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AIM: To investigate the effect of CDAG208A gene polymorphism on the efficacy and safety of gemcitabine in the first-line treatment of lung squamous cell carcinoma. METHODS: Sixty-five first-line treated patients with locally advanced or metastatic lung squamous cell carcinoma in The First Affiliated Hospital of Wannan Medical College hospital were screened. Group A included 31 patients tested with the GG (wild homozygous) CDAG208A gene, and group B included 34 patients without testing. All patients received gemcitabine plus platinum chemotherapy for at least 2 cycles. The efficacy and safety were evaluated following the RECIST 1.1 standard and the NCI-CTC 5.0 standard, respectively. The primary study endpoint was progression-free survival (PFS), overall survival (OS) and the secondary study endpoints included objective effective rate (ORR), disease control rate (DCR), adverse reactions, and influencing factors of PFS. RESULTS: The results showed that the DCR was 74.5% and 50% in group A and group B, respectively (P=0.045); mPFS was 6.1 months and 5.0 months in group A and group B, respectively (P=0.034); and the mOS was 13.3 months and 12.0 months in group A and group B, respectively, and there was no statistical difference (P=0.388). The number of cases of grade III-IV neutropenia in group A and group B was 2 and 10, respectively (P=0.017); grade III-IV neutropenia was an independent prognostic factor affecting patients with PFS (P=0.045); the group with unknown G208A gene status was more likely to develop grade III-IV neutrophils (P= 0.029). The AUC of CDA-G208A gene predicting neutropenia caused by gemcitabine chemotherapy was 0.756. CONCLUSION: Non-GG type of CDAG208A gene can reduce the metabolic rate of gemcitabine in the body and cause neutropenia after chemotherapy. In severe cases, it can indirectly reduce the clinical efficacy of gemcitabine. The detection of CDA-G208A gene status before treatment can predict the neutropenia caused by gemcitabine chemotherapy.
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AIM: The pre-prescription system of outpatient was established and implemented based on six sigma DMAIC model to ensure the safety of drug use and promote rational of drug use. METHODS: The rules database was made scientifically and precisely, according to DMAIC model of Six Sigma-define, measure, analyze, improve and control. The pre-prescription system of our hospital was established and improved, through adopting the prescription review mode of interception and Intervention. And the process management was continued to optimize. RESULTS: The rule-making of pre-trial system for outpatient prescription in our hospital was reasonable, and the rate of clinical approval and acceptance was high. After the system audit, the average rate of doctor's revision was 76.32%, and the average rate of Pharmacist's intervention was 63.23%, the effective rate and qualified rate of pharmacist intervention were 97.23% and 96.87%, respectively. CONCLUSION: Based on Six Sigma DMAIC model, the pre-trial system for outpatient prescription was established and implemented, which improved the level of rational drug use, effectively ensured the safety of drug use, and improved the satisfaction of patients.
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OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of semaglutide in the treatment of type 2 diabetes mellitus （T2DM）， and to provide reference for clinical drug use. METHODS Rapid health technology assessment was adopted. Retrieved from PubMed， Embase， Cochrane Library， Web of Science， CNKI， Wanfang database， CBM， domestic and foreign HTA official websites， HTA reports， systematic evaluation/meta-analysis and pharmacoeconomic studies about semaglutide in the treatment of T2DM were collected during the inception to May 1st， 2022. After data extraction and quality evaluation， descriptive analysis was performed on the results of included studies. RESULTS A total of 22 pieces of literature were included， involving 7 meta-analyses and 15 pharmacoeconomic studies. In terms of efficacy and safety， semaglutide showed significant advantages in controlling glycated hemoglobin （HbA1c）， fasting blood glucose， postprandial mean glucose， body mass index and achieving a target of glycosylated hemoglobin level ＜7%； also， there was no increased risk of hypoglycaemia or the incidence of serious adverse effects， but the risk of gastrointestinal adverse effects was significantly higher than other interventions. In terms of cost-effectiveness， results of foreign studies showed that semaglutide was more cost-effective， compared with other glucagon-like peptide-1 receptor agonists， sodium-glucose transporter protein 2 inhibitors， dipeptidyl peptidase-4 inhibitors. Research based on the perspective of China’s health system showed that semaglutide had a clear cost-effectiveness advantage over dulaglutide when using GDP per capita in 2020 （72477 yuan） as the payment threshold. CONCLUSIONS The semaglutide has excellent efficacy and good safety for the treatment of T2DM， with cost-effectiveness advantages over a number of drugs， but attention should be paid to the occurrence of gastrointestinal adverse effects.
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AIM: To study the distribution of CYP2C9∗3 and VKORC1-1639G>A gene polymorphism in Han population in Anhui province and their influence on the stable dose of warfarin. METHODS: The blood samples of 1 169 patients from 6 tertiary general hospitals in 5 areas of Anhui province from January 2020 to December 2021 were selected, the genotype of CYP2C9∗3 and VKORC1-1639G>A was detected by fluorescent staining in situ hybridization technique. RESULTS: The distribution of CYP2C9∗3 genotypes in 1 169 patients: the frequencies of AA, AC and CC genes were 90.16%, 9.24% and 0.60%, respectively; The distribution of VKORC1 genotype: the frequencies of AA, AG and GG genes were 84.26%, 14.71% and 1.03% respectively; There was no significant difference between the two genotypes in gender, age and regional distribution (P>0.05). The average daily warfarin dose of CYP2C9∗3 AA genotype in 755 patients with stable warfarin dose was (3.02±0.59) mg/d, which was significantly higher than patients with AC genotype and CC genotype; The average daily warfarin dose of patients with VKORC1-1639AA genotype was (2.72±0.40) mg/d, which was significantly lower than that of patients with AG genotype and GG genotype (P<0.05). And the difference was statistically significant (P<0.05); There are significant differences in gender, age and clinical diagnosis between patients with stable dose of warfarin and those without stable dose (P<0.05). CONCLUSION: CYP2C9 and VKORC1 genotypes are associated with the stable dose of warfarin. Clinical anticoagulation therapy guided by CYP2C9 and VKORC1 genotypes can provide guidance for individualized medication of warfarin.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it has diverse etiologies with multiple mechanisms. The diagnosis of HCC typically occurs at advanced stages when there are limited therapeutic options. Hepatocarcinogenesis is considered a multistep process, and hepatic macrophages play a critical role in the inflammatory process leading to HCC. Emerging evidence has shown that tumor-associated macrophages (TAMs) are crucial components defining the HCC immune microenvironment and represent an appealing option for disrupting the formation and development of HCC. In this review, we summarize the current knowledge of the polarization and function of TAMs in the pathogenesis of HCC, as well as the mechanisms underlying TAM-related anti-HCC therapies. Eventually, novel insights into these important aspects of TAMs and their roles in the HCC microenvironment might lead to promising TAM-focused therapeutic strategies for HCC.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it has diverse etiologies with multiple mechanisms. The diagnosis of HCC typically occurs at advanced stages when there are limited therapeutic options. Hepatocarcinogenesis is considered a multistep process, and hepatic macrophages play a critical role in the inflammatory process leading to HCC. Emerging evidence has shown that tumor-associated macrophages (TAMs) are crucial components defining the HCC immune microenvironment and represent an appealing option for disrupting the formation and development of HCC. In this review, we summarize the current knowledge of the polarization and function of TAMs in the pathogenesis of HCC, as well as the mechanisms underlying TAM-related anti-HCC therapies. Eventually, novel insights into these important aspects of TAMs and their roles in the HCC microenvironment might lead to promising TAM-focused therapeutic strategies for HCC.
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【Objective】 To study the fairness of blood bank resources allocation in China, aimed at providing references for reasonable allocation of blood bank resources. 【Methods】 A questionnaire survey was conducted among 32 provincial blood centers and 321 regional central blood banks across China in August 1~25, 2018. Resource allocation of blood banks in China was analyzed using descriptive methods, and the fairness of resource allocation were analyzed using Lorenz curve, Gini coefficient and Theil index. 【Results】 Blood bank resources and services showed an overall upward trend from 2013 to 2017. The fairness of institutional coverage was optimal in 2017 according to the Lorenz curve and Gini coefficient, suggesting the allocation of blood bank resources according to the population was better than geographic area. The fairness of health technicians staffing was the worst from the perspective of geographic area. The total Theil index was 0.448 5~0.526 7, and the differences was contributed more by intra group comparison than that of inter group. 【Conclusion】 The unbalanced development underlying in the provincial and regional blood centers has been observed, and the service capacity needs to be further improved. The resource allocation varies greatly among regions, and it is recommended to optimize the regional planning of blood bank resources.
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Currently, the corona virus disease 2019 was spreading globally, and more than 167.5 million confirmed cases worldwide. The new corona virus was highly contagious. The human body would have respiratory symptoms, fever, severe respiratory syndrome, organ failure, and even death after being infected with the virus. At present, there was no specific treatment for COVID-19. Most of the treatments were symptomatic and supportive treatment, and the prognosis was poor. Mesenchymal stem cells could not only repair damaged lung tissue, but also regulate immunity and anti-inflammatory effects, and had good clinical application prospects. We will review the application of MSCs in the treatment of COVID-19 for the reference of colleagues.
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AIM: To study the polymorphism distribution of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes and their influence on serum homocysteine (Hcy) concentration. METHODS: A total of 148 patients diagnosed with ischemic stroke from November 2020 to February 2021 in Yijishan Hospital of Wanan Medical College were selected for the study, and patients were typed for MTHFR 677C/T and MTRR 66A/G genes using fluorescent staining in situ hybridization technique. Serum Hcy concentrations were measured in 21 patients using a circulating enzyme assay. The distribution of MTHFR 677C/T and MTRR 66A/G gene polymorphisms were analyzed, and the differences in serum Hcy concentrations between patients with different genotypes were compared. RESULTS: The mutation rates of MTHFR 677C/T and MTRR 66A/G genes were 42.57% and 26.01%, respectively, and no significant differences in gene distribution frequencies were observed between men and women (P>0.05). The mean Hcy serum concentration was (16.04±4.34) μmol/L in 21 patients, including 8 patients (38.10%) with 0.05). CONCLUSION: MTHFR gene polymorphisms can affect serum Hcy concentrations. The MTHFR genotyping can be considered for individualized folic acid supplement. This conclusion should be further verified by expanding the clinical sample size.
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AIM: To study the chronological pharmacokinetic differences of melatonin (MEL) in non-dipper spontaneously hypertensive rats (SHR). METHODS: The HPLC detection method of MEL was established, and the specificity, precision, recovery rate and stability of the method were examined. Twelve male SD rats were divided into two groups, and a single dose of MEL (20 mg/kg) was given intragastrically at either 08:00 or 20:00, respectively. Plasma samples were collected at 0, 5, 10, 15, 20, 30, 40, 60, 90, 120, 240, 360 min after drug administration, and the plasma MEL concentration was determined by fluorescence HPLC. RESULTS: The specificity, precision, recovery rate and stability of the MEL detection method established in this study were in line with the requirements of the biological analysis method guidelines, proving that the method was mature and reliable. After MEL was administered at 08:00, the T
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OBJECTIVE:To provide reference for further promoting the clinical application of chronopharmacology and rational drug use.METHODS:The self-designed questionnairea was used to conduct on-site investigation among participants from 40 hospitals in Anhui province by dint of a meeting.The survey data were analyzed statistically.RESULTS:Totally 170 questionnaires were distributed,and 166 were retrieved,the total response rate was 97.65％.93.37％ of the interviewed pharmacists were aware of the circadian rhythms,and 87.35％ were aware of the circadian rhythms of more than two kinds;interviewed pharmacists expressed better awareness of indicators like gastric acid secretion (75.30％),blood pressure (67.47％) and growth hormone (66.87％) etc.while their awareness of other diseases like anaphylactic rhinitis (66.87％),gastric ulcer (50.60％) and migraine (50.00％) remained to improve.All the interviewed pharmacists recognized the better therapeutic efficacy (84.34％) and lower side effect (81.33％) of chronopharmacology-referred medication;chronopharmacology characteristics of glucocorticoid drugs were best known (34.34％),followed by antihypertensive drugs (25.30％).CONCLUSIONS:Pharmacists in Anhui province have certain knowledge of chronopharmacology such as biological rhythms,biological process or indicators,biological rhythms of disease and advantage of chronopharmacology-referred medication.It indicates that there has been a foundation for popularizing the concept of chronopharmacology in clinical medication in China;but not often contacted physiological processes or indexes,the understanding of biological rhythm of uncommon diseases are still insufficient,and the understanding of chronopharmacology characteristics of various drugs are far from ideal.
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AIM:Antioxidants act mainly through two routes:induction of antioxidant enzymes(enzymatic)or direct reaction with reactive oxygen species(ROS)(non-enzymatic),but the one taken by the extract of Ginkgo biloba(EGb)remains to be investigated.In present study,EGb was tested for both of the antioxidant routes in vitro.METHODS:The induction of EGb on two antioxidant enzymes,glutamate cysteine ligase catalytic subunit (GCLC)and glutathione-S-transferage subunit-P1(GST-P1),in cell lines wag detected by Western-blot.The effects of EGb on superoxide anion radical(O2·-),hydroxyl radical(OH·),rat erythrocyte hemolysis and lipid peroxidation of rat liver homogenate were determined by activity methods respectively.RESULTS:EGb was dem onstrated significantly to induce the two antioxidant enzymes(GCLC and GST-P1),directly scavenge superoxide anion radical(O2·-),hydroxyl radical(OH·)and inhibit rat erythroeyte hemolysis and lipid peroxidation of rat liver homogenate.CONCLUSION:The results strongly support the notion that EGb plays dual antioxidant roles: induction of antioxidant enzymes and direct reaction with ROS.
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AIM: To investigate the effects and quantitative relations of co-administering probenecid OF different dosages on pharmacokinetics of cefaclor in rabbits and approach the possible mechanisms involved as well. METHODS: Monitor plasma and urine cefaclor concentrations. 24 male rabbits were randomly divided into 4 groups by Cefaclor 50 mg·kg-1,Cefaclor50 mg·kg-1+Probenecid 100 mg·kg-1,Cefaclor 50 mg·kg-1+Probenecid 250 mg·kg-1 and Cefaclor 50 mg·kg-1+Probenecid 625 mg·kg-1.Blood and urine samples were collected according to the regular time schedule after intragastric administration. The concentration of cefaclor in blood and urine were determined by HPLC. Pharmacokinetic parameters were calculated by DAS (Drug and Statistical) software. Measur plasma protein-binding rate of cefaclor. The experimental groups and drug dosage were same as described above. The blood sample was drawn at 1 hour after administration,and the protein-binding rate of cefaclor was determined by equilibrium dialysis. RESULTS: Within the dosages of probenecid ranged from 0-250 mg·kg-1,T1/2ka,Tmax,Cmax and AUC of cefaclor increased in accordance with increasing dosage of co-administering probenecid while CL/F and Vd/F were decreased(P＜0.01); However,when the dosage of co-administering probenecid was 625 mg·kg-1,Cmax of cefaclor strikingly decreased(P＜0.01),while AUC and CL/F maintained at the levels of those with probenecid250 mg·kg-1.In this experiment, urinary excretive peak time of cefaclor in its prototype pos tponed gradually,biological half life prolonged and urinary excretive accumulation percentage decreased obviously(P＜0.01).To the dosages of probenecid ranging from 0-250 mg·kg-1,protein-binding rate of cefaclor decreased notably(P＜0.01)going with increasing dosages of co-administration probenecid; While the dosage of co-administration probenecid reached 625 mg·kg-1,the protein-binding rate of cefaclor corresponded to that of cefaclor 50 mg·kg-1 without probenecid (P＜0.01).CONCLUSION: Co-administering probenecid can strikingly change pharmacokinetics of cefaclor and the influential degree of pharmacokinetics parameters is dependent on dosages of probenecid used in the experiment. Biological half life prolongs and urinary excretive accumulation percentage of cefaclor decreases obviously.