Minimum effective concentration of ropivacaine for ultrasound-guided transmuscular quadratus lumborum block in total hip arthroplasty: a randomized clinical trial

Abstract Objective: This trial aimed to identify the Minimum Effective Concentration (MEC90, defined as the concentration which can provide successful block in 90% of patients) of 30 mL ropivacaine for single-shot ultrasound-guided transmuscular Quadratus Lumborum Block (QLB) in patients undergoing Total Hip Arthroplasty (THA). Methods: A double-blind, randomized dose-finding study using the biased coin design up-and-down sequential method, where the concentration of local anesthetic administered to each patient depended on the response from the previous one. Block success was defined as a Numeric Rating Scale (NRS) score during motion ≤ 3 at 6 hours after arrival in the ward. If the block was successful, the next subject received either a 0.025% smaller dose (probability of 0.11) or the same dose (probability of 0.89); otherwise, the next subject received a 0.025% higher ropivacaine concentration. MEC90, MEC95 and MEC99 were estimated by isotonic regression, and the corresponding 95% Confidence Intervals (95% CIs) were calculated by the bootstrapping method. Results: Based on the analysis of 52 patients, MEC90, MEC95, and MEC99 of ropivacaine for QLB were estimated to be 0.352% (95% CI 0.334-0.372%), 0.363% (95% CI 0.351-0.383%), and 0.373% (95% CI 0.363-0.386%). The concentration of ropivacaine at 0.352% in a volume of 30 ml can provide a successful block in 90% of patients. Conclusions: For ultrasound-guided transmuscular QLB in patients undergoing THA, 0.352% ropivacaine in a volume of 30 ml can provide a successful block in 90% of patients. Further dose-finding studies and large sample size are required to verify the concentration.

Validation of automated image co-registration integrated into in-house software for voxel-based internal dosimetry on single-photon emission computed tomography images / Validação do corregistro automático de imagem integrado a software de análise de dosimetria interna baseada em voxel para tomografia computadorizada de emissão de fóton único

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.

Effect of mild moxibustion with moxa stick and infrared mild moxibustion on skin blood perfusion at Waiguan (TE 5) / 中国针灸

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.

Application of quantitative pharmacology in vaccine research and development: overview and prospect / 中国临床药理学与治疗学

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.

Relationship between cadmium exposure and pulmonary function level and chronic obstructive pulmonary disease / 中华劳动卫生职业病杂志

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.

Influencing factors of sleep disorders of employees of a steel enterprise / 环境与职业医学

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.

Impacts of cadmium on mouse neural stem cells based on dose-response metabomics / 环境与职业医学

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.

Dose-response relationship between pre-pregnancy body mass index and gestational diabetes mellitus / 预防医学

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.

Effects of different moxibustion time on knee cartilage morphology and the expression of TNF-α and IL-10 in rats with knee osteoarthritis / 针灸推拿医学（英文版）

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.

Effect of lidocaine on dose-effect relationship of remimazolam combined with alfentanil in inhibiting responses to gastroscope insertion in elderly patients / 中华麻醉学杂志

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.

Median effective dose of alfentanil combined with propofol inhibiting responses to laryngeal mask airway insertion in children / 中华麻醉学杂志

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.

Effect of age factors on pharmacodynamics of intranasal dexmedetomidine for sedation in pediatric patients undergoing transthoracic echocardiography / 中华麻醉学杂志

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.

Effects of different doses of simvastatin and atorvastatin combined with trimetazidine on blood lipids and cardiac function in patients with chronic heart failure / 中国基层医药

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.

Dose-response relationship between physical activity and sarcopenia in middle-aged and elderly people in Urumqi / 中国实用护理杂志

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.

Association between perfluorinated alkyl substances and depression / 环境与职业医学

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.

Effects of rapamycin intervention during pregnancy on cognitive function of autism model in rat offspring / 中国临床药理学与治疗学

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.

Interlaboratory method validation of slope ratio determination for anticoagulant activity of leeches / 中国药理学通报

Aim To investigate the slope ratio method for the determination of anticoagulant activity of leeches. Methods Three batches of leeches, four groups of Japanese medical vermiculite yinpian and fifteen groups of leech preparations were chosen, with contrast medicinal leeches herbs and Philippine cattle leech contrast medicinal materials, and different concentrations of leaching solutions were prepared in parallel. APTT value was determined after anticoagulant activity was determined by slope ratio method for the joint validation of laboratory, intermediate precision and accuracy between the linear range. Results The slope ratio method was accurate and accurate in the determination of anticoagulant activity of leeches, with linearity between 64% and 156% relative titer level. Conclusion Slope ratio method can be used to determine the anticoagulant activity of leeches.

Distributions of gut Akkermansia muciniphila and its non-linear associations with obesity / 中华内分泌代谢杂志

Objective:Investigating the distribution of intestinal Akkermansia muciniphila (AKK) and explore abundance-effect in obesity obesity to provide potential dose effect for obesity intervention.Methods:Clinical data of 6 986 subjects including body mass index, waist circumference, and common confounders such as gender, age, diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, and uric acid were collected from Guangdong Gut Microbiome Project in 2008. 16S ribosomal RNA (16S rRNA) sequencing data were used to estimate the genus abundance of AKK as well as its operational taxonomic unites (OTUs). Central obesity and overall obesity were diagnosed according to the criteria of China Obesity Working Group in 2002. Multivariate logistic regression was used to analyze the OR (95% CI) of obesity with one-unite elevation of AKK. The dose effect of AKK on obesity was estimated by comparing the trend of ORs from the 1st to the 20th quantile. Results:A total of three AKK OTUs(AKK OTU1, AKK OTU2, AKK OTU3) were identified: AKK OTU1 and AKK OTU2 were distributed in more than 90% of the population, while AKK OTU3 was distributed at 21.7%; All the OTUs showed a"bimodal"distributional pattern and their correlations with common factors were variable. Disparities of the association with obesity were found between the OTUs and the AKK. AKK OTU1, AKK OTU2, and the genus level of AKK showed significant protective effects against obesity; The ORs (95% CI) were 0.95(0.93-0.98), 0.97(0.94-0.99), 0.93(0.91-0.96), respectively for central obesity; And ORs(95% CI) were 0.88(0.80-0.97), 0.98(0.93-1.02), 0.81(0.74-0.89), respectively for overall obesity. The results were similar after adjustment for common confounders. According to the calculation of dose-effect, the protect effects of AKK increased with accumulated abundance and the minimum effective dose on central obesity and overall obesity was 1.83% and 4.98%, respectively. Conclusion:AKK is a protective factor for obesity, but the dose-effect of AKK and the strain-differences should be considered in the future interventional study.

Median effective dose of esketamine for preoperative sedation in pediatric patients of different ages / 中华麻醉学杂志

Objective:To determine the median effective dose (ED 50) of esketamine for preoperative sedation in different aged pediatric patients. Methods:Pediatric patients, aged 1-6 yr, of American Society of Anaesthesiologists physical status Ⅰ, with the preoperative parental Separation Anxiety Scale (PSAS) score ≥3, undergoing elective surgery under general anesthesia, were selected.According to the age, the children were divided into 1 yr≤age<4 yr low-age group (group L) and 4 yr≤age< 6 yr high-age group (group H). Esketamine 0.5 mg/kg was intravenously injected in the first child in each group.The dose in the next child was determined according to PSAS scores, and the two consecutive dose gradient was 0.1 mg/kg; when the PSAS score in the previous child was ≥3, the dose in the next child was increased; when the PSAS score in the previous child was< 3, the dose in the next child was decreased until appearance of 7 turning points, and then the experiment was terminated.The ED 50 and 95% confidence interval of esketamine for preoperative sedation were calculated by probit analysis. Results:A total of 54 children were enrolled in this study, including 26 cases in group L and 28 cases in group H. The ED 50 and 95% confidence interval of esketamine were 0.413 (0.314-0.530) mg/kg and 0.282 (0.252-0.318) mg/kg in group L and group H, respectively.Compared with group L, ED 50 of esketamine was significantly decreased in group H ( P<0.05). Conclusions:The ED 50 of esketamine for preoperative sedation is 0.413 mg/kg in pediatric patients of 1 yr≤age<4 yr old and 0.282 mg/kg in those of 4 yr≤age<6 yr old, and the efficacy of esketamine for preoperative sedation increases with age.

Effects of different inhalation time on minimum alveolar concentration of sevoflurane in adult rats / 中华麻醉学杂志

Objective:To evaluate the effects of different inhalation time on the minimum alveolar concentration (MAC) of sevoflurane in adult rats.Methods:Two hundred SPF healthy adult Sprague-Dawley rats (half male, half female), aged 8-10 weeks, weighing 200-260 g, were divided into 2 groups using a random number table method: inhalation of sevoflurane for 1 h group and inhalation of sevoflurane for 20 min group, with 100 rats in each group.Each group was subdivided into 10 subgroups with 10 rats in each subgroup, the initial concentration was preset at 1.50%, and the ratio between two successive concentrations r was 1.08.The tail clamping stimulus was applied to evaluate the efficacy of anesthesia in each subgroup, a positive response was defined as a body movement occurred within 1 min after tail clamping stimulus, and the response was defined as negative when no body movement occurred within 1 min after tail clamping.The Bliss method was used to calculate the MAC, EC 95 and 95% confidence interval (CI) of sevoflurane. Results:The MAC and EC 95 (95% CI) of sevoflurane were 2.09% (1.98%-2.20%) and 2.75% (2.56%-3.04%), respectively, in inhalation of sevoflurane for 1 h group, and 2.35% (2.22%-2.49%) and 3.10% (2.87%-3.45%), respectively, in inhalation of sevoflurane for 20 min group ( P<0.05). Conclusions:The MAC of sevoflurane in adult rats inhaled sevoflurane for 1 h is decreased than that inhaled for 20 min.