1.Effect of finite element method in treatment of developmental dysplasia of the hip in children
Xiaojun SUN ; Huaming WANG ; Dehong ZHANG ; Xuewen SONG ; Jin HUANG ; Chen ZHANG ; Shengtai PEI
Chinese Journal of Tissue Engineering Research 2025;29(9):1897-1904
BACKGROUND:Developmental dysplasia of the hip often leads to limb deformities in children,and the research related to its diagnosis and treatment has been gradually clarified.Recently,the finite element method has been paid attention to by scholars in the research related to developmental dysplasia of the hip because of its advantages. OBJECTIVE:Through literature search and review of the relevant research progress of finite element method in children's developmental dysplasia of the hip and treatment,analyze and summarize its advantages and disadvantages,and explore the direction of further research in the future. METHODS:PubMed,SCI,CBM,and CNKI were searched for relevant articles published from January 2014 to November 2023 with the key words of"developmental dysplasia(dislocation)of the hip,dysplasia of the hip,finite element analysis(method),pavlik harness,fixation in herringbone position,biomechanics,pelvic osteotomies,pemberton,salter,dega,periacetabular osteotomy,children"in Chinese and English.A small number of long-term articles were included,and 62 articles were finally included for analysis through screening. RESULTS AND CONCLUSION:(1)The mechanical environment of hip joint in children with developmental dysplasia of the hip was abnormal.The pressure in acetabulum was uneven.The stress increased and concentrated;the joint contact area decreased,and the local stress concentrated in femoral neck.(2)In the Pavlik sling and herringbone fixation,the mechanical environment of the hip was improved;the concentrated high stress area disappeared and the joint contact area increased,but the excessive abduction angle led to the increase of stress in the acetabulum and the lateral femoral head.(3)After pelvic osteotomy,the stress environment of hip joint and sacroiliac joint was improved.There was no single hinge in the three kinds of osteotomy,and the stress load position was different according to the age of the children.(4)After peri-acetabular osteotomy,the joint contact pressure was close to normal,but it was difficult to recover in patients with non-spherical femoral head.(5)The postoperative X-ray film findings could not show that the joint contact mechanics was the best.(6)It is indicated that the information that cannot be measured in the body can be obtained by using the finite element method,which can be operated in a virtual environment without the limitation of time and ethics.It can directly see the stress change area of normal and developmental dysplasia of the hip,explain the effectiveness of treatment from the point of view of mechanics,establish a specific finite element model and tailor-made operation plan for patients who need osteotomy.There is no standard or unified standard for the finite element modeling of developmental dysplasia of the hip and the material characteristic parameters of children's hip joint.Due to the inherent limitations of finite element method,it is impossible to analyze the model that contains bone,cartilage,ligament,muscle and other elements at the same time.The operation of finite element analysis is difficult,although it has advantages,it is not universal,and the current research sample size is small,which needs to be further expanded and verified.
2.Identification of terpenoid synthases family in Perilla frutescens and functional analysis of germacrene D synthase.
Pei-Na ZHOU ; Zai-Biao ZHU ; Lei XIONG ; Ying ZHANG ; Peng CHEN ; Huang-Jin TONG ; Cheng-Hao FEI
China Journal of Chinese Materia Medica 2025;50(10):2658-2673
Based on whole-genome identification of the TPS gene family in Perilla frutescens and screening, cloning, bioinformatics, and expression analysis of the synthetic enzyme for the insect-resistant component germacrene D, this study lays the foundation for understanding the biological function of the TPS gene family and the insect resistance mechanism in P. frutescens. This study used bioinformatics tools to identify the TPS gene family of P. frutescens based on its whole genome and predicted the physicochemical properties, systematic classification, and promoter cis-elements of the proteins. The relative content of germacrene D was detected in both normal and insect-infested leaves of P. frutescens, and the germacrene D synthase was screened and isolated. Gene cloning, bioinformatics analysis, and expression profiling were then performed. The results showed that a total of 99 TPS genes were identified in the genome, which were classified into the TPS-a, TPS-b, TPS-c, TPS-e/f, and TPS-g subfamilies. Conserved motif analysis showed that the TPS in P. frutescens has conserved structural characteristics within the same subfamily. Promoter cis-element analysis predicted the presence of light-responsive elements, multiple hormone-responsive elements, and stress-responsive elements in the TPS family of P. frutescens. Transcriptome data revealed that most of the TPS genes in P. frutescens were highly expressed in the leaves. GC-MS analysis showed that the relative content of germacrene D significantly increased in insect-damaged leaves, suggesting that it may act as an insect-resistant component. The germacrene D synthase gene was screened through homologous protein binding gene expression and was found to belong to the TPS-a subfamily, encoding a 64.89 kDa protein. This protein was hydrophilic, lacked a transmembrane structure and signal peptide, and was predominantly expressed in leaves, with significantly higher expression in insect-damaged leaves compared to normal leaves. In vitro expression results showed that germacrene D synthase tended to form inclusion bodies. Molecular docking showed that farnesyl pyrophosphate(FPP) fell into the active pocket of the protein and interacted strongly with six active sites. This study provides a foundation for further research on the biological functions of the TPS gene family in P. frutescens and the molecular mechanisms underlying its insect resistance.
Perilla frutescens/chemistry*
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Plant Proteins/chemistry*
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Multigene Family
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Sesquiterpenes, Germacrane/metabolism*
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Alkyl and Aryl Transferases/chemistry*
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Phylogeny
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Gene Expression Regulation, Plant
3.Analysis of gene expression in synovial fluid and blood of patients with knee osteoarthritis of Yang deficiency and blood stasis type.
Hao-Tian HUA ; Zhong-Yi ZHANG ; Zhao-Kai JIN ; Peng-Qiang LOU ; Zhuo MENG ; An-Qi ZHANG ; Yang ZHANG ; Pei-Jian TONG
China Journal of Orthopaedics and Traumatology 2025;38(8):792-799
OBJECTIVE:
To reveal the molecular basis of knee osteoarthritis (KOA) with Yang deficiency and blood stasis syndrome by analyzing the gene expression profiles in synovial fluid and blood of KOA patients with this syndrome.
METHODS:
A total of 80 KOA patients were recruited from October 2022 to June 2024, including 40 cases in the non-Yang deficiency and blood stasis group (27 males and 13 females), with an average age of (61.75±3.45) years old;and 40 cases in the Yang deficiency and blood stasis group (22 males and 18 females), with an average age of (62.00±2.76) years old. The levels of body mass index (BMI), high-density lipoprotein (HDL), low-density lipoprotein (LDL), fibrinogen, total cholesterol, and D-dimer were recorded and summarized. Blood and synovial fluid samples from patients were collected for gene expression profile microarray sequencing, and then PCR and immunohistochemistry were used for clinical verification on the patients' synovial fluid and cartilage samples.
RESULTS:
Logistic regression analysis showed that compared with KOA patients with non-Yang deficiency and blood stasis syndrome, those with Yang deficiency and blood stasis syndrome had increased BMI, LDL, fibrinogen, total cholesterol, and D-dimer, and decreased HDL, with a clear correlation between the two groups. There were 562 differential genes in the blood, among which 322 were up-regulated and 240 were down-regulated;755 differential genes were found in the synovial fluid, with 350 up-regulated and 405 down-regulated. KEGG signaling pathway analysis of synovial fluid revealed changes in lipid metabolism-related pathways, including cholesterol metabolism, fatty acid metabolism, and PPARG signaling pathway. Analysis of the involved differential genes identified 6 genes in synovial fluid that were closely related to lipid metabolism, namely LRP1, LPL, ACOT6, TM6SF2, DGKK, and PPARG. Subsequently, PCR and immunohistochemical verification were performed using synovial fluid and cartilage samples, and the results were consistent with those of microarray sequencing.
CONCLUSION
This study explores the clinical and genomic correlation between traditional Chinese medicine syndromes and knee osteoarthritis from the perspective of lipid metabolism, and proves that abnormal lipid metabolism is closely related to KOA with Yang deficiency and blood stasis syndrome from both clinical and basic aspects.
Humans
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Male
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Female
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Middle Aged
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Synovial Fluid/metabolism*
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Osteoarthritis, Knee/metabolism*
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Yang Deficiency/complications*
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Aged
4.Association between metabolic parameters and erection in erectile dysfunction patients with hyperuricemia.
Guo-Wei DU ; Pei-Ning NIU ; Zhao-Xu YANG ; Xing-Hao ZHANG ; Jin-Chen HE ; Tao LIU ; Yan XU ; Jian-Huai CHEN ; Yun CHEN
Asian Journal of Andrology 2025;27(4):482-487
The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
Humans
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Male
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Erectile Dysfunction/metabolism*
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Hyperuricemia/metabolism*
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Adult
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Middle Aged
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Cross-Sectional Studies
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Glycated Hemoglobin/metabolism*
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Blood Glucose/metabolism*
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Uric Acid/blood*
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Young Adult
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Triglycerides/blood*
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Adolescent
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Cholesterol, LDL/blood*
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Penile Erection/physiology*
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Surveys and Questionnaires
5.Genetic profiling and intervention strategies for phenylketonuria in Gansu, China: an analysis of 1 159 cases.
Chuan ZHANG ; Pei ZHANG ; Bing-Bo ZHOU ; Xing WANG ; Lei ZHENG ; Xiu-Jing LI ; Jin-Xian GUO ; Pi-Liang CHEN ; Ling HUI ; Zhen-Qiang DA ; You-Sheng YAN
Chinese Journal of Contemporary Pediatrics 2025;27(7):808-814
OBJECTIVES:
To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies.
METHODS:
A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene.
RESULTS:
For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295).
CONCLUSIONS
Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans
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Phenylketonurias/epidemiology*
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Female
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Male
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Retrospective Studies
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Phenylalanine Hydroxylase/genetics*
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Mutation
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Child, Preschool
;
China/epidemiology*
;
Child
;
Infant
6.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
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Practice Guidelines as Topic
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Drugs, Chinese Herbal/therapeutic use*
7.Associations of Genetic Risk and Physical Activity with Incident Chronic Obstructive Pulmonary Disease: A Large Prospective Cohort Study.
Jin YANG ; Xiao Lin WANG ; Wen Fang ZHONG ; Jian GAO ; Huan CHEN ; Pei Liang CHEN ; Qing Mei HUANG ; Yi Xin ZHANG ; Fang Fei YOU ; Chuan LI ; Wei Qi SONG ; Dong SHEN ; Jiao Jiao REN ; Dan LIU ; Zhi Hao LI ; Chen MAO
Biomedical and Environmental Sciences 2025;38(10):1194-1204
OBJECTIVE:
To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease.
METHODS:
This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used.
RESULTS:
During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity.
CONCLUSION
Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans
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Pulmonary Disease, Chronic Obstructive/epidemiology*
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Exercise
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Male
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Female
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Middle Aged
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Prospective Studies
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Aged
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Genetic Predisposition to Disease
;
Risk Factors
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United Kingdom/epidemiology*
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Incidence
;
Adult
8.Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China
Chuan ZHANG ; Ling HUI ; Bing-Bo ZHOU ; Lei ZHENG ; Yu-Pei WANG ; Sheng-Ju HAO ; Zhen-Qiang DA ; Ying MA ; Jin-Xian GUO ; Zong-Fu CAO ; Xu MA
Chinese Journal of Contemporary Pediatrics 2024;26(1):67-71
Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.
9.Clinical trial of intra-arterial nimodipine perfusion after interventional embolization in the treatment of patients with symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage
Jin-Ming QIAN ; Qian ZHANG ; Pei-Dong YUE
The Chinese Journal of Clinical Pharmacology 2024;40(3):325-329
Objective To observe the effect of intra-arterial nimodipine perfusion after interventional embolization in the treatment of symptomatic cerebral vasospasm(SCVS)after aneurysmal subarachnoid hemorrhage(aSAH)and explore its influence on vascular endothelial function.Methods Patients with SCVS after aSAH were divided into treatment group and control group according to cohort methods.Both groups received interventional embolization based on symptomatic supportive treatment,and were given conventional 3H treatments such as blood dilution,dilatation and pressure enhancement after surgery,and the treatment group was additionally given intra-arterial perfusion of nimodipine(20%nimodipine was injected by electronic pump through the femoral artery sheath at a rate of 0.2 mg·min-1 for 2 mg once a day,vascular sheath was removed and nimodipine tablet after 7 days of medication was taken orally for 60-120 mg twice a day after meals),and both groups were treated for 14 days.The cerebrovascular blood flow velocity,laboratory indicators,postoperative complications and prognosis were compared between the two groups.Results There were 41 cases in treatment group,and 38 cases in control group.After 2 weeks of treatment,the average blood flow velocities of anterior cerebral artery(ACA)in treatment group and control group were(84.32±5.27)and(93.46±5.61)cm·s-1,the average blood flow velocities of middle cerebral artery(MCA)were(86.05±5.94)and(95.23±6.37)cm·s-1,the average blood flow velocities of posterior cerebral artery(PCA)were(59.41±4.82)and(71.56±5.39)cm·s-1 respectively(all P<0.05).The levels of serum endothelin-1(ET-1)in treatment group and control group after 2 weeks of treatment were(76.32±10.58)and(94.16±10.98)pg·mL-1;the levels of vascular endothelial growth factor(VEGF)were(127.45±14.83)and(164.85±15.62)ng·mL-1;the levels of soluble fms-like tyrosine kinase-1(sFlt-1)were(103.67±15.34)and(114.98±16.43)ng·L-1;the levels of plasma soluble intercellular adhesion molecule-1(sCAM-1)were(234.81±62.79)and(285.36±90.24)ng·mL-1;the levels of hypoxia-inducible factor-2α(HIF-2α)were(98.74±7.56)and(102.49±8.35)pg·mL-1;the levels of serum nitric oxide(NO)were(43.16±4.91)and(39.72±5.37)mmol·L-1,all with significant difference(all P<0.05).The incidence rates of delayed cerebral vasospasm(DCVS)and hydrocephalus were 4.88%and 9.76%in treatment group after surgery,lower than 21.05%and 28.95%in control group(all P<0.05).The proportion of Glasgow outcome scale(GOS)score of 5 points in treatment group at 3 months after surgery was higher than that in control group(78.05%vs 55.26%,P<0.05).Conclusion After interventional embolization,intra-arterial perfusion of nimodipine for SCVS after aSAH can help to relieve the inflammatory response,improve the vascular endothelial function and reduce the cerebral blood flow velocity,and it plays a positive role on reducing the cerebral tissue injury and improving the prognosis of patients.
10.Clinical trial of olanzapine tablets combined with magnesium valproate sustained-release tablets in the treatment of adolescent patients with depression
Pei-Jin CUI ; Yue WANG ; Mao-Lin CAO ; Yi-Fei ZHANG ; Liang FANG
The Chinese Journal of Clinical Pharmacology 2024;40(19):2817-2821
Objective To observe the clinical efficacy and safety of olanzapine tablets combined with magnesium valproate sustained-release tablets in the treatment of adolescent depressed patients.Methods Adolescents with depression were divided into control group and treatment group by simple random method.The control group was treated with oral olanzapine tablets with 5 mg·d-1 as the starting dose.After 1 week of treatment,the drug dose was adjusted according to the symptoms and kept within 20 mg·d-1.The treatment group was given oral magnesium valproate sustained-release tablet combined treatment on the basis of the control group,with 0.5 g as the initial dose,and the maximum dose was adjusted according to clinical symptoms after 1 week of treatment,and the maximum dose was no more than 1 g·d-1.Both groups were treated for 12 weeks.The clinical efficacy,excitatory amino acid(EAA),connectin level,intestinal fatty acid binding protein(Ⅰ-FABP),Hamilton depression scale(HAMD),Bech-Rafaelsen Mania Rating Scale(BRMS)and safety of the two groups were compared.Results Sixty-three cases were included in the treatment group and control group,respectively.After treatment,the total effective rates of the treatment group and the control group were 92.06%(58 cases/63 cases)and 79.37%(50 cases/63 cases),respectively,and the difference was statistically significant(P<0.05).After treatment,the levels of EAA in the treatment group and the control group were(29.98±3.44)and(27.97±3.88)μg·mL-1;the levels of zonulin were(189.45±19.56)and(182.33±19.89)ng·mL-1;the levels of Ⅰ-FABP were(99.27±9.13)and(103.84±9.36)pg·mL-1,respectively;the HAMD scores of the treatment group and the control group were 9.88±1.03 and 10.74±1.95;the BRMS scores were 5.08±0.32 and 5.32±0.51,respectively.Compared with the control group,the differences of above indexes in the treatment group were statistically significant(all P<0.05).The main adverse drug reactions in the two groups were weight gain,dry mouth,and drowsiness.The total incidences of adverse drug reactions in the treatment group and the control group were 12.70%and 15.87%,respectively,and the difference was not statistically significant(P>0.05).Conclusion Olanzapine tablets combined with magnesium valproate sustained-release tablets can effectively increase plasma Ⅰ-FABP,EAA,and zonulin levels in adolescent depressed patients,and improve HAMD and BRMS scores,with good safety.

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