1.Identification of a natural PLA2 inhibitor from the marine fungus Aspergillus sp. c1 for MAFLD treatment that suppressed lipotoxicity by inhibiting the IRE-1α/XBP-1s axis and JNK signaling.
Yong RAO ; Rui SU ; Chenyan WU ; Xingxing CHAI ; Jinjian LI ; Guanyu YANG ; Junjie WU ; Tingting FU ; Zhongping JIANG ; Zhikai GUO ; Congjun XU ; Ling HUANG
Acta Pharmaceutica Sinica B 2024;14(1):304-318
Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.
2.Research status of sodium-glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes mellitus with heart failure with preserved ejection fraction
Ming-Yan LIU ; Bing-Qi ZHANG ; Hu-Hu LI ; Nai-Ru YUN ; Si-Miao FAN ; Rong-Rong YANG ; Rui-Ying GUO ; Yong-Na DAI
The Chinese Journal of Clinical Pharmacology 2024;40(13):1977-1981
Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.
3.Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing
Li Ya ZHANG ; Zhe Wen SU ; Chen Rui WANG ; Yan LI ; Feng Jun ZHANG ; Hui Sheng LIU ; He Dan HU ; Xiao Chong XU ; Yu Jia YIN ; Kai Qi YIN ; Ying HE ; Fan LI ; Hong Shi FU ; Kai NIE ; Dong Guo LIANG ; Yong TAO ; Tao Song XU ; Feng Chao MA ; Yu Huan WANG
Biomedical and Environmental Sciences 2024;37(3):294-302
Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
4.Effects and mechanism of Yiqi huoxue decoction on lumbar disc herniation in rats
Xue BAI ; Xiaoxian SUN ; Yang GUO ; Yong MA ; Mengmin LIU ; Hong JIANG ; Shun LIN ; Rui CAO ; Yongfeng YUAN ; Jintao LIU
China Pharmacy 2024;35(10):1186-1192
OBJECTIVE To investigate the effects and mechanism of Yiqi huoxue decoction (YQHX) on lumbar disc herniation in rats. METHODS Rats were randomly divided into sham operation group, model group, NF-κB inhibitor group (QNZ group, 1 mg/kg), YQHX group (9.1 g/kg) and combination group (YQHX+QNZ group, the same dose as each single drug group), with 10 rats in each group. Except for sham operation group, lumbar disc herniation model of rats was induced in other groups; administration groups were given QNZ intraperitoneally or/and YQHX intragastrically, once a day, for 8 consecutive weeks. The severity of intervertebral disc herniation was evaluated in each group; the pathological changes of intervertebral discs and the changes of autophagy of nucleus pulposus cells were all observed; the level of tumor necrosis factor-α (TNF-α) in serum, and the ratios of Bcl-2/adenovirus E1B interacting protein 3 (BNIP3) and Beclin-1 positive cells in intervertebral disctissues were detected; the phosphorylation of nuclear factor-κB (NF-κB) p65, the expressions of tumor necrosis factor receptor- associated factor-2 (TRAF-2), TRAF-3, BNIP3 and LC3B protein, and mRNA expressions of NF-κB p65, LC3B, p62,BNIP3 and Beclin-1 were determined. RESULTS Compared with model group, Pfirrmann grading score decreased significantly,the pathological injury of intervertebral disc tissue was relieved in YQHX group; the number of autophagosomes in nucleus pulposus cells increased; serum level of TNF-α and mRNA expression of p62 in intervertebral disc tissue decreased significantly; the ratios of BNIP3 and Beclin-1 positive cells, the phosphorylation of NF-κB p65, the expressions of TRAF-2, TRAF-3, BNIP3 and LC3B protein as well as the mRNA expressions of NF- κB p65, LC3B, BNIP3 and Beclin-1 decreased significantly in intervertebral disc tissues (P<0.05). The changes of above indexes in YQHX group were reversed partly in YQHX+QNZ group. CONCLUSIONS YQHX promotes the elevation of autophagy level of intervertebral discs, slows down the inflammatory response and the progression of lumbar disc herniation by activating the NF-κB signaling pathway.
5.Analysis Method for Freshness of Stored Paddy Rice Based on Volatile Components and Multivariate Statistical Analysis
Rui GUO ; Pan-Pan LI ; Wei ZHANG ; Nan-Xi WANG ; Yong-Tan YANG
Chinese Journal of Analytical Chemistry 2024;52(9):1244-1253
By using paddy rice harvested between 2019 and 2023 as the research object,the volatile components of rice grains were detected by headspace solid-phase microextraction coupled with gas chromatography-triple quadrupole mass spectrometry.Qualitative analysis of the compounds was complemented by a standard mass spectrometry database and retention index,while a selected ion monitoring approach was established to quantify the contents of each component through the internal standard method.Multivariate statistical analyses including principal component analysis and orthogonal partial least squares discriminant analysis were employed to identify differential compounds related to freshness of the paddy rice.Subsequently,a classification model for identifying stored paddy rice based on volatile component analysis was developed.A total of 44 kinds of volatile compounds were identified across different harvest years,including aldehydes,alcohols,ketones,acids,esters,phenols and furans.The results of the multivariate statistical analysis revealed that the content-based orthogonal partial least squares discriminant analysis model could effectively distinguish 2023 harvested paddy rice from those harvested between 2019 and 2022 into two distinct categories.Notably,compounds such as hexanoic acid and nonanoic acid along with twelve others were identified as differential compounds based on variable improtance in projection(VIP)values exceeding 1 and p values less than 0.05.The classification model established through volatile component analysis was expected to provide a theoretical foundation for assessing the freshness of stored paddy rice.
6.ZHOU Peng's Experience in Treating Psoriasis Vulgaris of Blood Stasis Type Based on the Analysis of Dermoscopic Signs
Guo-Ao SHI ; Rui-Ming CHEN ; Xiang JI ; Zhong-Xian LI ; Yong-Qin XIONG ; Xia-Yun ZHOU ; Jing-Jing LI ; Peng ZHOU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2109-2115
Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.
7.Construction of Standardized Platform of Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment for Acute Myocardial Infarction
Rui-Xiang ZENG ; Li-Heng GUO ; Xiao-Xuan ZHANG ; Jian-Yong QI ; Shuai MAO ; Min-Zhou ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2631-2635
Acute myocardial infraction(AMI)has now become a threat to human health worldwide.Therefore,it is urgent to construct the standardized platform of integrated traditional Chinese and western medicine diagnosis and treatment for AMI.The Intensive Care Unit(ICU)team of the Second Clinical Medical School of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine)has taken up the mission of exploring the prevention and treatment of AMI with traditional Chinese medicine and promoting and the construction of the diagnosis and treatment system of integrated traditional Chinese and western medicine for AMI.The team pioneered the trinity mode of'saving heart,treating heart and nourishing heart'for AMI,focusing on the construction of standardized platform of integrated traditional Chinese and western medicine diagnosis and treatment for AMI,creating the key technology system of Yiqi Huoxue Huatan method(the therapy mainly for replenishing qi,activating blood and dissolving phlegm)for AMI and putting it into the practice,which highlighted the achievements in the construction of the standardized platform.
8.Clinical Observation on Buqi Qingchang Decoction Combined with XELOX Chemotherapy and Bevacizumab Regimen in the Treatment of Patients with Metastatic Colorectal Cancer of Qi Deficiency and Damp-Heat Syndrome and Damp-Heat Syndrome
Rui TANG ; Guo-Hang XIAO ; Yong-Huan PENG ; De-Qi ZHOU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2720-2726
Objective To explore the influence of Buqi Qingchang Decoction(composed of Buzhong Yiqi Decoction plus Baitouweng Decoction with Curcumae Radix and Curcumae Longae Rhizoma added)combined with XELOX chemotherapy and Bevacizumab targeted therapy on the clinical efficacy,quality of life and survival period of patients with metastatic colorectal cancer of qi deficiency and damp-heat syndrome.Methods A retrospective study was conducted in 70 patients with metastatic colorectal cancer of qi deficiency and damp-heat syndrome who were admitted to the Department of Oncology,Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine(Chongqing Beibei District Hospital of Traditional Chinese Medicine)from December 2020 to December 2023.The patients were divided into an observation group and a control group according to the therapy,with 35 cases in each group.The control group was treated with XELOX chemotherapy combined with Bevacizumab targeted therapy,while the observation group was given oral administration of Buqi Qingchang Decoction together with chemotherapy and targeted therapy.The changes in the serum levels of tumor markers such as carcinoembryonic antigen(CEA)and carbohydrate antigen 199(CA199),and Karnofsky Performance Status(KPS)scores for quality of life in the two groups were observed before and after treatment.Moreover,the clinical efficacy,progression-free survival(PFS)and overall survival(OS)were compared between the two groups.Results(1)After treatment,the objective response rate(ORR)and disease control rate(DCR)in the observation group were 51.42%(18/35)and 85.71%(30/35),respectively,which were significantly higher than those in the control group[25.71%(9/35)and 54.29%(19/35),respectively],and the differences between the two groups were statistically significant(P<0.05 or P<0.01).(2)The PFS of the observation group was 16.7 months and that of the control group was 12.9 months,and the OS of the observation group was 23.3 months and that of the control group was 17.7 months.The PFS and OS of the observation group were significantly longer than those of the control group,and the differences were statistically significant(P<0.05 or P<0.01).(3)After treatment,the levels of serum CEA and CA199 in the two groups were significantly decreased compared with those before treatment(P<0.05),and the KPS scores were significantly increased compared with those before treatment(P<0.05).The decrease of serum CEA and CA1 99 levels and the increase of KPS scores in the observation group were superior to those in the control group,and the differences were statistically significant(P<0.05).Conclusion XELOX chemotherapy and Bevacizumab regimen combined with Buqi Qingchang Decoction exerts certain effect in treating metastatic colorectal cancer.The combined therapy is effective on enhancing the efficacy to a certain extent,prolonging the survival period of patients,reducing the risk of disease progression,decreasing the levels of serum tumor markers,and improving the quality of life of patients.
9.Clinical Observation of Shen Jiang Zhouche Powder in the Treatment of Malignant Pleural Effusion with Fluid Retention in the Chest and Hypochondrium Syndrome
Guo-Hang XIAO ; Rui TANG ; Yong-Huan PENG ; Wei ZHENG ; De-Qi ZHOU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(11):2924-2930
Objective To investigate the clinical efficacy of Shen Jiang Zhouche Powder(composed of modified Lizhong Pill,Erchen Decoction,and Zhouche Pill)in the treatment of malignant pleural effusion(MPE)patients with fluid retention in the chest and hypochondrium syndrome.Methods Eighty MPE patients with fluid retention in the chest and hypochondrium syndrome were randomly divided into the treatment group and the control group,with 40 cases in each group.Both groups were given conventional western medical treatment,and additionally the control group was treated with Spironolactone and Furosemide Tablets orally while the treatment group was treated with Shen Jiang Zhouche Powder orally.A total of 21 days constituted one course of treatment,and both groups were treated for two courses and then were followed up for one month.The changes of traditional Chinese medicine(TCM)syndrome scores,scores of Karnofsky Performance Status(KPS)established by Eastern Cooperative Oncology Group(ECOG),and scores of self-rating scale of sleep(SRSS)in the two groups were observed before and after treatment.After treatment,the clinical efficacy,TCM syndrome efficacy and clinical safety of the two groups were evaluated.Results(1)After treatment and one-month follow-up,the total clinical effective rate in the treatment group was 67.5%(27/40)and that in the control group was 45.0%(18/40),and the intergroup comparison(by chi-square test)showed that the clinical efficacy of the treatment group was significantly superior to that in the control group(P<0.05).(2)After two courses of treatment,the total effective rate of TCM syndrome improvement in the treatment group was 92.5%(37/40)and that of the control group was 50.0%(20/40),and the intergroup comparison(by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P<0.01).(3)After treatment,except for the score of dyspnea in the control group,the scores of each of the main symptoms(including dry cough,chest tightness,chest pain,tightness of breath,dyspnea)and accompanied symptoms as well as the total TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P<0.05 or P<0.01),and the decrease of the scores of each of the main symptoms and accompanied symptoms as well as the total TCM syndrome scores were significantly superior to those in the control group(P<0.05 or P<0.01).(4)After treatment,the scores of KPS and SRSS in the two groups were significantly improved compared with those before treatment(P<0.01),and the improvement in the treatment group was significantly superior to that in the control group(P<0.05 or P<0.01).(5)There were no obvious adverse reactions occurring in both groups,while only mild symptoms of the adverse reactions were presented.The incidence of adverse reactions in the treatment group was 7.5%(3/40)and that in the control group was 12.5%(5/40),and the difference was not statistically significant between the two groups(P>0.05).Conclusion Shen Jiang Zhouche Powder exerts certain clinical efficacy in the treatment of MPE patients with fluid retention in the chest and hypochondrium syndrome,which is effective on alleviating the clinical symptoms of TCM,and improving the quality of life of patients,without obvious toxicity or side effects.
10.Safety and efficacy of domestically produced novel bioabsorbable vascular scaff old in the treatment of complex coronary artery lesions for 3 years
Deng-Shuang ZHOU ; Qiong YOU ; Hai-Liang MO ; Zi-Jun WU ; Yu-Biao LIN ; Lu-Jun CHEN ; Jun-Yu FAN ; Yong-Jian LIN ; Rui-Sheng ZHANG ; Pei-Shan WAN ; Wei-Guo ZHOU ; Keng WU
Chinese Journal of Interventional Cardiology 2024;32(9):509-515
Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P<0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P>0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95%CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.

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