Protein aggregation is a critical issue in the production of biopharmaceuticals. During protein production, transport and storage, various factors can lead to protein aggregation. With the in-depth study, different ways of protein aggregation and various influencing factors were identified. This includes physical and chemical factors, translation modifications and protein structure. Since protein aggregation exerts major impact on the activity and homogeneity of proteins, it is of great importance to study the ways of protein aggregation and how to control it to obtain high-quality proteins. The review focuses on three ways of protein aggregation, namely 3D domain swapping, salt bridge formation, and oxidative stress, as well as methods to control protein aggregation during protein production, transport and storage. This may facilitate reducing the loss caused by the formation of protein aggregation and improving the purity and homogeneity of protein in research and commercial production.
Protein Aggregates ; Proteins/chemistry* ; Oxidative Stress

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

Objective:To explore the relationship between metabolic score for insulin resistance (METS-IR) and chronic kidney disease (CKD) and albuminuria in the Chinese population.Methods:This cross-sectional study was conducted from January to December 2018 among residents aged 20 to 70 years in ten regions of eight provinces in China; all residents had lived in their region for more than 5 years. Various parameters were measured, included fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin (HbA 1c), blood lipids, renal function, urinary albumin/creatinine ratio (UACR), etc. Data of 5 060 subjects meeting the criteria were included in the study. CKD was defined as estimated glomerular filtration rate (eGFR)<60 ml·min -1·1.73 m -2 or UACR≥30 mg/g. Albuminuria was defined as UACR≥30 mg/g. METS-IR was calculated and categorized into quartiles: Q1, METS-IR≤32.19; Q2, METS-IR 32.20-37.10; Q3, METS-IR 37.11-42.58; and Q4, METS-IR>42.58. The correlation between METS-IR and CKD and albuminuria was analyzed by binary logistic regression, and subgroup analyses were performed. Results:There were 1 266, 1 266, 1 265, and 1 263 participants included in Q1-Q4 groups, respectively. With the increase of METS-IR quartile, various parameters increased, including age, fasting blood glucose, HbA 1c, triglycerides, serum uric acid, waist circumference, body mass index, and systolic and diastolic blood pressure, and the proportion of males also increased (all P<0.05). The proportion of patients with CKD and albuminuria increased significantly with the increase in interquartile range (Q) of METS-IR (all P<0.05). Logistic regression analysis showed that for every 1-unit increment of METS-IR, the risk of CKD and albuminuria were both increased by 2% [for both: odds ratio ( OR)=1.02, 95% confidence interval ( CI) 1.01-1.03]. Compared with the lowest METS-IR group (Q1), the ORs for CKD and albuminuria in the highest METS-IR group (Q4) were 1.57 (95% CI 1.17-2.10) and 1.46 (95% CI 1.09-1.96), respectively. In the subgroup analyses, increased METS-IR was significantly associated with CKD and albuminuria among women (CKD: OR=1.62, 95% CI 1.14-2.31; albuminuria: OR=1.53, 95% CI 1.07-2.18), individuals with HbA 1c<7% ( OR=1.64, 95% CI 1.21-2.23; OR=1.55, 95% CI 1.14-2.11), individuals with eGFR≥90 ml·min -1·1.73 m -2 ( OR=1.78, 95% CI 1.27-2.49; OR=1.80, 95% CI 1.28-2.53), and the Chinese Han population ( OR=1.56, 95% CI 1.13-2.17; OR=1.41, 95% CI 1.01-1.96). Conclusions:METS-IR is significantly associated with CKD and albuminuria in a Chinese population. Furthermore, the higher the METS-IR, the higher the risk of CKD and albuminuria.

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.
Benchmarking ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Ginsenosides/analysis* ; Glycyrrhizic Acid/analysis* ; Quality Control

Objective:To explore the clinical value of "hydration therapy" in the treatment of severe acute paraquat poisoning (APP).Methods:A prospective historical control observation was conducted. Fifty-eight patients with severe APP admitted to Shouguang People's Hospital Affiliated to Weifang Medical College from February 2014 to June 2019 were enrolled. Twenty-six patients admitted before May 10th, 2016 were enrolled in the standard treatment group. After being admitted to intensive care unit (ICU) from the department of emergency, patients in the standard treatment group were immediately given standard treatment such as repeated gastric lavage, catharsis, adsorption of poison by activated carbon or montmorillonite powder, drug treatment and blood purification. From May 10th, 2016, 32 patients were enrolled in the intensive treatment group. On the basis of standard treatment, "hydration therapy" was carried out, that was, 0.9% NaCl and/or 5% glucose injection were used for continuous intravenous infusion throughout the day, so as to ensure that the total amount of fluid infusion per day reached 200 mL/kg within 48-72 hours after ICU admission. At the same time, furosemide was used to strengthen diuresis to ensure the balance of water and electrolyte. If heart failure or acute pulmonary interstitial edema occurred during the treatment, "hydration therapy" should be stopped immediately. Six months after treatment, all patients were followed up. The patients with normal activity, no complaints of discomfort and no damage of heart, lung, liver, kidney and other organs were regarded as cured. The therapeutic effect of "hydration therapy" was evaluated.Results:There was no significant difference in gender, age, dosage or time from taking poison to ICU between the two groups. In the intensive treatment group, 32 patients did not appear heart failure during continuous rehydration treatment. Follow-up after 6 months showed that the overall cure rate in the intensive treatment group was significantly higher than that in the standard treatment group [59.4% (19/32) vs. 19.2% (5/26), P < 0.05]. In the 6-month follow-up, there was no significant difference in age or time from taking poison to ICU between the two groups, but the dosage in the intensive treatment group was significantly higher than that in the standard treatment group (mL: 54.06±26.03 vs. 23.00±4.47, P < 0.05). After 6 months of follow-up, chest CT showed that the lesions of pulmonary fibrosis of cured patients in both group gradually reduced with time, not completely progressive and irreversible. Conclusion:"Hydration therapy" with intensive diuresis can significantly improve the rescue success rate of patients with severe APP.

Heat stroke is the most serious type of heat-related diseases, and the induced multiple organ dysfunction syndrome (MODS) is an important cause of death for heat stroke patients. The cardiovascular system is one of the important targets of heat injury. Studies have reported that heat stress can lead to myocardial inhibition, abnormal heart conduction and blood flow redistribution, thus changing the hemodynamic state, leading to obvious abnormalities in electrocardiogram, echocardiography, myocardial injury biological markers and hemodynamic indicators of patients with heat stroke. In this article, the pathophysiological and histological changes and clinical manifestations of heatstroke-induced myocardial injury are reviewed, aiming to provide references for further understanding and research of myocardial damage caused by hyperthermia.

Objective? To investigate the effect of mobile health education platform in the continuous nursing after discharge for rectal cancer patients with preventive colostomy. Methods? From January to December 2017, 60 rectal cancer patients with preventive colostomy in the Department of Gastrointestinal Surgery in the First Affiliated Hospital of University of Science and Technology of China were selected as the subjects by convenient sampling. Patients were divided into two groups: observation group (n=30) and control group(n=30). The control group received regular health education and continuous nursing care of telephone follow-up after discharge, apart from which the observation group received nursing care based on the mobile health education platform. One month after discharge, the two groups were compared in terms of the effects of intervention by the use of Colostomy Patient Colostomy Knowledge Attitude and Practice Scale (CPCKAPS),Ostomy Adjustment Inventory(OAI),and Patients＇ Satisfactory Questionnaire. Results? One month after surgery, the observation group were higher than the control group in the " knowledge on stoma care(11.80±3.13)", "health belief(51.70±11.72)" and "health behavior (31.73±7.19)"with statistical significances (t=3.76, 2.90, 3.05;P＜ 0.05). There were statistical significance in the score of OAI between the observation group (43.23±11.90) and the control group (37.43±6.33); the observation group was higher than the control group in the "overall satisfaction degree towards continuous care" (76.67% vs. 43.33%) with statistical significance(χ2=7.69,P＜ 0.05). Conclusions? Compared with conventional continuous nursing mode, continuous nursing based on mobile health education platform can improve the knowledge, belief and behavior of colostomy care for rectal cancer patients with preventive colostomy, and improve the patients＇adaptability on colostomy, as well as their satisfaction.

Heat stroke is the most serious type of heat-related diseases, and the induced multiple organ dysfunction syndrome (MODS) is an important cause of death for heat stroke patients. The cardiovascular system is one of the important targets of heat injury. Studies have reported that heat stress can lead to myocardial inhibition, abnormal heart conduction and blood flow redistribution, thus changing the hemodynamic state, leading to obvious abnormalities in electrocardiogram, echocardiography, myocardial injury biological markers and hemodynamic indicators of patients with heat stroke. In this article, the pathophysiological and histological changes and clinical manifestations of heatstroke-induced myocardial injury are reviewed, aiming to provide references for further understanding and research of myocardial damage caused by hyperthermia.
Biomarkers ; Heart Injuries ; Heart Rate ; Heat Stroke ; Humans ; Multiple Organ Failure

Objective To understand the regional epidemiology and antibiotic resistance pattern of diarrheagenic E .coli infection in children ,and to clarify the pathogenic association between diarrheagenic E .coli infection and childhood diarrhea .Methods Totally 680 diarrheal children in the outpatient setting and 680 non-diarrheal control children were enrolled prospectively .The stool samples were collected and the potential enteric pathogens were detected .Minimal inhibitory concentration (MIC) method was used to determine the antimicrobial susceptibility for diarrheagenic E .coli isolates .Results The isolation rates of diarrheagenic E .coli in diarrhea group and control group were 15 .6％ and 13 .1％ ,respecitvely ,and diarrheagenic E .coli was the most commonly detected enteric bacteria .Multivariate logistic regression analysis adjusted for age suggested no clinical association between diarrhea and infection with enteropathogenic E .coli (EPEC) (aOR=1 .2 ,95％ CI:0 .8-1 .8) ,enteroadhesive E .coli (EAEC) (aOR=1 .1 ,95％ CI:0 .7 -1 .6) and enterotoxigenic E .coli (ETEC) (aOR= 1 .8 ,95％ CI:0 .5 -6 .2) . Among 199 diarrheagenic E .coli strains ,the rates of resistance to ampicillin ,tetracycline ,trimethoprim-sulfamethoxazole ,azithromycin ,and ceftriaxone were 63 .8％ ,55 .8％ ,48 .2％ ,34 .2％ and 26 .6％ , respectively ,while the rates of resistance to ciprofloxacin , amoxicillin-clavulanate and cefoxitin were 4 .5％ ,1 .5％ and 0 .5％ ,respectively .Conclusions Diarrheagenic E .coli is the most common enteric bacteria detected in the stool samples from children with and without diarrhea in this study . The pathogenic role of infections with EPEC ,EAEC and ETEC in childhood diarrhea is not determined .EHEC and EIEC are rarely detected and further studies are needed to clarify the pathogenic association between infection with EHEC ,EIEC and childhood diarrhea .