Objective To explore the factors that affect the excretion rate of methotrexate and the occurrence of adverse reactions in high-dose methotrexate chemotherapy for osteosarcoma patients.Methods Retrospectively analyzed methotrexate excretion,liver injury,kidney injury,bone marrow suppression and other adverse drug reactions in 97 high-dose methotrexate chemotherapy cycles of 28 patients with osteosarcoma.The concentration of methotrexate in the blood at 0,24,48,72 h and the level of white protein in the blood were also analyzed.Results When the peak concentration of methotrexate(0h,Cmax)≥700 μmol·L-1 the risk of excretion delay increases:the incidence was 23.21％in group with Cmax ≥ 700 μmol·L-1,and it was 5.00％in group with Cmax＜700 μmol·L-1,(P＜0.05),but when the peak concentration was≥1 000 μmol·L-1,the risk of delayed excretion did not increase further:the incidence was 16.00％in group with Cmax 1 000 μmol·L-1,and it was 15.49％in group with Cmax＜1 000 μmol·L-1,(P＞0.05).Methotrexate blood Cmax has no significant correlation with the occurrence of important adverse reactions such as liver injury and bone marrow suppression.There was significant correlation between low serum albumin level and bone marrow suppression in patients.The average albumin level in group with bone marrow suppression was(39.1±3.4)g·L-1,which in without bone marrow suppression group was(41.2±4.0)g·L-1(P＜0.05).Conclusion During high-dose methotrexate chemotherapy in patients with osteosarcoma,delayed excretion and adverse reactions should not be prevented by lowering the peak concentration.The albumin level of patients is an important factor affecting the occurrence of bone marrow suppression.

OBJECTIVE: To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching. METHODS: The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up. RESULTS: The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). CONCLUSION Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bortezomib/therapeutic use* ; Dexamethasone ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Multiple Myeloma/drug therapy* ; Propensity Score ; Retrospective Studies ; Transplantation, Autologous/methods* ; Treatment Outcome

COVID-19/epidemiology* ; Humans ; Mental Health ; Pandemics ; Surveys and Questionnaires

With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.
China ; Disaster Planning ; Humans ; Public Health ; Public Health Administration

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree

BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.
Adolescent ; Adult ; Aged ; Aspartate Aminotransferases ; blood ; Betacoronavirus ; Case-Control Studies ; Child ; Child, Preschool ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; physiopathology ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; L-Lactate Dehydrogenase ; blood ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; epidemiology ; physiopathology ; therapy ; Retrospective Studies ; Young Adult

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.
Albumins/analysis* ; Antiviral Agents/administration & dosage* ; Betacoronavirus ; C-Reactive Protein/analysis* ; COVID-19 ; Case-Control Studies ; China ; Coronavirus Infections/drug therapy* ; Glucocorticoids/pharmacology* ; Hospitalization ; Humans ; Interferon alpha-2/administration & dosage* ; Nasal Sprays ; Pandemics ; Pneumonia, Viral/drug therapy* ; Propensity Score ; Retrospective Studies ; SARS-CoV-2 ; Sodium/blood* ; Virus Shedding/drug effects* ; COVID-19 Drug Treatment

Objective: In this study, primary cultured human hepatocytes were used to study the induction of P450 enzyme by the sesquiterpene lactone derivative ACT001, which provided reference for the clinical use of ACT001. Methods Three batches of frozen primary human hepatocytes were inoculated and cultured, and CYP1A2, CYP2B6 and CYP3A4 were induced by ACT001. Real-time fluorescence quantitative PCR was used to determine the mRNA expression level of P450 enzyme, and the activity of P450 enzyme was determined by LC-MS/MS method. Results The expression level of P450 enzyme mRNA and the activity of P450 enzyme showed that the P450 enzyme induction model was successfully established. Compared with the control group, the CYP1A2 mRNA expression level and enzyme activity of ACT001 1 μmol/L and 6 μmol/L group showed no significant changes. The mRNA expression level of CYP1A2 in ACT001 30 μmol/L group was significantly decreased, and the enzyme activity was decreased, but not as significantly as that of mRNA. With the increase of ACT001 concentration, the expression level of CYP2B6 mRNA was gradually increased. Compared with the control group, the expression level of CYP2B6 mRNA in the ACT001 group at 30 μmol/L was significantly increased, which was seven times higher than that in the control group, and the increase of enzyme activity was four times higher than that in the control group, which was 40% higher than that in the phenobarbital sodium induction multiple. Compared with the control group, the CYP3A4 mRNA expression level of cells in the ACT001 1 μmol/L group was significantly increased, which was four times higher than that of the control group, but did not reach 40% of the positive inducer rifampicin, and the CYP3A4 mRNA expression level was decreased gradually with the increase of ACT001 concentration. At the same time, there was no significant increase in CYP3A4 enzyme activity after ACT001 administration at different concentrations, which was less than two times of that in the control group. Conclusion The data indicated that ACT001 had no induction potential for CYP1A2 and CYP3A4, and had potential for CYP2B6 induction. In combination with CYP2B6 substrates, it should be avoided in clinical combination therapy to reduce adverse reactions caused by P450-mediated drug drug interaction.

"Karoshi" originates from Japan's economic take-off period in the 1960s and 1970s. It is generally believed that overwork lead to the accumulation of fatigue, which triggers the outbreak of potential diseases, and results in sudden death. Karoshi causes great harm to both the community and families because it occurs primarily in 30 to 60 year old young adults. Japan put Karoshi into the category of industrial injury for the first time in 2001 and started to undertake a series of studies in the sociological and pathological fields. However, there is a tremendous gap in the forensic pathological diagnosis domain. In China, research on Karoshi started from the 1990s and is closely related to the reform and opening up policy as well as economic development. According to the incomplete statistics, 600 thousand people die from overwork each year in China, the highest in the world. Karoshi has become one of the most serious social problems in China at the present stage, thus a systematic study in the sociology and forensic pathology fields is urgently required. This paper summarizes the past and present status of Karoshi, and puts forward the problems that need attention during the judicial expertise of Karoshi from forensic pathology perspective.
Adult ; China ; Death, Sudden/etiology* ; Fatigue/epidemiology* ; Forensic Pathology ; Humans ; Middle Aged ; Occupational Stress/epidemiology* ; Risk Factors

Objective:To observe the effect of moxibustion on the protein and mRNA expressions of corticotropin-releasing factor (CRF)and corticotropin-releasing factor receptor 1 (CRFR1) in hypothalamus of trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis rats,and to explore the central mechanisms of moxibustion in improving visceral pain and the pain-related emotions in experimental colitis rats.Methods:Thirty-six Sprague-Dawley (SD) rats were randomly divided into a normal group (NG),a model group (MG),a herb-partitioned moxibustion group (HPMG) and a sham herb-partitioned moxibustion group (SHPMG).Except the NG,rats in the remaining three groups all received TNBS enema to establish experimental colitis models.The HPMG received herb-partitioned moxibustion (HPM) at bilateral Tianshu (ST 25) and Qihai (CV 6) for intervention;for the SHPMG,the herbal cakes and moxa cones were only placed on the acupoints but not ignited;rats in the MG and NG were only fixed in the same way as those in the HPMG but did not receive any treatment.At the end of the intervention,the abdominal withdrawal reflex (AWR) score,the open field test (OFT) score and the elevated plus maze (EPM) score were observed to measure the changes in visceral pain and pain-related emotions of the rats.The enzyme-linked immunosorbent assay (ELISA) was used to examine the expressions of CRF and CRFR1 proteins in hypothalamus;the fluorescence-based quantitative polymerase chain reaction (PCR) was used to detect the expressions of CRF and CRFR1 mRNAs in hypothalamus.Results:Compared with the NG,the AWR score increased significantly and the OFT and EPM scores dropped significantly in the MG (all P＜0.05),and the expressions of hypothalamic CRF and CRFR1 proteins and mRNAs increased significantly (all P＜0.01).Compared with the MG and SHPMG,the AWR score dropped significantly and the OFT and EPM scores increased significantly in the HPMG (all P＜0.01),and the expressions of hypothalamic CRF and CRFR1 proteins and mRNAs decreased significantly (all P＜0.05).There were no significant differences between the MG and the SHPMG (all P＞0.05).Conclusion:HPM can down-regulate the abnormally increased expressions of CRF and CRFR1 proteins and mRNAs in hypothalamus of the TNBS-induced experimental colitis rats,which is plausibly one of its action mechanisms in mitigating visceral pain and the pain-related emotions in the experimental colitis rats.