Relationship of serum FAK and F ABP4 levels with myocardial injury and cardiac function in elderly patients with acute myocardial infarction / 中华老年心脑血管病杂志

Objective To explore the analysis of the relationship of the serum levels of focal adhe-sion kinase(FAK)and fatty acid-binding protein 4(FABP4)with myocardial injury and cardiac function in elderly patients with acute myocardial infarction(AMI).Methods A total of 211 AMI patients admitted to our hospital from January 2020 to April 2023 were enrolled and assigned into the AMI group,while another 60 healthy volunteers who took routine physical examinations in our hospital during the same period served as the control group.The serum FAK and FABP4 lev-els were compared between the two groups.Multivariate logistic regression analysis was employed to identify influencing factors associated with AMI,and ROC curve was plotted to assess the pre-dictive efficacy of the serum FAK and FABP4 levels for AMI in the elderly population.Pearson correlation analysis was conducted to explore the relationship between serum FAK and FABP4 levels and myocardial injury as well as cardiac function.Results The AMI group exhibited signifi-cantly elevated serum FAK,FABP4,CK-MB,cTnⅠ and CK levels,and larger LVESD and LVEDD,but lower LVEF when compared with the control group(P＜0.05,P＜0.01).For the AMI patients,the serum FAK and FABP4 levels were positively correlated with CK-MB,cTnⅠ and CK levels,as well as LVESD and LVEDD,and negatively with LVEF(P＜0.05).Multivariate logistic regression analysis revealed that both serum levels of FAK(OR=2.872,95％CI:2.230-3.698,P=0.000)and FABP4(OR=2.667,95％CI:1.713-4.154,P=0.000)were influencing factors for AMI.ROC analysis indicated that the cut-off value of FAK level for diagnosing AMI was 25.60 pg/L,with an AUC value of 0.801(95％CI:0.750-0.852).Similarly,the cut-off value of FABP4 in the diagnosis was 23.22 pg/L,with an AUC value of 0.760(95％CI:0.707-0.812).Combined FAK and FABP4 levels yielded,with an AUC value of 0.899(95％CI:0.839-0.918).Conclusion Serum FAK and FABP4 levels are abnormally high in the elderly patients with AMI,which is closely related to myocardial injury and cardiac function.The two indicators alone or in combination can effectively predict the occurrence of AMI.

Evaluation of tegacycline regimens in treatment of gram-negative bacterial infections with Monte Carlo simulation / 中国临床药理学与治疗学

AIM: To evaluate the dose regimens of tegacycline for treatment of hospital-acquired pneumonia, complex abdominal infection and complex skin and soft tissue infection caused by Gram-negative bacterial infections with Monte Carlo model. METHODS: The minimum inhibitory concentrations (MICs) of tegacycline against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae were collected from the CHINET in 2018. The target probability (PTA) and cumulative response fraction (CFR) of different regimens were calculated using Monte Carlo simulation based on PK/PD theory of tegacycline. RESULTS:In the treatments of HAP caused by gram-negative bacteria, when MIC≤0.5 μg / mL, the PTA of 50 mg q12h was greater than 90%, and when MIC≥1 μg / mL, PTA and CFR of 100 mg q12h were both greater than 90%, When MIC≥2 μg/mL, 50 mg q12h, 75 mg q12h and 100 mg q12h doses of PTA were less than 90%. In the treatment of cIAI, when MIC≤0.5 μg / mL, PTA of 50 mg q12h reached the target value, and when MIC=1 μg/mL, PTA of 100 mg q12h was greater than 90%. For complex skin and soft tissue infection, when the MIC≤0.25 μg/mL, the PTA of 75 mg q12h and 100 mg q12h was greater than 90%, and the PTA of the three administration regimen was less than 90%, when the MIC≥0.5 μg/mL. CONCLUSION:The dose of 50 mg q12h is more suitable for the treatment of HAP, when MIC>0.5 μg/mL, tigecycline may need 100 mg q12h to obtain the best clinical efficacy in the treatment of cIAI. For cSSSI. when MIC≤0.25 μg/mL, tigecycline can be administered with 75 mg q12h and 100 mg q12h. For the three types of infections caused by Escherichia coli, the conventional dose of tigecycline may achieve clinical efficacy.

Effect of miR-20b on the motor dysfunction after traumatic brain injury in mice and the underlying mechanism / 中华创伤杂志

Objective:To investigate effect of miR-20b on the motor dysfunction after traumatic brain injury (TBI) in mice and the underlying mechanism.Methods:Sixty C57BL/6J mice were divided into sham group, TBI group and TBI+miR-20b Agomir (Agomir-20b) group according to the random number table, with 20 mice per group. A model of severe TBI was induced by controlled cortical impact. After injury, the mice in TBI group were subjected to tail-vein injection of 200 μl Agomir-negative control at dosage of 50 μmol/L and the mice in TBI+Agomir-20b group were subjected to tail-vein injection of 200 μl Agomir-20b at dosage of 50 μmol/L. At days 3 and 7 postinjury, the rate of neuronal apoptosis in the pericontusional region was detected by TUNEL assay, expression levels of apoptosis-related proteins in the pericontusional region were detected by Western blot analysis, including cleaved caspase-3, cleaved poly adenosine diphosphate-ribose polymerases (PARP), B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), motor function was evaluated by beam walking test, and expression levels of cytokine mRNAs in the pericontusional region were detected by real-time quantitative PCR (RT-qPCR), including interleukin (IL)-1β, IL-6, IL-10, inducible nitric oxide synthase (iNOS), arginase (Arg) and macrophage mannose receptor 1 (CD206).Results:In TUNEL assay, the rate of neuronal apoptosis in sham group was significantly lower than that in TBI group and TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01), and there was a significantly lower rate of neuronal apoptosis in TBI+Agomir-20b group as compared with TBI group (all P<0.01). In Western blot analysis, significantly increased levels of cleaved caspase-3, cleaved PARP and Bax proteins and lowered level of Bcl-2 protein were observed in TBI group at days 3 and 7 postinjury as compared with sham group (all P<0.01); similar levels of cleaved caspase-3, cleaved PARP and Bax proteins were found in TBI+Agomir-20b group at days 3 and 7 postinjury as compared with sham group (all P>0.05), and level of Bcl-2 protein in TBI+Agomir-20b group also showed no obvious variation at day 7 postinjury as compared with sham group ( P>0.05) in regardless of a significant reduction at day 3 postinjury ( P<0.01). Significantly increased levels of cleaved caspase-3, cleaved PARP and Bax proteins as well as a significantly reduced level of Bcl-2 protein were found in TBI group at days 3 and 7 postinjury as compared with TBI+Agomir-20b group (all P<0.05 or 0.01). In beam walking test, the latency and foot slip rate in TBI group were significantly higher than those in sham group and TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01). In RT-qPCR analysis, levels of IL-1β, IL-6 and iNOS mRNA in TBI group were significantly higher than those in TBI+Agomir-20b group at days 3 and 7 postinjury (all P<0.01), but the two groups were similar in levels of IL-10, Arg and CD206 mRNA (all P>0.05). In comparison with sham group, levels of IL-1β, IL-6, iNOS and IL-10 mRNA in TBI+Agomir-20b group had no obvious change at days 3 and 7 postinjury (all P>0.05); level of Arg mRNA in TBI+Agomir-20b group was significantly increased at days 3 and 7 postinjury (all P<0.01); level of CD206 mRNA in TBI+Agomir-20b group did not change significantly at day 3 postinjury ( P>0.05), but was significantly increased at day 7 postinjury ( P<0.01). Conclusions:miR-20b can obviously inhibit neuronal apoptosis to improve motor function after TBI in mice, for which the underlying mechanism is related to Agomir-20b inhibiting the transformation of microglia to pro-inflammatory M1 type after TBI.

Pedigree analysis of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene / 中华内分泌代谢杂志

Objective:To investigate clinical phenotypes of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene and the correlation between genotype and phenotype, exploring ferritin cutoff value for screening.Methods:One case of type Ⅳ hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene and 5 generations of their family lineage with a total of 47 members who were seen at the First Affiliated Hospital of Nanjing Medical University in July 2020 were studied for systematic clinical investigation. Thirty-nine surviving individuals were tested for ferritin, liver function, fasting plasma glucose (FPG), and sex hormones, and Sanger sequencing was performed to verify the mutation loci and to map the family tree. Spearman correlation analysis was used to explore the relationship between ferritin and other indicators, and receiver operating characteristic curves were used to calculate the ferritin cutoff value for screening for this genotype of hemochromatosis.Results:Ten patients with c. 430A>G heterozygous mutation in the SLC40A1 gene were identified among 39 family members, and five of them were diagnosed with hemochromatosis, presenting incomplete penetrance. The differences in levels of ferritin, aspartate aminotransferase (AST; both P<0.01) and FPG, as well as incidences of hypogonadotropic hypogonadism and arthritis (all P<0.05) between group of mutation positive and group negative were statistically significant, while the difference in alanine aminotransferase (ALT) was not. Spearman correlation analysis showed that, ferritin levels were significantly associated with ALT ( r=0.903), AST ( r=0.879), FPG ( r=0.782), and the incidences of hypogonadotropic hypogonadism ( r=0.798) and arthritis ( r=0.798; all P<0.01) in those with the c. 430A>G heterozygous mutation in the SLC40A1 gene. The ferritin cutoff value for screening of hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene was 1 036.7 μg/L, with a sensitivity and specificity of 100% and 94.3%, respectively. Conclusion:The SLC40A1 gene c. 430A>G heterozygous mutation is closely associated with elevated levels of AST and FPG, increased incidences of hypogonadotropic hypogonadism and arthritis, and the ferritin cutoff value is a useful screening parameter.

Comparison of Chemical Constituents Differences between Angelicae dahuricae with and without Sulphur- fumigation and Selection of Chemical Markers Based on 1H-NMR Metabolomics / 中国药房

OBJECTIVE：To study the diff erences in the overall chemical constituents of Angelicae dahuricae with and without sulphur-fumigation，and to select chemical markers that can be used for identification. METHODS ：Each 16 batches of A. dahuricae with and without sulphur-fumigation were selected as samples. Deuterated methanol-deuterium oxide （1 ∶ 0.2，V/V）was used as extraction solvent ，and 1H-NMR metabolomics was used to detect the primary and secondary metabolites in A. dahuricae . In addition ，visual analysis ，principal component analysis （PCA）and t-test were used to compare the component differences of A. dahuricae by two kinds of pretreatment methods. RESULTS ：A total of 19 chemical constituents such as coumarins ，amino acids and sugars were simultaneously detected and identified from two kinds of A. dahuricae . Visual analysis showed that the chemical profiles of the two kinds of A. dahuricae were similar ，but their coumarins and carbohydrates were quite different in 1H-NMR signal intensity. PCA analysis showed that all samples could be divided into two categories according to different treatment methods. The results of t-test showed that the contents of oxypeucedanin ，imperatorin，glucose and sucrose of A. dahuricae were decreased significantly after sulphur fumigation （P＜0.01 or P＜0.001），while the contents of alanine and leucine were significantly increased （P＜0.01 or P＜0.001）. There was no statistical significance in the contents of other 13 kinds of components （P＞0.05）. CONCLUSIONS：There are obvious differences in the 6 chemical compounds of oxypeucedanin ，imperatorin，glucose，sucrose， alanine and leucine in A. dahuricae with and without sulphur-fumigation ，which can be used as chemical markers for the identification of sulphur-fumigated A. dahuricae in the market.

Study on Main Treatment Diseases and Medication Rule in Sichuan Nanpai Tibetan Medicine Based on Data Mining / 中国药房

OBJECTIVE： To study the academic characteristics and connotation of Sichuan Nanpai Tibetan medicine （SNTM）， to provide relevant information for the inheritance and development of Nanpai Tibetan medicine， and to provide reference for the development and utilization of commonly used medicinal materials in SNTM. METHODS： The type characteristics， medication frequency， main treatment disease and medication rule of 672 preparations of Tibetan hospital of SNTM were analyzed by means of data mining， statistical analysis and inductive deduction methods of TCM inheritance support system （TCMISS）. Based on the core combination drugs， the new prescriptions were evolved by the entropy hierarchical clustering method. RESULTS： A total of 624 medicinal materials were used in formulation of SNTM， involving 509 plant drugs （81.67％）， 61 mineral drugs （9.77％） and 54 animal drugs （8.65％）. There were 16 medicines with frequency＞120； among them， top 3 medicines were Terminalia chebula （57.44％）， Carthamus tinctorius （43.15％） and Aucklandia lappa （42.26％）. Main treatment diseases involved 13 categories， and top 3 categories were gastric diseases （28.13％）， hepatobiliary diseases （12.80％） and neurological diseases （11.90％）. In the treatment of stomach diseases， T. chebula， C. tinctorius， Alpinia katsumadai， Piper longum， A. lappa and Punica granatum were mainly used； totally 61 commonly used drug combinations were obtained and the most commonly used combination was P. longum-A. katsumadai. In the treatment of hepatobiliary diseases， T. chebula， C. tinctorius， Herpetospermum caudigerum， Swertia bimaculata， Zhaxun were mainly used； 64 commonly used drug combinations were obtained and the most commonly used combination is T. chebula-C. tinctorius. In the treatment of neurological diseases， Myristica fragrans， T. chebula， A. lappa， Syzygium aromaticum， Aquilaria sinensis， Choerospondias axillaris were mainly used； 73 commonly used drug combinations were obtained， and the most commonly used combination was T. chebula-M. fragrans. 5 candidate new formulations had been evolved by the entropy hierarchical clustering method， involving Lacciferlacca-Lithospermum erythrorhizon-Rubia cordifolia- Punica granatum. CONCLUSIONS： Obtained high frequency drug pairs and evolved new candidate formulation based on the core combinations drugs of SNTM for commonly diseases can provide reference for the development of modern new Tibetan medicines for gastric， hepatobiliary and neurological diseases.

Study on the Current Use Situation of National Essential Medicine and Its Related Factors of Priority Use Based on Our Hospital and Parts of the Country / 中国药房

OBJECTIVE:To understand the status of the use of national essential medicines,and provides reference for further implementing the national essential medicine system and promoting the priority use of national essential medicines. METHODS:Ac-cording to the statistics analysis of the use of national essential medicines(for example the antihypertensives and oral hypoglycemic agents)in Beijing,Shanghai and Guangzhou areas,the related influential factors about priority use of national essential medicines were explored. RESULTS:The proportions of use amount of national essential medicines in our hospital in 2012-2013 to the total amount of medicines were 21.20% and 18.75%,respectively,with a downtrend;the proportion of antihypertension drugs to total amount was only 14.05%and 13.70%,respectively;compared with the same generic drugs with individual pricing,the GMP prod-ucts of Valsartan capsule,Bisoprilol tablet and Amlodipine tablet had no advantages in DDDs,or even lower. DDDs of individual pricing drugs of Acarbose tablet in medical institutions in Beijing area and tertiary hospitals in Shanghai and Guangzhou area in 2011-2012 were much higher than the generic GMP products with the same generic drugs. CONCLUSIONS:The clinical use of na-tional essential medicines in our hospital and parts of the country still remains to be further improved,the influential factors includ-ed reimbursement mechanism,awareness rate of related knowledge,physicians’habit to drug use and pursuing economic benefits. The propaganda and training should be strengthened,awareness rate of medical staff and publics to national essential medicines, the availability of national essential medicines and national essential medicine system and medicare reimbursement payment policy should be improved,and the priority use of national essential medicines should be promoted by more measures combination use.

Research on the Standardized Package of Metformin Tablets / 中国药房

OBJECTIVE:To explore the standardized package of Metformin tablets to meet clinical needs. METHODS:Statis-tics was conducted for the utilization data of Metformin tablets in medical and health institutions from 6 cities of China;question-naires were designed to investigate and analyze the evaluation for the suitability of physicians,pharmacists and patients in the pre-scription,deployment and use links to Metformin tablets with different packaging loaded amount in Beijing and Haikou. RE-SULTS:For 0.5 g/tablet,the daily dose of 1.5 g accounted for the largest proportion (32.23%-69.91%) in 5 cities except for Chengdu. Totally 490 questionnaires about package suitability of Metformin tablets in outpatient department were sent out,includ-ing 478 valid questionnaires with effective rate of 97.5%. Results showed that packaging quantity with 4 weeks was considered as appropriate by physicians,pharmacists and patients in Beijing;however,packaging quantity with 1-2 week(s) was considered as appropriate by physicians,pharmacists and patients in Haikou;300-500 tablets of packaging quantity were preferred to be appropri-ate with the matching degree of automatic dispensing machines in both places. CONCLUSIONS:Considering the results in 2 plac-es,for 0.5 g/tablet,2 weeks is appropriate for the packaging loaded amount in outpatient department,that is 0.5 g×45 tablets/box;and 300-500 tablets/box is appropriate for inpatient pharmacies.