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Objective: To evaluate two-drug combination interaction between pyrifazimine(TBI-166) and anti-drug-resistant tuberculosis group A drugs Bedaquiline (BDQ), Moxifloxacin (MFX) and the new anti-tuberculosis drug Delamanid (DLM), SQ109, Q203, and PBTZ169 in vitro and in vivo in mouse, so as to provide basis for TBI-166 combination therapy. Methods: This study was performed from September 2020 to July 2021. The chessboard method was used to evaluate the interaction between TBI-166 and BDQ, MFX, DLM, SQ109, and PBTZ169. The time-killing kinetics method was used to evaluate the anti-tuberculosis activity of the two-drug combination with partial synergy. The BALB/c mouse acute infection model was used to evaluate the anti-tuberculosis activity at 4 and 8 weeks in the two-drug combination group (TBI-166+BDQ, TBI-166+SQ109, TBI-166+PBTZ169, TBI-166+Q203) and monotherapy groups (TBI-166, BDQ, SQ109, PBTZ169, Q203). Data analysis was performed using an independent sample t-test. Results: After TBI-166 combined with anti-tuberculosis drugs, MIC was reduced to 6.25% to 25.00% of TBI-166 monotherapy. After TBI-166 combined with BDQ, SQ109 and PBTZ169, the partial inhibitory concentration index (FICI) values were 0.53, 0.75 and 0.75, respectively; the time sterilization experiment showed that the viable population of Mycobacterium tuberculosis treated with two-drug combination of TBI-166 and BDQ, SQ109, PBTZ169 for 14 days decreased at least 3 log10 CFU/ml. In the mouse experiments, it was found that, the amount of viable bacteria in lung tissue of BDQ, SQ109 and PBTZ169 combined with TBI-166 groups was lower than that of the monotherapy group,respectively. The lung tissue culture of mice in the TBI-166+BDQ group was negative after 4 weeks of treatment, and the number of live bacteria in the lungs of the TBI-166+BDQ group was 1.49 log10CFU lower than that of the BDQ monotherapy group(P<0.01). Conclusion: In vitro and in vivo experiments in mice revealed that TBI-166 had synergistic anti-tuberculosis activity after being combined with BDQ, SQ109 and PBTZ169, respectively.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Animais , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Combinação de Medicamentos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
Objective: To examine the influence of sacroiliac joint reduction quality on the clinical effect of bionic reduction and internal fixation for pelvic ring injury. Methods: From January 2014 to February 2019,the clinical data of 78 patients diagnosed with pelvic ring injury involving sacroiliac joints and treated with bionic reduction and internal fixation at Honghui Hospital Affiliated to Medical College of Xi'an Jiaotong University were retrospectively analyzed.There were 48 males and 30 females,aged (48.3±8.3)years (range:28 to 68 years).After bionic reduction and internal fixation,the patients were grouped according to the maximum displacement distance (d) of sacroiliac joint residual on the damaged side measured by CT examination. Patients with d≤5 mm were included in anatomical bionic reduction group,and patients with d>5 mm were included in non-anatomical bionic reduction group.In non-anatomical bionic reduction group,according to the direction of residual displacement,the patients were divided into separation displacement group and anterior-posterior displacement group. The X-ray examination was performed immediately and at the last follow-up after operation.If sacroiliac joint was relocated,or internal plant loosening,displacement,fracture and re-displacement of fracture,it was defined as internal fixation failure.Majeed pelvic fracture scoring system was used to evaluate the postoperative functional status of the two groups,and visual analogue scale (VAS) was used to evaluate the postoperative pain.Comparison between groups was performed by completely random design ANOVA,χ2 test,Fisher's exact test,Mann-Whitney U and Kruskal-Wallis H test. Results: According to the CT examination,28 cases were included in anatomical bionic reduction group,and 50 cases were included in non-anatomical bionic reduction group.In non-anatomical bionic reduction group,27 cases were divided into separation displacement group and 23 cases were in anterior-posterior displacement group.There was no significant difference in general data among anatomical bionic reduction group,separation displacement group and anterior-posterior displacement group (P>0.05). The follow-up time was (37.8±6.6) months (range:25 to 51 months). At the last follow up,the excellent and good rate of Majeed score in anatomical bionic reduction group was 96.4%(27/28),which was better than that in separation displacement group(74.1%(20/27)) and anterior-posterior displacement group (30.4%(7/23)),the difference was statistically significant (Z=-6.479,P<0.01;Z=-6.256,P<0.01); and the good rate of the separation displacement group was better than that of the anterior-posterior displacement group(Z=-3.607,P<0.01).The VAS of anatomical bionic reduction group (17 cases with 0 point, 11 cases with 1 to 3 points) were lower than that of the displacement group (6 cases with 0 point,16 cases with 1 to 3 points,5 cases with 4 to 6 points) and anterior-posterior displacement group (3 cases with 0 point,7 cases with 1 to 3 points,13 cases with 4 to 6 points),the difference was statistically significant (Z=-3.515,P<0.01;Z=-3.506,P<0.01),and there was no difference between separation displacement group and anterior-posterior displacement group.Total of 8 cases of internal fixation failure occurred,and the failure rate of anatomical bionic reduction group (0,0/28) was lower than that of the separation displacement group (11.1%,3/27) and anterior-posterior displacement group (21.7%,5/23) (P=0.111,P=0.014),and there was no difference between separation displacement group and anterior-posterior displacement group(P=0.444). Conclusions: In the bionic reduction and internal fixation of pelvic fracture involving sacroiliac joint injury,the functional status,pain and internal fixation failure rate of patients with anatomical bionic reduction of sacroiliac joint are significantly better than those in the non-anatomical bionic reduction.The functional recovery of patients with separation displacement is better than that of the patients with anterior and posterior displacement.
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Fraturas Ósseas , Articulação Sacroilíaca , Biônica , Parafusos Ósseos , Feminino , Fixação Interna de Fraturas , Fraturas Ósseas/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Articulação Sacroilíaca/lesões , Articulação Sacroilíaca/cirurgiaRESUMO
Objective: To analyze the characteristic changes of corneal nerve fibers in patients with Parkinson's disease (PD) by corneal confocal microscopy (CCM) and investigate the association of corneal nerve fiber parameters with disease severity and motor symptoms. Methods: Forty-two patients with PD were recruited from the Department of Neurology, Henan University People's Hospital from June 2018 to October 2019. Meanwhile, 40 healthy controls who visited the hospital for physical examination at the same period were enrolled. Corneal nerve fibers in both eyes of all participants were detected by using CCM. The differences of corneal nerve fibers were comparatively analyzed between PD group and healthy controls. Associations of corneal nerve parameters with clinical characteristics such as course of disease, Hoehn and Yahr stage (H-Y stage), unified Parkinson disease rating scale (UPDRS), levodopa equivalent daily dosage (LEDD) were analyzed by using partial correlations. The receiver operating characteristic (ROC) curve was used to analyze the capability of corneal nerve fibers for distinguishing patients with PD from healthy controls. Results: Corneal nerve fiber density (CNFD) in PD group ((19±3)/mm2) was significantly decreased compared with healthy controls ((28±4)/mm2) (t=10.798, P<0.001). However, corneal nerve branch density (CNBD) was significantly increased in PD group ((25±11)/mm2) compared with healthy controls ((18±6)/mm2) (t=-3.427, P=0.001). Meanwhile, corneal nerve fiber length (CNFL) was decreased in PD group ((11.0±2.5) mm/mm2) in comparison with healthy controls ((12.5±1.6) mm/mm2) (t=3.139, P=0.002). ROC curve analysis revealed that CNFD could discriminate PD patients from healthy controls, with an area under the curve of 0.961 3 (95%CI: 92.42-99.84, P<0.000 1). CNFD was negatively correlated with H-Y stage and UPDRS-â ¢ (r=-0.501 and -0.399, both P<0.05). CNBD was significantly negatively associated with H-Y stage, UPDRS-â ¢ and UPDRS-Total (r=-0.622, -0.394 and -0.354, respectively, all P<0.05). CNFL was negatively correlated with H-Y stage, UPDRS-â ¢ and UPDRS-total (r=-0.574, -0.484 and -0.422, respectively, all P<0.05). Conclusion: Small nerve fiber injuries exist in PD patients. Corneal nerve fibers negatively correlates with motor symptoms. CNFD have a good discriminative power to distinguish PD patients from healthy controls and may serve as a marker for PD.
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Doença de Parkinson , Córnea , Humanos , Levodopa , Microscopia Confocal , Fibras NervosasRESUMO
Objective: To explore a modified CT scoring system, its feasibility for disease severity evaluation and its predictive value in coronavirus disease 2019 (COVID-19) patients. Methods: This study was a multi-center retrospective cohort study. Patients confirmed with COVID-19 were recruited in three medical centers located in Beijing, Wuhan and Nanchang from January 27, 2020 to March 8, 2020. Demographics, clinical data, and CT images were collected. CT were analyzed by two emergency physicians of more than ten years' work experience independently through a modified scoring system. Final score was determined by average score from the two reviewers if consensus was not reached. The lung was divided into 6 zones (upper, middle, and lower on both sides) by the level of trachea carina and the level of lower pulmonary veins. The target lesion types included ground-glass opacity (GGO), consolidation, overall lung involvement, and crazy-paving pattern. Bronchiectasis, cavity, pleural effusion, etc., were not included in CT reading and analysis because of low incidence. The reviewers evaluated the extent of the targeted patterns (GGO, consolidation) and overall affected lung parenchyma for each zone, using Likert scale, ranging from 0-4 (0=absent; 1=1%-25%; 2=26%-50%; 3=51%-75%; 4=76%-100%). Thus, GGO score, consolidation score, and overall lung involvement score were sum of 6 zones ranging from 0-24. For crazy-paving pattern, it was only coded as absent or present (0 or 1) for each zone and therefore ranging from 0-6. Results: A total of 197 patients from 3 medical centers and 522 CT scans entered final analysis. The median age of the patients was 64 years, and 54.8% were male. There were 76(38.8%) patients had hypertension and 30(15.3%) patients had diabetes mellitus. There were 75 of the patients classified as moderate cases, as well as 95 severe cases and 27 critical cases. As initial symptom, dry cough occurred in 170 patients, 134 patients had fever, and 125 patients had dyspnea. Reparatory rate, oxygen saturation, lymphocyte count and CURB 65 score on admission day varied among patients with different disease severity scale. There were 50 of the patients suffered from deterioration during hospital stay. The median time consumed for each CT by clinicians was 86.5 seconds. Cronbach's alpha for GGO, consolidation, crazy-paving pattern, and overall lung involvement between two clinicians were 0.809, 0.712, 0.678, and 0.906, respectively, showing good or excellent inter-rater correlation. There were 193 (98.0%) patients had GGO, 147 (74.6%) had consolidation, and 126(64.0%) had crazy-paving pattern throughout clinical course. Bilateral lung involvement was observed in 183(92.9%) patients. Median time of interval for CT scan in our study was 7 days so that the whole clinical course was divided into stages by week for further analysis. From the second week on, the CT scores of various types of lesions in severe or critically patients were higher than those of moderate cases. After the fifth week, the course of disease entered the recovery period. The CT score of the upper lung zones was lower than that of other zones in moderate and severe cases. Similar distribution was not observed in critical patients. For moderate cases, the ground glass opacity score at the second week had predictive value for the escalation of the severity classification during hospitalization. The area under the receiver operating characteristic curve was 0.849, the best cut-off value was 5 points, with sensitivity of 84.2% and specificity of 75.0%. Conclusions: It is feasible for clinicians to use the modified semi-quantitative CT scoring system to evaluate patients with COVID-19. Severe/critical patients had higher scores for ground glass opacity, consolidation, crazy-paving pattern, and overall lung involvement than moderate cases. The ground glass opacity score in the second week had an optimal predictive value for escalation of disease severity during hospitalization in moderate patients on admission. The frequency of CT scan should be reduced after entering the recovery stage.
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COVID-19 , Pulmão/diagnóstico por imagem , Radiografia Torácica/normas , Tomografia Computadorizada por Raios X/métodos , China , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Radiografia Torácica/métodos , SARS-CoV-2 , Análise EspacialRESUMO
Multi-photon-excited thermal-correlated green and red upconversion (UC) emissions have been quantified in Ho3+/Yb3+ co-doped fluotellurite (BZLFT) glass phosphor under the 978 nm laser excitation. The temperature dependence of the fluorescence intensity ratio (FIR) originated from UC emissions bands centered at 550 nm and 661 nm has been verified in the range of 303-543 K. The net emission photon numbers of 5F4+5S2â5I8 and 5F5â5I8 transition emissions are up to 40.08×1012 and 68.51×1012cps in the 0.4wt.%Ho2O3-0.4wt.%Yb2O3 co-doped BZLFT case under the 6.95W/mm2 laser power density. Furthermore, the quantum yield (QY) and luminous flux are determined to be dependent on pumping power. When the excitation power increases 874 mW, the QY values for 550 nm and 661 nm emissions are as high as 0.94×10-5 and 1.60×10-5. In addition, the high photon producing efficiency is conducive to ensuring high feedback to thermosensitive performance. The temperature thermal sensor can be manipulated steadily in medium temperature range, and the relative sensitivity reaches 0.4%K-1 at 303 K, which is 1 order of magnitude larger than those in several rare-earth-doped materials. Efficient photon conversion ability and high temperature sensitivity indicate that the rare-earth-ion-doped fluotellurite material has a prospective application in the construction of optical temperature sensors based on the FIR technique allowing for self-referenced temperature determination.
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Ce3+ doped M3Al5O12 (MAG, M=Lu, Y) glass ceramics (GCs) have been proved to be shapeable phosphors for white lighting driven by a 453 nm laser. Quantitative characterization reflects that the net emission powers of 4 wt% LuAG-doped GC and 4 wt% YAG-doped GC are 59.99 mW and 66.22 mW at the pump power of 117.63 mW, and the quantum yields reach up to 71.1% and 78.0%, respectively. Miniaturization of devices can be achieved for LuAG/YAG-GCs by optimizing sample size and phosphor concentration with maintaining fluorescence intensity of the samples. Presupposed color coordinate trace reveals that the high-brightness white fluorescence can be realized when the appropriate intensity ratio is determined between residual laser and sample emission. The tunable white fluorescence and the efficient radiation releasing illustrate that LuAG/YAG-GCs are potential candidates for application in solid-state laser illumination.
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Objective: To investigate the therapeutic effect of compound allantoin in Kunming mice infected with Helicobacter pylori (H. pylori). Methods: Eighty four male Kunming mice were randomly divided into normal control group, H. pylori infection control group, compound allantoin group, allantoin group, aluminum hydroxide group, triple therapy group, and compound allantoin combined with triple therapy group(drug combination group). The normal control group was administered with normal saline, and other groups were infected with H. pylori for 5 times by intragastric(IG) administration. After 4 weeks, mice were given corresponding drug solutions for 6 times by IG administration. H. pylori infection status was detected by rapid urease test(RUT) and immunohistochemistry assay(IHC). Mucosa damages were assessed by microscopic examination and electron microscopy. Results: The positive rates of the compound allantoin group detected by RUT and IHC were 9.1% and 0, respectively, which were significantly lower than those in the H. pylori infection control group (81.8% and 72.7%).The positive rates of aluminum hydroxide group(54.5% and 54.5%) have no significant difference with those in the allantoin group (27.3% and 18.2%), but were higher than those of compound allantoin group (P<0.05).The positive rate of both methods in the drug combination group were 0, and they were significantly lower than those in the triple therapy group (36.4%,45.5%) (P<0.05). There was no difference between the triple group and the compound allantoin group(P>0.05). The pathological and ultrastructural damage of compound allantoin group was obviously relieved than that of H. pylori infection group. Conclusion: Compound allantoin has therapeutic effect on H. pylori infection in mice, which can be further enhanced by combination with triple therapy group. In addition, compound allantoin can repair gastric mucosal injury caused by H. pylori, and its repair effect may be related to mitochondrial pathway.
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Infecções por Helicobacter , Helicobacter pylori , Alantoína , Animais , Quimioterapia Combinada , Mucosa Gástrica , Masculino , CamundongosRESUMO
OBJECTIVE: For patients who had hemipelvectomies involving the resection of a portion or the whole of the pubis, bony reconstruction was not recommended commonly. However, the soft tissue reconstruction of the lower abdominal wall may benefit these patients. The object of the study was to determine the clinical effect of lower abdominal wall reconstruction with LARS ligament after pubic tumor resection interms of patient-reported and objective outcome. METHODS: In this series, we reviewed twenty-five patients who underwent pubic tumor resection followed by reconstruction with LARS ligament between February 2012 and February 2018 retrospectively. We evaluated the clinical outcome and complication of this surgical treatment. The function outcome was evaluated according the musculoskeletal tumor society scores (MSTS) for all the patients at the end of the last follow-up. RESULTS: All the patients were stable during the surgery. There were eight patients who underwent resection of superior ramus of pubis, five patients who had resection of inferior ramus of pubis, and twelve patients who received both superior and inferior ramus of pubis. For all the patients, the mean blood loss was (774±580) mL. The mean operation time was (138±25) min. The mean hospital stay was (19±6) d. For the patients who had resection of superior ramus, inferior ramus, as well as both superior and inferior ramus, the mean blood loss were (763±802) mL, (730±315) mL and (808±485) mL, respectively. The mean operation time were (133±27) min, (135±35) min and (143±20) min, respectively. The mean hospital stay were (18±5) d, (22±9) d and (19±6) d, respectively. The mean follow-up time was (37±21) months. Local recurrence was observed in one patient with chondrosarcoma. One patient with renal cancer metastasis died of the disease. No ligament infection, ligament related complication and incisional hernias were observed. Twenty-three patients could ambulate without assistive devices, and the remaining two could walk by crutches. Postoperative pain was reported as none in nineteen patients, mild in three, and moderate in three. From a functional point, the mean MSTS score was 87±4. CONCLUSION: Lower abdominal wall reconstruction with LARS ligament after pubic tumor resection could have satisfactory clinical outcome. It could prevent the occurrence of herniation, decrease the infection rate by minishing the dead space, and achieve good patient-reported outcome.
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Parede Abdominal , Procedimentos de Cirurgia Plástica , Próteses e Implantes , Osso Púbico , Humanos , Ligamentos , Recidiva Local de Neoplasia , Osso Púbico/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The giant panda, Ailuropoda melanoleuca (Ursidae), has a unique bamboo-based diet; however, this low-energy intake has been sufficient to maintain the metabolic processes of this species since the fourth ice age. As mitochondria are the main sites for energy metabolism in animals, the protein-coding genes involved in mitochondrial respiratory chains, particularly cytochrome c oxidase subunit II (COX2), which is the rate-limiting enzyme in electron transfer, could play an important role in giant panda metabolism. Therefore, the present study aimed to isolate, sequence, and analyze the COX2 DNA from individuals kept at the Giant Panda Protection and Research Center, China, and compare these sequences with those of the other Ursidae family members. Multiple sequence alignment showed that the COX2 gene had three point mutations that defined three haplotypes, with 60% of the sequences corresponding to haplotype I. The neutrality tests revealed that the COX2 gene was conserved throughout evolution, and the maximum likelihood phylogenetic analysis, using homologous sequences from other Ursidae species, showed clustering of the COX2 sequences of giant pandas, suggesting that this gene evolved differently in them.
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Complexo IV da Cadeia de Transporte de Elétrons/genética , Ursidae/genética , Animais , Metabolismo Energético/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Ursidae/metabolismoRESUMO
Objectives: To explore the expression of micro RNA-24-3p (miR-24-3p) in different gastric mucosa lesions, and analyze the potential correlation between Helicobacter pylori (H.pylori) infection and miR-24-3p expression in different gastric lesions. Methods: 158 gastric biopsy specimens were divided into four groups, including 35 chronic superficial gastritis (CSG) samples, 43 chronic atrophic gastritis (CAG) samples, 41 intestinal metaplasia (IM) samples and 39 dysplasia (Dys) samples. Those samples were collected from patients undergoing gastroscopy at the Department of Gastroenterology, Aerospace Center Hospital, from September 2005 to June 2012. The expression of miR-24-3p was detected using in situ hybridization. H. pylori infection status was determined by rapid urease test and Warthin-Starry stain. Results: Higher expression rate of miR-24-3p was observed in CSG compared with those in CAG, IM and Dys, respectively. The miR-24-3p expression rate in CSG with H. pylori infection was significantly lower than that without H. pylori infection (P=0.001), but it was not observed in CAG, IM and Dys groups (all P>0.05). Conclusions: MiR-24-3p was highly expressed at the early stage of gastric mucosal lesion. Attenuation of miR-24-3p expression is associated with the development of severe gastric mucosa lesions. H. pylori may play a role in miR-24-3p regulation in the early stage of gastric mucosa lesions.
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Infecções por Helicobacter , Helicobacter pylori , Mucosa Gástrica , Humanos , Metaplasia , MicroRNAsRESUMO
Giant panda cubs have a low survival rate during the newborn and early growth stages. However, the growth and developmental parameters of giant panda cubs during the early lactation stage (from birth to 6 months) are not well known. We examined the growth and development of giant panda cubs by the Chapman growth curve model and estimated the heritability of the maximum growth rate at the early lactation stage. We found that 83 giant panda cubs reached their maximum growth rate at approximately 75-120 days after birth. The body weight of cubs at 75 days was 4285.99 g. Furthermore, we estimated that the heritability of the maximum growth rate was moderate (h(2) = 0.38). Our study describes the growth and development of giant panda cubs at the early lactation stage and provides valuable growth benchmarks. We anticipate that our results will be a starting point for more detailed research on increasing the survival rate of giant panda cubs. Feeding programs for giant panda cubs need further improvement.
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Peso Corporal/genética , Padrões de Herança , Ursidae/crescimento & desenvolvimento , Ursidae/genética , Algoritmos , Animais , Animais Recém-Nascidos , Feminino , Lactação , Masculino , Modelos GenéticosRESUMO
An interesting aspect of Newcastle disease virus (NDV) is the ability to selectively replicate in tumor cells. Recently, using reverse genetics technology to enhance the oncolytic properties and therapeutic potential of NDV for tumor therapy has become popular in immunocompetent carcinoma tumor models. Expressing foreign genes by recombinant NDV (rNDV-FG) has been shown to be more effective in cancer therapy in preclinical studies. This paper provides an overview of the current studies on the cytotoxic and anti-cancer effects of rNDV-FG via direct oncolysis and immune stimulation. Safety of rNDV-FG as a therapeutic agent for cancer immunotherapy and virotherapy is also discussed.
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Expressão Gênica , Neoplasias Experimentais/terapia , Vírus da Doença de Newcastle/fisiologia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/fisiologia , Replicação Viral/imunologia , Animais , Humanos , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologiaRESUMO
OBJECTIVE: Residual kidney function (RKF) is an important prognostic indicator in peritoneal dialysis (PD) patients. So far, there are no prediction tools available for RKF, and the association between serum bicarbonate and RKF has received little attention in patients with PD. We aimed to develop a nomogram for the preservation of RKF based on the time-averaged serum bicarbonate (TA-Bic) levels. PATIENTS AND METHODS: A prediction model was established by conducting a retrospective cohort study of 151 PD patients who had been treated at the First Affiliated Hospital of Anhui Medical University. The nomogram was developed using a multivariate Cox regression model. The discrimination, calibration, and clinical utility of the model were evaluated by the C-index, receiver operating curve (ROC) curve, calibration curve, and decision curve analysis. RESULTS: In the elderly PD onset, higher baseline values of residual glomerular filtration rate, total Kt/V and higher TA-Bic levels were identified as protective predictors of RKF loss. The nomogram was conducted on the basis of the minimum value of the Akaike Information Criterion and Bayesian Information Criterion with a reasonable C-index of 0.766, showing great discrimination, proper calibration, and high potential for clinical practice. Through the total score of the nomogram, the patients were classified into the high-risk group and low-risk group, and a higher cumulative incidence of complete RRF loss was found in the high-risk group compared with the patients in the low-risk group. CONCLUSIONS: The novel predictive nomogram model can predict the probability of RKF preservation in long-term PD patients with high accuracy. Future studies are needed to externally validate the current nomogram before clinical application.
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Bicarbonatos , Diálise Peritoneal , Humanos , Idoso , Estudos Retrospectivos , Nomogramas , Teorema de Bayes , Fatores de Risco , RimRESUMO
Antimicrobial peptides represent ancient host defense effector molecules present in organisms across the evolutionary spectrum. Lots of antimicrobial peptides were synthesized based on well-known structural motif widely existed in a variety of lives. Leucine-rich repeats (LRRs) are sequence motifs present in over 60,000 proteins identified from viruses, bacteria, and eukaryotes. To elucidate if LRR motif possesses antimicrobial potency, two peptides containing one or two LRRs were designed. The biological activity and membrane-peptide interactions of the peptides were analyzed. The results showed that the tandem of two LRRs exhibited similar antibacterial activity and significantly weaker hemolytic activity against hRBCs than the well-known membrane active peptide melittin. The peptide with one LRR was defective at antimicrobial and hemolytic activity. The peptide containing two LRRs formed α-helical structure, respectively, in the presence of membrane-mimicking environment. LRR-2 retained strong resistance to cations, heat, and some proteolytic enzymes. The blue shifts of the peptides in two lipid systems correlated positively with their biological activities. Other membrane-peptide experiments further provide the evidence that the peptide with two LRRs kills bacteria via membrane-involving mechanism. The present study increases our new understanding of well-known LRR motif in antimicrobial potency and presents a potential strategy to develop novel antibacterial agents.
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Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Leucina/química , Sequências Repetitivas de Aminoácidos , Sequência de Aminoácidos , Antibacterianos/síntese química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias/efeitos dos fármacos , Desenho de Fármacos , Dados de Sequência Molecular , Estrutura Secundária de ProteínaRESUMO
To observe the evolution of the intestinal microbiota in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and discuss the relationship between the intestinal microbiota and graft-versus-host disease (GVHD). In this study, 11 patients who underwent allo-HSCT in the Aerospace Central Hospital from January 2021 to October 2021 were selected, along with 11 donors. Fecal specimens were collected 7 times: at admission, after pre-treatment, and every 3 weeks after transplantation from patients and once from donors. The composition of the intestinal microbiota and its association with GVHD after allogeneic hematopoietic stem cell transplantation were analyzed by 16S rRNA sequencing. Of the 11 patients, 5 developed GVHD, and 6 did not. The diversity of the intestinal microbiota among GVHD patients first increased and then decreased after transplantation, while that among non-GVHD patients first increased and then tended to be stable. The diversity of the intestinal microbiota among GVHD patients was lower than that among non-GVHD patients before pre-treatment and after transplantation. The taxa diversity of the intestinal microbiota in the non-GVHD group was better than that in the GVHD group before allo-HSCT, and the difference was statistically significant (P<0.05 for OTUs and CHAO1 index). The taxa abundance of Enterococcaceae 2.16% (2.13%, 2.22%) before allo-HSCT was significantly higher than that in the non-GVHD group 1.33% (0.27%, 1.52%), and the difference was statistically significant (P=0.004). There was no significant difference between the GVHD group and the non-GVHD group in the diversity of the intestinal microbiota of donors (P<0.05). The characteristics of the intestinal microbiota in the final sample of patients in the GVHD group were similar to the preoperative structure of the intestinal microbiota. In conclusion: The decrease in the diversity of the intestinal microbiota after HSCT may be a risk factor for the occurrence of GVHD. The presence of Enterococcaceae in the intestinal microbiota may be associated with an increased risk of developing GVHD. The intestinal microbiota reconstitute to be close to the intestinal microbiota composition of the donors in the non-GVHD group.
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Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , RNA Ribossômico 16S/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Fatores de RiscoRESUMO
AIMS: The aim of this paper is to check the effect of salinity on the bioremediation process of petroleum hydrocarbons in the saline-alkaline soil. METHODS AND RESULTS: In this study, soil salinity was adjusted to different levels by water leaching method and the bioremediation process was conducted for 28 days. Soil pH increased after leaching and decreased during bioremediation process. At initial time, moderate salinity enhanced the biodegradation and addition of microbial consortium was not effective in enhancing degradation rate of petroleum hydrocarbons. At day of 28 days, higher degradation rate was found in treatments with more leaching times with a maximum value of 42·36%. Dehydrogenase activity increased with the progress of bioremediation and positive correlation was found between dehydrogenase activity and degradation rate of petroleum hydrocarbons. Denaturing gradient gel electrophoresis analysis result showed decreased microbial community diversity with increased salt content. CONCLUSIONS: The result suggested that salinity had great impact on bioremediation, and leaching and addition of inoculated consortium were effective in enhancing biodegradation of petroleum hydrocarbons in the saline-alkaline soil. SIGNIFICANCE AND IMPACT OF THE STUDY: The result of this study is important for understanding the bioremediation process of petroleum in contaminated soil. New remediation method of petroleum contaminated soil can be developed based on this study.
Assuntos
Hidrocarbonetos/metabolismo , Petróleo/metabolismo , Salinidade , Microbiologia do Solo , Poluentes do Solo/metabolismo , Biodegradação Ambiental , Concentração de Íons de Hidrogênio , Consórcios Microbianos , Campos de Petróleo e Gás , Oxirredutases/metabolismoRESUMO
Pudong White (PDW) pigs, historically originating from Shanghai, are the only Chinese indigenous pigs characterised by their completely white coats, with the exception of Rongchang pigs. However, there is limited information concerning their overall genetic structure or relationship with other breeds, especially the East Chinese (ECN) and European pigs. To uncover the genetic structure, selection signatures, and potential exotic introgression in PDW pigs, we sampled 15 PDW pigs using whole-genome sequencing (~20×). We then conducted in-depth population genetic analyses in 320 pigs from 27 global pig groups, namely, European wild boars, Chinese wild boars, and outgroup. Neighbour-joining tree and principal component analysis confirmed that PDW pigs belonged to the ecotype of ECN pigs. Both f3, D-statistics, and structure analysis showed that PDW pigs shared apparent alleles with Large White (LW) pigs. Three statistics, rIBD, a haplotype heat map and copy number variation, further indicated that PDW pigs shared apparent alleles with LW pigs at the KIT Proto-Oncogene, Receptor Tyrosine Kinase (KIT) and PARG-MARCHF8 loci, suggesting that the lineage of European pigs in PDW originated from LW pigs. After further detecting the KIT mutations in different pig breeds, PDW was confirmed to have the same duplication region 1, duplication region 2, and the splicing mutation on intron 17 of KIT as LW pigs that determine the white coat colour phenotype in European white pigs. We hypothesised that LW pigs were imported to China â¼110-160 years ago according to the admixture time estimate and then crossed with ECN pigs, resulting in the introgression of the KIT alleles that produce the white coat colour phenotype in the PDW pig breed. To our knowledge, this study presents the first thorough description of the genetic structure of PDW pigs via whole-genome resequencing data; moreover, the results provide a basis for the national project for the conservation of this unique Chinese local population.
Assuntos
Variações do Número de Cópias de DNA , Suínos/genética , Alelos , Animais , China , Variação Genética , Genética Populacional , Fenótipo , Sequenciamento Completo do Genoma/veterináriaRESUMO
Ten soil samples collected in Linfen were analyzed for 21 organochlorine pesticides. The concentration of total organochlorine pesticides ranged from 4.3 to 23.2 ng g(-1) in soil from urban areas and from 26.3 to 247.4 ng g(-1) in soil from industrial plants. The highest levels of contamination were observed in northwest and central Linfen, reflecting the distribution of industrial plants. The HCH and DDT profiles revealed that the sources were associated mainly with lindane and technical DDT, respectively, while HCHs in the soil of industrial plants might originate from a new source.
Assuntos
Hidrocarbonetos Clorados/análise , Praguicidas/análise , Poluentes do Solo/análise , China , Cidades , Monitoramento Ambiental , Hidrocarbonetos Clorados/química , Indústrias , Praguicidas/química , Poluentes do Solo/químicaRESUMO
This work describes the induction, purification and partial biochemical characterizations of an antimicrobial protein from the housefly larvae induced by ultrasonic wave. It has been purified to apparent homogeneity by ammonium sulfate precipitation followed by Sephadex G-75, Bio-gel P6 gel filtration, and CM-Sepharose Fast Flow cation exchange chromatography. The protein is a cationic protein with an apparent molecular weight of 16315 Da determined by no-denaturing electrophoresis and SDS-PAGE, respectively. Biochemical profile assays show that this protein has good thermal stability, and repeatedly frozen and defrosted durability. The optimum pH for antimicrobial activity is around pH5. The antimicrobial range of the protein includes Gram-positive, Gram-negative bacteria and some fungi. Results of the membrane permeability assays suggest that the probable mode of action of this protein is membrane-disrupting mechanism.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Moscas Domésticas/metabolismo , Proteínas de Insetos/isolamento & purificação , Proteínas de Insetos/farmacologia , Temperatura , Ultrassom , Fosfatase Alcalina/metabolismo , Animais , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Galactosidases/metabolismo , Concentração de Íons de Hidrogênio , Larva/metabolismoRESUMO
Objective: To explore the evaluation of joint injury by HEAD-US-C (Hemophilic Early Arthropathy Detection with UltraSound in China, HEAD-US-C) in patients with moderate or severe hemophilia A treated with prophylaxis vs on-demand. Methods: The patients from June 2015 to July 2017 with moderate or severe hemophilia A were examined by ultrasound imaging of the elbows, knees and ankles; Meanwhile the HEAD-US-C ultrasound assessment scale and hemophilia joint health score scale 2.1 (HJHS2.1) were used to score the joint status. The correlation between the HEAD-US-C and HJHS score was performed in prophylaxis group and on-demand group patients, respectively. Results: A total of 925 cases of joint ultrasonography were conducted in 70 patients with moderate or severe hemophilia A. Among patients with moderate hemophilia, the median (IQR) of HEAD-US-C score and HJHS score in on-demand group were significantly higher than those in the prophylaxis group[1 (0, 6) vs 0.5 (0, 3) , z=0.177, P=0.046],[2 (0, 4) vs 2 (0, 3) z=0.375, P=0.007], even though there was no significant difference of the median (IQR) number of annualized target joints bleeding episodes between on-demand and prophylaxis groups[1 (0, 7) vs 1 (0, 5) , z=1.271, P=0.137]. Unlike in moderate cases, on-demand treatment group had more annualized target joints bleeding episodes than prophylaxis group among patients with severe hemophilia[3 (0, 8) vs 2 (0, 8) , z=0.780 P=0.037]. The prophylaxis group compared favorably with on-demand therapy group in terms of HEAD-US-C score[1 (0, 6) vs 4 (0, 7) , z=2.189, P=0.008], and HJHS score[2 (0, 5) , 4 (1, 6) , z=3646, P<0.001]for the severe hemophilia patients. The positive correlation between HEAD-US-C score and HJHS score was identified (P<0.05) , whether on-demand treatment or prophylaxis groups. The correlation coefficient between HEAD-US-C score and HJHS score in on-demand treatment and prophylaxis groups were 0.739 (95% CI 0.708-0.708) , 0.865 (95% CI 0.848-0.848) respectively, and 95% CI didn't overlap (P<0.05) , indicating that the correlation coefficient in prophylaxis group had stronger correlation than that in on-demand group. Conclusions: Clinical effects of prophylaxis were significantly better than those of on-demand treatment in patients with moderate or se-vere haemophilia A. HEAD-US-C scoring system could effectively evaluate joints damage in hemophilia A patients treated with on-demand or prophylaxis, companied by significantly positive correlation with HJHS clinical evaluation system, and provided objective index for clinical effect assessment.