1.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
2.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
3.Let ′Rare Disease′ Been Seen: Delving into the Building up of Resource and Information Service in Medical Libraries for Rare Diseases
JOURNAL OF RARE DISEASES 2024;3(1):144-150
With the development of the diagnosis and treatment for rare diseases and the promotion of the construction of ′Double First-Class′ Universities in China, the libraries of medical schools have to make full use of their strengths to better face new challenges in discipline construction proactively. This article refers to resource and information service practices related to the rare disease carried out by medical libraries in China and in other countries; explores the possibilities of building up the resource and information in the future, aiming at improving the awareness of rare diseases among medical students, researchers, and the general public. The article also focuses on the need for strengthening the support for teaching and research into rare diseases, hoping to contribute to the overall improvement of the diagnosis, treatment, and educational research in rare diseases in China.
4.Role of exosome-derived miRNA-21-5p/Smad7 in quartz dust-induced pulmonary fibrosis in rats
Yang LU ; Xiaohui DING ; Tiantian WANG ; Mengtong XU ; Jiarui HAO ; Wenjing LI ; Jing SONG
Journal of Environmental and Occupational Medicine 2024;41(8):861-866
Background Quartz dust cannot be degraded in the lungs, and inhalation of a large amount of quartz dust in the occupational production process will lead to the occurrence of pulmonary fibrosis, and then develop into silicosis. In recent years, studies have found that exosomes may be involved in the pathogenesis of fibrotic diseases by carrying microribonucleic acid (miRNA), but the mechanism of their actions in silicosis still needs to be studied. Objective To investigate the role of exosome-derived miRNA-21-5p/mothers against decapentaplegic homolog 7 (Smad7) in quartz dust-induced pulmonary fibrosis in rats. Methods Twenty-four healthy male SD rats were randomly divided into four groups (six rats in each group): control 4-week group, control 16-week group, quartz 4-week group, and quartz 16-week group. At the beginning of the experiment, 1 mL of quartz suspension (50 mg·mL−1) and 1 mL of normal saline were injected into the trachea of rats in the quartz group and the control group, respectively, by means of one-time non-exposure intratracheal dust staining. Alveolar lavage was performed at the 4th and 16th weeks after dust staining, the exosomes in lavage solution were extracted by polyethylene glycol (PEG) precipitation, morphological identification was conducted by transmission electron microscopy (TEM), particle size of exosomes was detected by nano-tracking analysis (NTA), and the marker proteins CD9 and CD63 of exosomes were detected by Western blotting (WB). The expression of miRNA-21-5p in exosomes was determined by reverse transcription polymerase chain reaction (RT-PCR). The degree of lung tissue injury and fibrosis was observed by hematoxylin-eosin staining (HE) and Masson staining. The collagen content of lung tissue was detected by hydroxyproline (HYP) method. The expression of Smad7 protein in lung tissue was detected by WB. Results The results of pathological staining showed that compared with the control group, lung inflammatory cell infiltration, alveolar wall thickening, and collagen increase were observed after 4 weeks of dusting, and collagen deposition and silicon nodules appeared after 16 weeks of dusting. Compared with the control group, the expression level of HYP in the lung tissue of the quartz group was increased after 4 weeks and 16 weeks of dust staining (P<0.05). Transmission electron microscopy showed that exosomes were saucer-shaped, and the average particle size of exosomes was 95.8 nm by NTA. Positive expression of exosome marker proteins CD9 and CD81 was found by WB. Compared with the control group, the expression of exosome-derived miRNA-21-5p in alveolar lavage fluid in the quartz group increased in the 4th week and the 16th week (P<0.05), and the expression of Smad7 protein in lung tissue decreased (P<0.05). Conclusion Exosome-derived miRNA-21-5p and Smad7 may be involved in the mechanism of quartz dust-induced pulmonary fibrosis in rats.
5.Analysis of the progress in the field of oral microbiology and regenerative medicine from 2014 to 2023
Jin WEN ; Wenjing DING ; Xinquan JIANG
Chinese Journal of Stomatology 2024;59(5):463-471
Objective:To analyze the trends in literature related to oral microbiology and regenerative medicine from 2014 to 2023. By identifying key research countries, institutions, and their collaboration networks, as well as exploring research hotspots and development directions, the study seeks to provide references for researchers and decision-makers in the field of oral microbiology and regenerative medicine, thereby guiding the direction of future research.Methods:Relevant literature was retrieved using the Web of Science Core Collection database, with data processing and analysis conducted using CiteSpace 6.2.R6 software. Time slicing, node type selection, and the application of the g-index (g-index) were used for filtering, analyzing countries, institutions, authors, journals, and keywords.Results:The volume of literature in the field of oral microbiology and regenerative medicine has steadily increased from 2014 to 2023, with the number of publications first exceeding one hundred in 2020 and reaching 134 in 2022, accompanied by a citation frequency of 3 363 times. China and the United States have been at the forefront in terms of the volume of publications, while the United States and Germany lead in terms of intermediary centrality. The research primarily spans disciplines such as oral medicine, interdisciplinary studies, materials science, and immunology. High-frequency keywords include stem cells, scaffold materials, and gut microbiota, while cluster analysis indicates that inflammation, drug delivery, and antimicrobial activity remain consistent research themes. In recent years, the research heat in "tissue regeneration""gut microbiota " and "maxillofacial surgery" has risen, suggesting these may become focal points of future research.Conclusions:Over the past decade, the volume of literature published in the fields of oral microbiology and regenerative medicine, along with their citation frequencies, has increased annually. The research focus has shifted over time. Understanding the interactions between oral and gut microbiomes is crucial for developing innovative regenerative treatment strategies.
6.Effect of SRS Treatment Timing on Survival of EGFR-mutated Lung Adenocarcinoma with Brain Metastasis
Wenjing GUO ; Guangcheng DING ; Changli SHI
Journal of Medical Research 2024;53(6):59-64
Objective To investigate the timing of stereotactic radiosurgery(SRS)in lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation treated with tyrosine kinase inhibitor(TKI).Methods A total of 90 patients with EGFR-mutated lung adenocarcinoma patients with brain metastasis admitted to the Fifth Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were collected.All patients received TKI treatment and were divided into two treatment groups according to the timing of SRS treatment:those who received SRS immediately after the diagnosis of lung cancer brain metastasis were called early SRS group(n=52),and those who received TKI treatment and then SRS after the progression of brain metastasis were called deferred SRS group(n=38).Objective response rate(ORR),disease control rate(DCR),intracranial progression-free survival(iPFS)and overall survival(OS)were compared between the two groups.Multivariate COX regression model was used to analyze the prognosis.Results There was no significant difference in ORR(59.6%vs 50.0%,P=0.365)and DCR(76.9%vs 73.7%,P=0.724)between the two groups.The median OS and iPFS of the whole group were 31.5months and 12.5months,respectively.The OS of the early SRS group was signifi-cantly longer than that of the late SRS group(35.5months vs 27.0months,P=0.001).iPFS was also significantly better in the early SRS group than in the late SRS group(15.0months vs 11.5months,P=0.004).The median OS was longer in patients with no symptoms of brain metastases than in patients with symptoms of brain metastases(35.5months vs 27.Omonths,P=0.011).Multivariate COX regression analysis showed that early SRS treatment was a protective factor for OS and iPFS(HR<1,P<0.05),and Lung-mol GPA score of 3.5-4.0 was a protective factor for OS(HR<1,P<0.01).Conclusion For patients with advanced EGFR-mutated lung adenocarcinoma with brain metastases,early SRS treatment after diagnosis of brain metastases has better intracranial control effect and greater survival benefit.
7.Research progress on the treatment of Candida albicans infection by metal nanoparticles
Aiqiong ZHOU ; Wenjing DING ; Wei QU ; Fei MO
International Journal of Laboratory Medicine 2024;45(18):2250-2257,2263
Candidiasis has a high morbidity and mortality worldwide,and its main causative agent is Candi-da albicans.At present,the treatment effect of candidiasis is not ideal due to the shortcomings of antifungal drugs,such as toxicity,drug resistance,single route of administration,and high price.In order to overcome this situation,metal nanoparticles with antifungal activity and the potential to deliver antifungal drugs have been extensively studied.In this paper,the mechanism and application of gold,silver,copper and iron nanoparticles against Candida albicans are reviewed.Compared with traditional antifungal drugs,metal nanoparticles exert antifungal effects through a multi-target mechanism,which minimizes the emergence of antifungal resistance.Cytotoxicity limits the application of metal nanoparticles,but green synthesis can reduce the cytotoxicity of metal nanoparticles and improve antimicrobial properties.
8.Application of whole-process nutritional management in patients undergoing thoracoabdominal laparoscopic radical esophagectomy
Wenjing ZHU ; Min DING ; Yuan DING ; Jie ZHANG ; Chen QIAN
Chinese Journal of Modern Nursing 2024;30(32):4438-4442
Objective:To explore the application effects of whole-process nutritional management in patients undergoing thoracoabdominal laparoscopic radical esophagectomy.Methods:A total of 144 patients who underwent thoracoabdominal laparoscopic radical esophagectomy at the Jiangsu Cancer Hospital between February 2022 and February 2024 were selected using convenience sampling method. Patients were randomly assigned to a control group ( n=72) receiving routine care and an observation group ( n=72) receiving whole-process nutritional management in addition to routine care. Nutritional status, postoperative recovery, nursing satisfaction, and weight loss were compared between the two groups. Results:On the day before surgery, the Nutritional Risk Screening (NRS-2002) score of the observation group was significantly lower than that of the control group, the difference was statistically significant ( P<0.05). The observation group had earlier times to first ambulation, bowel movement, flatus, and fewer total complications compared to the control group, the differences were statistically significant ( P<0.05). Nursing satisfaction scores in the observation group were significantly higher than in the control group, the differences were statistically significant ( P<0.05). One month postoperatively, the observation group experienced less weight loss than the control group, the difference was statistically significant ( P<0.05) . Conclusions:Whole-process nutritional management improves preoperative nutritional status scores, reduces postoperative complications and weight loss, and enhances patient satisfaction with nursing care in esophageal cancer patients undergoing thoracoabdominal laparoscopic radical esophagectomy.
9.Guijiajiao (Colla Carapacis et Plastri, CCP) prevents male infertility via gut microbiota modulation.
Wen SHENG ; Wenjing XU ; Jin DING ; Baowei LU ; Lumei LIU ; Qinghu HE ; Qing ZHOU
Chinese Journal of Natural Medicines (English Ed.) 2023;21(6):403-410
Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semi-automatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-1β), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3+ T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-1β in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.
Humans
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Rats
;
Male
;
Animals
;
Gastrointestinal Microbiome
;
Lipopolysaccharides/pharmacology*
;
RNA, Ribosomal, 16S
;
Semen
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Sperm Motility
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Infertility, Male/prevention & control*
;
Testosterone
10.Effect of Yishen Daluo Prescription on Rho/ROCK Signaling Pathway in EAE Mice Based on Silencing of β-arrestin1
Wenjing DING ; Zhongmin WANG ; Jiayan REN ; Xiang WANG ; Xiaoling SHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):110-116
ObjectiveTo investigate the effects of Yishen Daluo prescription (YSDL) on Ras homolog(Rho)/Rho-associated coiled-coil containing protein kinase(ROCK)signaling pathway in mice with experimental autoimmune encephalomyelitis (EAE) based on the silencing of β-arrestin1 gene. MethodSixty C57BL/6 female mice were randomly divided into a blank group, a model group, a virus group, a YSDL group, a virus + YSDL group, and a prednisone acetate group (hormone group). The EAE model was induced in mice except for those in the normal group. Adeno-associated virus(AAV)solution (150 μL, 1×1011 vg·mL-1) was injected into the tail vein of each mouse in the virus group and the virus + YSDL group on the 4th day of immunization. Drugs were administered on the 8th day of modeling. Specifically, normal saline was given to the mice in the normal group,the model group,and the virus group at 10 mL∙kg-1, prednisone acetate suspension to those in the hormone group at 3.9 g∙kg-1,and YSDL to those in other groups at 20 g∙kg-1 for 14 consecutive days. The mice were weighed and scored every day. The neurological function scores of mice in each group were recorded every day after immunization. Hematoxylin-eosin (HE) staining was used to determine the inflammatory response and lesion location in the brain tissues and spinal cord tissues of mice. The protein expression of β-arrestin1,Ras homolog gene family member A(RhoA), and Rho-associated coiled-coil forming protein kinase Ⅰ(ROCK Ⅰ) in spinal cord and brain tissues of EAE mice was determined by Western blot. ResultCompared with the model group, the virus group and the virus + YSDL group showed decreased neurological function scores (P<0.01),and the YSDL group also showed decreased neurological function scores(P<0.05). HE results showed that there was obvious inflammatory reaction in the central nervous system (CNS) of the model group, which was alleviated to varying degrees in other groups compared with the model group. Western blot results showed that compared with the blank group, the model group showed increased protein expression levels of β-arrestin1, RhoA, and ROCK Ⅰ in the spinal cord tissues (P<0.01). Compared with the model group, the virus group, the YSDL group, the virus + YSDL group, and the hormone group showed decreased protein expression levels of β-arrestin1, RhoA, and ROCKⅠ in the spinal cord tissues (P<0.01). Compared with the blank group, the model group showed increased protein expression levels of β-arrestin1, RhoA, and ROCK Ⅰ in the brain tissues (P<0.01). Compared with the model group, the virus group, the YSDL group, the virus + YSDL group, and the hormone group showed decreased protein expression level of β-arrestin1 in the brain tissues (P<0.01), and the virus group and the YSDL group showed decreased protein expression levels of RhoA, and ROCKⅠ in the brain tissues (P<0.05). Additionally, the virus + YSDL group and the hormone group showed decreased protein expression levels of RhoA and ROCKⅠ in the brain tissues (P<0.01). ConclusionYSDL can improve the clinical symptoms of EAE mice and improve the inflammatory response of CNS. The mechanism is presumably attributed to the fact that YSDL inhibits the expression of β-arrestin1 in CNS,thereby reducing the expression of Rho/ROCK signaling pathway. Furthermore, YSDL may have a synergistic effect with the inhibition of β-arrestin1 gene expression.

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