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Abstract Objective: To develop an automated co-registration system and test its performance, with and without a fiducial marker, on single-photon emission computed tomography (SPECT) images. Materials and Methods: Three SPECT/CT scans were acquired for each rotation of a Jaszczak phantom (to 0°, 5°, and 10° in relation to the bed axis), with and without a fiducial marker. Two rigid co-registration software packages-SPM12 and NMDose-coreg-were employed, and the percent root mean square error (%RMSE) was calculated in order to assess the quality of the co-registrations. Uniformity, contrast, and resolution were measured before and after co-registration. The NMDose-coreg software was employed to calculate the renal doses in 12 patients treated with 177Lu-DOTATATE, and we compared those with the values obtained with the Organ Level INternal Dose Assessment for EXponential Modeling (OLINDA/EXM) software. Results: The use of a fiducial marker had no significant effect on the quality of co-registration on SPECT images, as measured by %RMSE (p = 0.40). After co-registration, uniformity, contrast, and resolution did not differ between the images acquired with fiducial markers and those acquired without. Preliminary clinical application showed mean total processing times of 9 ± 3 min/patient for NMDose-coreg and 64 ± 10 min/patient for OLINDA/EXM, with a strong correlation between the two, despite the lower renal doses obtained with NMDose-coreg. Conclusion: The use of NMDose-coreg allows fast co-registration of SPECT images, with no loss of uniformity, contrast, or resolution. The use of a fiducial marker does not appear to increase the accuracy of co-registration on phantoms.
Resumo Objetivo: Desenvolver corregistro automático e testar seu desempenho com ou sem marcador fiducial em imagens de tomografia computadorizada de emissão de fóton único (SPECT). Materiais e Métodos: Três SPECT/CTs foram adquiridas para cada rotação de um simulador de Jaszczak em relação ao eixo da maca (0°, 5° e 10°), com e sem fiducial. Dois métodos de corregistro inelástico foram aplicados - SPM12 e NMDose-coreg -, e a porcentagem do erro quadrático médio (%RMSE) foi usada para analisar a qualidade do corregistro. Uniformidade, contraste e resolução foram medidos antes e após o corregistro. NMDose com corregistro automático foi usado para calcular a dose renal de 12 pacientes tratados com 177Lu-DOTATATE e comparado com OLINDA/EXM. Resultados: A marcação fiducial não modificou a qualidade do corregistro das imagens SPECT, medida pela %RMSE (p = 0,40). Não houve impacto na uniformidade, contraste e resolução após o corregistro de imagens adquiridas com ou sem fiduciais. Aplicação clínica preliminar mostrou tempo total de processamento de 9 ± 3 min/paciente para NMDose e 64 ± 10 min/paciente para OLINDA/EXM, com alta correlação entre ambos, apesar de menor dose renal em NMDose. Conclusão: NMDose-coreg permite o corregistro rápido de imagens SPECT, sem perda de uniformidade, contraste ou resolução. O uso da marcação fiducial não aumentou a precisão do corregistro em fantomas.
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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.
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OBJECTIVES@#To observe the changes of skin blood flow perfusion at Waiguan (TE 5) caused by mild moxibustion with moxa stick and infrared mild moxibustion using laser speckle contrast imaging technology, and to compare the microcirculatory effect during and after both moxibustion methods and explore the dose-response relationship of moxibustion.@*METHODS@#Twenty-four healthy participants were treated with mild moxibustion with moxa stick and infrared mild moxibustion at left Waiguan (TE 5). The record started when the skin temperature reached (44±1) °C, and both moxibustion methods were provided within this temperature range. The 20-minute moxibustion process was divided into four stages (5, 10, 15, and 20 min) using interpolation method, and each participant completed eight interventions with a minimum 24-hour interval between different interventions. The skin surface temperature of the left Waiguan (TE 5) was monitored when both moxibustion interventions were given for 10 min using a TES1306 thermocouple thermometer. The skin microcirculatory blood perfusion units (MBPU) of left Waiguan (TE 5) was measured using a PSIN-01087 laser speckle blood flow imager 1 min before moxibustion, at 5, 10, 15, 20 min during moxibustion and continuously for 20 min after moxibustion in each intervention.@*RESULTS@#The skin surface temperature of the left Waiguan (TE 5) remained within the range of (44±1) °C during both moxibustion methods, with no statistically significant difference (P>0.05). Compared with that before moxibustion, the MBPU of the left Waiguan (TE 5) was increased significantly at 5, 10, 15, and 20 min of both moxibustion methods (P<0.05, P<0.01). Compared with moxibustion for 10, 15 and 20 min, the MBPU of the left Waiguan (TE 5) of moxibustion for 5 min was lower in both moxibustion methods (P<0.01). For both moxibustion methods with the same moxibustion course, the MBPU of the left Waiguan (TE 5) 20 min after intervention was significantly higher than that at 1 min before moxibustion (P<0.001), and there was no significant difference in MBPU between 1 min before moxibustion and 20 min after moxibustion among different groups (P>0.05). Within the same moxibustion method, the MBPU of the left Waiguan (TE 5) 20 min after moxibustion with the intervention of 5 min was lower compared to that of 10, 15, and 20 min of moxibustion (P<0.001), with no significant differences between 10, 15, and 20 min of moxibustion (P>0.05).@*CONCLUSIONS@#When controlling the skin temperature at Waiguan (TE 5) within (44±1) °C, infrared mild moxibustion has similar effects on skin microcirculatory blood perfusion as traditional mild moxibustion with moxa sticks. From a dose-response perspective, microcirculation reached a stable state after 10 min of moxibustion, and moxibustion interventions lasting for more than 10 min shows better therapeutic effects.
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Humanos , Moxibustão/métodos , Microcirculação , Pele/irrigação sanguínea , Temperatura CutâneaRESUMO
Background Steel workers are exposed to occupational hazardous factors such as dust, noise, and heat, and often work in shifts, making them prone to sleep disorders. Objective To explore potential influencing factors of sleep disorders among workers in a steel enterprise in Gansu Province, and provide a basis for reducing the risk of sleep disorders among them. Methods From January to March 2022, a self-made questionnaire combined with the Pittsburgh Sleep Quality Index (PSQI) were used to investigate the employees of a steel enterprise in Gansu Province. According to their PSQI scores, they were divided into a normal sleep group and a sleep disorder group. The general demographic variables of the two groups were balanced by 1∶1 propensity score matching (PSM). Multiple logistic regression was used to analyze the contributing factors of sleep disorders. Restricted cubic spline (RCS) model was used to analyze potential dose-response relationship between weekly working hours and sleep disorders. Results The prevalence of sleep disorders in the steel workers was 48.06% (6029/12544). After PSM, 5847 pairs were successfully matched, and the distributions of matched variables were well balanced between the two groups. The results of multiple logistic regression showed that hypertension (OR=1.39, 95%CI: 1.24, 1.56), diabetes mellitus (OR=1.34, 95%CI: 1.07, 1.66), three-shift system (OR=1.26, 95%CI: 1.12, 1.41), dust exposure (OR=1.14, 95%CI: 1.01, 1.29), noise exposure (OR=1.23, 95%CI: 1.09, 1.39), heat exposure (OR=1.16, 95%CI: 1.04, 1.29), and work injury (OR=1.22, 95%CI: 1.02, 1.46) increased the risk of sleep disorders. Compared with workers with < 10 years of service, those with 10-20 years (OR=1.31, 95%CI: 1.19, 1.44), 20-30 years (OR=1.34, 95%CI: 1.19, 1.52), and ≥30 years of service (OR=1.35, 95%CI: 1.19, 1.53) had a higher risk of sleep disorders. Compared with non-exercise workers, the risk of developing sleep disorders was lower in workers with occasional exercise (OR=0.61, 95%CI: 0.56, 0.66) and regular exercise (OR=0.55, 95%CI: 0.49, 0.62). The RCS model showed that the weekly working hours and sleep disorders in the steel workers showed a nonlinear dose-response relationship (P<0.05 for overall trend, P<0.05 for nonlinear test). The relationship between weekly working hours and sleep disorders showed a "U" shaped distribution, with a significant increase in the risk of sleep disorders when the weekly working hours exceeded 49 h. Conclusion The non-occupational influencing factors of sleep disorders of employees in the steel enterprise include hypertension, diabetes, physical exercise, and occupational influencing factors include length of service, weekly working hours, shifts, dust exposure, noise exposure, heat exposure, and work injuries. It is recommended to consider both occupational and non-occupational factors to formulate appropriate sleep disorder prevention and control measures for steel employees to reduce the risk of sleep disorders.
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Objective@#To explore the dose-response relationship between pre-pregnancy body mass index (BMI) and gestational diabetes mellitus (GDM), so as to provide insights into the cut-off values of pre-pregnancy BMI and optimizing GDM prevention and control strategies. @*Methods@#Pregnant women that admitted to Zhengzhou Central hospital in 2021 were recruited, and demographics, family history, pregnancy and delivery history and blood glucose levels during pregnancy were collected. The dose-response relationship between pre-pregnancy BMI and GDM was analyzed using restricted cubic spline (RCS) analysis. The predictive ability of pre-pregnancy BMI for GDM risk was evaluated using receiver operating characteristic (ROC) curve. @*Results@#A total of 2 279 participants were included in the study. The median age was 29.0 (interquartile range, 5.0) years. The median pre-pregnancy BMI was 21.1 (interquartile range, 3.8) kg/m2. There were 312 underweight women (13.69%), 825 women with low-normal weight (36.20%), 730 women with high-normal weight (32.03%), 345 overweight women (15.14%) and 67 obese women (2.94%).The prevalence of GDM was 17.20%. RCS analysis suggested a linear dose-response relationship between age, pre-pregnancy BMI and GDM (P<0.05). When pre-pregnancy BMI was higher than 21.1 kg/m2, the risk of GDM increased with pre-pregnancy BMI (P<0.05). When women aged over 29.0 years, the risk of GDM increased with age, and the dose-response relationship of GDM caused by pre-pregnancy BMI was stronger in the women aged over 29.0 years than in the women aged 29.0 years and below (P<0.05). The area under curve (AUC) was 0.654 (95%CI: 0.624-0.684). If the cut-off value of pre-pregnancy BMI was 23.0 kg/m2, the Youden index, sensitivity and specificity was 0.238, 0.472 and 0.766, respectively. If it was 24.0 kg/m2, the Youden index, sensitivity and specificity was 0.195, 0.342 and 0.853, respectively. If it was 21.1 kg/m2, the Youden index, sensitivity and specificity was 0.213, 0.676 and 0.537, respectively.@* Conclusions @# There is a linear dose-response relationship between pre-pregnancy BMI and GDM, and higher than 21.1 kg/m2 of the pre-pregnancy BMI could increase the risk of GDM.
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Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P＜0.05),while the expression of serum IL-10 was significantly decreased(P＜0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P＜0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P＜0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P＜0.05),and the serum IL-10 level was increased(P＜0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P＞0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.
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Objective:To evaluate the effect of lidocaine on the dose-effect relationship of remimazolam combined with alfentanil in inhibiting responses to gastroscope insertion in elderly patients.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱelderly patients of either sex, aged 65-80 yr, with body mass index of 18-28 kg/m 2, undergoing painless gastroscopy under general anesthesia, were divided into 2 groups using a random number table method: remimazolam group (group C) and lidocaine combined with remimazolam group (group L). Alfentanil 6 μg/kg was given at anesthesia induction in all the patients, and then lidocaine 2 mg/kg was intravenously injected in the patients in group L. Modified Dixon′s up-and-down method was used for the study. Remimazolam was intravenously injected at a dose of 0.18 mg/kg in the first patient, and the gastroscope was placed when the eyelash reflex disappeared and the modified observational alertness/sedation assessment score ≤3. Gastroscope insertion response was defined as swallowing, bucking, body movement and other responses affecting the quality of examination during the gastroscope insertion. The dose of remimazolam was increased/decreased by 0.02 mg/kg in the next patient if the gastroscope response was positive or negative, and the process was repeated until 9 turning points occurred. The median effective dose (ED 50) and 95% confidence interval ( CI) of remimazolam were calculated by probit method. Results:The ED 50 (95% CI) of remidazolam in inhibiting responses to gastroscope insertion in elderly patients when combined with alfentanil was 0.158 (0.133-0.183) mg/kg in group C. The ED 50 (95% CI) of remidazolam in inhibiting responses to gastroscope insertion in elderly patients when combined with fentanyl was 0.139 (0.127-0.151) mg/kg in group L. The ED 50 was significantly lower in group L than in group C ( P=0.003). Conclusions:Intravenous lidocaine in combination with alfentanil increases the efficacy of remimazolam for painless gastroscopy in elderly patients.
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Objective:To determine the median effective dose(ED 50) of alfentanil combined with propofol inhibiting responses to the laryngeal mask airway(LMA) insertion in children. Methods:American Society of Anesthesiologists Physical Status classification Ⅰ children, aged 6-10 yr, with body mass index of 18-24 kg/m 2, undergoing facial skin pigmented nevus resection, were selected. Propofol(target plasma concentration 3 μg/ml) was given by the target-controlled infusion, alfentanil was intravenously injected, 2 min later LMA was inserted, and anesthesia was maintained with 2%-3% sevoflurane until the end of surgery. The dose of alfentanil was determined by the up-and-down sequential method, the initial dose of alfentanil was 15 μg/kg, when the response to LMA insertion was positive/negative, the dose of alfentanil increased/decreased by 1 μg/kg in the next case. The LMA insertion response was defined as swallowing, bucking, body movement occurred during insertion of the LMA, and this process was repeated until 7th turning points appeared. The ED 50 and 95% confidence interval of alfentanil combined with propofol inhibiting responses to LMA insertion in children were calculated using probit method. Results:The ED 50 of alfentanil combined with propofol inhibiting responses to LMA insertion was 13.18(95% confidence interval 12.43-13.79) μg/kg in children. Conclusions:The ED 50 of alfentanil combined with propofol inhibiting responses to LMA insertion is 13.18 μg/kg in children.
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Objective:To evaluate the effect of age factors on the pharmacodynamics of intranasal dexmedetomidine for sedation in the pediatric patients undergoing transthoracic echocardiography(TTE).Methods:American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients, aged 1-24 months, undergoing TTE from August 2019 to May 2022, were selected. This trial was performed in two parts. Part Ⅰ Pediatric patients were divided into 4 age groups: 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The initial dose of dexmedetomidine was 2.0 μg/kg in 0.1 μg/kg increment/decrement. The dose of dexmedetomidine was determined by using modified Dixon′s up-and-down method. The ED 50 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated by the Dexon-Massey method. Part Ⅱ One hundred patients were divided into 4 age groups ( n= 25 each): 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The 4 groups were further divided into 5 subgroups ( n=5 each) according to the dose of dexmedetomidine: 2.1 μg/kg subgroup, 2.2 μg/kg subgroup, 2.3 μg/kg subgroup, 2.4 μg/kg subgroup, and 2.5 μg/kg subgroup. Part Ⅰ and part Ⅱ trials were combined, and the ED 95 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated using the probit method. Results:A total of 220 pediatric patients were enrolled. There was no significant difference in ED 50 and ED 95 of dexmedetomidine intranasally administered for sedation among groups ( P>0.05). Conclusions:The pharmacodynamics of intranasal dexmedetomidine for sedation shows no significant difference in age in the pediatric patients aged 1-24 months undergoing TTE.
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Objective:To investigate the effects of different doses of simvastatin and atorvastatin combined with trimetazidine on blood lipids and cardiac function in patients with chronic heart failure.Methods:A total of 100 patients with chronic heart failure who received treatment in Jinan Second People's Hospital from September 2019 to August 2021 were included in this study. These patients were divided into three groups according to different treatment methods: group A ( n = 33), group B ( n = 33), and group C ( n = 34). Group A was treated with a conventional dose of simvastatin combined with trimetazidine. Group B was treated with a high dose of simvastatin combined with trimetazidine. Group C was treated with atorvastatin combined with trimetazidine. All patients were treated for 6 months. Cardiac function, blood lipids, inflammatory factors, and excellent and good rates of therapeutic effects post-treatment were compared between the three groups. The adverse events during the treatment were recorded. Results:There were no significant differences in blood lipids, cardiac function, inflammatory factors, and excellent and good rates of therapeutic effects between the two groups (all P > 0.05). After 6 months of treatment, high-density lipoprotein cholesterol [(1.99 ± 0.25) mmol/L, (2.01 ± 0.16) mmol/L] and left ventricular ejection fraction [(51.29 ± 4.15)%, (51.37 ± 4.44)%] in groups B and C were significantly higher than those in group A [(1.52 ± 0.16) mmol/L, (42.28 ± 4.86)%, t = 9.10, 6.24; 8.10, 11.38, all P < 0.05). Caspase-1 [(42.33 ± 3.19) ng/L, (41.87 ± 3.55) ng/L], interleukin-18 [(54.55 ± 4.39) ng/L, (53.98 ± 4.45) ng/L], left ventricular end-systolic diameter [(35.13 ± 2.13) mm, (35.68 ± 2.46) mm], left ventricular end-diastolic diameter [(44.39 ± 3.65) mm, (44.42 ± 3.32) mm], low-density lipoprotein cholesterol [(2.69 ± 0.39) mmol/L, (2.57 ± 0.13) mmol/L], total cholesterol [(3.79 ± 0.13 ) mmol/L, (3.56 ± 0.69) mmol/L], triacylglycerol [(1.12 ± 0.05) mmol/L, (1.10 ± 0.07) mmol/L] levels in groups B and C were significantly lower than those in group A [(68.41 ±10.23) ng/L, (88.37 ± 6.65) ng/L, (42.63 ± 3.13) mm, (51.68 ± 5.42) mm, (3.13 ± 0.11) mmol/L, (4.21 ± 0.11) mmol/L, (1.51 ± 0.11) mmol/L, t = -13.98, -24.38, -14.27, -24.95, -6.41, -5.64, -8.00, -10.12, -14.17, -18.54, -12.53, -19.01, -5.35, -18.26, all P < 0.05]. 6-minute walking distances [(352.19 ± 25.4) m, (351.74 ± 24.29) m] in groups B and C were significantly longer than that in group A [(319.71 ± 21.11) m, t = 6.63, 5.75, both P < 0.05). The excellent and good rates at 3 and 6 months after surgery in group B was significantly higher than that in group A ( χ2 = 4.00, 4.16, both P < 0.05), but the incidence of adverse reactions in group B [18.18% (6/33)] was significantly higher than 3.03% (1/33) in group A and 2.94% (1/34) in group C (both P < 0.05). There was no significant difference in the incidence of adverse reactions between group A and group C ( P > 0.05). Conclusion:Atorvastatin and high-dose simvastatin alone combined with trimetazidine can achieve good therapeutic effects on chronic heart failure. Both combined therapies are beneficial to improve heart function and reduce myocardial damage. However, atorvastatin combined with trimetazidine is safer than high-dose simvastatin combined with trimetazidine.
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Objective:To investigate the dose-response relationship between physical activity and sarcopenia in middle-aged and elderly people in Urumqi, and then provide the reference to guide the middle-aged and elderly people to arrange exercise reasonably.Methods:A total of 1886 middle-aged and elderly people (aged ≥ 50 years old) from December 2018 to December 2019 in Cihui Health Management Center in Urumqi were selected as the research objects to conduct a questionnaire survey, collected general information and physical examination data, and used the International Physical activity questionnaire to investigate and evaluate their daily activities. Diagnostic criteria of the Asian Working Group on Sarcopenia (AWGS) 2019 were used. Logistic regression model was used to analyze the relationship between physical activity and sarcopenia, and restricted cubic spline was used to analyze the dose-response relationship between physical activity and sarcopenia.Results:Among the investigated subjects, 208 people suffered from sarcopenia, and the prevalence rate was 11%. Multivariate analysis showed that after adjusting for confounding factors such as demographic characteristics, moderate and high intensity physical activity was associated with a lower risk of sarcopenia compared with low intensity physical activity ( OR = 0.389, 95% CI 0.261-0.580; OR = 0.055, 95% CI 0.025-0.122). The dose-response relationship between physical activity and sarcopenia showed an approximate 1-shaped dose-response relationship between total physical activity and sarcopenia ( P<0.01). Conclusions:The strength of the association between physical activity and sarcopenia was approximately an "L" shaped curve, and increased physical activity was associated with a lower risk of sarcopenia when physical activity was between 2500 and 3500 MEt-min/week.
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Background Perfluorinated alkyl substances (PFAS) are a class of synthetic organic fluorides, which have adverse health effects on brain function, and limited research has been conducted on their effects on depression. Objective To assess potential correlation between serum PFAS and depression. Methods Using the 2015—2016 and 2017—2018 National Health and Nutrition Examination Survey (NHANES) datasets, 2626 subjects with complete relevant information in people ≥20 years old were selected. Logistic regression and restricted cubic splines were used to analyze the association and dose-response relationship between serum PFAS concentration and depression. Subgroup analysis was performed on sex, age, race, education level, marital status, family income to poverty ratio, moderate exercise, body mass index, and drinking status. Results Among the 2626 subjects, there were 666 patients (25.4%) with mild or above depression. After adjusting for race, education level, marital status, body mass index, moderate exercise, drinking history, cotinine, and other types of PFAS, serum perfluorooctane sulfonate (PFOS) was positively associated with the risk of depression (OR=1.85, 95%CI: 1.14, 3.02), and showed a nonlinear dose-response relationship (χ2=6.37, Pnonlinear=0.012). Perfluorononanoic acid (PFNA) was inversely associated with the risk of depression (OR=0.23, 95%CI: 0.14, 0.39), and showed a linear dose-response relationship (Ptrend<0.001, χ2=35.13, Poverall<0.001). After subgroup analysis, it was found that males, 20-39 year-olds and 40-64 year-olds were more sensitive to PFNA exposure (OR=0.15, 95%CI: 0.06, 0.37; OR=0.16, 95%CI: 0.06, 0.40; OR=0.18, 95%CI: 0.08, 0.39). PFOS only showed a statistically significant health effect in people aged 20-39 years (OR=3.00, 95%CI: 1.14, 7.94). In addition, among subgroups of non-Hispanic blacks, cohabitants, current drinkers, high school graduates, and obese patients, exposure to PFAS was significantly associated with the risk of depression. Conclusion PFOS exposure may be associated with increased levels of depression, whereas PFNA exposure may be protective.
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Objective: To analyze the levels and distribution characteristics of blood cadmium and urinary cadmium in American adults, to analyze the relationship between blood cadmium and urinary cadmium and pulmonary function dose response, and to explore the effect of this index on the risk of chronic obstructive pulmonary disease. Methods: In March 2022, 3785 patients from 2007 to 2012 in NHANES database were selected as the subjects. Collect demography data such as gender and age, and test data such as lung function, blood cadmium concentration and Urine cadimium concentration. The relationship between blood and urine cadmium levels and lung function and pulmonary function and chronic obstructive pulmonary diease (COPD) was analyzed by Mann-Whitney U test or Kruskal-Wallis H test, multivariate linear regression and restricted cubic spline method. Results: The geometric mean of blood cadmium and urine cadmium in American adults was 0.37 g/L and 0.28 g/L, FEV(1) and FEV(1)/FVC among different cadmium exposure groups was statistically significant, and there was a negative linear dose-response relationship between serum Cd and urine Cd concentrations and FEV(1)/FVC levels (P(overall)<0.001, P(non-linear)=0.152; P(overall)<0.001, P(non-linear)=0.926). Compared with the lowest quartile concentration (Q1), the highest quartile blood cadmium concentration (Q4) (OR=1.934, P(trend)=0.000) and urinary cadmium concentration (OR=1.683, P(trend)=0.000) may increased the risk of chronic obstructive pulmonary disease. Conclusion: There is a negative correlation between blood cadmium, urinary cadmium levels and lung function in American adults, and cadmium may increase the risk of chronic obstructive pulmonary disease.
Assuntos
Adulto , Humanos , Cádmio , Inquéritos Nutricionais , Pulmão , Doença Pulmonar Obstrutiva Crônica , Testes de Função RespiratóriaRESUMO
Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl2 at designed doses (0, 0.5, 1.0, and 1.5 μmol·L−1). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L−1 dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.
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Objective:To evaluate the effect of obesity on the dose-effect relationship of remimazolam when combined with alfentanil in painless gastroscopy.Methods:American Society of Anesthesiologists physical status Ⅰor Ⅱ patients of both sexes, scheduled for elective painless gastroscopy, aged 18-64 yr, were divided into 2 groups according to the body mass index (BMI): normal (BMI 19-24 kg/m 2) group and obese (BMI≥28 kg/m 2) group.Alfentanil 5 μg/kg combined with remimazolam was given intravenously in all the patients, and the dose of remimazolam was determined by the modified Dixon′s up-and-down method.The initial dose of remimazolam was 0.25 mg/kg, and each time the dose was increased or decreased by 0.05 mg/kg based on the sedative effect.The response was defined as positive when the responses that affected the operation of examination developed during insertion of the gastroscope and within the first 2 min of examination such as swallowing, bucking or body movement.This process was repeated until the seventh intersection occurred.The 50% effective dose (ED 50), 95% effective dose (ED 95), and 95% confidence interval ( CI) of remimazolam were calculated by probit method. Results:There were 26 patients in normal group and 18 patients in obese group.The ED 50 (95% CI) of remimazolam was 0.196 (0.087-0.274) mg/kg, and the ED 95 (95% CI) was 0.322 (0.256-1.397) mg/kg in normal group.The ED 50 (95% CI) of remimazolam was 0.125 (0.102-0.148) mg/kg, and the ED 95 (95% CI) was 0.161 (0.141-0.242) mg/kg in obese group.The ED 50 and ED 95 were significantly lower in obese group than in normal group ( P<0.001). Conclusions:Obesity increases the potency of remimazolam when combined with alfentanil 5 μg/kg in the patients undergoing painless gastroscopy.
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Objective:To evaluate the dose-effect relationship of compound lidocaine hydrochloride for transverse abdominal plane-rectus abdominis sheath block (TAP-RSB) for postoperative analgesia in elderly patients undergoing laparoscopic radical colon cancer surgery with general anesthesia.Methods:Elderly patients of either sex, aged≥65 yr, with body mass index <30 kg/m 2, of American Society Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective laparoscopic radical colon cancer surgery with general anesthesia, were selected.After induction of general anesthesia, compound lidocaine hydrochloride was given under ultrasound guidance for bilateral TAP block (20 ml on each side) and for bilateral RSB (10 ml on each side), with the initial concentration of 0.4%.Each time the concentration increased/decreased in the next patient depending on whether or not the analgesia was effective.The ratio between the two successive concentrations was 1.00∶1.15.The analgesic effects were evaluated by the Numerical Rating Scale at 1 h intervals from the time of postoperative admission to the post-anesthesia care unit until 8 h after TAP-RSB (Numerical Rating Scale ≤ 3 was considered as effective analgesia). The probit method was used to calculate the half effective concentration (EC 50) and 95% effective concentration (EC 95) and 95% confidence interval of compound lidocaine hydrochloride. Results:The EC 50 and EC 95(95% confidence interval)of compound lidocaine hydrochloride for TAP-RSB were 0.289% (0.232%-0.352%) and 0.404% (0.345%-0.970%), respectively, when used for postoperative analgesia in elderly patients undergoing laparoscopic radical colon cancer surgery with general anesthesia. Conclusions:The EC 50 and EC 95 of compound lidocaine hydrochloride for TAP-RSB are 0.289% and 0.404%, respectively, when used for postoperative analgesia in elderly patients undergoing laparoscopic radical colon cancer surgery with general anesthesia.
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Objective:To investigate the clinical efficacy and safety of intravenous thrombolysis with different doses of alteplase in the treatment of acute cerebral infarction in older adult patients.Methods:A total of 65 older adult patients with acute cerebral infarction (onset within 4.5 hours, age ≥ 75 years) who underwent intravenous thrombolysis in Wenzhou Central Hospital from February 2021 to February 2022 were included in this study. They were randomly assigned to undergo intravenous thrombolysis with either low dose alteplase (0.6 mg/kg, low dose group, n = 32) or standard dose alteplase (0.9 mg/kg, standard dose group, n = 33). The National Institutes of Health Neurological Stroke Scale score before and 24 and 48 hours after treatment, modified Rankin scale score before and 7, 14 and 90 days after treatment, serum C-reactive protein (CRP), neuron-specific enolase (NSE) and tumor necrosis factor-α (TNF-α) levels before and 24 hours after treatment, 24-hour incidence of intracranial hemorrhage, 24-hour incidence of symptomatic intracranial hemorrhage, and 90-day mortality were compared between the two groups. Results:Compared with before treatment, the National Institutes of Health Neurological Stroke Scale scores in each group were significantly decreased at 24 and 48 hours after treatment (low dose group, t24 h = 6.78, t48 h = 7.86; standard dose group: t24 h = 8.09, t48 h = 10.13, all P < 0.001). Compared with before treatment, the modified Rankin scale score in each group was significantly decreased at 7, 14 and 90 days after treatment (low-dose group: t7 d = 5.19, t14 d = 8.47, t90 d = 9.85; standard dose group: t7 d = 6.83, t14 d = 7.74, t90 d = 13.66, all P < 0.001). At 24 hours after treatment, serum levels of CRP, NSE, TNF-α in each group were significantly decreased (low-dose group: tCRP = 5.13 , tNSE = 4.22, tTNF-α = 34.29; standard dose group: tCRP = 4.87, tNSE = 5.53, tTNF-α = 31.98, all P < 0.001). At each time point after treatment, there were no significant differences in these indices between the two groups (all P > 0.05). The 24-hour incidence of intracranial hemorrhage in the low dose group was significantly lower than that in the standard dose group ( χ2 = 4.58, P = 0.032). There were no significant differences in incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups (all P > 0.05). Conclusion:Intravenous thrombolysis with low dose alteplase (0.6 mg/kg) for the treatment of acute cerebral infarction in older adult patients exhibits equivalent clinical efficacy to that with standard dose alteplase (0.9 mg/kg), and the former is much safer than the latter.
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Objective:To investigate the effects of ultrasound-guided erector spinae plane block on analgesic dosage, lumbar function and pain in patients undergoing percutaneous kyphoplasty.Methods:A total of 100 patients who underwent percutaneous kyphoplasty in Hangzhou Cancer Hospital from November 2018 to October 2021 were included in this study. They were randomly assigned to undergo either local infiltration anesthesia (control group, n = 50) or ultrasound-guided erector spinae plane block (observation group, n = 50). Analgesic dosages, pain status at different phases (Visual Analogue Scale score) and lumbar function (Oswestry Disability Index score), intraoperative and postoperative conditions (operative time, time to get out of bed, time to first exhaust), and the incidence of adverse reactions were compared between the two groups. Results:At 24 and 48 hours after surgery, the amount of analgesics infused in the observation group was (24.54 ± 2.52) mL and (55.68 ± 5.61) mL, respectively, and the number of analgesic pump pressings was (1.01 ± 0.26) times and (3.15 ± 1.02) times, which were significantly lower than those in the control group [amount of analgesics infused at 24 and 48 hours after surgery: (32.78 ± 3.31) mL, (62.57 ± 6.42) mL; the number of analgesic pump pressings at 24 and 48 hours after surgery: (6.42 ± 1.53) times, (10.78 ± 2.45) times, t = 14.00, 5.71, 24.65, 20.33, all P < 0.001]. Visual Analogue Scale score at the time at which the balloon was pressurized and expanded in the observation group was significantly lower than that in the control group [(4.10 ± 0.87) points vs. (4.65 ± 1.01) points, t = 2.92, P < 0.05]. At 1 day and 1 month after surgery, Oswestry Disability Index score in the observation group was (18.37 ± 2.78) points and (12.15 ± 2.02) points, respectively, which were lower than (23.56 ± 3.42) points and (17.53 ± 2.34) points in the control group ( t = 8.33, 12.31, both P < 0.05). The time to get out of bed and the time to first exhaust in the observation group were (9.12 ± 2.54) days and (23.56 ± 4.56) hours, respectively, which were significantly shorter than those in the control group [(11.64 ± 3.12) days, (28.14 ± 5.12) hours, t = 4.43, 4.72, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Ultrasound-guided erector spinae plane block for percutaneous kyphoplasty can effectively ameliorate lumbar spine function, reduce postoperative pain, and facilitate postoperative recovery, without affecting the dosage of narcotics and analgesics. The method is safe and effective.
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Background The association between serum nickel (Ni) and oral cancer incidence is unclear and most of the previous studies were observational studies that did not control for confounding factors between groups. Objective To assess the correlation of serum Ni with oral cancer incidence based on propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Methods A cohort of 456 newly diagnosed oral cancer patients was recruited from the First Hospital of Fujian Medical University during November 2011 to May 2019, and residents ordered their health check-up in hospitals or local community health centers over the same period were selected as a control group, which included a total of 1410 participants. Serum Ni was evaluated by inductively coupled plasma mass spectrometry. Case-control pairs were selected using a 1:1 PSM (caliper value of 0.02), and the study subjects in the case group and control group were weighted for subsequent analysis by IPTW. The general characteristics of the study subjects were tested for equilibrium before and after matching by chi-square test and standardized mean difference (SMD). This was followed by exploring the potential nonlinear dose-response relationship between serum Ni and oral cancer using restricted cubic splines as well as analyzing the association between serum Ni and oral cancer incidence by conditional logistic regression and weighted logistic regression. Results After controlling for between-group covariates by PSM and IPTW, the dose-response curves demonstrated that the risk of developing oral cancer tended to decline and then increase with the increasing serum Ni level. The outcome of the analysis using PSM demonstrated that as compared to the control group, the risk of developing oral cancer in the 0.09-16.80 μg·L−1 serum Ni group was negatively correlated with serum Ni level (OR=0.36, 95%CI: 0.24-0.54), whereas the risk of developing oral cancer in the >16.80 μg·L−1 serum Ni group was positively correlated with serum Ni level (OR=5.43, 95%CI: 2.76-10.68). After applying IPTW, a negative association was found between the risk of oral cancer and serum Ni concentration within a serum Ni window ranging from 0.09 to 20.55 μg·L−1 (OR=0.39, 95%CI: 0.29-0.52), while a positive association with an OR and 95%CI of 5.54 (3.62-8.49) for the Ni concentration > 20.55 μg·L−1. Conclusion In this study, a J-shaped relationship between serum Ni concentration and the risk of developing oral cancer is found, which shows that high serum Ni concentration (>20.55 μg·L−1) may be a risk factor for oral cancer.
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AIM: To observe the effects of rapamycin pregnancy intervention on cognitive function of autism model in rat offspring. METHODS: Fourteen pregnant rats were randomly divided into normal group (n = 3), model group (n = 4), rapamycin (RAPA) control group (n =3) and intervention group (n = 4). The model group and intervention group were i.p. injected with sodium valproate 600 mg/kg at embryonic day (E) 12.5 to establish autism model in rat offspring. RAPA control group and intervention group were i.g. given RAPA 4 mg/kg every day from the 13th day of gestation until the offspring rats were weaned at 23 days. After the birth of the above four groups of pregnant rats, 15, 27, 21 and 26 offspring male rats were selected to conduct behavioral tests to identify the model. Then, paw withdrawal mechanical threshold (PWMT), tail flick latency (TFL) evoked under different light intensity and learning and memory function of offspring rats were further detected. RESULTS: Rat offspring in the model group had lower growth and development indexes and exploratory behavior ability, but stronger repetitive stereotyped behavior compared with the normal group (P < 0.05), while the indexes between the intervention group and model group were reversed (P < 0.05). The model group had higher PWMT than normal group (P < 0.01) and the PWMT of intervention group was lower than that of model group (P < 0.01). The TFLs of rats in 4 groups showed a timed dose-response relationship (TDRR, P < 0.01), that is, TFLs were shortened with the increase of light intensity. The TDRR curve of model group shifted to right compared with normal group (P < 0.01) and intervention group shifted to left compared with model group (P < 0.01). At the light intensity of Focus 34, 51 and 76, the TFLs of model group were longer than those of normal group (P < 0.01) and intervention group had shorter TFLs compared with model group (P<0.01). In spatial probing trial of Morris water maze test, the platform crossover number in model group was less than that in normal group (P<0.01) and that in intervention group was more than model group (P < 0.05). CONCLUSION: RAPA intervention during pregnancy may alleviate behavior disorder, pain tolerance and memory function of autism model in rat offspring to some extent.