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Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.
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ObjectiveTo investigate the intervention effect of heat shock protein 60 (HSP60) on learning and memory impairment induced by combined exposure to lead and hypertension in mice, and the relative mechanism of triggering receptor expressed on myeloid cells 2 (TREM2). Methods Specific pathogen-free C57BL/6J male mice were randomly divided into control group, hypertension group, lead-exposed group and lead-exposed + hypertension group, or into control group, heat shock protein 60 (HSP60) control group, lead-exposed + hypertension group and HSP60 intervention group, with 10 mice in each group. Mice of hypertension group and lead-exposed + hypertension group were intraperitoneally injected with angiotensin Ⅱ at a dose of 0.5 mg/(kg·d) for seven consecutive days to induce hypertension model. Mice of the lead-exposed group, lead-exposed + hypertension group, and HSP60 intervention group were given lead acetate drinking water with a mass concentration of 250.0 mg/L, while mice in the control group, hypertension group, and HSP60 control group were given purified water for 12 weeks. Mice of the HSP60 control group and HSP60 intervention group were intraperitoneally injected with a solution of HSP60 at a dose of 4 mg/kg body weight, every other day for a total of three times at the 12th week. The learning and memory ability of mice was detected using the Morris water maze test. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the hippocampal tissues of the mice. The relative expression of ionized calcium binding adaptor molecule-1 (IBA1) and TREM2 protein in the hippocampus of mice was detected using Western blot. Results i) The number of platform crossings of the mice in the hypertension group and the lead-exposed group was lower than that in the control group (both P<0.05). The escape latency of the mice on the third day was longer and the number of platform crossings was lower in the lead-exposed + hypertension group compared with the control group, hypertension group and lead-exposed group (all P<0.05). The levels of IL-1β, IL-6, and TNF-α in the hippocampus of the other three groups increased compared with the control group (all P<0.05). The relative expression of IBA1 protein in the hippocampus of lead-exposed group and lead-exposed + hypertension group increased (all P<0.05), while the relative protein expression of TREM2 decreased compared with the control group (all P<0.05). The levels of IL-1β, IL-6, TNF-α, and the relative protein expression of IBA1 protein in the hippocampus of the lead-exposed+hypertension group were higher (all P<0.05), and relative expression of TREM2 protein was lower (P<0.05) than those in the hypertension group. The level of TNF-α and the relative expression of IBA1 protein in the hippocampus of lead-exposed+hypertension group were higher than those in lead-exposed group (all P<0.05). ii) The escape latency of mice in the lead-exposed + hypertension group was longer than that in the control group (P<0.05), and the number of platform crossings was fewer than that in the control group (P<0.05). The escape latency of mice in the HSP60 intervention group was shortened (P<0.05), the number of platform crossings increased (P<0.05), and the levels of IL-1β, IL-6, TNF-α and relative expression of IBA1 protein decreased in the hippocampus (all P<0.05), while the relative expression of TREM2 protein increased (P<0.05) compared with the lead-exposed+hypertension group. Conclusion Combined exposure of lead and hypertension has a synergistic effect on learning and memory impairment in mice. The mechanism may be related to the inhibition of TREM2 expression by lead in the hippocampus of hypertensive mice and aggravating the neuroinflammatory response. Intervention with TREM2 receptor agonist HSP60 can alleviate learning and memory impairment in mice exposed to lead and hypertension by up-regulating TREM2 expression in the hippocampus.
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Objective:To establish an in vivo infection model of H5N1 pseudovirus and to detect the neutralizing activity of FHA3 antibody using this model. Methods:Based on the sequence information of hemagglutinin (HA) and neuraminidase (NA) of A/Anhui/1/2005/H5N1 strain, two recombinant plasmids of pcDNA3.1-HA5 and pcDNA3.1-NA1 were constructed. The two plasmids and plasmid pNL4-3.Luc.R-E- were co-transfected into 293T cells to prepare H5N1 pseudovirus supernatant. The morphology of pseudovirus particles in the supernatant was observed by electron microscopy. MDCK cells were infected with the pseudovirus supernatant and the virus titer was detected. BALB/c mice were injected with the pseudovirus supernatant by intraperitoneal injection and subjected to bioluminescence imaging at 2, 5, 8, and 12 d after infection to detect the pseudovirus infection in vivo. The functional activity of FHA3 antibody in vivo was evaluated using the established mouse infection model. Results:The recombinant plasmids pcDNA3.1-HA5 and pcDNA3.1-NA1 were correctly constructed and could be used to prepare pseudovirus supernatants of high titer by co-transfecting 293T cells with the plasmid pNL4-3.Luc.R-E-. The virus particles were round under electron microscope. H5N1 pseudovirus-infected mice exhibits strong fluorescence signals, which were attenuated by FHA3 treatment before challenge.Conclusions:The in vivo infection model of H5N1 pseudovirus was successfully constructed and FHA3 antibody was proved to be protective against the pseudovirus infection.
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Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers [nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)], M2 markers [arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)] and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.
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Objective:To investigate the effect of nano lead oxide (nano-PbO) exposure on learning and memory as well as spatial exploration ability in the mice, and the role of leukocyte infiltration of brain tissue in neurobehavioral damage caused by nano-PbO exposure.Methods:A total of 60 male SPF grade Kunming mice were divided into control group, low-dose nano-PbO group, medium-dose nano-PbO group and high-dose nano-PbO group according to body mass matching method, with 15 mice in each group.Mice in low, medium and high dose groups of nano-PbO were intraperitoneally injected with 5 mg·kg -1, 10 mg·kg -1, 20 mg·kg -1 nano-PbO, respectively. And mice in the control group were intraperitoneally injected with the same volume of 0.9% normal saline.The frequency of intervention was once a day for 28 days.Morris water maze test and open field test were used to detect the ability of learning and memory and spatial exploration of mice. Western blot was used to detect the protein expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in hippocampus of mice, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in mouse microvessels and lymphocyte function-associated antigen-1 (LAF-1) in mouse blood leukocyte. The proportion of leukocytes in mouse brain was detected by flow cytometry. All statistical analyses were performed by SPSS 20.0. Morris water maze data were analyzed by repeated measures ANOVA, the other data among multiple groups were compared by one-way ANOVA, and Tukey's test was used for further pairwise comparison.Pearson correlation analysis was performed to evaluate the correlation between neurobehavioral indexes and the proportion of white blood cells, TNF-α and IL-1β in brain tissue. Results:Morris water maze results showed that the escape latency of the four groups of mice had a significant interaction between group and time( F=3.21, P<0.05). The escape latencies of mice in middle and high dose groups of nano-PbO were higher than that in the control group (both P<0.05), and the numbers of crossing the platform of the two groups were lower than that in the control group (both P<0.05). The results of open field test showed that there was a statistically significant difference in the residence time of the mice in the four groups ( F=119.10, P<0.01). The total standing times of mice in the middle group and high dose group of nano-PbO were lower than that in the control group (both P<0.01). The results of Western blot showed that the levels of TNF-α and IL-1β in hippocampus tissue of mice were significant differences among the four groups ( F=7.21, 9.89, both P<0.05). The levels of TNF-α and IL-1β in the hippocampus of mice in the high-dose nano-PbO group were higher than those in the control group (TNF-α: (0.35±0.10), (1.03±0.30), P<0.05; IL-1β: (0.32±0.10), (0.50±0.15), P<0.05). The results of flow cytometry analysis showed that the proportions of leukocytes in the brain tissue of mice in the low, medium and high dose groups of nano-PbO were (9.99±1.09)%, (13.03±0.94)% and (16.51±3.89)%, respectively. Among them, the proportions of leukocytes in the middle and high dose groups of nano-PbO were significantly higher than that in the control group((8.13±1.29)%) (both P<0.05). The results of correlation analysis showed that the proportion of leukocytes, levels of TNF-α, IL-1β protein of hippocampus in the medium, high dose groups of nano-PbO were negatively correlated with the behavioral indexes ( r=-0.815, -0.744, -0.578, all P<0.01; r=-0.771, -0.836, -0.704, all P<0.05; r=-0.823, -0.876, -0.695, all P<0.05). The results of Western blot showed that the levels of ICAM-1 and VCAM-1 in cerebral microvessels of mice in the four groups were significantly different ( F=5.51, 16.19, both P<0.05). The levels of ICAM-1 and VCAM-1 in the middle and high dose groups of nano-PbO were higher than those in the control group(ICAM-1: (1.07±0.16), (1.21±0.35), (0.59±0.19), all P<0.05; VCAM-1: (0.68±0.12), (1.92±0.23), (0.23±0.05), both P<0.05). In addition, there was a significant difference in the level of LFA-1 protein in blood leukocytes of mice in the four groups ( F=41.80, P<0.05). The levels of LFA-1 in the middle and high dose groups of nano-PbO were higher than that in the control group((0.33±0.06), (0.89±0.23), (0.05±0.01), both P<0.05). Conclusion:The nano-PbO exposure can lead to cognitive impairment and increased inflammatory factors in the hippocampus of mice, which may be related to the increase of ICAM-1 and VCAM-1 in vascular endothelial cells, which promotes leukocyte infiltration into brain tissue.
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Objective:To prepare and identify a broad-spectrum antibody FHA3 targeting influenza A virus hemagglutinin (HA).Methods:According to the single-chain antibody fragment (scFv) sequence, the heavy chain (VH) and light chain (VL) variable regions of FHA3 were amplified by PCR and a recombinant plasmid pFRT-IgG1κ-FHA3 was constructed by linking the expression vector pFRT-IgG1κ. FHA3 was expressed in the ExpiCHO system and purified by affinity purification. The binding activity of FHA3 to influenza A virus HA was detected by ELISA. The neutralizing activity of FHA3 was detected in vitro by infecting host cells with pseudovirus. Results:SDS-PAGE showed that high-purity FHA3 was obtained. FHA3 could bind to H1N1 HA, H2N2 HA, H3N2 HA, H5N1 HA, H7N9 HA and H9N2 HA in a concentration-dependent manner. FHA3 had good neutralizing activity in vitro that was it could effectively block the invasion of H5N1 and H7N9 pseudoviruses into target cells at a low concentration of 5 μg/ml and H1N1 pseudovirus at 0.012 5 μg/ml. Conclusions:A broad spectrum antibody targeting HA protein of influenza A virus with neutralizing activity in vitro was obtained.
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Objective:To prepare and identify a functional antibody FNA1 targeting the neuraminidase (NA) of influenza A virus N1 subtype.Methods:According to single-chain antibody fragment (scFv) sequence, the heavy chain and light chain variable region sequences of FNA1 were synthesized, and the recombinant expression plasmid pFRT-IgG1κ-FNA1 was constructed by linking the expression vector pFRT-IgG1κ. The FNA1 antibody was expressed in ExpiCHO cells and purified using affinity purification technique. The binding ability of FNA1 to the target proteins, influenza A virus N1 subtype NA antigens, was detected by ELISA. Flow cytometry was performed to analyze the binding ability of FNA1 to the NA antigens expressed on the surface of cell membrane. The in vitro activity of FNA1 against NA was evaluated by infecting 293T cells with pseudovirus. Results:Protein electrophoresis showed that FNA1 with high purity was obtained. FNA1 specifically recognized and bound to N1 subtype NA antigens in a concentration-dependent manner. FNA1 could effectively block NA activity by binding to N1 subtype NA protein expressed on the surface of cell membrane, thus inhibiting the release of packaged pseudovirus from cell surface and further inhibiting target cell infection.Conclusions:An antibody FNA1 targeting influenza A virus N1 subtype NA with in vitro functional activity was obtained.
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Objective:To explore the effects of general anesthesia and combined spinal and epidural anesthesia on inflammatory factors and pain in patients with osteoarthritis after total knee arthroplasty.Methods:A total of 84 patients with osteoarthritis who underwent unilateral total knee arthroplasty in Hulunbuir People's Hospital from January 2020 to May 2021 were selected as the research subjects. They were randomly divided into general anesthesia group (40 cases) and combined spinal and epidural anesthesia group (44 cases). Venous blood samples of 5 ml were collected before operation and 6, 24, 48 hours after operation, and the contents of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6] in serum were determined by enzyme-linked immunosorbent assay (ELISA). The visual analogue pain scale (VAS) of the two groups at 30 min, 6, 24 and 48 hours after operation was compared.Results:At 6 and 24 hours after operation, TNF-α, IL-1β and IL-6 levels in the combined spinal and epidural anesthesia group were lower than those in the general anesthesia group ( t = 4.17, 3.85, 8.95, 10.98, 10.04, 9.87, P < 0.05). There were significant differences in the levels of TNF-α, IL-1β and IL-6 at different time points between the general anesthesia group and combined spinal and epidural anesthesia group ( F = 271.67, 149.26, 81.70, 189.36, 102.44, 157.32, P < 0.001). At 6 and 24 hours after operation, the VAS scores of patients in the combined spinal and epidural anesthesia group were significantly lower than those in the general anesthesia group ( t = 6.60, 3.66, P < 0.05). There were statistically significant differences in VSA scores between the two groups at different time points ( F = 67.47, 52.37, P < 0.05). Conclusion:The effect of combined spinal and epidural anesthesia is significantly higher than general anesthesia in inhibiting the expression of TNF-α, IL-1β and IL-6 in patients with osteoarthritis after operation, and the effect of analgesia is obvious.
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Helicobacter pylori (HP) infection is one of the most prevalent chronic bacterial infections in the world, which is closely related to the development of gastrointestinal diseases, such as chronic gastritis, gastroduodenal ulcer and gastric cancer. Empirical treatment of HP infection may lead to antibiotic resistance, adverse reactions and poor compliance. The decreased HP eradication rate is related to antibiotic resistance, HP converting to coccoid form and admission of proton pump inhibitors (PPI). The implementation of precise therapy can effectively enhance the HP eradication rate, through antibiotics selecting based on detection of drug sensitivity phenotype and drug resistance genes, reducing adverse drug reactions, increasing patient compliance, and rationally administrating PPI, etc. This article reviews the research progress of precision therapy for HP infection to provide reference for clinicians.
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OBJECTIVE: To investigate the effect of liver X receptor(LXR)-adenosine triphosphate-binding cassette transporter A1(ABCA1) signaling pathway on the free silica(SiO_2)-induced foaming of macrophages. METHODS: Human histiocytic lymphoma U937 cells were induced to differentiate into macrophages by phorbol myristate acetate. The macrophages at logarithmic growth phase were randomly divided into 4 groups: the cells in the control group received no treatment, the cells in the SiO_2 stimulation group were stimulated with SiO_2 suspension at a dose of 50 mg/L, and the cells in the oxidized low-density lipoprotein(ox-LDL) group were treated with ox-LDL at the dosed 50 mg/L, the cells in the combination group were simultaneously stimulated with SiO_2 suspension and ox-LDL at a dose of 50 mg/L. Cells were collected after 48 hours of culture. Macrophage foaming was observed by oil red O staining. The levels of total cholesterol(TC), free cholesterol(FC), cholesteryl ester(CE) and CE specific gravity(CE%) in macrophages were detected using a microplate reader. The expression of LXR and ABCA1 was detected using Western blotting. RESULTS: The results of the oil red O staining showed that all the macrophages in the SiO_2 stimulation group, ox-LDL group and the combination group had foaming changes. The degree of foaming in the macrophages in the combination group was higher than that in the other two groups. The levels of TC, FC, CE and CE% in macrophages increased(P<0.05), and the protein relative expression of LXR and ABCA1 decreased(P<0.05), in SiO_2 stimulation group, ox-LDL group and combination group compared with the control group. The macrophages in the combination group were transformed into foam cells. The levels of TC, FC, CE and CE% in macrophages of the combination group increased(P<0.05), and the protein relative expression of LXR and ABCA1 decreased(P<0.05), compared with the SiO_2 stimulation group and the ox-LDL group. CONCLUSION:sFree SiO_2 can induce foaming of macrophages, and ox-LDL in combination with SiO_2 has a synergistic effect on the formation of foaming of macrophages.The process of macrophage foaming may be achieved by inhibiting the LXR-ABCA1 signaling pathway.
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OBJECTIVE: To investigate the preventive effect of rock salt aerosol on the development of silicosis in rats. METHODS: The specific pathogen free adult male SD rats were randomly divided into normal control group, rock salt control group, silicosis model group and rock salt intervention group, 18 rats in each group. Rats in the silicosis model group and the salt rock intervention group were treated with silica dust at the concentration of 2 000.0 mg/m~3 by dynamic dusting method for 3 hours daily. Rats in the rock salt control group and the rock salt intervention group inhaled the rock salt aerosols with the mass concentration of 20.0 mg/m~3 for 30 minutes daily. The normal control group was not treated with the dust or rock salt aerosol. At the time points of 14, 28 and 56 days after exposure to dust or rock salt aerosol, 6 rats were randomly selected from each group and samples were collected. The pathological change of lung was observed, the total cell count in the bronchoalveolar lavage fluid(BALF) was performed, the enzyme-linked immunosorbent assay was used to detect the change of transforming growth factor-β(TGF-β) in BALF, surfactant D(SP-D) and superoxide dismutase(SOD) in lung tissue. RESULTS: The results of hematoxylin-eosin and Masson staining showed that the inflammatory changes of lung tissue and the pulmonary interstitial fibrosis in the rock salt intervention group were less severer than that in the silicosis model group. At 14, 28, and 56 days after dust exposure, the total cell counts in BALF and SP-D levels in lung tissue of rats in silicosis model group and rock salt intervention group were higher(P<0.05), the SOD activities in lung tissue were lower(P<0.05), as well as the TGF-β levels in BALF in silicosis model group were higher(P<0.05),compared with the normal control group and rock salt control group. The total cell counts and TGF-β levels in BALF, and SP-D levels in lung tissue of rock salt intervention group were lower(P<0.05), the SOD activities in lung tissue were higher(P<0.05), compared with the silicosis model group. CONCLUSION: Rock salt aerosol intervention may delay the pathogenesis of silicosis by improving the inflammatory response, regulating oxidative stress and reducing interstitial fibrosis of lungs.
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Objective:To explore the effect of match between childhood stress and adulthood stress on mental health status.Methods:Adult healthy volunteers( n=239) and adult mental disorder patients were examined by questionnaires or telephone interviews.Childhood trauma questionnaire (CTQ) and lifetime stress event list were used for measure of CS and AS, DSM5-level-1-cross-cutting-symptom-measure (DSM5-L1CCSM) and self-rating depression scale (SDS) for mental health outcomes.Subjects were grouped according to positive (+ ) / negative (-) stress events into five groups: CS+ AS+ Matched ( n=108), CS+ AS+ mismatched( n=240), CS-AS+ ( n=100), CS+ AS-( n=79), and CS-AS-( n=99). The data of stress and mental health status were compared and analyzed among stress groups. Results:The distributions of positive stress events among 626 volunteers were 68.2% with CS+ , 71.6% with AS+ , 17.3% with C+ A+ M+ .There were differences among groups in all parameters (all P<0.05) except for gender.Age, years of education, CS and emotional abuse were influencing factors of onset of AS( P<0.01). MANCOVA analysis showed that factors about the interaction of AS and CS had attribution on DSM5-L1CCSM and SDS ( P<0.01). Conclusion:CS has a facilitatory effect on AS.The match of CS-AS is an important risk factor of adulthood mental health outcomes.Re-experiencing the same type of CS in adulthood would worsen adulthood mental health status.
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To investigate the risk factors for hypoparathyroidism after thyroidectomy. Methods: Clinical data of 492 patients, who underwent thyroidectomy from April 2015 to December 2016 from Xiangya Hospital of Central South University, were studied retrospectively. Chi-square test and multivariable logistic regression were performed to find the risk factors for postoperative hypoparathyroidism. Results: The incidence of postoperative hypoparathyroidism was 43.5%, and the incidence of temporary and permanent hypoparathyroidism was 43.1% and 0.4%, respectively. Univariate analysis showed that tumor pathology, thyroidectomy types, the extent of lymph node dissection, application of carbon nanoparticles, and merged Hashimoto's thyroiditis were risk factors for postoperative hypoparathyroidism (all P<0.01). Logistic regression analysis showed that: thyroidectomy types (OR=0.149, 95% CI 0.078 to 0.28), the extent lymph node dissection (OR=0.779, 95% CI 0.617 to 0.983) and application of carbon nanoparticles (OR=1.729, 95% CI 1.067 to 2.801) were independent risk factors for postoperative hypoparathyroidism (all P<0.05). Conclusion: Hypoparathyroidism is a common complication after thyroidectomy. The incidence of postoperative hypoparathyroidism is significantly increased in patients underwent total thyroidectomy and cervical lymph node dissection. Application of carbon nanoparticles intraoperatively can reduce the incidence of postoperative hypoparathyroidism.
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Humains , Hypoparathyroïdie , Chirurgie générale , Complications postopératoires , Études rétrospectives , Facteurs de risque , Tumeurs de la thyroïde , ThyroïdectomieRésumé
OBJECTIVE: To investigate the effect and mechanism of lead exposure on hypothalamic inflammatory factors in mice fed with high-fat diet. METHODS: Specific pathogen free healthy male Kunming mice were randomly divided into control group, high-fat diet group, lead exposure group, and combined exposure group, with 8 rats in each group. The control group and the lead exposure group were given regular diet, while high-fat diet group and combined exposure group were given high-fat diet. The lead exposure group and combined exposure group were given water with 250 mg/L lead acetate. The control group and high-fat diet group were given double distilled water. Continuous lead exposure was given for 9 weeks, 7 days per week. Body weights of the mice were measured every other week. After 9 weeks of exposure, the behavioral changes of mice were detected by open field test. The levels of triglyceride(TG), low density lipoprotein(LDL) and high density lipoprotein(HDL) in serum were detected by microplate reader. Western blotting was used to detect the relative protein expression of interleukin(IL)-1β, IL-6, IL-17 A, IL-22, tumor necrosis factor-α(TNF-α) and transforming growth factor-β(TGF-β) in the hypothalamus of mice. The relative expression of mRNA of IL-1β, IL-6, IL-17 A and TNF-α mRNA was detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS: Beginning from the first week, the body weights of mice in the high-fat diet group and the combined exposure group were higher than that in the control group and the lead exposure group(P<0.05). The numbers of standing in the lead exposure group and the combined exposure group were lower than that in the control group and the high-fat diet group(P<0.05). The distances of central area activity in the high-fat diet group, the lead exposure group and the combined exposure group were lower than that in the control group(P<0.05). The total distances in the high-fat diet group and the combined exposure group were lower than that in the control group(P<0.05). The serum levels of TG and LDL in the combined exposure group increased(P<0.05), and the HDL level decreased(P<0.05), when compared with the control group and the lead exposure group. The relative protein expression of IL-1β, IL-6, IL-17 A and IL-22 in the hypothalamus of the high-fat diet group and lead exposure group was higher than those of the control group(P<0.05). The relative protein expression of TNF-α and TGF-β in the hypothalamus of the lead exposure group was higher than that in the control group(P<0.05). The relative protein expression of IL-1β, IL-6, IL-17 A, TGF-β in the hypothalamus of the combined exposure group was higher than the other 3 groups(P<0.05). The relative protein expression of IL-22 in the hypothalamus of the combined exposure group was higher than that of the control group(P<0.05), while the relative protein expression of TNF-α was higher than that of the control group and the high-fat diet group(P<0.05). The relative expression of IL-1β, IL-6, IL-17 A, and TNF-α mRNA in the hypothalamus of the high-fat diet group, the lead exposure group and the combined exposure group was higher than that in the control group(P<0.05). The above indicators of mice in the lead exposure group were higher than that in the high-fat diet group(P<0.05). The above indicators of mice in the combined exposure group were higher than those in the high-fat diet group and the lead exposure group(P<0.05). CONCLUSION: Lead exposure can promote neurobehavioral changes and hypothalamic inflammatory damage in high-fat diet mice. IL-1β, IL-6, IL-17 A, TGF-β and TNF-α might involve in the process of synergistic effect of lead and high-fat diet exposure on inflammatory hypothalamic injury.
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Objective To explore the effect of childhood trauma on escitalopram treatment of adult depression. Methods There were 68 adult patients with major depression disorder recruited. All patients were assessed with Childhood Trauma Questionnaire ( CTQ ) and given 8 weeks of standardized treatment with escitalopram. Beck Depression Inventory ( BDI) and HAMD-17 were assessed at the end of the 2nd,4th and 8th week respectively. The changes of BDI score and HAMD-17 score in patients with different CTQ fac-tors were observed. Results ( 1) The overall effect of intervention was 25. 0% at the end of 4th week and 45. 6% at the end of 8th week. The total effective rate was 94. 1%. At the end of 4th week,there was no sig-nificant difference in the clinical recovery rate between the positive group(19. 5%) and the negative group (33. 3%)(χ2=1. 66,P>0. 05). There was no significant difference in clinical recovery between the two groups at the end of 8th week(positive group :39. 0%,negative group :55. 6%,χ2=1. 79,P>0. 05). (2) The total score reduction rate of HAMD-17((46. 26±24. 79)%,(58. 39±23. 25)%) and BDI((51. 63± 16. 03)%,(66. 28±18. 05)%) at the end of 4th week and the total score reduction rate of BDI at the end of 8th week ((59. 13±15. 42)%,(68. 50±20. 91)%)in the positive group were lower than those in the nega-tive group (P<0. 05) . ( 3) Except for sexual abuse,there was a significant negative correlation between CTQ scores and the reduction rate of BDI scores at end of 4th and 8th week( r=-0. 46--0. 06,P<0. 05) . Conclu-sion Childhood trauma has adverse effects on the efficacy of escitalopram in the treatment of adult depres-sion.
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BACKGROUND:The tensile and stress-relaxation mechanical properties of sciatic nerve injury after repaired with autologous nerve and poly(lactic acid-glycolic acid) (PLGA) scaffold are rarely reported. OBJECTIVE:To analyze the tensile and stress relaxation characteristics of sciatic nerve injury after the transplantation of autologous nerve and PLGA scaffold. METHODS:Sixty sciatic nerves were extracted from the fresh cadavers dead within 24 hours, processed into 35 mm samples, and were then randomly divided into three groups. The nerve samples in control group received no intervention;the nerves in artificial and autologous groups were modeled into 20 mm defects, followed by repaired with PLGA scaffold and autologous nerve, respectively. Afterwards, the tension and stress-relaxation tests were performed in each group. RESULTS AND CONCLUSION:The stress in each group descended fast at the first 600 seconds, then descended slowly and was closed to the horizontal level until 7200 seconds, and the stress-relaxation curves in each group were in logarithmic decrease. The order of the elastic limit load, elastic limit stress, maximum load, maximum stress, elastic limit strain and maximum strain during tension was as follows:control group>artificial group>autologous group (P<0.05). Our results indicate that the PLGA scaffold holds good tension and stress-relaxation properties, which meets the mechanical requirements of the biomaterials used for sciatic nerve repair.
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BACKGROUND: With age and blood pressure increasing, the damaged elastic membrane induced by degenerative vascular matrix results in calcium and collagen deposition, and finally expanded large arteries and aortas are easy to cause arteriosclerosis. OBJECTIVE: To compare the rheological properties of the common carotid artery in the youth and elderly, thus providing a basis for the study on the pathogenesis of atherosclerosis of the common carotid artery. METHODS: Common carotid arteries were respectively removed from the young and elderly cadavers. Ten samples from each group were randomly selected, and subjected to stress relaxation and creep tests. Meanwhile, one sample from each group was selected for histological observation. RESULTS AND CONCLUSION: The stress at 7200 s in the young group was significantly decreased compared with the elderly group (P < 0.05). The strain at 7200 s in the young group was significantly increased compared with the elderly group (P < 0.05). Scanning electron microscope observed that in the elderly group, there were lipid plaques and foam cell accumulation; the internal elastic lamina and middle elastic plate presented with degeneration, rupture and disintegration; and there were abundant plaques and inflammatory cells in the intimal and media, which characterized as atherosclerosis. While no lipid plaques were found in the young group. These results indicate that the elastic fibers and collagen fibers in the common carotid artery arrange in disorder as age increases, and the rheological properties are also changed.
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Objective To analyze the relationship of self-consciousness,internet addiction and life satisfaction in rural adolescents.Methods 443 rural adolescents were investigated with Children's Self-concept Scale,Adolescent Life Satisfaction Scale (ALSS) and Secondary School Students Internet Addiction Diagnostic Scale (IADDS).Results ①The differences between left-behind and non-left-behind rural adolescents were significant in self-concept ((51.28± 12.86) vs (55.01 ± 11.58)),ALSS((27.68±7.38) vs (31.25± 4.36)) and IADDS((4.87±3.38) vs (3.22±2.39))(t=-3.121,P<0.05;t=-6.384,P<0.05;t=5.968,P <0.05).The differences between boys and girls were significant in self-concept ((52.28± 12.44) vs (55.35±11.66)),ALSS((29.36±6.36) vs (30.71±5.16)) and IADDS((29.36±6.36) vs (30.71±5.16))(t=-2.680,P<0.05;t=-2.424,P<0.05;t=5.146,P<0.05).The differences between only child and non-only child were significant in ALSS ((29.04± 6.77) vs (30.56 ± 5.18)) and IADDS ((4.44± 3.08) vs (3.05 ±2.45))(t=-2.659,P<0.05;t=2.818,P<0.05).The differences of different academic performance were significant in self-concept,ALSS and IADDS (F=-4.788,P<0.05;F=9.127,P<0.05;F=17.387,P<0.05).②There was a significant negative correlation between self-consciousness and internet addiction(r=-0.337,P<0.01).There was a significant positive correlation between self-consciousness and life satisfaction (r=0.660,P<0.01),and there was a significant negative correlation between life satisfaction and internet addiction.(r=-0.484,P<0.01).③Life satisfaction was the mediator variable between self-consciousness and internet addiction,and the mediating effect accounted for 90.8% of the total effect.Conclusion Self-awareness influence internet addiction through life satisfaction.
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The medical ethics professionals which have resourceful ethical knowledge ought to give full play to subjects superiority in the review of the clinical trials involving human subjects. Before ethical review, it is needed to learn the series of international and domestic laws, regulations, and documents, and communicate with peers timely. In the review, they should focus on the necessity and security of the research project, conduct a compre-hensive review combined with the principle of medical ethics, and master the review key point of informed consent, to fulfill their duty of protection of human rights of subjects.
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OBJECTIVE@#To explore two transcript variants expression of long noncoding RNA C6orf176 in non-small cell lung cancer (NSCLC) and the clinical pathological significance. @*METHODS@#The expressions of transcript variant 1 (TV1) and transcript variant 2 (TV2) of long noncoding RNA C6orf176 in 57 NSCLC and adjacent cancerous tissues were examined by qPCR with β-actin as internal control. @*RESULTS@#Based on the results of qPCR, for C6orf176-TV1, 42 cases were down-regulated and 15 cases were up-regulated. The C6orf176-TV1 level was correlated to the grade of differentiation (P<0.05) but it was not correlated with gender, age, smoking history, tumor type and TNM stage. The expression of C6orf176-TV1 had a potential value in diagnosis of NSCLC by receiver operator characteristic (ROC) curve. Area under curve (AUC) of ROC curve was 0.708 (95% CI 0.615 to 0. 802). The sensitivity and specificity were 51% and 88%, respectively. For C6orf176-TV2, 39 cases were down-regulated and 18 cases were up-regulated. The C6orf176-TV2 level was correlated with the grade of differentiation (P<0.05) but it was not correlated with gender, age, tumor size, smoking history and TNM stage. C6orf176-TV2 level had value in diagnosis of NSCLC by ROC curve. AUC of ROC curve was 0.64 (95% CI 0.531 to 0.749). The sensitivity and specificity were 49% and 75%, respectively. Of the 57 specimens, 53 cases were simultaneous up or down-regulation of C6orf176-TV1 and C6orf176-TV2. The correlation coefficient was 0.99. @*CONCLUSION@#The expression of C6orf176-TV1 or C6orf176-TV2 is down-regulated in NSCLC and it is correlated with the grade of differentiation. It may act as a diagnosis indicator for NSCLC patients.