Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To assess the influence of extreme temperature events on the mortality risk of nervous system diseases in residents of Jiangsu Province and identify patients with nervous system diseases who are susceptible to extreme temperature events.Methods:Acase-crossover design was used to investigate the cumulative lagged effects of extreme temperature events on the mortality risk of nervous system disease in local residents by using the data on causes of death from nervous system diseases in Jiangsu from 2014 to 2020 with conditional logistic regression model. The final definition of extreme temperature events was established using Akaike information criterion. The heat wave was defined as 4 or more consecutive days with daily mean temperatures above the 92.5 th percentile of annual daily mean temperatures, and the cold spell was defined as 2 or more consecutive days with daily mean temperatures below the 10 th percentile of annual daily mean temperatures. Furthermore, stratified analyses was conducted to compare the effects of extreme temperature events on mortality risk in populations in different gender, age and marital status groups to identify susceptible populations to extreme temperature event. Results:Statistical results showed that the effect values of heat wave and cold spell on the mortality risk of nervous system diseases all peaked at the 7 th day of the cumulative lag, with OR of 1.60 (95% CI: 1.44-1.76) and 1.33 (95% CI: 1.13-1.56), respectively. Heat wave exposure increased mortality risk for individuals with Alzheimer's and Parkinson's diseases, while cold spell exposure increased the mortality risk for those with Alzheimer's disease. Stratified analyses showed that the mortality risk for nervous system disease and Alzheimer's disease was higher in partnerless population after heat wave exposure. Conclusions:Heat wave and cold spell were associated with increased mortality risks for nervous system disease, highlighting the need for improved early warning systems for extreme temperature event. In the context of heat wave, interventions to protect individuals with nervous system disease should prioritize partnerless population.

Objective:This study aimed to evaluate the immunoprotective effect of anti-rabies virus cocktail monoclonal antibody Zamerovimab/Mazorelvimab after rabies exposure.Methods:The dynamic data of rabies virus neutralizing antibody (RVNA) were analyzed in the Zamerovimab/Mazorelvimab Chinese phase Ⅲ study (clinical trial registration number: CTR20201819).Results:The full analysis set showed that RVNA geometric mean titers (GMT) on the 4 th, 8 th, 15 th, 43 rd, and 99 th day in the Zamerovimab/Mazorelvimab group were 4.413 IU/ml, 5.178 IU/ml, 17.062 IU/ml, 14.672 IU/ml, and 2.836 IU/ml, respectively, while those in the human rabies immunoglobulin (HRIG) group were 0.299 IU/ml, 0.451 IU/ml, 11.374 IU/ml, 18.063 IU/ml, and 6.769 IU/ml, respectively. The positive rates of RVNA on the 4 th, 8 th, 15 th, 43 rd, and 99 th day in the Zamerovimab/Mazorelvimab group were 99.9%, 99.6%, 100%, 100%, and 97.4%, respectively, while those in the HRIG group were 23.3%, 34.1%, 97.6%, 99.6%, and 98.4%, respectively. Conclusions:Compared with HRIG, Zamerovimab/Mazorelvimab cocktail monoclonal antibody reached the required protection level of RVNA very soon, thus effectively provided an immediate neutralizing effect of passive immunization therapies against rabies virus.

OBJECTIVE Cannabinoids modulate do-pamine(DA)transmission and DA-related behavior,which has been thought to be mediated initially by acti-vation of cannabinoid CB1 receptors(CB1Rs)on GABA neurons.However,the cellular and receptor mechanisms underlying cannabinoids' psychoactive effects are not fully understood.The present study is to explore the pos-sible expression character of CB1Rs and elucidated the underlying mechanism of them.METHODS We took advantage of RNAscope in situ hybridization(ISH)assays and triple-staining assays to detect the CB1R-expressing neurons.We established an optical intracranial self-stimulation(OICSS)behavioral model by using opto-genetics to study dopaminergic reinforcement function.Natural and synthetic cannabinoids were used to study the function of CB1Rs.Conditional genetic depletion of CB1Rs and behavioral assay were performed to study the modulatory role of CB1Rs in DA-related behaviors.RESULTS We found that CB1Rs are also expressed in a subset of DA neurons and functionally underlie cannabi-noid action in male and female mice.ISH assays demon-strated CB1 mRNA in tyrosine hydroxylase(TH)-posi-tive DA neurons in the ventral tegmental area(VTA)and glutamate decarboxylase 1(GAD1)-positive GABA neu-rons.The CB1R expressing DA neurons were located mainly in the middle portion of the VTA with the number of CB1-TH colocalization progressively decreasing from the medial to the lateral VTA.Triple-staining assays indi-cated CB1R mRNA colocalization with both TH and vesicular glutamate transporter 2(VgluT2,a glutamate neuronal marker)in the medial VTA close to the midline of the brain.Optogenetic activation of this population of DA neurons was rewarding as assessed by OICSS.D9-tetrahydrocannabinol(D9-THC)or ACEA(a selective CB1R agonist)dose-dependently inhibited optical intra-cranial self-stimulation in DAT-Cre control mice,but not in conditional knockout mice with the CB1R gene absent in DA neurons.In addition,deletion of CB1Rs from DA neurons attenuated D9-THC-induced reduction in DA release in the NAc,locomotion,and anxiety.CONCLU-SION Our results indicated that CB1Rs are expressed in a subset of DA neurons that corelease DA and gluta-mate,and functionally underlie cannabinoid modulation of DA release and DA-related behavior.

Heparin and heparan sulfate are a class of glycosaminoglycans for clinical anticoagulation. Heparosan N-sulfate-glucuronate 5-epimerase (C5, EC 5.1.3.17) is a critical modifying enzyme in the synthesis of heparin and heparan sulfate, and catalyzes the inversion of carboxyl group at position 5 on D-glucuronic acid (D-GlcA) of N-sulfoheparosan to form L-iduronic acid (L-IdoA). In this study, the heparin C5 epimerase gene Glce from zebrafish was expressed and molecularly modified in Escherichia coli. After comparing three expression vectors of pET-20b (+), pET-28a (+) and pCold Ⅲ, C5 activity reached the highest ((1 873.61±5.42) U/L) with the vector pCold Ⅲ. Then we fused the solution-promoting label SET2 at the N-terminal for increasing the soluble expression of C5. As a result, the soluble protein expression was increased by 50% compared with the control, and the enzyme activity reached (2 409±6.43) U/L. Based on this, site-directed mutations near the substrate binding pocket were performed through rational design, the optimal mutant (V153R) enzyme activity and specific enzyme activity were (5 804±5.63) U/L and (145.1±2.33) U/mg, respectively 2.41-fold and 2.28-fold of the original enzyme. Modification and expression optimization of heparin C5 epimerase has laid the foundation for heparin enzymatic catalytic biosynthesis.
Animals ; Carbohydrate Epimerases ; biosynthesis ; chemistry ; genetics ; Escherichia coli ; Gene Expression ; Heparin ; metabolism ; Heparitin Sulfate ; metabolism ; Iduronic Acid ; metabolism ; Zebrafish Proteins ; biosynthesis ; chemistry ; genetics

Heparin is a very important anticoagulant drug. Currently, heparin is mainly extracted from porcine mucosa. However, animal-derived heparin shows low anticoagulant activity due to the low proportion of the anticoagulant active unit, the GlcNS6S-GlcA-GlcNS6S3S-Ido2S-GlcNS6S pentasaccharide. In this study we proposed an enzymatic strategy to sulfate the animal-sourced heparin to increase the proportion of anticoagulant pentasaccharide and the anticoagulant activity. First, three sulfotransferases HS2ST, HS6ST, and HS3ST were expressed tentatively in Escherichia coli and Pichia pastoris. After measuring the sulfotransferase activity, we confirmed P. pastoris GS115 is the better host for sulfotransferases production. Then, the maltose binding protein (MBP) and thioredoxin (TrxA) were fused separately to the N-terminal of sulfotransferases to increase enzyme solubility. As a result, the yields of HS2ST and HS6ST were increased to (839±14) U/L and (792±23) U/L, respectively. Subsequent sulfation of the animal-sourced heparin with the recombinant HS2ST, HS6ST and HS3ST increased the anticoagulant activity from (76±2) IU/mg to (189±17) IU/mg.
Animals ; Escherichia coli ; Heparin ; chemistry ; Oligosaccharides ; chemistry ; Pichia ; Sulfotransferases ; biosynthesis ; Swine

Objective To observe the influence of different altitudes on the basic vital signs of cardiopulmonary resuscitation (CPR) rescuers before and after CPR.Methods The experiment was completed in the Simulated Cabin for Special Environment of Northwest of China. Ninety healthy adult medical staff in General Hospital of Xinjiang Command were randomly and equally divided into 3 groups: plain (normal oxygen), 3700-meter high altitude and 4300-meter high altitude. According to the 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, the values of heart rate (HR), mean arterial pressure (MAP), respiration rate (RR), arterial oxygen saturation (SpO2), before and after 1 CPR cycle were recorded for statistical analysis and their changes were compared.Results The HR and RR significantly increased (P<0.05), but MAP and SpO2 did not change significantly (P>0.05) in the three groups. The HR and RR was faster in 4300 meter high-altitude than in 3700 meter high-altitude (P<0.05), and was faster in 3700 meter high-altitude than in the plain (P<0.05). But there was no significant difference between the three groups in MAP and SpO2 (P>0.05).Conclusions With the elevation of the altitude, HR and RR may significantly increase in CPR rescuers, but there is no significant influence on MAP and SpO2.

Objective To investigate the predictive values of serum complement C3, C4 and cholesterol levels in the prognosis of patients with sepsis. Methods The clinical data of all the patients with sepsis admitted to the Department of Critical Care Medicine of the General Hospital of Xinjiang Military Command from January 2015 to January 2017 were retrospectively analyzed. The levels of serum complement C3, C4, cholesterol, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure score (SOFA), etc. were recorded within 24 hours after admission, the patients were divided into survival group and death group according to the 28-day prognosis, and the differences in various indexes between the two groups were compared respectively;the predictive efficacies of C3, C4 and cholesterol levels in the prognosis of sepsis patients were evaluated by plotting receiver operating characteristic curves (ROC). Results Finally, 120 patients with sepsis were enrolled, including 57 patients in the survival group and 63 patients in the death group. Compared with the survival group, the APACHE Ⅱscore and the SOFA score of the death group were increased significantly (APACHE Ⅱ score: 20.29±5.90 vs. 15.32±5.98, SOFA score: 7.62±3.11 vs. 5.16±2.50, both P < 0.01), however, serum C3, C4 and cholesterol levels were obviously decreased [C3 (g/L): 0.67±0.22 vs. 0.82±0.24, C4 (g/L): 0.17±0.05 vs. 0.20±0.06, cholesterol (mmol/L): 2.77±1.23 vs. 3.46±1.02, all P < 0.01]. ROC curve analyses showed: each of the following items, complement C3, C4, and cholesterol, alone predicting the prognosis of sepsis patients, the area under ROC curve (AUC) and 95% confidence interval (95%CI) were as follows: AUC = 0.680 (95%CI = 0.583-0.777, P = 0.001), AUC =0.657 (95%CI = 0.560-0.754, P = 0.003), and AUC = 0.711 (95%CI = 0.619-0.804, P < 0.001) respectively; when complement C3, C4 and cholesterol combination to predict the prognosis of patients with sepsis, the resulting predictive value was better than the predictive value results obtained by each one of the items or each combination of any two of them (the AUC of C3+C4+cholesterol was 0.725, 95%CI = 0.633-0.817, P < 0.001; the AUC of C3+C4 was 0.697,95%CI = 0.603-0.791, P < 0.001; the AUC of C3 + cholesterol was 0.718, 95%CI = 0.626-0.811, P < 0.001; the AUC of C4+cholesterol was 0.722, 95%CI = 0.629-0.815, P < 0.001). Conclusion Using combination of serum complement C3, C4 and cholesterol levels to predict the prognosis of patients with sepsis may obtain important predicting value, that can provide a reference to clinical doctors.

The anesthetists not only pay attention to the exploitation and application of the information resource but also rely more and more on the convenience caused by the informatization. Based on HIS, LIS, and PACS, the Anesthesia information system has been constructed in order to guarantee the quality and safety of the anesthesia. The Anesthesia information system shares the information with HIS and LIS and manages the medical information such as the surgery and anesthesia closely. The paper introduces the notion of the anesthesia information system and its main function and also the predicted effect during the management of the anesthesia information system. Meanwhile, some problem about the application has been mentioned.