Objective To assess the impact of freeze-drying and dry heat virus inactivation processes on the activity ofα2-macroglobulin(A2M)derived from human plasma Cohn fraction Ⅳ.Methods A2M derived from human plasma Cohn fraction Ⅳ was prepared and subjected to programmed freeze-drying with dry heat virus inactivation.The lyophilized products were evaluated for their appearance,water content,and validation of the viral inactivation process.The bioactivity of the products before and after lyophilization as well as before and after dry heat inactivation was determined via trypsin inhibition,and the comparisons were studied.Results The appearance of the lyophilized product was fluffy,and the water content was(5.83±0.45)％.The specific activities of the samples before and after lyophilization were(10.199±0.137)and(10.033±0.201)μg/mg,respectively,with no statistically significantdifference between the two groups(P＞0.05).The viral inactivation of the samples was carried out by using dry heat inactivation conditions at 100 ℃ for 30 min.After inactivation,the reduction was ≥5.125 LgTCID50/0.1 mL in Pseudorabies virus(PRV)titers,≥4.500 LgTCID50/0.1 mL in Sindbis virus(SinV)titers,≥6.375 LgTCID50/0.1 mL in encephalomyocarditis virus(EMCV)titers,and≥4.500 LgTCID50/0.1 mL in porcine parvovirus(PPV)titers.The specific activities of the samples before and after dry heat were(9.921±0.292)and(10.091±0.278)μ g/mg,respectively,with no statistically significant difference between the two groups.Conclusion A2M derived from human plasma Cohn fraction Ⅳ,when subjected to freeze-drying followed by dry heat inactivation at 100 ℃ for 30 minutes,can effectively inactivate viruses without altering the biological activity of the product.

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors. Because of the abnormal secretion of catecholamine, the risk of disease is high. At present, the choice of drug treatment for these diseases is still controversial. The further understanding of the research has showed that the different molecular subtypes have different carcinogenic mechanism and therapeutic response. And a variety of corresponding targeted drugs have entered the clinical trial stage, showing a certain therapeutic potential. This article reviews the current treatment and the progress of targeted drugs for pheochromocytoma and paraganglioma.

The high elastic modulus of scaffolds or implants will result in stress shielding effect, which may lead to bone resorption and scaffold or implant loosening in the late stage. Porous scaffolds and implants can adjust their porosity and elastic modulus according to the mechanical environment, thereby reducing stress shielding; meanwhile, porous structures are beneficial to bone tissue growth, which is conducive to osseointegration. Three kinds of basic structure for porous scaffolds and implants by 3D printing were summarized, namely, uniform porous structure, bone-like trabecular structure and functionally graded structure. The design methods of these structures were introduced respectively, including computer-aided design (CAD)-based, implicit surface-based, image-based and topology optimization-based design method, so as to provide references for solving the stress shielding problem, as well as designing porous scaffolds and implants.

Objective To establish the three-dimensional (3D) finite element (FE) model of thoracolumbosacral T1-S spine based on the computed tomography (CT) images of patients with scoliosis and study its dynamic characteristics. Methods The established scoliotic model was validated by axial compression and shear loading, and the predicted responses were in good agreement with the experimental data. The modal and harmonic analyses were performed using the ABAQUS software, and during the harmonic analysis, the dynamic response of the model was collected at frequencies 5 Hz and 10 Hz. Results From the modal analysis, the first fourth-order modal was extracted. The first- and second-order resonant frequencies of the model were 1.097 Hz and 1.384 Hz, respectively, and the vibration mode was longitudinal bending and lateral bending, respectively. The distribution of the second- and third-order modal resonant frequencies were 5.688 Hz and 28.090 Hz, and the vibration mode was vertical vibration and twisting around the long axis, respectively. The peak amplitude in the harmonic analysis appeared near the modal frequencies, and the average amplitude of vertebral body of the lateral convex segment was larger than that of other segments of the scoliotic spine. Under the vibration frequencies of 5 Hz and 10 Hz, the stress inhomogeneously concentrated on the concave and convex sides of the segments of the vertebral deformity as well as on the intervertebral disc. Conclusions The segments of the spinal deformity in patients with scoliosis were the weak links of their spines and more vulnerable to damage in a vibrating environment. Patients with scoliosis should avoid a vibrating environment, particularly in a sensitive frequency range. The research outcomes provide methodological assistance and mechanical analysis references for the protection, rehabilitation treatment, and clinical pathological studies of patients with scoliosis.

OBJECTIVETo analyze the clinical characteristics and causative mutation in an ethnic Han Chinese family affected with punctate palmoplantar keratoderma (PPPK).

METHODSClinical characteristics and inheritance pattern of the family were analyzed. Two seriously affected individuals from the family were investigated by whole exome sequencing. Three healthy individuals from the family and 120 non-PPPK individuals were evaluated to validate the result.

RESULTSThe family was characterized by keratotic papules on the palms and soles, which gradually increased in size and number with age and coalesced with each other, particularly over the pressure part of the palms and soles. The family has featured autosomal dominant inheritance. A heterozygous frameshift variant c.419delC in exons of the CELA1 gene was identified in all affected individuals but not among non-affected members.

CONCLUSIONA heterozygous frameshift variant c.419delC in CELA1 gene probably underlies the disease in the family affected with PPPK.

Adult ; Base Sequence ; Female ; Frameshift Mutation ; Heterozygote ; Humans ; Keratoderma, Palmoplantar ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Pancreatic Elastase ; genetics ; Pedigree ; Young Adult

BACKGROUND: Inherent modal analysis and harmonic response analysis on the human normal lumbosacral vertebraehave been reported, but there is a lack of comparative research on their modal analysis results before and after pediclescrew fixation.OBJECTIVE: To explore the dynamic characteristics of human lumbosacral vertebrae using three-dimensional finiteelement method.METHODS: Finite element model of lumbosacral vertebrae (L1-S1) before and after pedicle screw fixation was developedand validated based on CT images, and the modal analysis and harmonic response analysis were then conducted.RESULTS AND CONCLUSION: (1) Representative nodes were selected at the spinous process segments of L1, L3 andL5, and numbered as A, B, and C, respectively. (2) The maximum displacement of each node in Y and Z directions oflumbosacral vertebral model after internal fixation was significantly decreased compared with those of the normallumbosacral vertebral model, suggesting that screw fixation system plays a protective role in lumbosacral vertebrae, andreduces its amplitude under external load, thus diminishing its sensitivity to external load. (3) The lumbosacral vertebralmodal analysis can provide basis for further study on dynamic analysis, and the parameters such as natural frequency,modal shape and vibration amplitude of the lumbar spine have been determined.

BACKGROUND: In the patients with congenital scoliosis, the spinal motor units exhibit developmental disorders and poor range of motion. It has been found that the compensation ability of coronal lumbosacral region (L4-S1) is associated with the occurrence of non-compensable trunk migration postoperatively.OBJECTIVE: To establish the three-dimensional finite element models of coronal lumbosacral region of normal and patients with congenital scoliosis and to compare the strain, displacement, stress and stiffness under different loading conditions among models.METHODS: One normal subject and two congenital scoliosis patients with different coronal lumbosacral region flexibility were selected, DICOM image datawere obtained by spiral CT scanning at the lumbosacral region, and then imported into MIMICS software, and a three-dimensional model was established according to the gray values of each tissue on CT,followed by simplified by GEOMAGIC, and finally imported into ABAQUS foftware to conduct a mechanic analysis under different loading conditions.RESULTS AND CONCLUSION: (1) Under different lateral forces, in the three models, the maximum stress mainly distributed on the frontal region of L4 cortical bone, and maximum displacement concentrated on L5. (2) There was no significant change in the stress distribution in the two scoliosis models, but the compensable model showed larger displacement change, and its stiffness was significantly less than that of the non-compensable model, indicating that the compensable model is easy to deform. (3) These findings suggest that three-dimensional finite element model is helpful to perform a biomechanical analysis for coronal lumbosacral region of congenital scoliosis, among which, a compensable model exhibits large displacement, suggesting a good flexibility.

Objective To investigate the relationship of vitamin D with the intestinal development and study the expression of vitamin D receptor (VDR) in the duodenum of C57BL/6 mice at different developmental stages.Methods Quantitative PCR (qPCR),histology using H&E staining and immunofluorescence staining,and Western blotting (WB) were performed to elucidate the expression of VDR in mice intestine at different growth and developmental stages.Results The peak of VDR mRNA expression reached on 21 d.The pathological result showed that VDR mainly distributed in the cytoplasm of epithelial cells and smooth muscle cells in the mouse duodenum.WB result indicated that there was no nuclear translocation of VDR protein in the mouse duodenum.Conclusions This study demonstrates the regularity of expression of VDR in the mouse duodenum during its development,and contributes to understanding the function of VDR in the intestines.

Objective: To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on leukemic cell line U937 cells with NPM1 mutation. Methods: Human acute myeloid leukemia cell line U937 was explored, NPM1 mutated (A type) plasmids were transfected into U937 to form stable clones A1 and A2, which were identified by Western blot and Co-immunoprecipitation. The cell proliferation was measured by methylthiazolyl tetrazolium bromide (MTT) ; cell cycle and cell apoptosis were explored by flow cytometric; cell colony formation was measured by microscope count, the molecular pathways related to cell proliferation were measured by Western blot. Results: ①The cell proliferations of mutant A1 and A2 were inhibited significantly by 52.6% and 35.8% (P<0.05) , respectively under ATRA exposure. ②The percentages of G₀/G₁ stage of mutant A1 and A2 increased by 20.1% and 35.8%, respectively under ATRA exposure. ③All the U937 leukemic cells were inhibited under ATRA exposure; the decreased percentages of vector, wild-type and mutant NPM1 cells were 32.7%, 57.9% and 90.9% respectively. ④p-ERK decreased obviously after ATRA exposure in NPM1 mutated leukemic cells. ⑤More mutant NPM1 cells inclined to apoptosis under the exposure of ATRA and cytotoxic drugs than cytotoxic drugs alone, meanwhile more cells apoptosis occurred when ATRA was administrated after cytotoxic drugs exposure. Conclusions ATRA could inhibit cell proliferation and colony formation, blocked the cell cycle in the G₀/G₁ stage accompanied by the significant reduction of p-ERK in U937 leukemic cells with NPM1 mutation. Besides, ATRA could synergize with drugs to suppress the leukemic cells survival more effectively when ATRA was administered after the cytotoxic drugs exposure in U937 leukemic cells with NPM1 mutation.

Objective To evaluate the therapeutic effects of methamphetamine (MA) dependence and the repairment of DA neuronal function by SPECT corpus striatum DAT visual digital neural molecular imaging techniques.Methods 25 MA dependent patients (BPRS score ≥ 35) were treated by self-designed treatment program for more than 6 months.The clinical therapeutic effects were scored with reducing rate of BPRS.MA dependent patients were examined by SPECT corpus striatum DAT imaging before and after treatment,while healthy volunteers were examined only once.The SPECT corpus striatum DAT images were analyzed visually and quantitatively.Results The reducing rate of BPRS showed that the total effective rate was 80.0％.Visual analysis of SPECT corpus striatum DAT images showed that the distribution of DAT in the corpus striatum was regionally reduced or defected in various degrees before treatment,and was significantly increased after treatment.Quantitative analysis showed that the bilateral striatal V ((19.26 ± 2.85) cm3),m((20.22±2.99) g) and Ra(4.78±0.79) ％) of MA dependent patients were significantly lower compared with those of the healthy volunteers(respectively (35.39±4.42) cm3,(37.16±4.64) g and (7.93± 0.86) ％) (all P＜ 0.01) before treatment and were significantly improved (P＜ 0.01) after treatment (V:(22.80±4.28) cm3,m:(23.93± 4.49) g and Ra:(5.64 ± 0.99) ％) with a 76.0％ corpus striatum DAT improvement rate.However,the bilateral striatal V,m and Ra of MA dependent patients after treatment were still lower than those of the healthy volunteers (P＜0.01).There was no significant difference between the striatal DAT improvement rate and the BPRS reduction rate (P＞ 0.05).Conclusion SPECT corpus striatum DAT visual digital neural molecular imaging techniques are reliable in the evaluation of the treatment programs for MA dependence and the repair of DA neuronal function.