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Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.
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Humans , Hepatitis B virus/genetics , Hepatitis B, Chronic , Antiviral Agents/therapeutic use , DNA, Viral/therapeutic use , Retrospective Studies , Mutation , Drug Resistance, Viral/genetics , Lamivudine/therapeutic useABSTRACT
OBJECTIVE@#To explore the effect of recombinant human thrombopoietin (rhTPO) on hematopoietic reconstruction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) model.@*METHODS@#The C57BL/6 mice were employed as the donors, and BALB/c mice as recipients. The bone marrow mononuclear cells of the donor mice were extracted and pretreated, which then were injected with 5×106 per mouse through the tail vein of the recipient to establish an allo-HSCT model. The implantation of hematopoietic stem cells in the recipient mice was detected by flow cytometry on the 28th day after transplantation. Next, the successfully modeled recipient mice were randomly divided into experimental group and control group. The rhTPO was injected into mice in the experimental group on the first day after transplantation, while the saline was injected into mice in the control group. Both groups were injected for 14 consecutive days. The peripheral blood and bone marrow hematopoiesis of the two groups were observed on day 1, 3, 7, 14, and 21 after transplantation.@*RESULTS@#The expression rate of H-2Kb in the bone marrow of recipient mice was 43.85% (>20%) on the 28th day after transplantation, which indicated that the recipient mice were successfully chimerized. Meanwhile, counts of PLTs on the day 3, 7, 14, and 21 after transplantation in the experimental group were higher than those in the control group with statistical significances (P<0.05). In addition, hematopoietic function of bone marrow was suppressed in both groups on day 1, 3 and 7 after transplantation, but hematopoietic bone marrow hyperplasia was better in the experimental group than in the control group. On day 14 and 21 after transplantation, the hematopoietic function of bone marrow in the two groups was recovered, and the experimental group showed more obvious than the control group.@*CONCLUSION@#rhTPO can effectively stimulate the production of PLTs and facilitate the recovery of white blood cells and hemoglobin after allo-HSCT, and promote hematopoietic recovery and reconstitution of bone marrow.
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Humans , Animals , Mice , Thrombopoietin , Mice, Inbred C57BL , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Bone Marrow , Recombinant Proteins , Mice, Inbred BALB CABSTRACT
BACKGROUND@#Endostatin, a biologically active fragment of collagen XVIII, has been observed in patients with ischemic heart disease. The aim of the present study was to investigate whether endostatin overexpression could attenuate cardiac hypertrophy by inhibiting the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling pathway.@*METHODS@#This study was examined in vivo in rats and in vitro in primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Twenty-four male Sprague-Dawley rats were randomized into adenovirus (Ad)-green fluorescent protein, Ang II, Ad-endostatin, and Ang II + Ad-endostatin groups (n = 6 in each group). Four weeks later, all the rats were weighed and sacrificed after transthoracic echocardiography. Cardiac function was evaluated by transthoracic echocardiography, cardiomyocyte size was evaluated by hematoxylin-eosin staining. Levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were evaluated by quantitative reverse-transcription polymerase chain reaction or Western blotting, PKA level was evaluated by Western blotting, and cAMP level was evaluated by enzyme-linked immunosorbent assay. Statistical significance among multiple groups was evaluated by one-way analysis of variance.@*RESULTS@#Endostatin overexpression reduced the increases in left ventricle (LV) mass (P = 0.0063), LV mass/body weight (BW) (P = 0.0013), interventricular septal thickness (IVS) in diastole (P = 0.0013), IVS in systole (P = 0.0056), left ventricular posterior wall thickness (LVPW) in diastole (P = 0.0291), LVPW in systole (P = 0.0080), heart weight (HW) (P = 0.0138), HW/BW (P = 0.0001), and HW/tibial length (P = 0.0372) in Ang II-treated rats. In addition, endostatin overexpression reduced cardiomyocyte cross-sectional area expansion, and reduced the levels of ANP and BNP in Ang II-treated rats (P = 0.0251 and 0.0477 for messenger RNA [mRNA]), and primary neonatal rat cardiomyocytes (P = 0.0188 and P = 0.0024 for mRNA; P = 0.0023 and 0.0013 for protein, respectively). Additionally, endostatin overexpression reduced the increase of cAMP (P = 0.0054) and PKA (P = 0.0328) levels in cardiomyocytes treated with Ang II. Treatment with cAMP reversed the effects of endostatin overexpression on ANP (P = 0.0263) and BNP (P = 0.0322) levels in cardiomyocytes induced by Ang II.@*CONCLUSION@#Endostatin overexpression could alleviate cardiac hypertrophy by inhibiting the cAMP-PKA signaling pathway.
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Objective To explore the efficacy of interventional therapy for central venous stenosis in maintenance hemodialysis patients. Methods The general clinical data of the maintenance hemodialysis patients with central venous stenosis, who received interventional therapy in Changzheng Hospital of Naval Medical University (Second Military Medical University) from Jan. 2014 to Mar. 2018, were retrospectively analyzed, and the patency of vascular access of interventional therapy were followed up. Results A total of 82 maintenance hemodialysis patients with central venous stenosis were enrolled. Six-eight patients (82.93%) had a history of temporary central venous catheterization. Among the 82 patients, 13 (15.85%) had double lesions of central vein and 69 (84.15%) had single lesion; and 5 (6.10%) had mild lesions, 17 (20.73%) had moderate lesions, 35 (42.68%) had severe lesions and 25 (30.49%) had complete occlusion. Of the 82 patients, 57 were treated by percutaneous transluminal angioplasty and 9 by percutaneous transluminal stenting. The follow-up period ranged from 12 to 62 months after operation. The patency rate of vascular access was 75.76% (50/66) at 6 months postoperatively and 68.18% (45/66) at 12 months postoperatively. The overall patency rate of vascular access was 59.09% (39/66). Conclusion Central venous stenosis of the maintenance hemodialysis patients can affect the life of vascular access. For the patients with symptoms that can not be alleviated, active intervention is recommended. Intervention therapy is safe and effective for the patients with central venous stenosis. Meanwhile, the central venous catheterization shall be avoided if possible to reduce central venous stenosis in the patients with chronic kidney disease.
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Objective:To compare the rate of recruitment in two types of active straight leg raise (ASLR) and to investigate the activation patterns of the related muscles. Methods:From June to October, 2018, eleven healthy subjects were recruited. Surface electromyography (sEMG) signals of unilateral rectus femoris, bilateral rectus abdominis, internal oblique abdominis, external oblique abdominis and multifidus were recorded in normal ASLR (Action A) and raising leg for ten seconds (Action B). %maximal voluntary isometric contraction (MVIC) of these muscles was processed and analyzed. Results:%MVIC of ipsilateral internal oblique muscle and external oblique muscle were greater than the opposite side (t > 2.549, P < 0.05) in Action A; %MVIC of ipsilateral internal oblique muscle, external oblique muscle and rectus abdominis muscle were greater than the opposite side (t > 2.240, P < 0.05) in Action B; compared with action B, Action A had higher %MVIC of bilateral internal oblique and rectus femoris (t > 3.549, P < 0.05). Conclusion:The activation mode of ipsilateral dominance was shown in both actions, and the different motion control strategies may be adopted by the neuromuscular system in different ASLR.
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Background@#Endostatin, a biologically active fragment of collagen XVIII, has been observed in patients with ischemic heart disease. The aim of the present study was to investigate whether endostatin overexpression could attenuate cardiac hypertrophy by inhibiting the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling pathway.@*Methods@#This study was examined in vivo in rats and in vitro in primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Twenty-four male Sprague-Dawley rats were randomized into adenovirus (Ad)-green fluorescent protein, Ang II, Ad-endostatin, and Ang II + Ad-endostatin groups (n = 6 in each group). Four weeks later, all the rats were weighed and sacrificed after transthoracic echocardiography. Cardiac function was evaluated by transthoracic echocardiography, cardiomyocyte size was evaluated by hematoxylin-eosin staining. Levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were evaluated by quantitative reverse-transcription polymerase chain reaction or Western blotting, PKA level was evaluated by Western blotting, and cAMP level was evaluated by enzyme-linked immunosorbent assay. Statistical significance among multiple groups was evaluated by one-way analysis of variance.@*Results@#Endostatin overexpression reduced the increases in left ventricle (LV) mass (P = 0.0063), LV mass/body weight (BW) (P = 0.0013), interventricular septal thickness (IVS) in diastole (P = 0.0013), IVS in systole (P = 0.0056), left ventricular posterior wall thickness (LVPW) in diastole (P = 0.0291), LVPW in systole (P = 0.0080), heart weight (HW) (P = 0.0138), HW/BW (P = 0.0001), and HW/tibial length (P = 0.0372) in Ang II-treated rats. In addition, endostatin overexpression reduced cardiomyocyte cross-sectional area expansion, and reduced the levels of ANP and BNP in Ang II-treated rats (P = 0.0251 and 0.0477 for messenger RNA [mRNA]), and primary neonatal rat cardiomyocytes (P = 0.0188 and P = 0.0024 for mRNA; P = 0.0023 and 0.0013 for protein, respectively). Additionally, endostatin overexpression reduced the increase of cAMP (P = 0.0054) and PKA (P = 0.0328) levels in cardiomyocytes treated with Ang II. Treatment with cAMP reversed the effects of endostatin overexpression on ANP (P = 0.0263) and BNP (P = 0.0322) levels in cardiomyocytes induced by Ang II.@*Conclusion@#Endostatin overexpression could alleviate cardiac hypertrophy by inhibiting the cAMP-PKA signaling pathway.
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AIM:To investigate the effect of homeodomain-interacting protein kinase 2 (HIPK2) on the viabi-lity, apoptosis and JAK2/STAT3 signaling pathway in NRK-52E renal tubular epithelial cells induced by hypoxia and reox-ygenation (H/R). METHODS:HIPK2 small interfering RNA (siRNA) was transfected into NRK-52E cells by Lipo-fectamineTM 2000, and normal control group (control group) and negative control group (HIPK2-NC group) were set up. After H/R, the cell viability was measured by CCK-8 assay, the apoptotic rate and Ca2+ fluorescence intensity were ana-lyzed by flow cytometry, and the protein levels of Ki67, cleaved caspase-3, caspase-12, Bcl-2, Bax, p-JAK2 and p-STAT3 were determined by Western blot. RESULTS:Compared with control group, the protein expression of HIPK2 in the NRK-52E cells was significantly decreased after transfection with HIPK2 siRNA (P<0.05). Compared with control group, the cell viability and the protein expression of Ki67 and Bcl-2 in H/R group were also significantly decreased, and the apoptotic rate, the Ca2+ fluorescence intensity and the protein levels of cleaved caspase-3, caspase-12, Bax, p-JAK2 and p-STAT3 were significantly increased (P<0.05). Compared with H/R group, the cell viability and the protein expression of Ki67 and Bcl-2 in HIPK2-siRNA+H/R group were significantly increased, while the apoptotic rate, the Ca2+ fluorescence inten-sity and the protein levels of cleaved caspase-3, caspase-12, Bax, p-JAK2 and p-STAT3 were significantly decreased (P<0.05). CONCLUSION:Inhibition of HIPK2 gene expression promotes H/R-induced growth of NRK-52E renal tubular epi-thelial cells, and reduces the apoptosis. The mechanism is related to down-regulating the JAK2/STAT3 signaling pathway.
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Objective To evaluate the efficacy and safety of tacrolimus (TAC) therapy in patients with refractory IgA nephropathy. Methods Nine IgA nephropathy patients were included in this study were treated from Jun. 2008 tc Sep. 2013 in Changzheng Hospital of Second Military Medical University. All patients received TAC therapy after the renin-angiotensin system (RAS) blockade therapy and steroid therapy failed. The main outcome was complete or partial remission. Secondary outcomes included the time required to remission, the frequency of recurrence, TAC dosage and adverse events. Results The initial dosage of TAC" was (1. 89 + 0. 33) mg/d. After treatment with TAC for 6 months, 6 patients achieved complete remission, 2 partial remission and 1 treatment resistance, and most of the remission patients achieved remission during the first 2 months of TAC therapy. The urine protein level of enrolled patients was significantly decreased ([3. 05 ± 1. 35] g/24 h vs [0. 85±1. 54] g/24 h. P<0. 05) and the serum album level of all patients was significantly improved ([27. 00±8. 37] g/L vs [37. 33±8. 08] g/L. P<0. 05). One patient receiving TAC" therapy presented worsened hypertension, and no other adverse event was observed in this study. Three of 8 proteinuria remission patients had relapses find achieved remission by adjusting the dosages of steroids and tacrolimus. Conclusion TAC ear improve proteinuria in patients with refractory IgA nephropathy, with less adverse reactions.
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Objective To evaluate the effect of lumbar multifidus muscle training on muscle thickness.Methods The morphological changes in volunteers' lumbar multifidus muscles were observed in response to 11 kinds of training.Muscle thickness was measured at rest and during contraction using ultrasonography and two examiners.The rate of change in muscle thickness and the contraction rate were calculated.Results There was no significant difference in the contraction rates determined by the two examiners using ultrasound imaging.There was no significant difference in average contraction rate between the males and females.Pairwise,there was no significant difference among contralateral leg-raising,ipsilateral leg-raising,contralateral hand-raising,ipsilateral hand-raising and contralateral leg-lifting.Pairwise,there was no significant difference among ipsilateral leg-lifting and ipsilateral arm-lifting compared with contralateral leg-lifting,contralateral arm-lifting or contralaleral lower limb-lifting.There was no significant difference between contralateral arm-lifting and ipsilateral arm-lifting.There was no significant difference between ipsilateral arm-lifting with contralateral leg-lifting and contralateral arm-lifting with ipsilateral leg-lifting.Pairwise,there was a significant difference in lumbar multifidus muscle contraction rates among these actions.Conclusion Lumbar multifidus muscle training has various effects.Muscle thickness as measured using ultrasonography can provide a basis for formulating a rehabilitation training plan.
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Objective To compare intravascular ultrasound (IVUS) and coronary angiography in measuring the lumen diameter and coronary arteries stenosis rate, to investigate the impact of IVUS in the choice of surgical indications, surgical procedure guidance and effects of operation.Methods The patients who underwent percutaneous coronary intervention(PCI) therapy from may 2013 to may 2014 were divided into IVUS-guided intervention therapy group (n=89) and coronary angiographyguided group (n=90).Their baseline parameters, lesion features, MACE and restenosis during follow-up were analyzed.Results Baseline clinical and angiographic characterisitcs were well matched and show no significant differences between the two groups.Compared to angiography-guided group, the minimum lumen diameter (MLD) of IVUS-guided group were higher, diameter stenosis (DS) and lesion length (LL) were lower in IVUS-guided intervention therapy group.The detection rate of calcified and eccentric lesion were significantly higher in IVUS-guided group.There were 204 (93.6 ％) and 195 (87.8％) high-pressure balloons used in post-inflation in two groups, respectively.The MLD and plaque burden of IVUS-guided group were obviously improved after stent implantation.Conclusions IVUS-guided intervention therapy in PCI is safe and effective, may be helpful for the judgment of lesion, evaluating stent implantation and guiding high-pressure balloon post-inflation.IVUS-guided intervention could get the bigger immediate lumen diameter and lower plaque burden than coronary angiography without serious short-term or long-term complications.
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Objective To evaluate the reliability of transversus abdominis muscles measure with ultrasonography. Methods The thick-ness of bilateral transversus abdominis muscles of 20 volunteers at rest and during different postures for training was measured with ultraso-nography by 2 examiners. The rate of contraction was calculated. Results The measurement was correlated strongly between examiners (r>0.7). There was significant difference in variety of thickness among postures except head rise to contralateral leg rise (P<0.01). Conclusion Ultrasonography is reliable in measuring transversus abdominis muscles.
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<p><b>OBJECTIVE</b>To investigate new bone formation of alveolar augmentation with recombinant human bone morphogenetic protein-7 (rhBMP-7) expressed in prokaryocyte.</p><p><b>METHODS</b>To create the model of rabbit extraction socket into which the composites of rhBMP-7 and the gelatin sponge was immediately implanted, then the samples were investigated 2, 4, 8 and 12 weeks postoperatively by gross observation, scanning electron microscope (SEM), quantitative measurement of calcium content and alkaline phosphatase (ALP) activity.</p><p><b>RESULTS</b>There was significant difference in height of alveolar ridge absorpted between the experimental groups and the carrier control groups through gross observation. The result of SEM showed that bone healing in rhBMP-7 groups was 4-6 weeks earlier than that of control groups. ALP activity in rhBMP-7 groups were obviously high compared with that of control groups.</p><p><b>CONCLUSION</b>The BMP-7 has a satisfactory osteoinduction ability to promote new bone formation and prevent alveolar bone absorption.</p>
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Animals , Humans , Rabbits , Alveolar Process , Alveolar Ridge Augmentation , Bone Morphogenetic Protein 2 , Bone Morphogenetic Proteins , Drug Carriers , Osteogenesis , Recombinant Proteins , Transforming Growth Factor betaABSTRACT
<p><b>OBJECTIVE</b>To investigate the efficacy of S-methylisothiourea (SMT) for treatment of temporomandibular joint osteoarthrosis (TMJOA) of goats.</p><p><b>METHODS</b>Nine purebred black goats were randomly devided into three groups: Normal control group, control group and experimental group. The upper compartments of both temporomandibular joint of the goats in control group and experimental group were injected with collagenase only once to induce osteoarthrosis. Normal control group received no treatment. The upper compartments of both TMJ were injected with 0.5 mL of normal saline, and experimental group, the upper compartments of both TMJ were injected with 0.5 mL of SMT. The TMJ of goats was examined with scanning electron microscopy and microscopy after sacrificed.</p><p><b>RESULTS</b>Examined in light microscopy and scanning electron microscopy, normal control group showed normal performance, the control group showed severe osteoarthrotic changes in the temporal surface, disk and condyle, while the experimental group showed improvement of different degree.</p><p><b>CONCLUSION</b>On the basis of 3-month following-up study, repeated intra-articular injection of SMT may play a role in inhibiting TMJOA progression.</p>