OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

OBJECTIVE: The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker. METHODS: A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL). RESULTS: The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m ³. The OELs for COEs exposure using the BBMD were 0.00170 mg/m ³ for the total population, 0.00158 mg/m ³ for males, and 0.00174 mg/m ³ for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m ³, respectively. CONCLUSION Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m ³. This value will provide a benchmark for determining possible OELs.
Male ; Female ; Animals ; Coke ; Polycyclic Aromatic Hydrocarbons ; DNA Copy Number Variations ; Benchmarking ; Occupational Exposure/analysis* ; DNA, Mitochondrial/genetics* ; DNA Damage

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective: To analyze the mortality trend and characteristics of chronic obstructive pulmonary disease (COPD) among residents in China from 2004 to 2020. Methods: From the area, gender, region, and age dimensions, the Joinpoint regression model was used to analyze the trend of COPD mortality rate from 2004 to 2020, extracted from the China Death Surveillance Dataset. Results: From 2004 to 2020, the mortality rate and age-adjusted mortality rate of COPD showed a downward trend (AAPC=-3.68%, P<0.001; AAPC=-7.27%, P<0.001), which were consistent with urban and rural subpopulations (mortality rate: AAPC=-3.62%, P=0.009, AAPC=-3.23%, P=0.014; age-adjusted mortality rate: AAPC=-7.26%, P<0.001, AAPC=-6.78%, P<0.001). The mortality rate of COPD in rural was higher than that of urban subpopulations (P<0.001). Also, the mortality rate and age-adjusted mortality rate of COPD showed a downward trend in males and females (mortality rate: AAPC=-3.00%, P<0.001, AAPC=-4.37%, P<0.001; age-adjusted mortality rate: AAPC=-6.73%, P<0.001, AAPC=-8.11%, P<0.001), and the COPD mortality rate for male was generally higher than female (P<0.001). Meanwhile, the mortality rate of COPD in eastern, central and western regions also showed a downward trend (AAPC=-3.87%, P<0.001; AAPC=-3.12%, P<0.001; AAPC=-1.37%, P=0.001), and western regions were significantly higher than that in central (P<0.001) and eastern (P<0.001) regions. The mortality rate of COPD in the age group of Chinese people showed a downward trend in<45, 45-59, and≥60 years groups (AAPC=-9.48%, P<0.001; AAPC=-9.03%, P<0.001; AAPC=-5.91%, P<0.001). Among them,≥60 years groups was significantly higher than that in<45 (P<0.001) and 45-59 (P<0.001) years groups, and the decline rate was slowest. Conclusion: In China, the mortality rate of COPD decreases from 2004 to 2020, and more efforts are needed to reduce COPD mortality, especially in western regions, rural populations, males and the elderly.
Aged ; Female ; Humans ; Male ; Middle Aged ; Asian People ; China/epidemiology* ; Mortality ; Pulmonary Disease, Chronic Obstructive ; Rural Population ; Urban Population ; Adult

Objective: To analyze the mortality trend and characteristics of chronic obstructive pulmonary disease (COPD) among residents in China from 2004 to 2020. Methods: From the area, gender, region, and age dimensions, the Joinpoint regression model was used to analyze the trend of COPD mortality rate from 2004 to 2020, extracted from the China Death Surveillance Dataset. Results: From 2004 to 2020, the mortality rate and age-adjusted mortality rate of COPD showed a downward trend (AAPC=-3.68%, P<0.001; AAPC=-7.27%, P<0.001), which were consistent with urban and rural subpopulations (mortality rate: AAPC=-3.62%, P=0.009, AAPC=-3.23%, P=0.014; age-adjusted mortality rate: AAPC=-7.26%, P<0.001, AAPC=-6.78%, P<0.001). The mortality rate of COPD in rural was higher than that of urban subpopulations (P<0.001). Also, the mortality rate and age-adjusted mortality rate of COPD showed a downward trend in males and females (mortality rate: AAPC=-3.00%, P<0.001, AAPC=-4.37%, P<0.001; age-adjusted mortality rate: AAPC=-6.73%, P<0.001, AAPC=-8.11%, P<0.001), and the COPD mortality rate for male was generally higher than female (P<0.001). Meanwhile, the mortality rate of COPD in eastern, central and western regions also showed a downward trend (AAPC=-3.87%, P<0.001; AAPC=-3.12%, P<0.001; AAPC=-1.37%, P=0.001), and western regions were significantly higher than that in central (P<0.001) and eastern (P<0.001) regions. The mortality rate of COPD in the age group of Chinese people showed a downward trend in<45, 45-59, and≥60 years groups (AAPC=-9.48%, P<0.001; AAPC=-9.03%, P<0.001; AAPC=-5.91%, P<0.001). Among them,≥60 years groups was significantly higher than that in<45 (P<0.001) and 45-59 (P<0.001) years groups, and the decline rate was slowest. Conclusion: In China, the mortality rate of COPD decreases from 2004 to 2020, and more efforts are needed to reduce COPD mortality, especially in western regions, rural populations, males and the elderly.
Aged ; Female ; Humans ; Male ; Middle Aged ; Asian People ; China/epidemiology* ; Mortality ; Pulmonary Disease, Chronic Obstructive ; Rural Population ; Urban Population ; Adult

The risk of plague epidemics and relapse of various types of plague foci persists in Inner Mongolia Autonomous Region. For Marmota sibirica plague foci, the animal plague has not been found but antibody has been detected positive. Nowadays, Marmota sibirica has been increasing in population and distribution in China. In bordering countries Mongolia and Russia, the animal plague has been continuously prevalent. For Spermophilus dauricus plague foci, the animal plague has been taken place now and then. Compared to the above foci, the animal plague is most prevalent in Meriones unguiculatus plague foci and frequently spread to humans. Due to higher strain virulence and historical disaster in Marmota sibirica plague foci and Spermophilus dauricus plague foci, plague prevention and control should be strengthened on these foci. In addition to routine surveillance, epidemic dynamics need to be further monitored in these two foci, in order to prevent their relapse and spread to humans.
Animals ; China/epidemiology* ; Epidemics ; Humans ; Plague/prevention & control* ; Prevalence ; Sciuridae ; Yersinia pestis

OBJECTIVE: To systematically evaluate the clinical efficacy of arthroscopy and traditional incision in the treatment of tibial avulsion fracture of anterior cruciate ligament (ACL). METHODS: From July 2010 to July 2020, clinical comparative trial about arthroscopy and traditional incision in the treatment of ACL tibial avulsion fracture was conducted by using computer-based databases, including Embase, Pubmed, Central, Cinahl, PQDT, CNKI, Weipu, Wanfang, Cochrane Library, CBM. Literature screening and data extraction were carried out according to the inclusion and exclusion criteria, and the quality of the included literature was evaluated by improved Jadad score and Ottawa Newcastle scale (NOS). The operation time, hospital stay, fracture healing time, knee range of motion, postoperative excellent and good rate, complication rate, Lysholm score, International Knee Documentation Committee (IKDC) score and Tegner score were statistically analyzed by Review Manager 5.3 software. RESULTS: Finally, 16 literatures were included, including 1 randomized controlled trial and 15 non randomized controlled trials, with a total of 822 patients (405 in arthroscopy group and 417 in traditional incision group). Meta analysis showed that the operation time [MD=-9.03, 95% CI(-14.36, -3.70), P<0.001], hospital stay [MD=-5.81, 95%CI(-9.32, -2.31), P=0.001] and fracture healing time [MD=-14.61, 95% CI(-17.93, -11.28), P<0.001] in the arthroscopy group were better than those in the traditional incision group. The incidence of complications in arthroscopy group was lower than that in traditional incision group[OR=0.15, 95%CI(0.07, 0.33), P<0.001]. The postoperative excellent and good rate[OR=4.39, 95%CI (1.96, 9.82), P<0.001], knee mobility[MD=6.78, 95%CI(2.79, 10.77), P<0.001], Lysholm score[MD=11.63, 95%CI(4.91, 18.36), P<0.001], IKDC score[MD=7.83, 95%CI(6.09, 9.57), P<0.001] and Tegner score[MD=0.60, 95%CI(0.31, 0.89), P<0.001] in the arthroscopic group were higher than those in the traditional incision group. CONCLUSION Compared with the traditional open reduction and internal fixation, arthroscopic surgery in patients with ACL tibial avulsion fracture can shorten the operation time, hospital stay and fracture healing time, reduce the incidence of postoperative complications, and obtain good postoperative knee function. It can be recommended as one of the first choice for patients with ACL tibial avulsion fracture.
Anterior Cruciate Ligament/surgery* ; Anterior Cruciate Ligament Injuries/surgery* ; Arthroscopy ; Fractures, Avulsion/surgery* ; Humans ; Randomized Controlled Trials as Topic ; Suture Techniques

Cholinesterases/genetics* ; Dimethoate/analogs & derivatives* ; Humans ; Occupational Exposure/adverse effects* ; Polymorphism, Genetic ; Telomere

OBJECTIVE: To investigate whether collagen peptides can improve the immune functions of mice under the condition of simulated weightlessness. METHODS: Mouse tail-suspension model was used to simulate the effects of weightlessness. Tail-suspended mice were intraperitoneally injected with 600 mg collagen peptides per kilogram body weight once a day for 10 days. Then, the mice were killed, and white blood cells were counted and classified. Lymphocyte subsets and T lymphocyte proliferations in spleens were analyzed. RESULTS: Compared with normal control group, total and differential count of leukocytes, lymphocytes, T cells，CD4 and CD8 T cells, B cells and NK cells, and splenic T lymphocyte proliferation all decreased in the weightlessness simulated mice (P＜0.05). Except for NK cells, the above-mentioned parameters were increased after administration of collagen peptides, and some of the parameters were recovered to the levels of normal control mice (P＜0.05). CONCLUSION Collagen peptides can effectively improve peripheral blood lymphocyte distributions and T lymphocyte proliferations of mice under the condition of simulated weightlessness. This study nay provid the experimental basis for improvement of immune functions of astronauts.
Animals ; CD8-Positive T-Lymphocytes ; Cell Proliferation ; Collagen ; Lymphocyte Count ; Mice ; Peptides ; Spleen ; Weightlessness ; Weightlessness Simulation

Objective: To explore the mechanism of long non-coding RNA POU3F3 (lncRNAPOU3F3) affecting temozolomide (TMZ)-resistance in high-grade glioma cells via regulating MGMT expression. Methods: Sixty cases of tissues from patients treated at the Department of Neurosurgery, Peking University International Hospital during January 2016 and January 2018 were collected for this study, including 12 cases from brain trauma patients (normal group), 30 cases from primary high-grade glioma patients (primary onset group) and 18 cases from recurrent high-grade glioma patients (recurrence group, accepted surgery+TMZ already). U251 cells were induced with TMZ at the concentration of 1, 2, 4 and 8 μg/ml and maintained normal growth for a week to construct TMZ-resistant U251cell line (U251 TMZ-resistance, U251-TR); and the normal control group was treated with equal volume of physiological saline. Reverse transcription polymerase chain reaction (qPCR) and Wb were used to detect the mRNA and protein expressions of POU3F3 and MGMT (methylguanine DNA methyltransferase) in normal brain tissues and glioma cells. Lentivirus transfection was used to construct U251 cell line with stable POU3F3 interference (U251-TR siPOU3F3); CCK-8 was used to detect TMZ IC50 value (the half maximal inhibitory concentration) in each group of U251 cells, and Wb was used to detect the expression of MGMT protein in each group of cells. Results: Compared with the normal group and primaryonset group, the expression of POU3F3 in recurrence group was significantly increased (P<0.01). The TMZ IC50 of U251-TR cells was significantly higher than that of U251 cells (P<0.01), and The TMZ IC50 of U251-TR siPOU3F3 cells was significantly lower than that of U251-TR cellsbut higher than that of U251 cells (all P<0.01). The protein and mRNA expressions of POU3F3 and MGMT in U251-TR cells were significantly higher than that in U251 cells (P<0.01), while those expressions in U251-TR siPOU3F3 cells were significantly lower than those in U251-TR cells (P<0.01).Conclusion: lncRNAPOU3F3 is the key factor to promote TMZ resistance in human high-grade gliomas cells, which may exert certain guiding significance in the clinical treatment for TMZ resistance.