1.Clinical trial of methylprednisolone sodium succinate combined with erythromycin in the treatment of Mycoplasma pneumoniae infection with elevated lactate dehydrogenase in children
Ren-Wei RUAN ; Xiao-Ling LIU ; Mei-Bao CHA ; Ting PEI ; Ping HE ; Pan-Ting YANG
The Chinese Journal of Clinical Pharmacology 2024;40(3):312-316
Objective To analyze the effect of low-dose methylprednone sodium succinate combined with erythromycin in the treatment of Mycoplasma pneumoniae infection with elevated lactate dehydrogenase(LDH)in children.Methods Children with Mycoplasma pneumoniae pneumonia(MPP)complicated with elevated LDH were divided into control group and treatment group by random number table method.The control group was given erythromycin treatment,and the treatment group was given low-dose methylprednisolone sodium succinate combined with erythromycin treatment.Clinical efficacy and clinical symptom disappearance time were recorded in both groups.Pulmonary X-ray signs,immune function[T cell subsets(CD4+,CD8+,CD4+/CD8+)],immunoglobulin(Ig)A,IgM and serum LDH were compared between the two groups before and after treatment,and the adverse drug reactions of treatment were observed.Results There were 51 cases in control group and 51 cases in treatment group.The total effective rate in treatment group was 96.00%,which was significantly higher than 81.63%in control group(P<0.05).The fever abatement times in treatment group and control group were(4.22±0.87)and(5.46±0.98)d;cough disappearance times were(6.31±0.98)and(7.49±1.10)d;disappearance times of pulmonary rales were(7.36±1.14)and(8.61±1.23)d,all with significant difference(all P<0.05).After treatment,the patchy infiltrating shadow sign rates in treatment group and control group were 2.00%and 16.33%;the bronchial wall thickening sign rates were 4.00%and 18.37%,all with significant difference(all P<0.05).After treatment,IgA levels in treatment group and control group were(0.55±0.11)and(0.68±0.12)g·L-1;IgM levels were(0.90±0.19)and(1.18±0.21)g·L-1;LDH levels were(229.45±10.30)and(240.18±11.17)U·L-1,all with significant difference(all P<0.05).The total incidence of adverse drug reactions in treatment group and control group were 6.00%and 4.08%respectively,without significant difference(P>0.05).Conclusion Erythromycin combined with low-dose methylprednone in systemic treatment of children with MPP and elevated LDH has a significant efficacy,and it can promote the reductions of inflammation and immune disorders and accelerate the disease outcomes,and it is safe and reliable.
2.Bioequivalence study of sidenafil citrate tablets in Chinese healthy subjects
Xiao-Bin LI ; Lu CHEN ; Xiu-Jun WU ; Yu-Xin GE ; Wen-Chao LU ; Ting XIAO ; He XIE ; Hua-Wei WANG ; Wen-Ping WANG
The Chinese Journal of Clinical Pharmacology 2024;40(3):430-434
Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33%and 25.00%,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.
3.Effects of sodium acetate on lowering uric acid and renal protection in mice with hyperuricemic nephropathy
Xue-Man LIN ; Shi-Qi ZHONG ; Yong-Mei LI ; Xiao-Yi QIN ; He-Yang JIANG ; Jia-Xin ZHOU ; Jian-Xin PANG ; Ting WU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2222-2226
Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9%NaCl+0.5%carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5%carboxymethyl cellulose sodium),model group(0.9%NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P<0.05,P<0.01,P<0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.
4.Variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip
Xu-Dong LUO ; Xin-Rong LI ; Cheng-Yi LI ; Peng QI ; Ting-Ting LIANG ; Shu-Bin LIU ; Zheng-Ze QIANG ; Jun-Gang HE ; Xu LI ; Xiao-Cheng WEI ; Xiao-Li FENG ; Ming-Wei WANG
Chinese Traditional Patent Medicine 2024;46(3):747-754
AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.
5.Prevalence of Echinococcus infections in small rodents in Yushu City, Qinghai Province in 2023
Gengcheng HE ; Shusheng WU ; Xianglan QIN ; Jilong MA ; Tingjun YU ; Chengxi SONG ; Xiaojin MO ; Xiao MA ; Jianfeng BA ; Guirong ZHENG ; Bin JIANG ; Tian TIAN ; Shijie YANG ; Ting ZHANG ; Xiaonong ZHOU
Chinese Journal of Schistosomiasis Control 2024;36(2):169-173
Objective To investigate the prevalence of Echinococcus infections in small rodents around human residential areas in Yushu City, Qinghai Province in 2023, so as to provide insights into precision echinococcosis control. Methods One or two quadrats, each measuring 50 m × 50 m, were randomly assigned in Shanglaxiu Township and Longbao Township, Yushu City, Qinghai Province on June 2023, respectively, and 300 plate-type mouse traps, each measuring 12.0 cm × 6.5 cm, were assigned in each quadrat. Small rodents were captured during the period between 10 : 00 and 18 : 00 each day for 4 days. Then, all captured small rodents were identified and dissected, and liver specimens with suspected Echinococcus infections were subjected to pathological examinations. The Echinococcus cytochrome c oxidase 1 (cox1) gene was amplified using PCR assay, and the sequence of the amplified product was aligned to that was recorded in the GenBank to characterize the parasite species. In addition, a phylogenetic tree of Echinococcus was generated based on the cox1 gene sequence using the neighbor-joining method. Results A total of 236 small rodents were captured in Shanglaxiu and Longbao townships, Yushu City, including 65 Qinghai voles and 51 plateau pikas in Shanglaxiu Township, and 62 Qinghai voles and 58 plateau pikas in Longbao Township, and there was no significant difference in the constituent ratio of small rodents between the two townships (χ2 = 0.294, P > 0.05). Seven plateau pikas and 12 Qinghai voles were suspected to be infected with Echinococcus by dissection, and pathological examinations showed unclear structure of hepatic lobules and disordered hepatocyte arrangement in livers of small rodents suspected of Echinococcus infections. PCR assay identified E. shiquicus DNA in 7 Qinghai voles, which were all captured from Shanglaxiu Township. Phylogenetic analysis showed that the cox1 gene sequence of Echinococcus in small rodents was highly homologous to the E. shiquicus cox1 gene sequence reported previously. Conclusion Plateau pika and Qinghai vole were predominant small rodents around human residential areas in Yushu City, Qinghai Province in 2023, and E. shiquicus infection was detected in Qinghai voles.
6.Diagnostic value of magnetic resonance T2*mapping sequence combined with texture feature indicator for postmenopausal osteoporosis
Xiao-Sheng YANG ; Mao-Ting LI ; Yan-Ning LI ; Song-He LIU
Chinese Medical Equipment Journal 2024;45(8):68-72
Objective To explore the application value of T2*mapping sequence combined with texture feature indicatoror in the diagnosis of postmenopausal osteoporosis(PMOP)in women.Methods The clinical data of 50 PMOP patients admitted to some hospital from March 2019 to April 2021(enrolled into an osteoporosis group)were analyzed retrospectively,and another two groups were established including a normal bone mineral density(BMD)group composed of 50 postmenopausal physical examiners with normal BMD(BMD>120 mg/cm3)and a reduced BMD group consisting of 50 postmenopausal women with decreased BMD(80 mg/cm3<BMD<120 mg/cm3).All the 3 groups underwent magnetic resonance lumbar spine conventional sequence and T2(mapping scanning and image texture feature extraction,which were compared in terms of lumbar T2*value and texture feature indicators including energy,contrast,correlation,deficit distance and entropy.Spearman correlation analysis was used to analyze the correlation between lumbar spine T2*values,texture feature indicators and the occurrence of POMP in women,independent predictors of the occurrence of PMOP in women were determined by multifactorial logistic regression analysis,the diagnostic efficacy of T2*mapping sequence combined with texture feature indicatoror for PMOP was analyzed using ROC curves,and a column-line diagram prediction model for POMP occurrence was constructed and validated.Results There were significant differences in T2*value,energy,contrast,correlation,deficit distance and entropy among the groups(P<0.05).Spearman correlation analysis showed that with the occurrence of POMP lumbar spine T2*value,contrast and entropy were significantly positively correlated,while energy,correlation and deficit distance were significantly negatively correlated(P<0.05).T2*value,energy,contrast,correlation,deficit distance and entropy were all independent predictors of the occurrence of POMP(P<0.05).T2*mapping sequence combined with texture feature indicatoror behaved better than any single indicator in AUC,sensitivity and specificity.The column-line diagram prediction model predicted a 75.00%probability of POMP in women,which was validated with advantages ind1iscrimination,calibration and net benefit rate.Conclusion Magnetic resonance T2*mapping sequence combined with texture feature indicator behaves well in diagnosing POMP of women,and T2*value,energy,contrast,correlation,deficit distance and entropy can be used as sensitive indicators for clinical screening of people at high risk for POMP.[Chinese Medical Equipment Journal,2024,45(8):68-72]
7.Hydrogen sulfide and neuroinflammation-mediated neurodegenerative diseases
Yu-Lian SHUI ; Zhi-Qiong REN ; Yi-Jie HE ; Bin-Bin CHEN ; Jia HONG ; Ke-Ting LIU ; Li XIAO
Journal of Regional Anatomy and Operative Surgery 2024;33(6):551-554
Hydrogen sulfide,as a third gas signal molecule and neurotransmitter,can play a neuroprotective role by anti-oxidative stress,anti-inflammatory response,metabolic inhibition and other mechanisms.It is of great significance for the occurrence and development of neurodegenerative diseases including Alzheimer's disease(AD)and Parkinson's disease(PD)mediated by neuroinflammation.This article reviews the research progress of hydrogen sulfide and neuroinflammation and its mediated neurodegenerative diseases,so as to provide new ideas for the treatment of neurodegenerative diseases.
8.MiR-513b-5p Inhibits Proliferation,Migration and Invasion of Laryngeal Squamous Cell Carcinoma by Targeting CXCL8
Yu-Liang ZHANG ; Xu-Ting XUE ; Ying WANG ; Long HE ; Xiao-Ya GUAN ; Chun-Ming ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(11):1627-1635
Metastasis is the main risk factor for poor prognosis of laryngeal squamous cell carcinoma (LSCC) .Chemokines are closely related to metastasis in the tumor microenvironment.CXCL8 is a cyto-kine-like secreted protein that plays key roles in the malignant development of a variety of tumors,but has not been elucidated in LSCC.In this paper,we elucidated the role of CXCL8 in LSCC cells and found miRNAs that targeted CXCL8,which may become new targets for the diagnosis and treatment of LSCC.Firstly,the GEPIA showed that CXCL8 was highly expressed in head and neck cancer (P<0.05).The real-time fluorescence quantification (qRT-PCR) found that CXCL8 was highly expressed in LSCC cells.The enzyme-linked immunoassay also found that CXCL8 was highly secreted in the superna-tant of LSCC cells (P<0.001) .Then,the CCK8 assay confirmed that knockdown of CXCL8 significant-ly inhibited the proliferation of FD-LSC-1 and AMC-HN8 cells (the average inhibition rate was 34.0%and 19.5%,respectively);The EdU assay also confirmed that knockdown of CXCL8 significantly inhibi-ted the proliferation of LSCC cells (P<0.05) .The transwell assay confirmed that knockdown of CXCL8 also significantly inhibited the migration and invasion of FD-LSC-1 cell (average inhibition rate was 40.0%,38.5%,respectively);Knockdown of CXCL8 also significantly inhibited the migration and inva-sion of AMC-HN8 cell (average inhibition rate was 37.5%,53.5%,respectively ) .The analysis of bioinformatics predicted that CXCL8 may be a target of miR-513b-5p.The dual luciferase reporter assay confirmed that miR-513b-5p could bind to the CXCL8-3'UTR.QRT-PCR assay also confirmed that over-expression of miR-513b-5p could decrease the 60% of the CXCL8 expression (P<0.01) .Cell function rescue assays found that overexpressed of CXCL8 could effectively reversed proliferation,migration and invasion of LSCC cells weakened by miR-513b-5p (P<0.05) .In summary,miR-513b-5p inhibited the proliferation,migration and invasion of LSCC cells by targeting CXCL8.
9.Pedigree Analysis of Hereditary Coagulation Factor Ⅻ Deficiency Caused by Compound Heterozygous Mutation p.Gly175Cys and p.Gly542Ser of F12 Gene
Xiao-Li CHENG ; Ting YANG ; Liu YANG ; Yi-Juan XIN ; Mu HE ; Lin ZHU ; Jia-Yun LIU
Journal of Experimental Hematology 2024;32(3):862-867
Objective:To analyze the clinical phenotype and gene mutation of a genetic coagulation factor Ⅻ(FⅫ)deficiency pedigree and explore the molecular pathogenesis.Methods:The activated partial thromboplastin time(APTT)and FⅫ activity(FⅫ:C)were detected by clotting method.The FⅫ antigen(FⅫ:Ag)was tested with ELISA.All exons and flanks of F12 gene were determined by Sanger sequencing.ClustalX-2.1-win,PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site,forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.Results:The APTT of the proband prolonged to 71.3 s.The FⅫ:C and FⅫ;Ag were decreased to 5%and 6%,respectively.There were two heterozygous missense mutations c.580G>T and c.1681G>A detected in exon 7 and exon 14 of F12 gene,resultingin p.Gly175Cys and p.Gly542Ser,severally.Proband's father carried the p.Gly175Cys heterozygous mutation,while mother,brother and daughter had the p.Gly542Ser heterozygous mutation.Software analysis showed that both Gly175 and Gly542 were conserved,the two mutations were harmful and when mutations had occurred,the corresponding sites affected the protein local structure.Conclusion:The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FⅫ deficiency pedigree.The p.Gly175Cys mutation has been detected for the first time in the world.
10.Loganin inhibits the ROS-NLRP3-IL-1β axis by activating the NRF2/HO-1 pathway against osteoarthritis
Miao LI ; Jiacong XIAO ; Baihao CHEN ; Zhaofeng PAN ; Fanchen WANG ; Weijian CHEN ; Qi HE ; Jianliang LI ; Shaocong LI ; Ting WANG ; Gangyu ZHANG ; Haibin WANG ; Jianfa CHEN
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):977-990
Loganin(LOG),a bioactive compound derived from Cornus officinalis Siebold & Zucc,has been understudied in the context of osteoarthritis(OA)treatment.In this study,we induced an inflammatory response in chondrocytes using lipopolysaccharide(LPS)and subsequently treated these cells with LOG.We employed fluorescence analysis to quantify reactive oxygen species(ROS)levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2(NRF2)using real-time quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunofluorescence(IF)techniques.Additionally,we developed an OA mouse model by performing medial meniscus destabilization(DMM)surgery and monitored disease progression through micro-com-puted tomography(micro-CT),hematoxylin and eosin(H&E)staining,safranin O and fast green(S&F)staining,and immunohisto-chemical(IHC)analysis.Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes,inhibited the activation of the NLRP3 inflammasome,and enhanced NRF2/heme oxygenase 1(HO-1)signaling.In vivo,LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery,decreased NLRP3 expression,and increased NRF2 expres-sion.These findings suggest that LOG has a protective effect against OA,potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.

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