Objective To evaluate the bioequivalence and safety of two pyrazinamide tablets in healthy Chinese subjects.Methods An open,randomized,single-dose,two-sequence,two-cycle,double-cross trial design was used.All 48 healthy subjects(24 in fasting and 24 in fed trial)were randomized to receive a single oral dose of a 0.5 g pyrazinamide tablet(test or reference)per cycle.The plasma concentration of the drug was determined by liquid chromatography coupled to tandem mass spectrometry method.The pharmacokinetic parameters were calculated by WinNonlin v8.2,and the bioequivalence was evaluated by SAS 9.4.Results In the fasting group,the Cmax of the test and reference preparation of pyrazinamide tablets were(13.28±2.82)and(12.88±4.49)μg·mL-1,the AUC0-t were(139.17±26.58)and(138.63±28.92)h·μg·mL-1,the AUC0-∞ were(148.96±33.65)and(148.71±36.97)h·μg·mL-1 respectively.In the fed group,the Cmax of the test and reference preparation of pyrazinamide tablets were(11.89±1.96)and(11.99±1.92)μg·mL-1,the AUC0-t were(138.22±37.21)and(141.68±25.80)h·μg·mL-1,the AUC0-∞ were(152.20±32.41)and(151.04±28.05)h·μg·mL-,respectively.The 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ geometric mean ratios of the test and reference preparation were all within 80.00％to 125.00％.The incidence of adverse events was 16.70％for both the test and reference preparation in the fasting group and 8.30％for both the test and reference preparation in the fed group,all of which were mild in severity.Conclusion The test and reference preparation of pyrazinamide tablets were bioequivalent,safe and well tolerated in healthy Chinese subjects under fasting and fed conditions.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective To develop a Traditional Chinese Medicine(TCM)syndrome diagnosis scale suitable for evaluating the overall health status of participants in long-term simulated weightlessness experiments,and preliminarily evaluate its reliability and validity.Methods Based on the understanding of the pathogenesis of TCM in different stages of long-term manned spaceflight,a scale was developed through literature research and expert consultation.Test-retest reliability and internal consistency coefficient were used to test the reliability of the scale.Item analysis and factor principal component analysis were used to evaluate the validity of the scale,and a rotating component matrix was used to analyze the correlation between each item and dimension using 36 volunteers in a 90 days head down bed rest experiment as the research subjects.Results The scale contains eight dimensions and 57 items.The reliability analysis showed that the correlation coefficient of the total score of the scale for the first and second tests of 30 participants was 0.889,indicating high stability of the scale.The Cronbach coefficient of the scale was 0.934,indicating very good internal consistency.The split half reliability after correction was 0.858,indicating a high reliability of the scale.The validity analysis showed that the difference between the high score group and the low score one for each of the 57 items was statistically significant(P<0.01),and the Pearson correlation coefficient between each item and the total score of the scale was greater than 0.4(P<0.001).The cumulative contribution rate of 8 common factors extracted using principal component factor analysis was 55.293%,and the results of rotating component matrix analysis,after applying TCM theory and expert feedback,had a coincidence of up to 87.5%with the initial 8 dimensions,indicating good structural validity of the scale.Conclusion The scale has good reliability and validity,and can diagnose TCM syndromes.It is suitable for long-term simulated weightlessness experiment and provides an objective and quantitative new method for evaluating the subjective feelings of participants.

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.
Female ; Humans ; Anastrozole ; Aromatase Inhibitors/therapeutic use* ; Bilirubin ; Breast Neoplasms/drug therapy* ; Letrozole ; Liver ; Retrospective Studies ; Toremifene ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over

BACKGROUND: To illustrate the research framework, overall knowledge structure, and development trends of Chinese medicine (CM) treatment for osteosarcoma (OS) by using a bibliometric analysis and newly developed visualization tools. METHODS: Research datasets were acquired from the Web of Science (WOS) database from January 1, 1980 to September 30, 2019. VOS viewer and Citespace software was used to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution of institutes, distribution of journals, citation and H-index status, co-authorship status, research hotspots and co-citation status were analyzed. RESULTS: A total of 223 publications in the WOS database met the requirement. The number of published articles showed a rise but the citation frequency and the H-index of China were relatively low. The cooperation between the countries, institutes and authors were relatively weak. Most publications were basic researches. Most of the previous researches focused on basic mechanisms of CM in treating OS, and therapy and improvement of dosage form may become a frontier in this research field. CONCLUSIONS Compared with other fields, the field of CM treatment for osteosarcome is still in infancy. The distribution of researches is imbalanced and cooperation between countries, institutions and authors remains to be strengthened. Furthermore, basic research occupies an absolute dominant position, and the exploration of the molecular mechanism of CM in preventing and treating OS may become a key point in the future.
Bibliometrics ; China ; Humans ; Medicine, Chinese Traditional ; Osteosarcoma/therapy* ; Publications

Objective:To explore the clinicalfactors related to allograft fibrosis after pediatric liver transplantation.Methods:The clinical data were respectively analyzed for 94 pediatric recipients from January 2013 to December 2016 at Tianjin First Central Hospital.The Patients were assigned into fibrotic and non-fibrotic groups based upon the results of protocol liver biopsies. Univariate and multivariate Logistic regression analyses were performed for examining the risk factors of fibrosis after pediatric livertransplantation. Then Logistic regression model was established to obtain the predicted value of combined predictive factors.Thereceiver operating characteristic curve (ROC) was conducted to evaluate the predictive value of combined predictive factors.Results:A total number of 54(57.5%) patients occurred fibrosis among the 94 patients. There weresignificant differences in cold ischemia time (Z=2.094), warm ischemia time (Z=2.421), biliary stricture( χ2=4.560), drug-induced liver injury ( χ2=7.389), hepatic artery thrombosis and rejection ( χ2=6.955)between two groups ( P<0.05). Logistic regression analysis showed that cold ischemia time (OR=1.003, 95%CI: 1.000~1.007, P=0.044), biliary stricture(OR=6.451, 95%CI: 1.205~33.295), rejection(OR=2.735, 95%CI: 1.057~7.077)and drug-induced liver injury (OR=4.977, 95%CI: 1.207~20.522, P=0.026) were independent risk factors for fibrosis 5 years after liver transplantation. The area under the ROC curve was 0.786(95%CI: 0.691~0.881), for predicting patient outcome.If using 0.311as a cutoff Value, the sensitivity was 90.70%, and the specificity was 60.00%. However, through the ROC curve comparison, there was statistical significance between combined predictive factors and the other independent risk factors ( P>0.05). Conclusions:The incidence of fibrosis 5 years after pediatricliver transplantation is 57.5%. Prolonged cold ischemia time, biliarystricture, rejectionand drug-induced liver injury after liver transplantation are independent risk factors for fibrosis 5 years after pediatric liver transplantation.And the combined predictive factors have a high predictive value forallograftfibrosis.

Objective: To study the clinicopathological features of minute meningothelial-like nodule (MMLN) in the lung and its histological origin. Methods: Clinicopathological data of 93 patients diagnosed with MMLN in Jiangsu Province Hospital(the First Affiliated Hospital of Nanjing Medical University) from September 2016 to September 2018 were collected and analyzed retrospectively, and the related literature was reviewed. Results: Ninety-three MMLNs were identified from 5 239 patients undergoing pulmonary resection. There were 18(19.6%) males and 75(80.6%) females; age ranged 38-81 years, with mean age 58 years. The frequency of MMLNs was related to the site of origin, and single lesion most commonly (43%) arose in right lobe. There was no significant relationship with patients′ age, gender and the co-existing malignant tumors. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) was 0.584 (P<0.05), and the best cut-off point was 11.5, indicating an appropriate increase in the number of slides to at least 12 would facilitate the discovery of MMLN. Histologically, MMLN cells showed bland morphology, located around the normal alveolar cavity or form nests or whorls centered on small veins. Immunohistochemistry was done in 55 cases, and all cells expressed vimentin; and a high proportion of cells expressed EMA, PR, CD56 and Calponin. They were all negative for TTF1, Syn, CgA, CKpan, SMA and CD34. The Ki-67 index was low in all cases (<2%). In addition odds ratio analysis showed that MMLN was not a risk factor for invasive carcinoma (including other malignant tumors in the lung, P=0.100). Conclusions MMLN closely resembles meningothelioma morphologically and immunophenotypically, although its origin remains uncertain. In the study, MMLN is considered as a reactive benign lesion around pulmonary pathology, functioning as an effector regulating small blood vessels caliber. MMLN probably provides nutritional support to the surrounding disease and affords a suitable environment for the development of tumor cells.

Intestinal transplantation is the only treatment option for irreversible intestinal failure and parenteral nutrition failure.Although the progress of immunosuppressive therapy and the improvement of surgical techniques have improved the prognosis of intestinal transplantation,it is still unsatisfactory compared with other solid organ transplantation,mainly due to the fact that the intestinal mucosa is susceptible to damage due to ischemia.The basic pathophysiological process of ischemia-reperfusion injury(IRI) is that ischemia/reperfusion induces the production of reactive oxygen species (ROS),inflammation and cell apoptosis,leading to tissue damage.In recent years,the pathophysiology of ischemia-reperfusion injury in intestinal transplantation has made some new progress,providing more possibilities for the prevention and treatment of intestinal transplantation IRI.Although most of them are animal experimental results,they have important reference value for clinical application.

Objective: To explore the expression of amphiregulin (AREG) in nasal polyps patients with different degrees of eosinophil infiltration, and to analyze the correlation between AREG and tissue remodeling. Methods: Forty-eight patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery, Remin Hospital, Wuhan University from July 2017 to August 2018 were recruited, including 40 males and 8 females, aged from 16 to 60 years old. The subjects were divided into three groups: control group (n=14), eosinophilic chronic sinusitis with nasal polyps (ECRSwNP) group (n=19) and noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group (n=15). The relative expression of AREG in nasal mucosa was detected by Western blot assay and immunohistochemical staining. Tissue remodeling was detected by HE staining, AB-PAS staining and Masson staining. Kruskal-Wallis test was used for comparison among multiple groups, and Spearman correlation analysis was conducted between the expression level of AREG and the related indexes of tissue remodeling. Results: The expression of AREG in ECRSwNP group was significantly higher than that in non-ECRSwNP group and control group (median protein expression of Western blot was 1.592 vs 0.617 vs0.582, all P<0.05). The degree of epithelial injury and goblet cell metaplasia in ECRSwNP group was significantly higher than that in control group (all P<0.05), the percentage of collagen fibrosis area in ECRSwNP group was significantly lower than that in control group (P=0.01). In chronic rhinosinusitis with nasal polyps (CRSwNP) patients, the area of mucous glands was negatively correlated with the expression of AREG (r=-0.616, P<0.05), and the percentage of collagen fibrosis area was negatively correlated with the expression of AREG (r=-0.738, P<0.05). Conclusion The expression of AREG is higher in ECRSwNP patients, which is related to the process of tissue remodeling.

Objective: To explore the difference of intestinal flora between the patients with acute cerebral hemorrhage due to hyperactivity of liver-Yang and the healthy population. Method: The fecal samples of 9 patients with acute cerebral hemorrhage due to hyperactivity of liver-Yang from the first affiliated hospital of Guangzhou university of traditional Chinese medicine in 2018 were selected as observation group,and 6 stool samples from healthy subjects were selected as the control group.The total bacterial DNA was extracted from the two groups of samples,amplified according to the 16S rRNA V4 region,and paired-end sequencing was performed on the Illumina MiSeq platform.The sequencing results were analyzed by bioinformatics analysis software.The flora composition and structure of the samples from two groups were compared. Result:Venn analysis of operational taxonomic units(OTU) showed significant difference in OTU numbers between the observation group and control group.Partial least squares-discriminant analysis(PLS-DA) showed that there was a significant difference in the composition of intestinal flora between patients with acute cerebral hemorrhage and healthy subjects.On the analysis of species and abundance,at the classification level of phylum,compared with the control group,the ratio of relative abundance values of Firmicutes and Bacteroidetes(F/B) in the observation group was significantly increased,and the relative abundance of Verrucomicrobia was significantly decreased(P<0.05);at the classification level of genus,there were significant differences between the two groups in the Prevotella,Bacteroides,Akkermansia,Blautia and Acidaminococcus(P<0.05,P<0.01),the ratio of relative abundance values of Bacteroides and Prevotella(B/P) in the observation group was significantly higher than that of the control group;at the classification level of species,there were significant differences between the two groups in P. copri,A. muciniphila,B. ovatus,B. fragilis and Ruminococcus callidus(P<0.05,P<0.01).Principal coordinate analysis showed that the two groups of samples were significantly separated,indicating that there were significant differences in flora structure between the two groups. Conclusion:Acute cerebral hemorrhage due to hyperactivity of liver-Yang is associated with structural disorder of intestinal flora,which is closely related to the decrease in relative abundance of P. copri and A. muciniphila.