cells were investigated by SRB assay and cell apoptosis analysis, and the protein expression levels of SNCG, ER-α, Results: SGJY significantly reduced the tumor weight and volume, and the level of estradiol in serum. The results of IPA analysis reveal SGJY upregulated 7 canonical pathways and downregulated 16 canonical pathways. Estrogen receptor signaling was the key canonical pathway with 9 genes downregulated. The results of upstream regulator analysis reveal beta-estradiol was the central target; the upstream regulator network scheme showed that 86 genes could affect the expression of the beta-estradiol, including SNCG, CCL21 and MB. Additionally, SGJY was verified to significantly alter the expression of SNCG mRNA, CCL21 mRNA and MB mRNA which was consistent with the data of RNA-Seq. The inhibition effects of SGJY exhibited a dose-dependent response. The apoptosis rates of MCF7 and T47D cells were upregulated. The protein expression of SNCG, ER-α, Conclusion: The results demonstrate that SGJY may inhibit the growth of breast cancer. The mechanism might involve downregulating the level of serum estradiol, and suppressing the protein expression in the SNCG/ER-α/AKT-ERK pathway.
MeSH term(s)	Animals ; Female ; Humans ; Rats ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Estradiol ; gamma-Synuclein/genetics ; gamma-Synuclein/metabolism ; MAP Kinase Signaling System ; MCF-7 Cells ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Estrogen/metabolism ; RNA, Messenger/metabolism ; RNA-Seq
Chemical Substances	Estradiol (4TI98Z838E) ; gamma-Synuclein ; Neoplasm Proteins ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Receptors, Estrogen ; RNA, Messenger ; SNCG protein, human
Language	English
Publishing date	2024-02-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2182320-0
ISSN	1552-695X ; 1534-7354
ISSN (online)	1552-695X
ISSN	1534-7354
DOI	10.1177/15347354241233258
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Article ; Online: Protective effects of Huang-Lian-Jie-Du-Tang against A

Wu, Wenbin / He, Xiaojing / Xie, Shuling / Li, Bin / Chen, Jinxin / Qu, Yanqin / Li, Baiyang / Lei, Ming / Liu, Xuehui

The Journal of international medical research

2020 Volume 48, Issue 3, Page(s) 300060519893859

MeSH term(s)	Amyloid beta-Peptides/toxicity ; Animals ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Glutathione/metabolism ; Hippocampus/drug effects ; Hippocampus/pathology ; Hippocampus/physiopathology ; Hippocampus/ultrastructure ; Male ; Malondialdehyde/metabolism ; Memory Disorders/drug therapy ; Memory Disorders/pathology ; Memory Disorders/physiopathology ; Morris Water Maze Test ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Oxidative Stress/drug effects ; Peptide Fragments/toxicity ; Rats, Sprague-Dawley ; Spatial Learning/drug effects ; Superoxide Dismutase/metabolism
Chemical Substances	Amyloid beta-Peptides ; Drugs, Chinese Herbal ; Neuroprotective Agents ; Peptide Fragments ; amyloid beta-protein (25-35) ; oren gedoku to ; Malondialdehyde (4Y8F71G49Q) ; Superoxide Dismutase (EC 1.15.1.1) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2020-04-29
Publishing country	England
Document type	Journal Article
ZDB-ID	184023-x
ISSN	1473-2300 ; 0300-0605 ; 0142-2596
ISSN (online)	1473-2300
ISSN	0300-0605 ; 0142-2596
DOI	10.1177/0300060519893859
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Article: The TCM Prescription Yi-Fei-Jie-Du-Tang Inhibit Invasive Migration and EMT of Lung Cancer Cells by Activating Autophagy.

Wang, Shanshan / Wang, Zaichuan / Wu, Yinqiu / Hou, Chao / Dai, Xiaojun / Wang, Qingyin / Wu, Yongjian / Qian, Chao / Zhang, Xiaochun

Evidence-based complementary and alternative medicine : eCAM

2022 Volume 2022, Page(s) 9160616

Abstract: Yi-Fei-Jie-Du-Tang (YFJDT) is a traditional Chinese medicine formulation. Our previous studies have ...

Abstract	Yi-Fei-Jie-Du-Tang (YFJDT) is a traditional Chinese medicine formulation. Our previous studies have demonstrated that YFJDT can be used to treat non-small-cell lung cancer (NSCLC), but its protective effect against NSCLC and its mechanisms remain unclear. In the present study, we evaluated the protective effects and potential mechanisms of YFJDT on a tumor-bearing mouse lung cancer model and A549 cell model. Tumor-bearing mice and A549 cells were treated with YFJDT, tumors were measured during the experiment, and tumor tissues and cell supernatants were collected at the end of the experiment to assess the levels of autophagy and epithelial-mesenchymal transition (EMT)-related proteins. The results showed that YFJDT treatment reduced tumor volume and mass, increased the expression of the autophagy marker LC3, and inhibited EMT-related proteins compared with the model group. Cell survival was reduced in the YFJDT-treated groups compared with the model group, and YFJDT also reduced the migration and invasion ability of A549 cells in a dose-dependent manner. Western blotting detected that YFJDT also upregulated FAT4 in the tumor tissue and A549 cells and downregulated the expression of vimentin. Meanwhile, apoptosis in both tissues and cells was greatly increased with treatment of YFJDT. We further interfered with FAT4 expression in cells and found that the inhibitory effect of YFJDT on EMT was reversed, indicating that YFJDT affects EMT by regulating FAT4 expression. Taken together, results of this study suggested that the inhibitory effect of YFJDT on EMT in lung cancer tumors is through upregulating FAT4, promoting autophagy, and thus inhibiting EMT in cancer cells.
Language	English
Publishing date	2022-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2022/9160616
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Zs.A 5995: Show issues

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Article: Integrated Network Pharmacology and Metabonomics to Reveal the Myocardial Protection Effect of Huang-Lian-Jie-Du-Tang on Myocardial Ischemia.

Li, Li / Dai, Weixing / Li, Wenting / Zhang, Yumao / Wu, Yanqin / Guan, Chenfeng / Zhang, Anye / Huang, Hui / Li, Yuzhen

Frontiers in pharmacology

2021 Volume 11, Page(s) 589175

Abstract: ... mortality. Huang-Lian-Jie-Du-Tang (HLJDT) is a classic traditional Chinese prescription to clear "heat" and ...

Abstract	Myocardial ischemia (MI) is one of the most common cardiovascular diseases with high incidence and mortality. Huang-Lian-Jie-Du-Tang (HLJDT) is a classic traditional Chinese prescription to clear "heat" and "poison". In this study, we used a deliberate strategy integrating the methods of network pharmacology, pharmacodynamics, and metabonomics to investigate the molecular mechanism and potential targets of HLJDT in the treatment of MI. Firstly, by a network pharmacology approach, a global view of the potential compound-target-pathway network based on network pharmacology was constructed to provide a preliminary understanding of bioactive compounds and related targets of HLJDT for elucidating its molecular mechanisms in MI. Subsequently,
Language	English
Publishing date	2021-02-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.589175
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Article: Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE

Cai, Yinhe / Wen, Junmao / Ma, Siwen / Mai, Zhexing / Zhan, Qunzhang / Wang, Yijun / Zhang, Yueyao / Chen, He / Li, Haiyi / Wu, Wei / Li, Rong / Luo, Chuanjin

Frontiers in physiology

2021 Volume 12, Page(s) 666449

Abstract: ... regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable ...

Abstract	Macrophage polarization plays a vital impact in triggering atherosclerosis (AS) progression and regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable anti-inflammatory and lipid-lowering effects in different animal models. However, its effects and mechanisms on AS have not been clearly defined. We determined whether HLJDD attenuated atherosclerosis and plaques vulnerability by regulating macrophage polarization in ApoE
Language	English
Publishing date	2021-09-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.666449
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Article ; Online: Efficacy and safety of Xian-Lian-Jie-Du optimization decoction as an adjuvant treatment for prevention of recurrence in patients with stage IIIB/IIIC colon cancer: study protocol for a multicentre, randomized controlled trial.

Geng, Xuechen / Wang, Ziqiang / Feng, Li / Gu, Yanhong / Wang, Renjie / Yao, Qinghua / Xu, Yangxian / Wu, Jianyu / Jiang, Zhiwei / Chen, Kai / Hu, Wenwei / Tang, Dongxin / Huo, Jiege / Li, Ling / Bu, Qianqian / Zhao, Shuoqi / Zhang, Bei / Cheng, Haibo

BMC complementary medicine and therapies

2023 Volume 23, Issue 1, Page(s) 239

Abstract: ... remains unsatisfactory. Xian-Lian-Jie-Du optimization decoction (XLJDOD) is a Chinese herbal medicine (CHM ...

Abstract	Introduction: Colon cancer remains one of the most prevalent cancers worldwide. Unfortunately, there are no recognized and effective therapeutic strategies to prevent tumor recurrence after radical resection and chemotherapy, and the disease-free survival (DFS) in patients with stage IIIB or IIIC disease remains unsatisfactory. Xian-Lian-Jie-Du optimization decoction (XLJDOD) is a Chinese herbal medicine (CHM) empirical prescription, which has been validated experimentally and clinically that could inhibit the progression of colorectal cancer and ameliorate the symptoms. The purpose of this study is to evaluate the efficacy and safety of XLJDOD in prevention of recurrence of colon cancer. Methods: This study is a multi-center, double-blind, randomized, placebo-controlled trial conducted at 13 hospitals of China. Following the completion of surgery and adjuvant 5- fluorouracil-based chemotherapy, a total of 730 subjects with stage IIIB or IIIC colon cancer will be randomized in a 1:1 ratio to an intervention group (n = 365; XLJDOD compound granule) and a control group (n = 365; Placebo). Patients will receive 6-month treatments and be followed up with 3 monthly assessments for 2 years. The primary outcome is 2-year DFS rate and the secondary outcomes are 1, 2-year relapse rate (RR), overall survival (OS) and quality of life (QoL). Safety outcomes such as adverse events will be also assessed. A small number of subgroup analysis will be carried out to explore the heterogeneity of effects of XLJDOD. Discussion: The outcomes from this randomized controlled trial will provide objective evidences to evaluate XLJDOD's role as an adjuvant treatment in colon cancer. Trial registration: www. Clinicaltrials: gov , identifier: NCT05709249. Registered on 31 Jan 2023.
MeSH term(s)	Humans ; Quality of Life ; Treatment Outcome ; Colonic Neoplasms/drug therapy ; Disease-Free Survival ; Double-Blind Method ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic
Language	English
Publishing date	2023-07-17
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article
ISSN	2662-7671
ISSN (online)	2662-7671
DOI	10.1186/s12906-023-04052-2
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