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Relationships between people in real life are dynamically changed with the interaction process, and due to the heterogeneous preferences, this change is different from person to person. Based on this observation, we propose a new spatial and weighted prisoner's dilemma game model with heterogeneous individuals. Two types of tags, namely, tag-F (concerned about social fairness) and tag-W (concerned about personal well-being), are introduced to describe individuals' different preferences. The link weights indicating the interaction strength between individuals are updated based on different rules that depend on their tags. Through simulations, we verify that a large link weight control factor and a high proportion of tag-F individuals favor the emergence and persistence of cooperation. In addition, an increase in the link weight sensitivity factor favors the evolution of cooperation when the link weight control factor is small. Moreover, while the level of cooperation increases with the proportion of tag-F type in the population, contrary to our intuition, when the population consists entirely of tag-F individuals, in some cases, cooperation cannot reach a higher level compared with the situation when they are mixed with tag-W type. However, at high dilemma intensities, cooperators emerge only when the entire population consists of tag-F type. These results may provide some new insights into the impact of the evolutionary weighted network with heterogeneous preferences on collective cooperative behavior.
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Comportamento Cooperativo , Dilema do Prisioneiro , Humanos , Teoria dos Jogos , Simulação por Computador , Evolução BiológicaRESUMO
Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5â µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0â µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8â µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200â µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.
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Tiadiazóis , Humanos , Tiadiazóis/farmacologia , Antifúngicos/farmacologia , Antibacterianos/farmacologia , Fungos , Piridinas/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
Four series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC50 values of 0.017 and 0.025 µM, respectively. Compounds 15g and 18c efficiently inhibited extracellular matrix (ECM) deposition in TGF-ß-induced hepatic stellate cells (HSCs), and eventually suppressed HSC activation. Moreover, compound 15g showed a good pharmacokinetic (PK) profile with a favorable half-life (t1/2 = 9.14 h). The results indicated that these compounds exhibited activity targeting ALK5 and may have potential in the treatment of liver fibrosis; thus they are worthy of further study.
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Aminoácidos , Tiazóis , Humanos , Tiazóis/farmacologia , Aminoácidos/farmacologia , Cirrose Hepática/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Imidazóis/farmacologiaRESUMO
ObjectiveBody fluid stains left at crime scenes are frequently trace amounts, while the identification of body fluids through real time fluorogenic quantitative technique often necessitates the repeated detection within the limited sample, as multiple miRNA markers are the basis for the identification. Based on the goal of both the throughput and efficiency improvement of miRNA analysis in trace samples, a duplex real time fluorogenic quantitative PCR assay system was designed to accurately quantify two miRNAs simultaneously, and the system should be further verified by actual sample for the body fluid identification. MethodsThe duplex real time fluorogenic quantitative PCR system of miR-451a to miR-21-5p was established with specially designed primers and probes, and the concentrations of the primers and probes were both optimized. The specificity, sensitivity and reproducibility of the system were validated, while its capability for body fluid identification was assessed using the miR-451a to miR-21-5p ratio. ResultsThe optimized assay system exhibited excellent specificity and repeatability, with coefficients of variation consistently below 8% for both intra- and inter-batch variability. The amplification efficiency of miR-451a and miR-21-5p reached 71.77% and 74.81%, respectively, with high and relatively consistent results. By utilizing this duplex real time fluorogenic quantitative PCR assay system, a total of 58 body fluid samples were analyzed, exhibiting a discrimination rate of 100% between blood and non-blood samples, as well as between peripheral blood and menstrual blood samples. Moreover, the results, obtained from single real time fluorogenic quantitative PCR assay system and duplex real time fluorogenic quantitative PCR assay system, showed no statistically significant difference with randomly selected blood samples (n=20). Compared to previous single real time fluorogenic quantitative PCR assay system, the sensitivity of duplex real time fluorogenic quantitative PCR assay system exhibited remarkable improvement. A minimum input of only 0.1 ng total RNA was sufficient for accurate detection of peripheral blood and menstrual blood samples, while saliva, semen, and vaginal secretion required only 1 ng total RNA for precise identification purposes. Additionally, the duplex real time fluorogenic quantitative PCR assay system successfully differentiated between different types of body fluids in simulated samples under natural outdoor conditions. ConclusionThe duplex real time fluorogenic quantitative PCR assay system effectively reduced both the time and material costs by half compared to the single system, especially suitable for the examination of body fluid stains left at crime scenes, solving the contradiction between the trace amount and the multiple sample volumes demand of repeated real time fluorogenic quantitative PCR. The duplex real time fluorogenic quantitative PCR assay successfully distinguished blood and other body fluid, as well as peripheral blood and menstrual blood samples, which maintains an equivalent capability for body fluid identification with half sample, time and reagent consumption. This system provides an efficient tool for identifying suspicious body fluids, as well as a foundation for more multiplexed real time fluorogenic quantitative PCR assay system research.
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BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.
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The dilemma of global public issues is a grave challenge, characterized by conflicts between rich and poor nations, and a lack of national consensus on future benefits. The impact of initial wealth heterogeneity on the emergence of cooperation in collective risk dilemmas has been a topic of intense debate. In this study, we examine the impact of endogenous endowment heterogeneity on cooperation in collective risk dilemmas. Using a two-stage game model with endogenous endowments, we investigate the dynamics of cooperation and the potential stable-state composition of the population under various parameters. Simulation results show that a higher risk probability leads to greater investment. Besides, cooperative behavior thrives when individuals are encouraged to achieve higher targets by setting small contribution ratios in multiple stages. Moreover, the promotion of cooperation by the benefit coefficient of the first-stage public goods game is influenced by the second-stage contribution ratio. Generally, a higher enhancement factor increases the likelihood of averting risk. However, when the contribution ratio is in the middle range, a moderate level of the enhancement factor yields the best performance in terms of risk aversion. Our findings have offered some information for real-life collective risk games that involve economic game relations between countries.
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Administração Financeira , Humanos , Comportamento Cooperativo , Probabilidade , Investimentos em Saúde , Teoria dos JogosRESUMO
OBJECTIVES: Chromosome segregation 1-like (CSE1L) is abundant and strongly expressed in solid tumors. However, the expression and role of CSE1L in chronic myeloid leukemia(CML) remain largely unknown. MATERIALS AND METHODS: The relative expression levels of CSE1L in bone marrow granulocytes from patients with primary CML and non-hematologic controls were measured by flow cytometry. Cell counting kit-8 analysis, DNA Content Quantitation Assay, and Annexin V-PE/7-AAD staining were applied to assess the effects of CSE1L knockdown on cell proliferation, cell cycle progression, and apoptosis. RESULTS: Elevated expression of CSE1L was detected in bone marrow granulocytes of patients with primary CML. In the CML cell line K562 cells, CSE1L knockdown impaired cell proliferation blocked the cell cycle shift from G0/G1 phase to the S phase, and promoted apoptosis. Knockdown of CSE1L reduced Bcl-2 protein expression and increased Bax protein expression. Meanwhile, knockdown of CSE1L enhanced the expression of phospho-AMPK protein and decreased the expression of phospho-mTOR protein. The expression of total AMPK and mTOR proteins was not affected. In addition, CSE1L expression levels were decreased in imatinib-treated K562 cells. CONCLUSIONS: CSE1L plays a pivotal role in K562 cell survival and growth. These functions may be partially dependent on the AMPK/mTOR signaling pathway to achieve. In addition, CSE1L may have had a future impact on the treatment of CML patients.
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Proteínas Quinases Ativadas por AMP , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Apoptose , Proliferação de Células , Células K562RESUMO
Objective:To establish a visualized nomogram which can predict the rate of 30-day complications in the elderly patients after hip fracture.Methods:A retrospective study was conducted to analyze the clinical data of 1,074 patients with hip fracture aged 60 years and over who had been admitted to Department of Orthopedics, Beijing Hospital from January 2010 to December 2017. There were 335 males and 739 females with an average age of (80.3±7.3) yeas, 529 intertrochanteric fractures of the femur (all fixed with intramedullary nails after closed reduction), and 545 femoral neck fractures (including 470 ones treated with artificial femoral head replacement and 75 ones treated with artificial total hip replacement). The duration between injury to operation was (6.2±3.7) d. After the complications within 30 days after surgery were recorded, the risk factors for postoperative complications were screened using the binary multi-factor logistic regression analysis. The visualized nomogram and calibration graph were established with the risk factors screened.Results:Of the 1,074 patients, 28.49% (306/1,074) suffered from 30-day complications. The multivariate regression analysis showed that age ( OR=1.050, 95% CI: 1.022 to 1.080, P=0.001), time from injury to surgery ( OR=1.043, 95% CI: 1.005 to 1.083, P=0.027), white blood cell count ( OR=1.093, 95% CI: 1.033 to 1.158, P=0.002), serum albumin level ( OR=0.930, 95% CI: 0.883 to 0.980, P=0.007), troponin I ( OR=195.983, 95% CI: 2.224 to 17,268.296, P=0.021), respiratory system comorbidities ( OR=2.020, 95% CI: 1.287 to 3.170, P=0.002),cardiovascular comorbidities ( OR=1.388, 95% CI: 1.098 to 1.754, P=0.006), and neurological system comorbidities ( OR=1.778, 95% CI: 1.346 to 2.349, P<0.001) were the risk factors for 30-day complications after surgery in elderly patients with hip fracture. Based on these risk factors, a nomogram was created, with an area under the curve of 0.714. The calibration graph showed that the incidence predicted was close to that measured. Conclusion:The present study has established a visualized nomogram which can predict the rate of 30-day complications in the elderly patients after hip fracture based on age, time from injury to surgery, white blood cell count, serum albumin levels, troponin I, and cardiovascular, respiratory and neurological complications.
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BACKGROUND: The effects of consolidation chemotherapy (CC) in neoadjuvant therapy in locally advanced rectal cancer (LARC) have been explored. However, the optimal neoadjuvant chemoradiotherapy (NCRT) and surgery interval, regimen, and cycles of chemotherapy remains unclear. AIM: To evaluate the effects of one to two cycles of CC with capecitabine on high-risk patients with LARC without extending NCRT and surgery interval. METHODS: We retrospectively evaluated high-risk patients with LARC, who were defined as having at least one of the following factors by magnetic resonance imaging: depth of invasion beyond the muscularis propria of more than 5 mm (cT3c-cT3d), T4, meso-rectal fascia or extramural vascular invasion positive, and treatment date between January 2015 and July 2019 in our center. Patients were divided into the CC and non-CC group according to whether they received CC (capecitabine 1000 mg/m2 twice daily from days 1 to 14 every 21 d) after NCRT. Propensity score matching (PSM) and inverse probability of treatment weight (IPTW) were used to balance the differences between the two groups. The main outcome was the complete response (CR) rate. RESULTS: A total of 265 patients were enrolled: 136 patients in the CC group and 129 patients in the non-CC group. The median interval was 70 d (range, 37-168). The CR rate was 24.3% and 16.3% (P = 0.107) in the CC and non-CC groups' original samples, respectively. After PSM and IPTW, the CR rate in the CC group was higher than that in non-CC group (27.6% vs 16.2%, P = 0.045; 25.9% vs 16.3%, P = 0.045). The median follow-up was 39.8 mo (range, 2.9-74.8), and there were no differences in 3-year non-regrowth disease-free survival nor overall survival in the original samples (73.2% vs 71.9%, P = 0.913; 92.3% vs 86.7%, P = 0.294), PSM (73.2% vs 73.5%, P = 0.865; 92.5% vs 89.3%, P = 0.612), and IPTW (73.8% vs 72.1%, P = 0.913; 92.4% vs 87.4%, P = 0.294). There was also no difference in grade 2 or higher acute toxicity during neoadjuvant therapy in the two groups (49.3% vs 53.5%, P = 0.492). CONCLUSION: One to two cycles of CC with capecitabine after NCRT was safe and increased the CR rate in high-risk LARC but failed to improve the long-term outcomes.
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The hourly concentrations of 102 volatile organic compounds (VOCs) in Wuhan from June to July in 2019 were obtained using an online monitoring instrument. The ρ(VOCs) varied from 24.9 to 254 µg·m-3, with a mean value of (67.7±32.2) µg·m-3. According to the air quality standard of ozone, the observation period was divided into clean and polluted episodes of O3. The differences in meteorological parameters, VOC concentrations, compositions, sources, and ozone formation potential (OFP) between clean and polluted episodes were analyzed and compared. The average mass concentrations of NOx, CO, and VOCs in polluted periods exceeded those of clean periods by 34.9%, 25.0%, and 27.8%, respectively. The mass concentrations of alkanes, alkenes, aromatic hydrocarbons, and oxygenated volatile organic compounds in polluted periods were higher than those in clean periods by 40.7%, 39.5%, 26.9%, and 21.5%, respectively. The average OFP in polluted periods[(102±69.6) µg·m-3] exceeded that of clean periods by 33.5%. The average contribution rates of LPG combustion, industrial sources, vehicle emissions, natural sources, and solvent usage to VOCs were 3.4%, 2.5%, 0.2%, 1.3%, and 1.4% lower than those of the clean periods, respectively, whereas the gasoline evaporation increased by 8.8% in polluted periods. The contributions of vehicle emissions and gasoline evaporation exhibited higher values in the morning and evening, with lower values in the afternoon, which may have been related to peak vehicles emissions. The contribution of LPG combustion peaked along with the cooking time. The concentration weighted trajectory showed that the main sources of VOCs in polluted periods were from local emissions and surrounding regions in the northeastern direction of Wuhan. In polluted periods, gasoline evaporation and LPG combustion should be emphasized for preventing O3 pollution in the summer in Wuhan.
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Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Gasolina , Ozônio/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análiseRESUMO
Objective:To analyze the epidemiological characteristics of geriatric hip fractures.Methods:This study retrospectively analyzed the clinical characteristics of 2 054 elderly patients with hip fracture aged 60 years and over who were admitted to Beijing Hospital from January 2011 to December 2020.The epidemiological characteristics of geriatric hip fractures were analyzed from the aspects of age, gender, fracture type, length of stay, surgical method and surgical complications.Results:The total number of hip fractures patients admitted from 2011 to 2020 showed a general upward trend in quantity.Among them, there were 1 177 femoral neck fractures(57.3%, 1 177/2 054), and 877 intertrochanteric femoral fractures(42.7%, 877/2 054)with statistical differences in the distribution of fracture types between patients at different ages( χ2=61.727, P<0.001). A total of 1 839 patients chose surgical treatment, accounting for 89.5% of the total number of patients.Artificial femoral head arthroplasty was the most common operation mode for patients with femoral neck fractures(783 cases, 75.4%).534 patients with intertrochanteric femoral fractures(66.8%)were treated with closed reduction and femoral intramedullary nailing.There was a statistically significant difference in operation modes among different fracture types( χ2=1 480.800, P<0.001). The length of hospital stay in patients with femoral neck fracture was(14.2±8.3)days, which was significantly longer than in patients with femoral neck fracture(13.2±10.9)days( t=2.417, P=0.016). There was no significant difference in the time from admission to operation between the two groups[(5.7±3.5)days vs.(5.4±3.3)days]( t=1.954, P=0.051). Among all the comorbidities of hip fracture patients, the top 5 diseases were cardiovascular system diseases(2 001 cases, 97.4%), nervous system diseases(1 105 cases, 53.8%), endocrine system diseases(814 cases, 39.6%), skeletal and muscular system diseases(623 cases, 30.3%), digestive system diseases(472 cases, 23.0%).1 485 patients(72.3%)had 3 or more comorbidities. Conclusions:Hip fractures in the elderly have some epidemiological distribution characteristics in terms of age, gender, length of hospitalization, injury mechanism and comorbidities, which is conducive to further improve the prevention and treatment strategies for hip fractures and promote the rational allocation of medical resources.
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Objective:To evaluate the effects of percutaneous kyphoplasty(PKP)and percutaneous vertebroplasty(PVP)operation in elderly patients with osteoporotic vertebral compression fracture(OVCF).Methods:From June 2019 to June 2020, a total of 58 patients with OVCF aged over 60 and under 80 years who had a loss of more than one-third of the anterior margin height of vertebral and agreed to participate in the study were randomly divided into PKP group and PVP group.The visual analogue pain scale(VAS)score, SF-36 quality of life score, anterior height of fractured vertebral body, leakage of bone cement, refracture and cost of high-value consumables were observed at the time point before operation, 1 day, 1 month, 3 month, 6 month, 12 month after operation.Results:VAS scores in PKP and PVP groups were decreased after operation as compared with preoperation( F=115.380, 175.010, both P<0.001). VAS score was lower in the PKP group than in the PVP group at 6 months after operation with statistically significant difference( t=2.219, P=0.031), and no statistically significant difference at other time points between the two groups(all P>0.05). In the PKP and PVP groups, the height of the anterior edge of the vertebral body recovered significantly on the first day after operation, and there was a significant difference in the height compared with that before operation( F=43.020, 51.010, both P<0.001). The SF-36 scores at the latter time point in PKP and PVP groups were increased as compared with the previous time point.The increment of the SF-36 scores was statistically significant at 1 month after operation than pre-operation, and also at 3 months after operation than at 1 month after operation.The leakage rate of bone cement was 37.0%(10/27)in PKP group and 25.0%(7/28)in PVP group, with no significant difference between the two groups( χ2=0.930, P=0.391). The refracture rate was 3.7%(1/27)in PKP group and 7.1%(2/28)in PVP group, with no significant difference between the two groups( χ2=0.000, P=1.000). The cost of high-value consumables for single segment fracture was 46 490 yuan in PKP group, and 36 700 yuan in PVP group.The cost of PKP group was higher than that of PVP group. Conclusions:PKP and PVP operation in the treatment of osteoporotic vertebral compression fractures have good effects in aspect of analgesia, restoring vertebral height and improving patients' quality of life.The analgesic effect is slightly better in PKP group than in PVP group.PVP group has more advantages in health economics.
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Objective:To analyze the risk factor of postoperative delirium in the elderly hip fracture patients.Methods:A total of 1051 patients with hip fracture aged 60 years and over, admitted to Beijing Hospital from January 2010 to December 2017 were retrospectively analyzed.They were divided into a postoperative delirium group(n=156)with 56 males and 100 females, 81 femoral neck fractures and 75 intertrochanteric fractures, and the control group(n=895)with no delirium, receiving the corresponding treatment in the same period.The complications, laboratory tests, fracture types, operation methods, the time from fracture to operation, operation time, intraoperative blood loss, intraoperative blood transfusion were compared between the two groups.Risk factors of postoperative delirium in the elderly hip fracture patients were screened using the binary multi-factor logistic regression analysis.Results:Of the 1 051 patients, 156 cases(14.8%)delirium occurred.There was no significant difference in fracture type and operation methods( P>0.05)between the 2 groups.The age was significantly older in the observation group(82.9±6.6)years than in the control group(79.9±7.2)years.The serum albumin before operation(37.1±2.9)g/L, creatinine clearance rate(52.4±22.2)ml·min -1·(1.73 m 2) -1in the observation group were significantly lower than in the control group[(37.8±3.8)g/L, (59.0±30.0)ml·min -1·(1.73 m 2) -1]( P<0.05). The past dementia rate was higher in delirium group[19.8%(31 cases)]than in control group[2.2%(20 cases)], with statistically significant difference( χ2=89.503, P<0.01). The proportion of patients with more than two medical diseases was higher in delirium group[51.9%(81 cases)]than in control group[40.3%(361)]( χ2=7.320, P<0.01). There were no significant differences(all P>0.05)between.the two groups in hemoglobin, white blood cell, serum K and Na, American Society of Anesthesiologists(ASA)grade, and the incidences of Parkinson's disease, pulmonary diseases and cardiovascular diseases(all P>0.05). The binary multi-factor Logistic regression analysis showed that the age, past dementia and kidney dysfunction were the risk factors for the postoperative delirium in the elderly hip fracture patients(all P>0.05). Conclusions:The incidence of postoperative delirium in the elderly hip fractures patients is high.Age, past dementia and kidney dysfunction are the risk factors for postoperative delirium in the elderly hip fracture patients, which should be prevented and improved preoperatively.
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OBJECTIVES@#To establish a system for simultaneous detection of miR-888 and miR-891a by droplet digital PCR (ddPCR), and to evaluate its application value in semen identification.@*METHODS@#The hydrolysis probes with different fluorescence modified reporter groups were designed to realize the detection of miR-888 and miR-891a by duplex ddPCR. A total of 75 samples of 5 body fluids (including peripheral blood, menstrual blood, semen, saliva and vaginal secretion) were detected. The difference analysis was conducted by Mann-Whitney U test. The semen differentiation ability of miR-888 and miR-891a was evaluated by ROC curve analysis and the optimal cut-off value was obtained.@*RESULTS@#There was no significant difference between the dual-plex assay and the single assay in this system. The detection sensitivity was up to 0.1 ng total RNA, and the intra- and inter-batch coefficients of variation were less than 15%. The expression levels of miR-888 and miR-891a detected by duplex ddPCR in semen were both higher than those in other body fluids. ROC curve analysis showed that the AUC of miR-888 was 0.976, the optimal cut-off value was 2.250 copies/μL, and the discrimination accuracy was 97.33%; the AUC of miR-891a was 1.000, the optimal cut-off value was 1.100 copies/μL, and the discrimination accuracy was 100%.@*CONCLUSIONS@#In this study, a method for detection of miR-888 and miR-891a by duplex ddPCR was successfully established. The system has good stability and repeatability and can be used for semen identification. Both miR-888 and miR-891a have high ability to identify semen, and the discrimination accuracy of miR-891a is higher.
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Feminino , Humanos , Masculino , Líquidos Corporais/química , MicroRNAs/análise , Reação em Cadeia da Polimerase em Tempo Real/métodos , Saliva/química , Sêmen/químicaRESUMO
OBJECTIVE@#To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice.@*METHODS@#Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation.@*RESULTS@#Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine.@*CONCLUSION@#ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.
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Animais , Camundongos , Remodelação das Vias Aéreas , Enzima de Conversão de Angiotensina 2 , Cloreto de Metacolina , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ozônio/efeitos adversos , PneumoniaRESUMO
BACKGROUND: p50-associated cyclooxygenase-2 extragenic RNA (PACER) is a recently identified antisense long non-coding RNA (lncRNA) located on the upstream of the promoter region of cyclooxygenase-2 (COX-2). Preliminary studies have suggested that PACER is involved in the regulation of COX-2 expression in macrophagocyte and osteosarcoma cells. However, the role of this lncRNA in colorectal cancer (CRC) remains elusive. Here, we investigated the expression of PACER and its effect on cell proliferation and invasion to explore the role of PACER in CRC. METHODS: Real-time quantitative PCR (RT-qPCR) analysis was used to evaluate the expression of PACER in CRC tissues and cells. Methyl thiazolyl tetrazolium (MTT) analysis was then used to investigate the inhibition effect of PACER knock-down in cell proliferation. The promoting role of this lncRNA on invasion by CRC cells was analysed by wound-healing assays, colony-formation assay, and transwell assays. We then used fluorescence in situ hybridization (FISH) to establish the subcellular localization of PACER. COX-2 protein levels were quantified by Western blot analysis and grayscale scanning analysis following the knock-down of PACER. Luciferase assay was carried out to monitor the modulation of the COX-2 promoter region by PACER. Tumor xenografts models were used to investigate the impact of PACER on the tumorigenesis of CRC cells in vivo. Enzyme-linked immunosorbent assay (ELISA) was then used to quantify prostaglandin E2 (PGE2) production upon knock-down of PACER. RESULTS: RT-qPCR analysis revealed that PACER was highly expressed in CRC tissues and cells, and a high PACER-expression level was associated with poor prognosis. MTT assay, wound-healing assay, colony-formation assay, and transwell assay revealed that PACER enhanced CRC-cell proliferation, invasion, and metastasis in vitro. Analysis of lncRNA localization by FISH showed that it mainly resided in the nucleus. RT-qPCR showed that PACER increased mRNA levels of COX-2. Western blot analysis demonstrated, under normal circumstances, that knock-down of PACER decreased the COX-2 protein level. In the case of p50 absence, COX-2 protein increased rapidly and remained highly expressed after knocking down PACER. Luciferase assay revealed that PACER modulated the COX-2 promoter region. Mouse xenograft models of CRC revealed that PACER promoted colorectal tumorigenesis in vivo. ELISA revealed that PACER knock-down inhibited PGE2 production. CONCLUSIONS: PACER modulates COX-2 expression through the nuclear factor kappa B (NF-κB) pathway in CRC. An increased level of PACER enhances proliferation, migration, and invasion of tumor cells by increasing COX-2 and PGE2 synthesis.
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Objective:To evaluate our self-designed stick supporting reposition which was used to treat irreducible intertrochanteric fractures.Methods:A retrospective study was conducted of the 138 patients with irreducible intertrochanteric fracture (an observational group) who had been treated by stick supporting reposition followed by intramedullary nailing at Department of Orthopaedics, Beijing Hospital between April 2015 and December 2019. They were 45 males and 93 females with an age of (79.9±8.2) years; by AO classification, there were 25 cases of type 31-A1, 98 cases of type 31-A2 and 15 cases of type 31-A3. The other 142 patients with irreducible intertrochanteric fracture were included as a control group who had been treated by open or limited open reduction and intramedullary nailing between January 2010 and March 2015. The 2 groups were compared in terms of reduction time, operation time, intraoperative blood loss, reduction quality, fracture union time and complications.Results:The 2 groups were comparable because there was no significant difference between them in preoperative general data or follow-up time ( P>0.05). The reduction time [(12.0±3.4) min], operation time [(64.1±6.5) min], and intraoperative blood loss [(228.0±40.0) mL] in the observational group were significantly less than those in the control group [(18.3±8.9) min, (72.3±11.2) min and (319.1±95.0) mL] ( P<0.05). The reduction quality in the observational group (82 excellent and 56 acceptable cases) was significantly better than that in the control group (63 excellent, 65 acceptable and 14 poor cases) ( P<0.05). The fracture union time for the observational group [(3.8±0.9) months] was significantly shorter than that for the control group [(4.0±0.9) months] ( P>0.05). There were 6 cases of internal fixation failure and 8 cases of hip varus deformity in the control group, but no such complications occurred in the observational group. Conclusion:In the treatment of irreducible intertrochanteric fractures, compared with open or limited open reduction, our stick supporting reposition may shorten operation time, reduce intraoperative blood loss and improve quality of fracture reduction.
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Objective:To explore the advantages and disadvantages of anterior versus posterior approach surgery in the treatment of cervical spinal cord injury without radiographic abnormality in elderly patients.Methods:Clinical data of 31 geriatric patients of spinal cord injuries without radiographic abnormality in our department from January 2014 to December 2018 were retrospectively analyzed for the cause of injury and the extent of injury.The patients were divided into two groups: anterior approach operation group and posterior approach operation group.The operation time, blood loss, volume of drainage, Japanese Orthopaedic Association(JOA)score before operation and 3 weeks, 3 months, 6 months, 12 months after operation, were recorded in the two groups.Results:Comparing the anterior versus posterior approach operation groups, the median operation time were 100.0(90.0, 110.0)min versus 132.5(123.7, 140.0)min, the median bleeding volume was 30.0(20.0, 35.0)ml versus 175.0(150.0, 202.5)ml, and the median postoperative drainage volume was 20.0(10.0, 20.0)ml versus 210.0(197.5, 237.5)ml, respectively, with statistically significantly differences between the two groups( U=18.00、0.00、0.00, all P<0.01). When comparing the anterior versus posterior approach operation groups, the median JOA scores at 5 time points were 4.0(3.0, 5.0), 6.0(5.5, 8.5), 9.0(8.5, 11.0), 11.0(10.0, 12.5), 12.0(11.0, 13.0)in the anterior operation group, and 4.0(3.0, 7.3), 6.5(5.7, 10.0), 10.5(8.7, 12.3), 12.5(11.0, 13.0), 13.0(11.0, 13.3)in the posterior operation group, with no significantly difference between the two groups( U=89.01, 90.03, 85.50, 74.02, 89.54, P=0.52, 0.55, 0.42, 0.20, 0.52), but there was significant difference in the median JOA scores at each of five different time points( χ2=82.46, 39.23, all P<0.01). Interestingly, the JOA score was higher at the latter time point than at the previous time point, with statistically significantly differences(all P<0.05). Conclusions:Both anterior and posterior approaches for decompression surgery have good effects on the recovery of spinal cord function in geriatric patients with cervical spinal cord injury without radiographic abnormality.Anterior approaches for decompression surgery are better than posterior approaches for the less operation time, less bleeding, less drainage and quickly recovery.
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Objective:To investigate the clinical effectiveness of vertebroplasty for osteoporotic vertebral compression fractures in the elderly aged 90 years and over.Methods:Clinical data of 64 elderly patients aged 90 years and over who had undergone percutaneous vertebroplasty for vertebral compression fractures between January 2015 and January 2021 were retrospectively analyzed.Changes in preoperative and postoperative pain, intraoperative bone cement leakage, postoperative pneumonia, bedsores, urinary tract infections, lower extremity venous thrombosis and changes in preoperative and postoperative physical mobility were evaluated.Pain scores, physical mobility scores, bone cement extravasation and complications such as re-fractures of the vertebral body, postoperative pneumonia, bedsores, urinary tract infections and thrombosis were recorded before surgery, 3 and 30 days after surgery.Results:The visual analogue scale(VAS)scores of 64 patients before surgery, 3 and 30 days after the procedure were 8.34±1.12, 2.17±1.45 and 1.83±1.15, retrospectively( F=540.876, P<0.01). The physical mobility scores before surgery, 3 and 30 days after the procedure were 2.83±0.94, 1.59±0.70 and 1.39±0.60, retrospectively( F=65.492, P<0.01). There were 18 cases(28.13%)of bone cement leakage during surgery, 4 cases(6.25%)of pneumonia within 30 days after surgery, 9 cases(14.06%)of urinary tract infections, 3 cases(4.69%)of lower extremity venous thrombosis, 1 case(1.56%)of bedsores, and 2 cases(3.13%)of vertebral re-fractures after surgery.No patient died during the 30-day follow-up. Conclusions:Percutaneous vertebroplasty can reduce pain and improve physical mobility and is an effective and safe minimally invasive treatment for elderly patients with spinal compression fractures aged 90 years and over.
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Background: The impact of the timing of bone metastasis (BM) diagnosis on colorectal cancer (CRC) patients is unclear. Our study aimed to explore the differences in clinicopathological characteristics, treatments and prognosis between synchronous BM (SBM) and metachronous BM (MBM) from CRC. Methods: We retrospectively investigated clinical data of CRC patients with SBM or MBM from 2008 to 2017 at Chinese National Cancer Center. Cancer specific survival (CSS) after BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the prognostic factors of CSS. Results: Finally, 63 CRC patients with SBM and 138 CRC patients with MBM were identified. Compared to SBM from CRC, MBM significantly was more involving multiple bone lesions (63.0 vs. 7.9%; p < 0.001), and more frequently originated from rectal cancer (60.9 vs. 41.3%; p = 0.033). The therapeutic strategies in SBM and MBM group were contrasted including systemic treatment, bisphosphonates, radiotherapy and metastasectomy for BM. 85.5% of patients in MBM group and 25.4% of patients in SBM group underwent primary tumor resection at initial diagnosis (p < 0.001). The median CSS was 11 months in both SBM and MBM group (p = 0.556), yet MBM patients developed from CRC in early AJCC stage presented obviously longer survival than those from advanced stage. Furthermore, patients could have improved CSS from primary tumor resection while there might be no survival benefit from targeted therapy in both SBM and MBM groups. Bisphosphonates was associated with a better CSS for patients with SBM, while radiotherapy for BM was related to a better CSS for patients with MBM. Conclusion: The CRC patients in SBM and MBM group represented different clinicopathological characteristics and treatment modalities, which affected the prognosis in different ways. Distinct consideration for CRC patients with SBM and MBM in clinical decision making is required.