Human fibroblast growth factor 21 (hFGF21) has become a candidate drug for regulating blood glucose and lipid metabolism. The poor stability and short half-life of hFGF21 resulted in low target tissue availability, which hampers its clinical application. In this study, the hFGF21 was fused with a recombinant human serum albumin (HSA), and the resulted fusion protein rHSA-hFGF21 was expressed in Pichia pastoris. After codon optimization, the recombinant gene fragment rHSA-hFGF21 was inserted into two different vectors (pPIC9k and pPICZαA) and transformed into three different strains (X33, GS115 and SMD1168), respectively. We investigated the rHSA-hFGF21 expression levels in three different strains and screened an engineered strain X33-pPIC9K-rHSA-hFGF21 with the highest expression level. To improve the production efficiency of rHSA-hFGF21, we optimized the shake flask fermentation conditions, such as the OD value, methanol concentration and induction time. After purification by hollow fiber membrane separation, Blue affinity chromatography and Q ion exchange chromatography, the purity of the rHSA-hFGF21 protein obtained was 98.18%. Compared to hFGF21, the biostabilities of rHSA-hFGF21, including their resistance to temperature and trypsinization were significantly enhanced, and its plasma half-life was extended by about 27.6 times. Moreover, the fusion protein rHSA-hFGF21 at medium and high concentration showed a better ability to promote glucose uptake after 24 h of stimulation in vitro. In vivo animal studies showed that rHSA-hFGF21 exhibited a better long-term hypoglycemic effect than hFGF21 in type 2 diabetic mice. Our results demonstrated a small-scale production of rHSA-hFGF21, which is important for large-scale production and clinical application in the future.
Animals ; Blood Glucose/metabolism* ; Diabetes Mellitus, Experimental ; Fibroblast Growth Factors ; Humans ; Hypoglycemic Agents/metabolism* ; Methanol/metabolism* ; Mice ; Pichia/metabolism* ; Recombinant Fusion Proteins ; Recombinant Proteins/metabolism* ; Saccharomycetales ; Serum Albumin/metabolism* ; Serum Albumin, Human/metabolism*

Objective:To investigate thromboprophylaxis of patients with COVID-19.Methods:Clinical data of 31 patients with COVID-19 in Zhongnan Hospital of Wuhan University was analyzed retrospectively, including basic information, clinical characteristics, examination results, therapy and Padua scores. 5G remote ultrasound diagnosis system was used in the ultrasonography of lower limb vein, inferior vena cava and the heart. According to the patient′s status, the thromboprophylaxis was established, and the incidence of venous thromboembolism (VTE) was observed.Results:There were 20 cases of general types and 11cases of severe types. All patients underwent dynamic assessment and thromboprophylaxis. Basic prevention was applied in 28 cases and mechanical prevention was used in 3 cases. There was no VTE event in all patients during hospitalization.Conclusions:Prevention and monitoring of VTE is an important part of the treatment of patients with COVID-19, which can effectively reduce the incidence of lower extremity deep vein thrombosis and fatal pulmonary embolism in isolation ward.

Objective To evaluate the feasibility of wholeGtumor texture analysis of contrastGenhanced T1 WI (T1 Ce)in differentiating cystic glioma (CG)from brain abscess (BA).Methods MRI data of 25 cases of ringGenhanced CG and 24 cases of BA proven pathologically were retrospectively studied.All the patients underwent preGsurgery MRI plain and contrastGenhanced scans.FireVoxel software was used to outline the ROI of the wholeGtumor.The signal intensity histogram and related texture parameters of the 3D ROI were obtained,including mean, median,standard deviation,inhomogeneity,skewness,kurtosis and entropy.The data were first tested for normality and the differences in wholeG tumor texture analysis parameters of T1 Ce between CGs and BAs were compared using the independentGsample t test(normal distribution)and MannGWhitney rank sum test (skewed distribution).ROC curve was used to evaluate the efficacy of the parameter in differentiating CG from BA.Results There were statistical significances in the parameters of mean,median,standard deviation,inhomogeneity and skewness between CGs and BAs(P＜0.05),and there were no any statistical significances in kurtosis and entropy between CGs and BAs(P＞0.05).In all the texture parameters,the AUC of inhomogeneity was the largest(0.988),and when the threshold was 0.314, the sensitivity and the specificity were 92.60% and 9 7.1 0%,respectively.Conclusion Some of the quantitative parameters of the wholeGtumor texture analysis of T1 Ce(mean,median,standard deviation,inhomogeneity and skewness)could provide reliable and objective evidences for imaging differential diagnosis of CG and BA preGsurgery.

The purpose of the present work is to establish an ultra-minimal invasive percutaneous puncture inoculation method for a VX2 orthotopic lung cancer rabbit model with fewer technical difficulties, lower mortality of rabbits, a higher success rate and a shorter operation time, to evaluate the growth, metastasis and apoptosis of tumor by CT scans, necropsy, histological examination, flow cytometry and immunohistochemistry. The average inoculation time was 10–15 min per rabbit. The tumor-bearing rate was 100%. More than 90% of the tumor-bearing rabbits showed local solitary tumor with 2–10 mm diameters after two weeks post-inoculation, and the rate of chest seeding was only 8.3% (2/24). The tumors diameters increased to 4–16 mm, and irregularly short thorns were observed 3 weeks after inoculation. Five weeks post-inoculation, the liquefaction necrosis and a cavity developed, and the size of tumor grew further. Before natural death, the CT images showed that the tumors spread to the chest. The flow cytometry and immunohistochemistry indicated that there was less apoptosis in VX2 orthotopic lung cancer rabbit model compared to chemotherapy drug treatment group. Minimal invasive percutaneous puncture inoculation is an easy, fast and accurate method to establish the VX2 orthotopic lung cancer rabbit model, an ideal in situ tumor model similar to human malignant tumor growth.
Apoptosis ; Drug Therapy ; Flow Cytometry ; Humans ; Immunohistochemistry ; Lung Neoplasms* ; Lung* ; Methods* ; Mortality ; Necrosis ; Neoplasm Metastasis ; Punctures* ; Rabbits ; Thorax ; Tomography, X-Ray Computed

Objective To investigate the effects of parenteral nutrition with ω-3 fatty acids on nutrition,inflammatory response,immunity and prognosis in criticallyill cancer patients.Methods 60 critically ill cancer patients were randomly divided into study group and the control group,30 cases each.All Patients were given isonitrogen and isocalorie enteral and parenteral nutrition for 2 weeks,which added ω-3 fatty acids in the study group by parenteral nutrition.The indicators of nutrition,inflammation,immune function were detected weekly.prognostic indicators (mortality,intensive care unit [ICU] length of stay,infectious complications) were compared.Results The indicators of nutrition,inflammatory reaction and immune function of study group were significantly improved than control group,and length of stay in ICU of study group was shorter than control group.There were less mortality and morbidity of infection complications in the study group compared with control group,but difference were not significant (P =0.13 and P=0.165).Conclusion ω-3 fatty acids supplementation of parenteral nutrition in critically ill cancer patients can improve nutritional status and immune function,reduce inflammatory response,shorten ICU length of stay,but not significantly improve ICU mortality and reduce infectious complications.

Objective To explore the value of 64-row helical CT multi-phase enhancement scan combined with angiography (CTA)in the diagnosis of pulmonary mass.Methods Two hundred and sixty-five patients with pulmonary mass confirmed by pa-thology were checked,analyzed the CT sign of multi-phase enhancement scan and the blood supply of pulmonary mass displayed by CTA.Results Lung cancer was mainly supplied by bronchial arteries,some by body arteries,the feeding arteries display rate of lung cancer group was significantly higher than that of benign disease group(P <0.05).CT enhancement peak value of lung cancer group was significantly higher than that of tuberculoma group,inflammatory pseudotumor group and hamartoma group(P <0.05), but no significant difference between hemanginoma group(P >0.05).Enhancement dynamic curves of lung cancer group was differ-ent from benign lesion groups:Lung cancer without obvious enhancement in pulmonary artery phase,CT value increased rapidly in aorta phase,120 s reached peak,and declined slowly in delay phase;CT value of tuberculoma was increased slowly without obvious peak;CT value of inflammatory increased gradually in pulmonary artery phase,90 s reached the peak;hamartoma was no obvious enhancement;Hemangioma enhanced rapidly after strengthening in the pulmonary artery phase,reached the peak at about 15 s,and then decreased slowly.Conclusion 64-row helical CT multi-phase enhancement scan combined with angiography have important clinical value,which can differentiate malignant mass from benign ones.

OBJECTIVETo evaluated the manganese (Mn), cobalt (Co) and molybdenum (Mo) levels in blood and urine among general population in China, and thereby to analyze their prevalent features.

METHODSFrom 2009 to 2010, a total of 18 120 subjects of general population aged 6-60 years were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and their blood and urine samples were also collected.Inductive coupled plasma mass spectrometry (ICP-MS) was applied to test the Mn, Co and Mo levels of blood and urine samples, and the Mn, Co, Mo distribution in blood and urine among groups of population in different ages and genders were then analyzed.

RESULTSAmong general population in China, the geometric mean (GM) of Mn concentration in blood was 8.98 µg/L. The Mn concentration in blood among males and females were separately 8.14 µg/L and 9.88 µg/L (Z = -18.84, P < 0.01). The GM of Mn concentration in urine was 0.63 µg/L. The Mn concentration in urine among males and females were separately 0.62 µg/L and 0.63 µg/L (Z = -0.67, P > 0.05). The geometric mean (GM) of Co concentration in blood was 0.194 µg/L. The Co concentration in blood among males and females were separately 0.166 µg/L and 0.225 µg/L (Z = -23.04, P < 0.01). The GM of Co concentration in urine was 0.282 µg/L. The Co concentration in urine among males and females were separately 0.260 µg/L and 0.307 µg/L (Z = -7.35, P < 0.01). The GM of Mo concentration in blood was 0.25 µg/L. The Mo concentration in blood among male and female group were separately 0.27 µg/L and 0.23 µg/L (Z = -5.03, P < 0.01). The GM of Mo concentration in urine was 27.7 µg/L. The Mo concentration in urine among males and females were 29.8 µg/L and 25.6 µg/L (Z = -6.31, P < 0.01), respectively.

CONCLUSIONThe Mn, Co and Mo levels in blood and urine varied by gender and area among general population in China, the study provided basic data evidence for the following Mn, Co and Mo biological monitoring studies in near future.

Adolescent ; Adult ; Child ; China ; epidemiology ; Cobalt ; Environmental Exposure ; Environmental Monitoring ; Female ; Humans ; Male ; Manganese ; Middle Aged ; Molybdenum

OBJECTIVETo investigate the level of zinc (Zn) and copper (Cu) in whole blood among general population from 8 provinces in China, and to analyze the characteristics of distribution among different regions.

METHODSThis cross-sectional study was performed in 8 provinces from eastern, middle and western China between 2009 and 2010, including 13 110 subjects from 24 regions, and the blood and urine samples were collected. The ICP-MS was applied to test the content of ICP-MS in blood samples, and the results were used to analyze the characteristics of contents and distributions of Zn and Cu among population from different ages, genders and regions groups.

RESULTSTotally, the mean (95%CI) contents of Cu and Zn in blood were 795 (791-799)µg/L and 3 996(3 976-4 015) µg/L, respectively. The characteristics of distribution of Cu content were as followed, the content of males were lower than it of females (male:767 µg/L; female: 822 µg/L, t = -13.302, P < 0.01). The contents of blood Cu in groups of people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 860(853-868), 758(748-769), 734(728-734), 782(774-790), 811(795-827) and 820(815-826) µg/L. The differences showed statistical significance (F = 78.77, P < 0.01). The blood Cu content of people in eastern China (800µg/L) were also significantly higher than it in middle (774 µg/L)and western China (782 µg/L) (F = 10.94, P < 0.01). Distribution of blood Zn content showed characteristics as follows: the Zn content was higher in males than in females (male 4 085 µg/L and female 3 908 µg/L, t = 8.78, P < 0.01). The contents of blood Zn in groups of people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 3 306 (3 261-3 350), 3 888 (3 839-3 937), 3 948 (3 902-3 994), 4 272(4 228-4 315), 4 231(4 180-4 281) and 4 250 (4 205-4 294)µg/L, which showed significant statistical differences (F = 233.68, P < 0.01). The blood Zn content of people in eastern China (3 938 µg/L) were significantly lower than it in middle (4 237 µg/L)and western China (4 105 µg/L) (F = 53.16, P < 0.01). In addition, the study also compared the relation between content of Cu and Zn and the frequency of eating seafood. The results found that the frequency of eating seafood could influence the content of Cu and Zn (Cu: F = 13.54, P < 0.01; Zn: F = 200.20, P < 0.01).

CONCLUSIONThe contents and distributions of Cu and Zn in blood differs among people from different groups in ages, genders and regions. The baseline data of this study provided reliable scientific evidence for further research.

Adolescent ; Adult ; Child ; China ; epidemiology ; Copper ; blood ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Zinc ; blood

OBJECTIVETo assess the levels of polycyclic aromatic hydrocarbons monohydroxy metabolites in urine of general population in China among 8 provinces, provide the baseline of the metabolites in the general population.

METHODSFrom 2009 to 2010, 18 120 subjects of general population aged 6-60 years old were recruited from 24 areas among 8 provinces in east, west and central areas of China mainland by cluster random sampling. The information of the living environment and health condition were collected by questionnaire and spot urine samples were collected, 4 680 urine samples were analysed by high performance liquid chromatography with tandem mass spectrometry, and monohydroxy metabolites distribution in urine among groups of gender and ages were analysed.

RESULTSGeometric means (GM) of 2-naphthol, 1-naphthol, 3-phenanthrol and 1-hydroxypyrene concentration in urine (95%CI) were 1.85 (1.75-1.95), 1.55 (1.50-1.61), 0.57 (0.54-0.59) and 0.82 (0.78-0.85) µg/L, respectively;and median are 2.44, <0.50, 0.72 and 0.90 µg/L, respectively. The concentration between male and female were significantly different (P < 0.01), and the concentration among the groups of population were significantly different (P < 0.01), the GM of 2-naphthol among the groups of population aged 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were 1.60, 1.56, 1.69, 2.23, 1.91 and 1.86 µg/L (χ(2) = 17.90, P < 0.01), the GM of 1-naphthol in the groups were 1.30, 1.16, 1.53, 1.68, 1.80 and 1.52 µg/L (χ(2) = 76.22, P < 0.01), the GM of 3-phenanthrol in the groups were 0.78, 0.76, 0.55, 0.42, 0.50 and 0.99 µg/L (χ(2) = 66.48, P < 0.01), the GM of 1-hydroxypyrene in the groups were 0.77,0.64, 1.00, 0.84, 0.84 and 0.57 µg/L (χ(2) = 51.48, P < 0.01), respectively.

CONCLUSIONThe distribution of monohydroxy metabolites levels in urine of general population were different, it provided a basic data for the further study of polycyclic aromatic hydrocarbons biomonitoring in the population.

Adolescent ; Adult ; Child ; China ; epidemiology ; Cross-Sectional Studies ; Environmental Exposure ; Female ; Humans ; Male ; Middle Aged ; Naphthols ; urine ; Polycyclic Aromatic Hydrocarbons ; urine ; Pyrenes ; urine ; Sentinel Surveillance ; Young Adult

OBJECTIVETo evaluated the levels of arsenic (As) in blood and urine among general population in China and analyze its influencing factors.

METHODSA total of 18 120 subjects from general population aged 6-60 years were recruited from 24 districts in 8 provinces in eastern, central and western China mainland from 2009 to 2010, by cluster random sampling method. Blood samples and urine samples were collected, the information of the life-style was collected by questionnaire.Inductive coupled plasma mass spectrometry was applied to test the As level in the samples, and the distribution of As in blood and urine for different ages, genders, areas and life habits were then analyzed.

RESULTSThe geometric mean (GM) of blood As concentration among general population was 2.33 µg/L;the GM of blood As in male (2.35 µg/L) was higher than and female (2.30 µg/L) (Z = -1.42, P < 0.05); from eastern, central to western China, the blood As level were 2.94, 1.30 and 0.98 µg/L (χ(2) = 643.22, P < 0.05) , respectively; the GM in smokers (2.84 µg/L) was higher than non-smokers (2.27) (Z = -6.28, P < 0.05) ;the seafood consumer had a higher blood As level (2.59 µg/L) than people not consuming seafood (1.47 µg/L) (Z = -23.68, P < 0.05). The urine As level of the whole population was 13.72 µg/L;while its GM in male (14.10 µg/L) was higher than female (13.33 µg/L) (Z = -3.94, P < 0.05); the values from eastern, central to western China were 14.14, 16.02 and 9.57 µg/L (χ(2) = 353.89, P < 0.05), respectively;the level in smokers (16.06 µg/L) was higher than nonsmokers (13.70 µg/L) (Z = -2.63, P < 0.05); the level in seafood consumers (14.82 µg/L) was higher than people not consuming seafood (10.99 µg/L) (Z = -3.20, P < 0.05). The blood As level had a positive correlation with urine As level (correlation coefficient:0.285, P < 0.05).

CONCLUSIONThe As level in blood and urine varied by gender and area among general population in China, and related to life-styles. There was a positive correlation between As level in blood and that in urine.

Adolescent ; Adult ; Arsenic ; blood ; urine ; Child ; China ; epidemiology ; Cross-Sectional Studies ; Environmental Exposure ; Female ; Humans ; Male ; Middle Aged ; Sentinel Surveillance ; Young Adult