1.Preparation modification strategies for clinical treatment drugs of Parkinson's disease
Meng-jiao HE ; Yi-fang XIAO ; Xiang-an-ni KONG ; Zhi-hao LIU ; Xiao-guang WANG ; Hao FENG ; Jia-sheng TU ; Qian CHEN ; Chun-meng SUN
Acta Pharmaceutica Sinica 2024;59(3):574-580
Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.
2.A new pyrazine from Hypecoum erectum L.
Yun LIU ; Meng-ya HU ; Wen-jing ZHANG ; Yu-xin FAN ; Rui-wen XU ; Deng-hui ZHU ; Yan-jun SUN ; Wei-sheng FENG ; Hui CHEN
Acta Pharmaceutica Sinica 2024;59(1):183-187
Four pyrazines were isolated from the
3.Polyene phosphatidylcholine injection in the treatment of alcoholic liver disease:a systematic review and Meta-analysis
Baoqi ZENG ; Meng ZHANG ; Xiaozhi LIU ; Feng SHENG ; Feng SUN
China Pharmacist 2024;27(1):135-144
Objective To evaluate the efficacy and safety of polyene phosphatidylcholine injection in the treatment of liver disease.Methods Pubmed,Embase,The Cochrane Library,ClinicalTrial.gov,CNKI,SinoMed,VIP,and WanFang Data were electronically searched to collect randomized controlled trials(RCTs)of polyene phosphatidylcholine injection in the treatment of liver disease from inception to December 31st,2022.Two researchers independently screened literature,extracted data and assessed the risk of bias of the included studies.The Meta-analysis was performed using Stata 17.0 software.Results A total of 10 RCTs were included,including 809 patients.Meta-analysis showed that the effective rate in the polyene phosphatidylcholine injection group was higher than that in the control group(RR=1.12,95%CI 1.04 to 1.20,P=0.003 8).Compared with the control group,polyene phosphatidylcholine injection could decrease ALT level(MD=-18.92 U/L,95%CI-27.75 to-10.09,P<0.001),AST level(MD=-31.19 U/L,95%CI-46.27 to-16.11,P=0.000 1),TBiL level(MD=-7.31 μmol/L,95%CI-10.75 to-3.88,P<0.001),and GGT levels(MD=-48.93 U/L,95%CI-54.64 to-43.21,P<0.001).Only one study reported mild adverse events,and six studies reported no severe adverse events in patients.Conclusion Current evidence shows that polyene phosphatidylcholine injection in the treatment of alcoholic liver disease can increase the effective rate,improve the levels of liver function indicators(ALT,AST,TBiL,and GGT),and has less adverse events.Due to the limited number and quality of included studies,the above conclusions need to be verified by more high-quality studies.
4.A Comparative Study on the Version 2023 and the Version 2011 of the Standards of Health Information Data Elements
Han SUN ; Xiaolin YANG ; Sheng YANG ; Wei ZHOU ; Shengfa ZHANG ; Fanhong MENG ; Lihong LIU ; Yan ZHU
Journal of Medical Informatics 2024;45(8):14-19
Purpose/Significance To compare and analyze the 2023 edition and 2011 edition of the health information data element standards,and to discuss the differences and improvements,so as to provide useful references and guidance for the update and imple-mentation of the standards.Method/Process The updated contents of the 2023 and 2011 editions of the health information data element standards are sorted out and compared,and the effects of the revision on the degree of standardization,the level of standardization,and the completeness and accuracy of data are analyzed and summarized.Result/Conclusion It is found that the 2023 edition has achieved significant improvements in data completeness and standardization.Additionally,targeted suggestions and strategies are proposed for the challenges and issues that might be faced during the implementation of the 2023 edition standards.
5.A new pregnane steroid from Poria cocos
Chao-yuan XIAO ; Zhi-you HAO ; Meng YANG ; Shi-qi ZHOU ; Jun-yang ZHANG ; Xiao-ke ZHENG ; Yan-jun SUN ; Wei-sheng FENG
Acta Pharmaceutica Sinica 2024;59(12):3325-3329
The 95% ethanol extract of
6.Difference of lipid-lowering efficacy of "Xinjianqu" before and after fermentation and its mechanism based on LKB1-AMPK pathway and 16S rDNA sequencing technology.
De-Hua LI ; Rui-Sheng WANG ; Zhen-Ling ZHANG ; Jian-Guang ZHU ; Meng-Mei SUN ; Jia QIAO
China Journal of Chinese Materia Medica 2023;48(8):2146-2159
On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed_otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae_NK4A136_group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed_otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae_NK4A136_group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.
Rats
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Animals
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AMP-Activated Protein Kinases/metabolism*
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Rats, Sprague-Dawley
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Cholesterol, LDL
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Fermentation
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Aquaporin 2/metabolism*
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Lipid Metabolism
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Liver
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Lipids
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Hyperlipidemias/genetics*
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Adenosine Triphosphate/pharmacology*
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Diet, High-Fat/adverse effects*
7.Diagnosis and Treatment of Familial Hypokalemic Periodic Paralysis with Acidosis
Guo-juan LAO ; Cheng-zhi WANG ; Na LI ; Chu-lin HUANG ; Ying-na CHEN ; Hui-sheng XIAO ; Kan SUN ; Meng REN
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(3):479-484
ObjectiveTo investigate the diagnosis and treatment of familial hypokalemic periodic paralysis with acidosis. MethodsThe proband's medical history, clinical manifestations, laboratory examinations and imaging characteristics were retrospectively analyzed, and prevalence situation of family members was investigated in detail. Next generation sequencing technology was used to detect the pathogenic gene loci related to periodic paralysis, and the relevant literatures were summarized. ResultsThe proband was definitely diagnosed as familial hypokalemic periodic paralysis. There was a heterozygous mutation in the SCN4A gene of the proband, which was c.2006G>A, resulting in amino acid changes R669H.The proband's grandfather, father and uncle shared the same variation. ConclusionsFamilial hypokalemic periodic paralysis with paroxysmal acidosis is rare, which is easily misdiagnosed as renal tubular acidosis. c 2006G>A mutation in SCN4A gene is the molecular basis of the disease in this family. The clinical phenotypes of different gene mutations are different, and gene screening is helpful for diagnosis and treatment.
8.Alkaloids from fruit of Lycium chinense var. potaninii.
Meng-Ya HU ; Wen-Jing ZHANG ; Yun LIU ; Yan-Jun SUN ; Wei-Sheng FENG ; Hui CHEN
China Journal of Chinese Materia Medica 2023;48(6):1546-1552
Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 μmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.
Lycium/chemistry*
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Fruit/chemistry*
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Insulin Resistance
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Propionates
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Alkaloids/pharmacology*
9.Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis
Hao-qiang HU ; Meng-yuan LI ; Nian-sheng YANG ; Chao-huan GUO
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(2):254-261
ObjectiveThis study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS. Methods① The sera of primary FSGS patients (17 cases) were collected. Healthy volunteers (10 cases) and patients with other types of primary nephrotic syndrome (10 cases) were set as normal and disease controls. SuPAR levels were detected by ELISA; ② Podocytes were stimulated by suPAR in vitro, and cells were collected to analyze apoptosis by flow cytometry and for RNAseq analysis; ③ Differentially expressed genes (DEGs) were screened from RNAseq data. Both up-regulated and down-regulated genes were analyzed by KEGG and GO enrichment analysis. Heat map was used to show expression of genes related to podocyte focal adhesion, slit diaphragm and actin dynamics and endocytosis. Differentially expressed genes were verified by qPCR. Results① The level of suPAR in FSGS patients was significantly increased, and that in other nephrotic syndrome(NS) patients was also significantly increased; ② suPAR stimulation significantly altered the transcriptome pattern of human podocytes. A total of 272 up-regulated genes and 288 down-regulated genes were screened; ③ KEGG and GO enrichment analysis of up-regulated and down-regulated genes showed that Focal adhesion and DNA replication and DNA repair related pathways were significantly down-regulated; ④ suPAR did not increase podocyte apoptosis. ConclusionThe level of suPAR is significantly increased in patients with primary FSGS. SuPAR may promote podocyte injury by interfering with genomic homeostasis and disrupting focal adhesion, slit diaphragm, actin dynamics and endocytosis-related functional molecules of podocytes.

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