AIM: To explore the application effect of medical failure mode and effect analysis in the blood sample management of phase I clinical trials, and to provide a basis for improving the quality of blood sample management. METHODS: Convenient sampling was used to draw blood samples from healthy subjects in phase I clinical trials as the research objects. According to whether the medical failure mode and effect analysis method was implemented, they were divided into 3 080 control groups and 3 064 observation groups. The unqualified rate of blood samples, the number of unqualified items, the satisfaction of subjects and the passing rate of the researcher's examination between the two groups were compared. RESULTS: The unqualified rate of blood samples in the control group was 1.95%, and the unqualified rate of blood samples in the observation group was 0.59%. The difference between the two groups was statistically significant (P<0.05). The number of unqualified items in the blood samples of the observation group was lower than that of the control group, and the difference between the two groups was statistically significant (P<0.05). The satisfaction of subjects in the observation group and the passing rate of the investigator were higher than those in the control group, and the difference between the two groups was statistically significant (P<0.05). CONCLUSION: The implementation of medical failure mode and effect analysis not only provides qualified biological samples for the detection and analysis of drug concentration in clinical trials, but also enhances the standardization and specialization of researchers, and contributes to the improvement of the overall quality of clinical trials.

Migraine is a common nervous system disease, which could seriously affect the quality of life. However, the medical treatment of migraine cannot meet the clinical needs at present. With the deepening of research, serotonin 1F receptor agonists and drugs targeting CGRP are more and more developed and marketed. In this paper, the mechanism of action, safety and efficacy, metabolic characteristics of these drugs were systematically evaluated to provide a more scientific basis for clinical prevention and treatment of migraine.

To establish a murine carotid artery transplantation model for the study of the chronic re-jection,80 rats were divided into two groups,an allotransplant (ACI-Lewis) group and an isotrans-plant (Lewis-Lewis) group (control group).The donor carotid artery and the recipient carotid artery were anastomosed by using a polyethylene cuff (internal diameter:0.7 mm,length:3 mm).The pathological changes of carotid artery transplant were observed 14,28 and 56 days after the trans-plantation.The results showed that the model was successfully established in 95% of the animals.The chronic rejection-associated arteriosclerosis was induced 28 days after the transplantation.The new chronic rejection model of carotid artery by using cuff technique caused fewer traumas and was easy to make.The pathological changes of the transplant mimicked the chronic rejection-associated arteriosclerosis found in human transplant.

AIM: To discuss the standardized management methods of drug clinical trial instruments and equipment based on the analysis of current situation of the management in drug clinical trial instruments and equipment in institutions. METHODS: Through literature searching and our experience, we analyzed the nowadays problems in management of instruments and equipment, established and improved the management system, refined the standard operating procedures, promoted information management, and strengthened the construction of professional team of instrument and equipment management or database. RESULTS: The implementation of dedicated management ensured the whole implementation management, reduced the frequency in management problems, and improved the professional level of instrument and equipment management. CONCLUSION: The construction of standardized instrument and equipment management system is the premise of standardized development of drug clinical trials, which improves the management level of drug clinical trial instruments and equipment, ensures the authenticity and accuracy of trial data, and effectively enhances the quality of following drug clinical trials.

As a fluorinated hydrocarbon anesthetic, methoxyflurane may cause serious adverse reactions such as renal damage under anesthetic doses, but its analgesic effect at sub-anaesthetic doses is safe, high tolerability, and short-term acute Good choice for analgesia. This article describes the pharmacokinetics, clinical validity, adverse reactions and clinical application of methoxyflurane, and explores the feasibility of methoxyflurane as an analgesic in clinical application. Methoxyflurane is convenient to use as an inhaled analgesic. It can provide patients with emergency analgesia without intravenous administration. It is a good choice for emergency analgesia in pre-hospital and emergency settings.

Aim To screen the mechanism of Yiqi- Bushen-Tiaozhi formula ( YBTF) in treating non-alcoholic steatohepatitis ( NASH) by network pharmacology analysis and to verify it by animal experiments. Methods TCMSP database and HPLC-MS analysis were used to mine the active ingredients and targets of YBTF; GSE89632 dataset was used to screen the differential expressed genes ( DEGs) between the normal and the NASH groups; GeneCards and DisGeNET databases were used to screen NASH-related disease genes. The intersection genes of the three are the target genes of YBTF treatment of NASH. The intersection gene of the three sets of genes was the target gene of YBTF in treating NASH. GO, KEGG, DO enrichment analysis, protein-protein interaction network, and network topology analysis were used to identify the hub genes of YBTF in the treatment of NASH. Molecular docking was used to judge whether cmcial target genes, active ingredients could be combined and exer ted a curative effect; Oil red 0 and HE staining were used to determine whether YBTF could treat NASH mice; (3-galactosidase ( SA- (3-Gal) test was used to determine whether NASH mice had hepatocyte senescence and whether YBTF improved senescence; West-ern blot. Quantitative Real-time PGR ( qRT-PCR) combined with sequencing results were used to verify whether YBTF could regulate the expression of the essential target genes screened from the protein and RNA levels. Results YBTF could improve cellular aging and treat NASH through CDKN1A. Conclusion The rational application of Traditional Chinese medicine (TCM) network pharmacology and experiments can provide new ideas and directions for studying the mechanism of YBTF.

AIM: To study the bioequivalence of two tadalafil tablets in Chinese healthy male subjects. METHODS: A randomized, open-label, two-period, two-sequence, crossover study designing was adopted in the study. Thirty-six healthy male subjects were enrolled under fasting condition and fed condition, respectively. Each subject was given a single oral dose of tadalafil tablet (20 mg). The concentration of tadalafil in plasma was determined by LC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin 8.0 program, and statistical analysis was performed by using SAS 9.4 statistics software. RESULTS: Under fasting condition, the pharmacokinetic parameters of tadalafil of the test (T) and reference (R) preparation were as follows: C

BACKGROUNDEsophageal adenocarcinoma is becoming an increasingly important problem. It has been the most rapidly increasing malignancy in western countries in the last decades, and its prognosis is poor. The aim of this study was to evaluate the relationship between tumor invasion depth and lymph node metastasis for adenocarcinoma of the esophagus and esophagogastric junction, and to analyze the impact of lymph node metastases on survival of the patients.

METHODSThe study group comprised 121 patients with adenocarcinoma of the esophagus or esophagogastric junction, who underwent esophagectomy between January 1985 and December 2003 at either the Royal Adelaide Hospital or the Flinders Medical Center, Australia. Overall, there were 101 males and 20 females, with a mean age at surgery of 62 years (range 36 - 80). All of them were followed up for 6 months to 13 years (mean, 6.5 years). The relationship between tumor invasion depth and lymph node metastasis, as well as between survival and lymph node metastasis in these patients were analyzed by Chi-square or Fisher's exact test. A P < 0.05 was considered statistically significant.

RESULTSThe tumors were located entirely within the esophagus in 83 patients, and involved the gastro-esophageal junction in 38. The overall resection rate was 96.7% (117/121). When tumor invasion was within mucosa or submucosa of the esophagus (T1), the lymph node metastasis rate was 22.2% (10/45), the mean number of metastatic lymph nodes was 0.3, and the proportion of more than 4 lymph nodes metastases was 0% (0/45). When tumor invaded the adjacent structures of the esophagus (T4), the lymph node metastasis rate was 85.7% (6/7); the mean number of metastatic lymph nodes was 5.1, and the proportion of more than 4 lymph nodes metastases was 71.4% (5/7). There was a significant difference between T1 and T4 (P < 0.01). The 5-year survival rate for patients without lymph node metastasis was 52.9%, for those with 1 - 4 nodes involved was 11.5%, and for patients with more than 4 positive nodes was 0.0% (P < 0.01).

CONCLUSIONSThere is a close association between tumor invasion depth and lymph node metastasis for adenocarcinoma of the esophagus and esophagogastric junction. Both the number and rate of lymph node metastasis are significantly correlated to the depth of tumor invasion. Moreover, when the tumor invades deeper into the esophageal wall, the percentage of patients with more than 4 involved nodes increases. Both the lymph node status and the number of metastatic nodes are important prognostic factors for the disease.

Adenocarcinoma ; mortality ; pathology ; Adult ; Aged ; Aged, 80 and over ; Esophageal Neoplasms ; mortality ; pathology ; Esophagogastric Junction ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Stomach Neoplasms ; mortality ; pathology

This article introduces the mechanism including antigen presentation, adjuvant, lymphatic system and the characteristics of vaccine, and then summarizes the key applications of core pharmacometrics approaches including QSP, PK/PD, dose response analysis, MBMA, in dose-response, preclinical and clinical translation, and correlation between biomarkers and efficacy of vaccines. It is expected that the successful application of model informed drug development can promote model informed vaccine development so that pharmacometrics makes its due contributions to the development of safer, more effective and more controllable vaccine products.