Dose-response relationship between risk factors and incidence of COVID-19 in 325 hospitalized patients:A multicenter retrospective cohort study

BACKGROUND The epidemiological and clinical characteristics of coronavirus disease 2019(COVID-19)patients have been widely reported,but the assessment of doseresponse relationships and risk factors for mortality and severe cases and clinical outcomes remain unclear.AIM To determine the dose-response relationship between risk factors and incidence of COVID-19.METHODS In this retrospective,multicenter cohort study,we included patients with confirmed COVID-19 infection who had been discharged or had died by February 6,2020.We used multivariable logistic regression and Cox proportional hazard models to determine the dose-response relationship between risk factors and incidence of COVID-19.RESULTS It clarified that increasing risk of in-hospital death were associated with older age(HR:1.04,95%CI:1.01-1.09),higher lactate dehydrogenase[HR:1.04,95%confidence interval(CI):1.01-1.10],C-reactive protein(HR:1.10,95%CI:1.01-1.23),and procalcitonin(natural log-transformed HR:1.88,95%CI:1.22-2.88),and D-dimer greater than 1μg/m L at admission(natural log transformed HR:1.63,95%CI:1.03-2.58)by multivariable regression.D-dimer and procalcitonin were logarithmically correlated with COVID-19 mortality risk,while there was a linear dose-response correlation between age,lactate dehydrogenase,D-dimer and procalcitonin,independent of established risk factors.CONCLUSION Higher lactate dehydrogenase,D-dimer,and procalcitonin levels were independently associated with a dose-response increased risk of COVID-19 mortality.

A Study on the Dose-Response Relationship between Asbestos Exposure Level and Asbestosis among Workers in a Chinese Chrysotile Product Factory

The dose-response relationship for asbestos exposure in a chrysotile product factory was studied. The past gravimetric dust concentration values, obtained from different worksites, were converted into fiber concentration values according to conversion factors that were worked out by simultaneous sampling in this study. The conversions were made so that exposure could be expressed in fiber-years (f-yr). Asbestosis was diagnosed on the basis of chest radiographs and occupational histories. Cumulative dust exposure (f-yr) was calculated up to the date of diagnosis for asbestosis patients, and up to September 1982 for the remaining workers. A dose-response relationship expressed as fiber-years exposed vs cumulative prevalence of asbestosis was established by the life table method on the basis of these data. Predicted 3 and 1% prevalence of asbestosis corresponded to 43 and 22 f-yr exposure, respectively. Considering that a worker can work for 35 years, these doses are commensurate with dust concentrations of 1.22 and 0.63 f/ml, respectively. It is recommended that 1 f/ml be taken as the maximum allowable concentration of airborne asbestos dust for the workplace with an anticipated prevalence of about 2% asbestosis after 35 years of exposure. 1990 Academic Press, Inc.

Comparison of Two Dose-response Relationship of Noise Exposure Evaluation Results with High Frequency Hearing Loss

Background:Complex noise and its relation to hearing loss are difficult to measure and evaluate.In complex noise measurement,individual exposure results may not accurately represent lifetime noise exposure.Thus,the mean LAeq,8 h values of individuals in the same workgroup were also used to represent LAeq,8h in our study.Our study aimed to explore whether the mean exposure levels of workers in the same workgroup represented real noise exposure better than individual exposure levels did.Methods:A cross-sectional study was conducted to establish a model for cumulative noise exposure (CNE) and hearing loss in 205 occupational noise-exposed workers who were recruited from two large automobile manufacturers in China.We used a personal noise dosimeter and a questionnaire to determine the workers' occupational noise exposure levels and exposure times,respectively.A qualified audiologist used standardized audiometric procedures to assess hearing acuity after at least 16 h of noise avoidance.Results:We observed that 88.3％ of workers were exposed to more than 85 dB(A) of occupational noise (mean:89.3 ± 4.2 dB(A)).The personal CNE (CNEp) and workgroup CNE (CNEg) were 100.5 ± 4.7 dB(A) and 100.5 ± 2.9 dB(A),respectively.In the binary logistic regression analysis,we established a regression model with high-frequency hearing loss as the dependent variable and CNE as the independent variable.The Wald value was 5.014 with CNEp as the independent variable and 8.653 with CNEg as the independent variable.Furthermore,we found that the figure for CNEg was more similar to the stationary noise reference than CNEp was.The CNEg model was better than the CNEp model.In this circumstance,we can measure some subjects instead of the whole workgroup and save manpower.Conclusions:In a complex noise environment,the measurements of average noise exposure level of the workgroup can improve the accuracy and save manpower.

Serum Ferritin and the Risk of Metabolic Syndrome:A Systematic Review and Dose-Response Meta-Analysis of Cross-sectional Studies

Objective This study aims to assess the dose-response relationship between serum ferritin(SF)and metabolic syndrome(MetS)in the two sexes.Methods We searched for articles on PubMed,the Cochrane Library,EMBASE,and the Web of Science databases that were published from 1950 to 2020.The summary odds ratio(OR)and 95%confidence interval(CI)of the association between SF and MetS were estimated using a random-effects model through a meta-analysis.Based on the methods described by Greenland and Longnecker,we explored the dose-response relationship between the two sexes.Results This study included 14 studies and 74,710 samples.The results of the classical meta-analysis showed that SF was positively associated with MetS(OR=1.77,95%CI:1.59–1.98).Regarding the components of MetS(8 studies included),the results showed that SF was positively associated with abdominal obesity(OR=1.42,95%CI:1.24–1.62),elevated fasting plasma glucose(OR=1.84,95%CI:1.50–2.25),elevated blood pressure(OR=1.17,95%CI:1.08–1.26),elevated triglycerides(OR=2.09,95%CI:1.72–2.54),and reduced high-density lipoprotein cholesterol(OR=1.33,95%CI:1.19–1.49).In the linear dose-response meta-analysis,the ORs of males,females,and postmenopausal females were 1.14(95%CI:1.13–1.16),1.32(95%CI:1.26–1.39),and 1.34(95%CI:1.22–1.47),respectively.Conclusions Our study shows that SF is significantly and positively associated with MetS,and the risk in the male population is higher than that in the female population.This finding also supports the recommendation of using SF as an early warning marker of MetS.

An Analysis of Specific Categories of Birth Defects and Developmental Disabilities for Children of Participants of the Air Force Health Study

Background: The Air Force Health Study collected reproductive outcomes for live-born children of male Air Force veterans of the Vietnam War. Methods: Dioxin values for participants were obtained from blood samples. Analyses were conducted of occurrence of 16 specific categories of birth defects and developmental disabilities. Children were categorized as conceived before and after the start of participants’ Vietnam War service. Children conceived before the start of Vietnam War service were treated as being conceived when their fathers had unquantifiable dioxin values. Children conceived after the start of Vietnam War service for participants with missing dioxin values were excluded from primary analyses, but were used to assess the impact of their exclusion on conclusions. Correlation between values for specific categories for multiple children fathered by the same participant was accounted for. The dose-response relationship was treated as a step function increasing for dioxin values larger than adaptively identified individual thresholds changing with the specific category. Results: For 15 of 16 specific categories, the probability of occurrence increased substantially for a sufficiently high dioxin level above identified thresholds. Exclusion of children due to missing dioxin likely did not affect these results. Conclusions: Results supported the conclusion of substantial adverse effects on a wide variety of specific categories of birth defects and developmental disabilities due to sufficiently high exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War. Results may hold more generally, but might also have been affected by a variety of limitations.

Evaluation of Cytogenetic Effects of Isoproturon on the Root Meristem Cells of Allium sativum

Objective\ To validate the use of Allium sativum as a reliable test model for genotoxicity, isoproturon, a substituted phenylalkylurea herbicide, was evaluated on the root meristem cells by this plant system. Method\ Test concentrations were selected by determining EC50 and root tips were exposed to various concentrations for 6 or 24 hr. EC50 concentration was calculated to be 70.8 ppm for the root growth. In addition to root growth retardation exposure to isoproturon induced morpholoogical changes like discolouration and stiffness of roots. Results\ Exposure to various experimental concentrations of isoproturon (35-280 ppm), including EC50, significantly and dose-dependently inhibited the mitotic index and induced chromosome breaks/mitotic aberrations at 6 or 24 hr. Conclusion\ The frequency of aberrations was found to be decreased in a dose dependant manner at 24 or 48 hr post exposure, however in comparison of control cells the frequency of aberrations was considerably high which indicates genotoxicity potentials of isoproturon. Further, present study also suggests that Allium sativum is a sensitive, efficient, and reliable test system for measuring the genotoxicity potential of environmental chemicals.

The rise and fall of photosynthesis:hormetic dose response in plants

The recent recognition that low doses of herbicides,human and veterinary antibiotics,metallic elements,micro/nano-plastics,and various other types of environmental pollutants widely enhance chlorophylls in the framework of hormesis created the need to further evaluate the response of photosynthetic pigments and gas exchange to low doses of stresses.An analysis of about 370 values of maximum stimulatory response(MAX;percentage of control response,%)of chlorophylls in higher plants,algae and duckweeds,and other photosynthesizing organisms,mined from published literatures,revealed a greater MAX for higher plants(median=139.2%)compared to algae and duckweeds(median=119.6%).However,an analysis of about 50 mined values of MAX of carotenoids revealed no signifi-cant difference in the median MAX between higher plants(median=133.0%)and algae-duckweeds(median=138.1%).About 70 mined values of MAX were also concentrated for photosynthetic rate(median MAX=129.2%)and stomatal conductance(median MAX=124.7%)in higher plants.Within higher plants,there was no significant difference in the median MAX among chlorophylls,carotenoids,photosynthetic rate,and stomatal conductance.Similarly,there was no significant difference in the median MAX between chlorophylls and carotenoids of pooled algae and duckweeds.The results suggest that the MAX is typically below 160%and as a rule below 200%of control response,and does not differ among chlorophylls,carotenoids,photosynthetic rate,and stomatal conductance.New research programs with improved experimental designs,in terms of number and spacing of doses within the“low-dose zone”of the hormetic dose–response relationship,are needed to study the molecular/genetic mechanisms underpinning the low-dose stimulation of photosynthesis and its ecological implications.

Acute Inhalation Toxicity Study of 2-Fluoroaceta mide in Rats

One of the most potent rodenticides is 2_fluoroacetamide (2_FA). Toxicity of this chemical is well documented. However, its inhalation toxicity data is not available in the literature. Hence, \{acute\} inhalation toxicity study was carried out by exposing male and female rats to aerosols of 2_FA at different concentrations for 4 h in a dynamically operated whole body inhalation exposure chamber. During and after the inhalation exposure the rats were less active, and showed mild tremors and convulsions. At higher concentrations the rats died after 2_3 days. The estimated 4_h LC 50 for male and female rats was 136.6 and 144.5 mg·m -3 respectively. Exposure to 0.7 LC 50 for 4 h duration showed an increase in the liver weight of male and female rats 7 days after exposure. Various haematological and biochemical variables determined were within the normal limits. However, histological findings showed injured lung as indicated by desquamation and necrosis of the epithelium of the respiratory tract. Marked hypertrophy of hepatocytes displaying strong acidophilic granulated cytoplasm was observed. Focal dilatation of renal proximal tubules in kidney with cytoplasmic vacuolation, and irregularly placed pyknotic nuclei were seen. The present study shows that 2_FA is a highly toxic chemical through the inhalation route based on the LC 50 value. Consequently necessary precautions should be taken during its handling.

Ameliorating Effects of Thyroxine and Atropine in Phosphamidon Intoxicated Chick Embryos

The effects of thyroxine and atropine in ameliorating phosphamidon intoxication in chick embryos was studied. Treatment of phosphamidon significantly enhanced the moriality and abnormalityrates, decreased the average body weights, and cholinesterase activity in chick embryos. When thyroxine was administered to the phosphamidon intoxicated embryos, the above parameters changedsignificantly, indicating an ameliorating effect of thyroxine against phosphamidon intoxication in chick embryos. The combined thyroxine and atropine therapy did not further improve the ameliorating effect. Since in many respects chick embryo development parallels that of mammalian embryos,a short-term use of thyroxine as a protective agent against organophosphate toxicity might be useful

QSAR study on the non-monotonic dose-response curve of PCBs in chicken embryo hepatocyte bioassay

Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls congeners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might be related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.

Evaluation of entropy for monitoring the depth of anesthesia ：ompared with bispectral index： a multicenter clinical trial

Background As a new electroencephalogram （EEG） signal processing technique for monitoring the depth of anesthesia, entropy consists of two indices： reaction entropy （RE） and state entropy （SE）. Our study compared entropy with classical bispectral index （BIS） in reduction of myoelectrical interference and noxious stimuli with EEG signals. Methods Two hundred and eighty patients （ASA I-II, 18-60 years old） undergoing scheduled surgeries from seven medical centers were enrolled. Anesthesia induction was managed with propofol via the target-controlled infusion （TCI） system. The results of BIS, RE, SE, mean arterial pressure （MAP） and heart rate （HR） were recorded before anesthesia induction, at the moment of unconsciousness, before and 2 minutes after administration of muscle relaxant, and before and one and three minutes after the tracheal intubation. Results The values of half maximum effective concentrations （EC50）, 5% effective concentrations （EC05） and 95% effective concentrations （EC95） of propofol effect-site concentration at the onset of unconsciousness were 1.2 （1.1-1.3 μg/ml）, 2.5 （2.4-2.5 μg/ml） and 3.7 （3.7-3.8 μg/ml）, while those of the predicted plasma propofol concentration were 2.8 （2.7-2.9 μg/ml）, 3.9 （3.8-3.9 μg/ml） and 4.9 （4.8-5.0μg/ml）, respectively. The values of BIS, SE and RE were 62, 59 and 63 when 50% of patients lost consciousness, and 79, 80, 85 and 42, 37, 44, respectively, when 5% and 95% of patients were unconscious. The values of BIS, RE and SE dropped two minutes after the injection of muscle relaxant, but there were no significant differences between RE and SE. MAP and HR increased visibly, which indicated a reaction to tracheal intubation; the values of BIS, RE and SE, however, did not display any significant changes. Conclusions This large-sample multicentric study confirmed the values of RE and SE as approximating BIS value, at the onset of unconsciousness during propofol TCI anesthesia. After elimination of myoelectrical activation, all values of RE, SE and BIS decreased significantly and the three indices were less sensitive to noxious stimuli than cardiovascular responses.

Minimum effective local anesthetic dose of intrathecal hyperbaric ropivacaine and bupivacaine for cesarean section

Background Intrathecal anesthesia is commonly used for cesarean section. Bupivacaine and ropivacaine have all been used as intrathecal drugs. The minimum effective local anesthetic dose （MLAD） of intrathecal ropivacaine for nonobstetric patients has been reported. However, few data are available on the MLAD of hyperbaric ropivacine for obstetric patients and the relative potency to bupivacaine has not been fully determined. In this study, we sought to determine the MLAD of intrathecal ropivacaine and bupivacaine for elective cesarean section and to define their relative potency ratio.Methods We enrolled forty parturients undergoing elective cesarean section under combined spinal-epidural anesthesia and randomized them to one of two groups to receive intrathecal 0.5% hyperbaric ropivacaine or bupivacaine.The initial dose was 10 mg, and was increased in increments of 1 mg, using the technique of up-down sequential allocation. Efficacy was accepted if adequate sensory dermatomal anesthesia to pin prick to T7 or higher was attained within 20 minutes after intrathecal injection, and required no supplementary epidural injection for procedure until at least 50 minutes after the intrathecal injection.Results The intrathecal MLAD was 9.45 mg （95%confidence interval （CI）, 8.45-10.56 mg） for ropivacaine and 7.53 mg （95%CI, 7.00-8.10 mg） for bupivacaine. The relative potency ratio was 0.80 （95% Cl, 0.74-0.85） for ropivacaine/bupivacaine when given intrathecally in cesarean section.Conclusion Ropivacaine is 20% less potent than bupivacaine during intrathecal anesthesia for cesarean delivery.

Arsenic trioxide induces multiple myeloma cell apoptosis via disruption of mitochondrial transmembrane potentials and activation of caspase-3

OBJECTIVE: To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. METHODS: Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (delta psi m) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. RESULTS: Zero point one to 0.5 mumol/L As2O3 inhibited cell proliferation and 2.0 mumol/L As2O3 induced cell apoptosis, while 1.0 mumol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (delta psi m) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced delta psi m collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. CONCLUSION: As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.

Effective background infusion rate of ropivacaine 0.2% for patient-controlled interscalene brachial plexus analgesia after rotator cuff repair surgery

Background Continuous interscalene nerve block （CISB） is considered to be the most effective method for postoperative analgesia after shoulder surgery with prolonged severe pain.This study was performed to evaluate the minimum effective background infusion rate and the effective background infusion rate of ropivacaine 0.2％ for CISB after arthroscopic rotator cuff repair surgery in 95％ of patients.Methods Patients scheduled for arthroscopic rotator cuff repair surgery under general anesthesia at Peking University Third Hospital were prospectively enrolled from December 2011 to May 2012.Preoperatively,an interscalene catheter （ISC） was placed under the guidance of ultrasound and nerve stimulation in each patient.Consecutively,30 patients with successful nerve block were included.A continuous infusion of ropivacaine 0.2％ with a 5 ml patient-controlled bolus available hourly was started at postoperative anesthesia care unit （PACU） after completion of surgery.The initial background infusion rate was 6 ml/h,which was subsequently varied for each consecutive patient according to the analgesic effects of the previous one.The minimum effective background rate was determined using the Dixon and Massey up-and-down method.The effective background rate in 95％ of patients was calculated using isotonic analysis.Results The minimum effective background rate based on the Dixon and Massey up-and-down method was 2.8 ml/h （95％ CI,2.3-3.3 ml/h）.The effective background rate in 95％ of patients calculated with the isotonic regression analysis was 4.4 ml/h （95％ CI,3.8-6.5 ml/h）.Conclusion The effective background rate for patient-controlled interscalene brachial plexus analgesia after shoulder surgery in 50％ and 95％ of the patients was 2.8 and 4.4 ml/h,respectively.

Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin

BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. METHODS: Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P

耳鼻咽喉感染抗菌药物的PK/PD参数研究

耳鼻咽喉细菌感染多为革兰阳性菌如肺炎链球、流感嗜血杆菌和卡他莫拉菌等引起的扁桃体炎、鼻窦炎和中耳炎等。《抗菌药物临床应用指导原则》指出,细菌性咽炎及扁桃体炎的病原菌主要为A组β溶血性链球菌,少数为C组或G组β溶血性链球菌;