In silico acquirement of the accurate residue details of protein on chromatographic media is a bottleneck in protein chromatography separation and purification. Here we developed a novel approach by coupling with H/D exchange and nuclear magnetic resonance to observe hen egg white lysozyme (HEWL) unfolding behavior adsorbed on cation exchange media (SP Sepharose FF). Analysis of 1D 1H-NMR shows that protein unfolding accelerated H/D exchange rate, leading to more loss of signal of amide hydrogen owing to exposure of residues and the more unfolding of protein. Analysis of two-dimensional hydrogen-hydrogen total correlation spectroscopy shows that lysozyme lost more signals and experienced great unfolding during its adsorption on media surface. However, for several distinct fragments, the protection degrees varied, the adsorbed lysozyme lost more signal intensity and was less protected at disorder structures (coil, bend, and turn), but was comparatively more protected against exchange at secondary structure domains (α-helix, β-sheet). Finally, the binding site was determined by electrostatic calculations using computer simulation methods in conjunction with hydrogen deuterium labeled protein and NMR. This study would help deeply understand the microscopic mechanism of protein chromatography and guide the purposely design of chromatographic process and media. Moreover, it also provide an effective tool to study the protein and biomaterials interaction in other applications.
Adsorption ; Amides ; Cations ; Computer Simulation ; Deuterium ; Hydrogen ; Magnetic Resonance Spectroscopy ; Muramidase ; chemistry ; Protein Structure, Secondary ; Protein Unfolding ; Proteins ; chemistry

Objective To study the diagnostic significance and clinical value of genetic analysis in children with neonatal diabetes. Methods Gene mutation analysis was performed in four patients from Zhengzhou children ' s hospital with diagnosis of with neonatal diabetes. Therapeutic effect of glibenclamide in patients with or without gene mutation was compared. Results KCNJ11 gene mutation was found in two patients with neonatal diabetes. Glibenclamide was found only effective for blood glucose control in patients with KCNJ11 mutation. Therefore, Insulin remains the best therapeutic choice in patients without the genetic mutation. Conclusions Genetic mutation status may be useful in choosing treatment options of neonatal diabetic patients, therefore, should be performed in all children with neonatal diabetes.

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 To explore the diagnostic value of a wearable flexible patch ECG instrument in arrhythmia,the alarm situation during clinical application,patient satisfaction and safety.Methods A total of 1 443 subjects wore flexible patch ECG and conventional dynamic ECG(control)for 24 h to test the validity and consistency of arrhythmia diagnosis,and counted the alarm of remote ECG and the occurrence of related adverse events during the wearing of the instrument.Results There were 987 cases of arrhythmia detected by flexible patch ECG and 992 cases by conventional dynamic ECG.The total coincidence rate of arrhythmia diagnosis was 98.7%.The mean heart rate was measured by flexible patch ECG(75.4±11.4)times/min,conventional dynamic heart rate(71.5±12.1)times/min,the intra-group correlation coefficient(ICC)of 2 instruments was 0.892(95%CI:0.537-0.956),with good repeatability.The correct alarm rate of flexible patch ECG was 100%.The incidences of skin pruritus(0.28%vs.1.32%),skin allergy,redness and swelling(0.14%vs.0.69%)and electrode strip shedding(0 vs.0.28%)during wearing the flexible patch electrocardiogram were lower than those of the conventional holter electrocardiogram(P＜0.05).Conclusion The flexible patch ECG has few adverse reactions,high comfort,good safety and clinical applicability.

Objective To investigate the operation status and service level of radiation occupational health inspection institutions in Zhejiang Province, China, and to provide a basis for administrative departments and quality management departments to develop policies. Methods The investigation data of radiation occupational health inspection institutions in Zhejiang Province were collected for descriptive analysis of the regional distribution, nature, and service qualification of the institutions. Results There were 27 radiation occupational health inspection institutions in Zhejiang Province. These institutions were located in 11 cities, of which 85.18% were public institutions and 14.72% were private institutions. For the physical examination workload of radiation workers in Zhejiang Province in 2021, general hospitals accounted for 75.90%, private institutions accounted for 4.51%, and occupational prevention and treatment hospitals accounted for 19.59%. In the radiation occupational health inspection institutions, the stand-alone and online software installation rates were 33.33% and 37.04%, respectively. A total of 26 986 individuals (82.97%) underwent chromosome aberration examination. The examination rates of thyroid color Doppler ultrasound examination and eye lens examination were 41.24% and 82.97%, respectively. Pre-job, on-job, and off-job physical examination accounted for 25.81%, 70.52%, and 3.67%, respectively. For radiation workers who underwent on-job physical examination, diagnostic radiology workers accounted for the highest proportion of 34.90%. The excellent, qualified, and unqualified rates of 27 radiation occupational health inspection institutions were 7.41%, 88.89%, and 3.70%, respectively. Conclusion The network of radiation occupational health inspection institutions in Zhejiang Province is well-established and located mainly in general hospitals, occupational prevention and control institutions, and private institutions. To enhance the quality and proficiency of occupational health examinations, it is imperative to prioritize self-improvement and management, reinforce law enforcement supervision, actively engage in blind sample assessments, and advance the application of information technology and standardized services.